What is Journal Therapy?

Introduction

Journal therapy is a writing therapy focusing on the writer’s internal experiences, thoughts and feelings. This kind of therapy uses reflective writing enabling the writer to gain mental and emotional clarity, validate experiences and come to a deeper understanding of themself. Journal therapy can also be used to express difficult material or access previously inaccessible materials.

Like other forms of therapy, journal therapy can be used to heal a writer’s emotional or physical problems or work through a trauma, such as an illness, addiction, or relationship problems, among others. Journal therapy can supplement an on-going therapy, or can take place in group therapy or self-directed therapy.

Brief History

Ira Progoff created the intensive journal writing programme in 1966 in New York. The intensive journal method is a structured way of writing about nature that allows the writer to achieve spiritual and personal growth. This method consists of a three-ring, loose-leaf binder with four colour-coded sections: lifetime dimension, dialogue dimension, depth dimension and meaning dimension. These sections are divided into several subsections. Some of these subsections include topics like career, dreams, body and health, interests, events and meaning in life. Progoff created the intensive journal so that working in one part of the journal would in turn stimulate one to work on another part of the journal, leading to different viewpoints, awareness and connections between subjects. The intensive journal method began with recording the session in a daily log.

The field of journal therapy reached a wider audience in the 1970s with the publication of three books, namely, Progoff’s At a Journal Workshop (1978), Christina Baldwin’s One to One: Self-Understanding Through Journal Writing (1977) and Tristine Rainer’s The New Diary (1978).

In 1985, psychotherapist and journal therapy pioneer, Kathleen Adams, started providing journal workshops, designed as a self-discovery process.

In the 1990s, James W. Pennebaker published multiple studies which affirmed that writing about emotional problems or traumas led to both physical and mental health benefits. These studies drew more attention to the benefits of writing as a therapy.

In the 2000s, journal therapy workshops were conducted at the Progoff’s Dialogue House, Adams’ Centre for Journal Therapy and certificates were given through educational institutions. Generally, journal therapists obtain an advanced degree in psychology, counselling, social work, or another field and then enter a credentialing programme or independent-study programme.

Effects

Journal therapy is a form of expressive therapy used to help writers better understand life’s issues and how they can cope with these issues or fix them. The benefits of expressive writing include long-term health benefits such as better self-reported physical and emotional health, improved immune system, liver and lung functioning, improved memory, reduced blood pressure, fewer days in hospital, fewer stress-related doctor visits, improved mood and greater psychological well-being. Other therapeutic effects of journal therapy include the expression of feelings, which can lead to greater self-awareness and acceptance and can in turn allow the writer to create a relationship with his or herself. The short-term effects of expressive writing include increased distress and psychological arousal.

Practice

Many psychotherapists incorporate journal “homework” in their therapy but few specialise in journal therapy. Journal therapy often begins with the client writing a paragraph or two at the beginning of a session. These paragraphs would reflect how the client is feeling or what is happening in his or her life and would set the direction of the session. Journal therapy then works to guide the client through different writing exercises. Subsequently, the therapist and the client then discuss the information revealed in the journal. In this method, the therapist often assigns journal “homework” that is to be completed by the next session. Journal therapy can also be provided to groups.

Techniques

Journal therapy consists of many techniques or writing exercises. In all journal therapy techniques, the writer is encouraged to date everything, write quickly, keep writings and always tell the complete truth. Some of the journal therapy techniques are as follows:

TechniqueOutline
SprintCatharsis is encouraged by allowing a writer to write about anything for a designated period, such as for five minutes or for ten minutes.
ListsThe writer writes any number of connected items in order to help prioritize and organize.
Captured MomentsWriter attempts to completely describe the essence and emotional experience of a memory.
Unsent LettersThis attempts to silence a writer’s internal censor; it can be used in a grieving process or to get over traumas, such as sexual abuse.
DialogueThe writer creates both sides to a conversation involving anything, including but not limited to, people, the body, events, situations, time etc.
FeedbackImportant to journal therapy as feedback makes the writer be aware of his or her feelings; it also allows the writer to acknowledge, accept and reflect on what they he/she has written before (thoughts, feelings, etc.).

Setting

A quiet and private environment must be created and provided throughout the entire journal writing process. This environment should contain features or elements that can make the writer feel good such as music, candles, a hot drink etc. This environment works to empower the writer and for him/her to associate good feelings with journal writing. To transition into writing, a journal writing session can be started with a drawing or sketch. After journal writing, something active should be done, such as running, walking, stretching, breathing etc. or something that is enjoyable like taking a bubble bath, baking cookies, listening to music, talking to someone, etc.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Journal_therapy >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Writing Therapy?

Introduction

Writing therapy is a form of expressive therapy that uses the act of writing and processing the written word as therapy. Writing therapy posits that writing one’s feelings gradually eases feelings of emotional trauma. Writing therapeutically can take place individually or in a group and it can be administered in person with a therapist or remotely through mailing or the Internet.

The field of writing therapy includes many practitioners in a variety of settings. The therapy is usually administered by a therapist or counsellor. Several interventions exist online. Writing group leaders also work in hospitals with patients dealing with mental and physical illnesses. In university departments they aid student self-awareness and self-development. When administered at a distance, it is useful for those who prefer to remain personally anonymous and are not ready to disclose their most private thoughts and anxieties in a face-to-face situation.

As with most forms of therapy, writing therapy is adapted and used to work with a wide range of psychoneurotic issues, including bereavement, desertion and abuse. Many of these interventions take the form of classes where clients write on specific themes chosen by their therapist or counsellor. Assignments may include writing unsent letters to selected individuals, alive or dead, followed by imagined replies from the recipient, or a dialogue with the recovering alcoholic’s bottle of alcohol.

Research into the Therapeutic Action of Writing

The Expressive Writing Paradigm

Expressive writing is a form of writing therapy developed primarily by James W. Pennebaker in the late 1980s. The seminal expressive writing study instructed participants in the experimental group to write about a ‘past trauma’, expressing their very deepest thoughts and feelings surrounding it. In contrast, control participants were asked to write as objectively and factually as possible about neutral topics (e.g. a particular room or their plans for the day), without revealing their emotions or opinions. For both groups, the timescale was 15 minutes of continuous writing repeated over four consecutive days. It was also instructed that should a participant run out of things to write, they should go back to the beginning and repeat themselves, perhaps writing a little differently.

Typical writing instructions include:

For the next 4 days, I would like you to write your very deepest thoughts and feelings about the most traumatic experience of your entire life or an extremely important emotional issue that has affected you and your life. In your writing, I’d like you to really let go and explore your deepest emotions and thoughts. You might tie your topic to your relationships with others, including parents, lovers, friends, or relatives; to your past, your present or your future; or to who you have been, who you would like to be or who you are now. You may write about the same general issues or experiences on all days of writing or about different topics each day. All of your writing will be completely confidential.

Don’t worry about spelling, grammar or sentence structure. The only rule is that once you begin writing, you continue until the time is up.

Several measurements were made before and after, but the most striking finding was that relative to the control group, the experimental group made significantly fewer visits to a physician in the following months. Although many report being upset by the writing experience, they also find it valuable and meaningful.

Pennebaker has either written or co-written over 130 articles on expressive writing. One of these suggested that expressive writing has the potential to actually ‘boost’ the immune system, perhaps explaining the reduction in physician visits. This was shown by measuring lymphocyte response to the foreign mitogens phytohaemagglutinin (PHA) and concanavalin A (ConA) just prior to and 6 weeks after writing. The significantly increased lymphocyte response led to speculation that expressive writing enhances immunocompetence. The results of a preliminary study of 40 people diagnosed with Major Depressive Disorder suggests that routinely engaging in expressive writing may be effective in reducing symptoms of depression.

Reception and Criticism of Pennebaker’s Expressive Writing Theories

Pennebaker’s experiments, begun over twenty years ago, have been widely replicated and validated. Following on from Pennebaker’s original work, there has been a renewed interest in the therapeutic value of abreaction. This was first discussed by Josef Breuer and Freud in Studies on Hysteria but not much explored since. At the heart of Pennebaker’s theory is the idea that actively inhibiting thoughts and feelings about traumatic events requires effort, serves as a cumulative stressor on the body, and is associated with increased physiological activity, obsessive thinking or ruminating about the event, and longer-term disease. However, as Baikie and Wilhelm note, the theory has intuitive appeal but mixed empirical support:

Studies have shown that expressive writing results in significant improvements in various biochemical markers of physical and immune functioning (Pennebaker et al, 1988; Esterling et al, 1994; Petrie et al, 1995; Booth et al, 1997). This suggests that written disclosure may reduce the physiological stress on the body caused by inhibition, although it does not necessarily mean that disinhibition is the causal mechanism underlying these biological effects. On the other hand, participants writing about previously undisclosed traumas showed no differences in health outcomes from those writing about previously disclosed traumas (Greenberg & Stone, 1992) and participants writing about imaginary traumas that they had not actually experienced, and therefore could not have inhibited, also demonstrated significant improvements in physical health (Greenberg et al, 1996). Therefore, although inhibition may play a part, the observed benefits of writing are not entirely due to reductions in inhibition.

In a 2013 article by Nazarian and Smyth, writing instructions for the expressive writing task were manipulated – in that 6 conditions were created – i.e. cognitive-processing, exposure, self-regulation, and benefit-finding, standard expressive writing and a control group. While salivary cortisol was measured for each condition, none of the conditions significantly influenced cortisol, but instructions did impact mood differentially depending on the condition. For example, the cognitive-processing as measured post-intervention were influenced not only by the cognitive processing instructions but also by exposure and benefit-finding. These results demonstrate a spill-over effect from instructions to outcomes. In related research Travagin, Margola, Dennis and Revenson cognitive-processing instructions were compared to standard expressive writing for adolescents with peer problems and this research demonstrated better long-term social adjustment compared to standard expressive writing and greater increased positive affect for those adolescents who reported more peer problems than most.

Other Theories Related to Writing Therapy

An additional line of enquiry, which has particular bearing on the difference between talking and writing, derives from Robert Ornstein’s studies into the bicameral structure of the brain. While noting that what follows should be considered “wildly hypothetical”, L’Abate, quoting Ornstein, postulates that:

One could argue … that talk, and writing differ in relative cerebral dominance. … if language is more related to the right hemisphere, then writing may be more related to the left hemisphere. If this is the case, then writing might use or even stimulate parts of the brain that are not stimulated by talking.

Julie Gray, founder of Stories Without Borders notes that “People who have experienced trauma in their lives, whether or not they consider themselves writers, can benefit from creating narratives out of their stories. It is helpful to write it down, in other words, in safety and in non-judgement. Trauma can be quite isolating. Those who have suffered need to understand how they feel and also to try to communicate that to others.”

Clinical Implications of Writing Therapy

Additional research since the 1980s has demonstrated that expressive writing may act as an agent to increase long-term health. Expressive writing can result in physiological, psychological, and biological outcomes, and is part of the emerging medical humanities field. Experiments demonstrate quantitative physiological readout such as changes in immune counts, blood pressure, in addition to qualitative readouts relating to psychiatric symptoms. Past attempts at implementing expressive writing interventions in clinical settings indicate that there are potential benefits for treatment plans. However, the specifics of such expressive writing procedures or protocols, and the populations most likely to benefit are not entirely clear.

Potential Benefits of Expressive Writing

One of the most important aspects of expressive writing used in therapy is the short-term, and long-term effects on the individuals participating. Karen Baikie and Kay Wilhelm go into a brief description of the effects people will have after completing a therapeutic expressive writing session.

The short-term effects after utilising this form of therapy are usually a quick span of feeling distress or being in a negative mood. However, following up with clients after a longer amount of time to measure those effects finds evidence of many mental and physical health benefits.

These benefits include but are not limited to: “Reduced blood pressure, improved mood, reduced depressive symptoms, and fewer post-traumatic intrusion/avoidance symptoms.”

This study also showed that these positive long-term emotional outcomes correlated to positive physical outcomes such as: improved memory, improved performance at work, quicker re-employment and many more. While the short-term effects of this therapeutic practice may seem daunting, in reality they are just the steppingstones for individuals to begin a cycle of growth.

Potential Benefits for Cancer Patients

Illness and disease are experienced on multiple different fronts: biological, psychological, and social. Recent research has explored how narrative medicine and expressive writing, independently, may play a therapeutic role in chronic diseases such as cancer. Comparisons in practice have been made between expressive writing and psychotherapy. Similarly, practices such as: integrative, holistic, humanistic or complementary medicine have already been incorporated into the field. Expressive writing is self-administered with minimal prompting. With further research and refinement, it may be used as a more cost effective alternative to psychotherapy.

Recent experiments, systematic reviews, and meta-analyses examining the effects of expressive writing on ameliorating negative cancer symptoms yielded primarily non-significant initial results. However, analysis of sub-groups and moderating variables suggest that particular symptoms, or situations, may benefit some more than others with the implementation of an expressive writing intervention. For example, a review by Antoni and Dhabhar (2019) examined how psychosocial stress negatively impacts the immune response of patients with cancer. Even if an expressive writing intervention cannot directly impact cancer prognosis, it may play an important role in mediating factors such as chronic stress, trauma, depression, and anxiety.

Potential Benefits for Individuals Recovering from Addiction

The impact of writing therapy for those struggling with addiction plays a significant role in their recovery treatment. Writing exercises – even simple ones such as poetry or stories – have the potential to improve those in addiction recovery the ability to cope with their conditions, and overall health. This activity has not only been linked to alleviate the symptoms related to mental health disorders, but also provides those in recovery the chance to improve their emotional wellbeing by undergoing a therapeutic release of thoughts and feelings such as sadness, anger, guilt, and improving their self-awareness.

The Role of the Distance Therapies

With the accessibility provided by the Internet, the reach of the writing therapies has increased considerably, as clients and therapists can work together from anywhere in the world, provided they can write the same language. They simply “enter” into a private “chat room” and engage in an ongoing text dialogue in “real time”. Participants can also receive therapy sessions via e-text and/or voice with video, and complete online questionnaires, handouts, workout sheets and similar exercises.

This requires the services of a counsellor or therapist, albeit sitting at a computer. Given the huge disjunction between the amount of mental illness compared with the paucity of skilled resources, new ways have been sought to provide therapy other than drugs. In the more advanced societies pressure for cost-effective treatments, supported by evidence-based results, has come from both insurance companies and government agencies. Hence the decline in long term intensive psychoanalysis and the rise of much briefer forms, such as cognitive therapy.

Via the Internet

Currently, the most widely used mode of Internet writing therapy is via e-mail (see analytic psychotherapist Nathan Field’s paper “The Therapeutic Action of Writing in Self-Disclosure and Self-Expression”). It is asynchronous; i.e. messages are passed between therapist and client within an agreed time frame (for instance, one week), but at any time within that week. Where both parties remain anonymous the client benefits from the online disinhibition effect; that is to say, feels freer to disclose memories, thoughts and feelings that they might withhold in a face-to-face situation. Both client and therapist have time for reflecting on the past and recapturing forgotten memories, time for privately processing their reactions and giving thought to their own responses. With e-therapy, space is eliminated, and time expanded. Overall, it considerably reduces the amount of therapeutic input, as well as the speed and pressure that therapists habitually have to work under.

The anonymity and invisibility provides a therapeutic environment that comes much closer than classical analysis to Freud’s ideal of the “analytic blank screen”. Sitting behind the patient on the couch still leaves room for a multitude of clues to the analyst’s individuality; e-therapy provides almost none. Whether distance and reciprocal anonymity reduces or increases the level of transference has yet to be investigated.

In a 2016 randomised controlled trial, expressive writing was tested against direction to an online support group for individuals with anxiety and depression. No difference between the groups was found. Both groups showed a moderate improvement over time, but of a magnitude comparable to what one would expect to see over the time period concerned without intervention.

Journaling

The oldest and most widely practiced form of self-help through writing is that of keeping a personal journal or diary – as distinct from a diary or calendar of daily appointments – in which the writer records their most meaningful thoughts and feelings. One individual benefit is that the act of writing puts a powerful brake on the torment of endlessly repeating troubled thoughts to which everyone is prone. Kathleen Adams states that through the act of journal writing, the writer is also able to “literally [read] his or her own mind” and thus “to perceive experiences more clearly and thus feels a relief of tension”.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Writing_therapy >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is a Pharmaceutical Formulation?

Introduction

Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product.

The word formulation is often used in a way that includes dosage form.

Stages and Timeline

Formulation studies involve developing a preparation of the drug which is both stable and acceptable to the patient. For orally administered drugs, this usually involves incorporating the drug into a tablet or a capsule. It is important to make the distinction that a tablet contains a variety of other potentially inert substances apart from the drug itself, and studies have to be carried out to ensure that the encapsulated drug is compatible with these other substances in a way that does not cause harm, whether direct or indirect.

Preformulation involves the characterisation of a drug’s physical, chemical, and mechanical properties in order to choose what other ingredients (excipients) should be used in the preparation. In dealing with protein pre-formulation, the important aspect is to understand the solution behaviour of a given protein under a variety of stress conditions such as freeze/thaw, temperature, shear stress among others to identify mechanisms of degradation and therefore its mitigation.

Formulation studies then consider such factors as particle size, polymorphism, pH, and solubility, as all of these can influence bioavailability and hence the activity of a drug. The drug must be combined with inactive ingredients by a method that ensures that the quantity of drug present is consistent in each dosage unit e.g. each tablet. The dosage should have a uniform appearance, with an acceptable taste, tablet hardness, and capsule disintegration.

It is unlikely that formulation studies will be complete by the time clinical trials commence. This means that simple preparations are developed initially for use in phase I clinical trials. These typically consist of hand-filled capsules containing a small amount of the drug and a diluent. Proof of the long-term stability of these formulations is not required, as they will be used (tested) in a matter of days. Consideration has to be given to what is known as “drug loading” – the ratio of the active drug to the total contents of the dose. A low drug load may cause homogeneity problems. A high drug load may pose flow problems or require large capsules if the compound has a low bulk density.

By the time phase III clinical trials are reached, the formulation of the drug should have been developed to be close to the preparation that will ultimately be used in the market. A knowledge of stability is essential by this stage, and conditions must have been developed to ensure that the drug is stable in the preparation. If the drug proves unstable, it will invalidate the results from clinical trials since it would be impossible to know what the administered dose actually was. Stability studies are carried out to test whether temperature, humidity, oxidation, or photolysis (ultraviolet light or visible light) have any effect, and the preparation is analysed to see if any degradation products have been formed.

Container Closure

Formulated drugs are stored in container closure systems for extended periods of time. These include blisters, bottles, vials, ampules, syringes, and cartridges. The containers can be made from a variety of materials including glass, plastic, and metal. The drug may be stored as a solid, liquid, or gas.

It’s important to check whether there are any undesired interactions between the preparation and the container. For instance, if a plastic container is used, tests are carried out to see whether any of the ingredients become adsorbed on to the plastic, and whether any plasticiser, lubricants, pigments, or stabilisers leach out of the plastic into the preparation. Even the adhesives for the container label need to be tested, to ensure they do not leach through the plastic container into the preparation.

Formulation Types

The drug form varies by the route of administration, such as capsules, tablets, and pills etc.

Enteral Formulations

Oral drugs are normally taken as tablets or capsules.

The drug (active substance) itself needs to be soluble in aqueous solution at a controlled rate. Such factors as particle size and crystal form can significantly affect dissolution. Fast dissolution is not always ideal. For example, slow dissolution rates can prolong the duration of action or avoid initial high plasma levels. Treatment of active ingredient by special ways such as spherical crystallisation can have some advantages for drug formulation.

Tablet

A tablet is usually a compressed preparation that contains:

  • 5-10% of the drug (active substance);
  • 80% of fillers, disintegrants, lubricants, glidants, and binders; and
  • 10% of compounds which ensure easy disintegration, disaggregation, and dissolution of the tablet in the stomach or the intestine.

The dissolution time can be modified for a rapid effect or for sustained release.

Special coatings can make the tablet resistant to the stomach acids such that it only disintegrates in the duodenum, jejunum and colon as a result of enzyme action or alkaline pH.

Pills can be coated with sugar, varnish, or wax to disguise the taste.

Capsule

A capsule is a gelatinous envelope enclosing the active substance. Capsules can be designed to remain intact for some hours after ingestion in order to delay absorption. They may also contain a mixture of slow and fast release particles to produce rapid and sustained absorption in the same dose.

Sustained Release

There are a number of methods by which tablets and capsules can be modified in order to allow for sustained release of the active compound as it moves through the digestive tract. One of the most common methods is to embed the active ingredient in an insoluble porous matrix, such that the dissolving drug must make its way out of the matrix before it can be absorbed. In other sustained release formulations the matrix swells to form a gel through which the drug exits.

Another method by which sustained release is achieved is through an osmotic controlled-release oral delivery system, where the active compound is encased in a water-permeable membrane with a laser drilled hole at one end. As water passes through the membrane the drug is pushed out through the hole and into the digestive tract where it can be absorbed.

Parenteral Formulations

These are also called injectable formulations and are used with intravenous, subcutaneous, intramuscular, and intra-articular administration. The drug is stored in liquid or if unstable, lyophilised form.

Many parenteral formulations are unstable at higher temperatures and require storage at refrigerated or sometimes frozen conditions. The logistics process of delivering these drugs to the patient is called the cold chain. The cold chain can interfere with delivery of drugs, especially vaccines, to communities where electricity is unpredictable or non-existent. NGOs like the Gates Foundation are actively working to find solutions. These may include lyophilised formulations which are easier to stabilise at room temperature.

Most protein formulations are parenteral due to the fragile nature of the molecule which would be destroyed by enteric administration. Proteins have tertiary and quaternary structures that can be degraded or cause aggregation at room temperature. This can impact the safety and efficacy of the medicine.

Liquid

Liquid drugs are stored in vials, IV bags, ampoules, cartridges, and prefilled syringes.

As with solid formulations, liquid formulations combine the drug product with a variety of compounds to ensure a stable active medication following storage. These include solubilisers, stabilisers, buffers, tonicity modifiers, bulking agents, viscosity enhancers/reducers, surfactants, chelating agents, and adjuvants.

If concentrated by evaporation, the drug may be diluted before administration. For IV administration, the drug may be transferred from a vial to an IV bag and mixed with other materials.

Lyophilised

Lyophilised drugs are stored in vials, cartridges, dual chamber syringes, and prefilled mixing systems.

Lyophilisation, or freeze drying, is a process that removes water from a liquid drug creating a solid powder, or cake. The lyophilised product is stable for extended periods of time and could allow storage at higher temperatures. In protein formulations, stabilisers are added to replace the water and preserve the structure of the molecule.

Before administration, a lyophilised drug is reconstituted as a liquid before being administered. This is done by combining a liquid diluent with the freeze-dried powder, mixing, then injecting. Reconstitution usually requires a reconstitution and delivery system to ensure that the drug is correctly mixed and administered.

Topical Formulations

Cutaneous

Options for topical formulation include:

  • Cream: Emulsion of oil and water in approximately equal proportions. Penetrates stratum corneum outer layers of skin well.
  • Ointment: Combines oil (80%) and water (20%). Effective barrier against moisture loss.
  • Gel: Liquefies upon contact with the skin.
  • Paste: Combines three agents – oil, water, and powder; an ointment in which a powder is suspended.
  • Powder: A finely subdivided solid substance.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Pharmaceutical_formulation >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Route of Administration?

Introduction

A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.

Routes of administration are generally classified by the location at which the substance is applied. Common examples include oral and intravenous administration. Routes can also be classified based on where the target of action is. Action may be topical (local), enteral (system-wide effect, but delivered through the gastrointestinal tract), or parenteral (systemic action, but delivered by routes other than the GI tract).

Route of administration and dosage form are aspects of drug delivery.

Classification

Routes of administration are usually classified by application location (or exposition).

The route or course the active substance takes from application location to the location where it has its target effect is usually rather a matter of pharmacokinetics (concerning the processes of uptake, distribution, and elimination of drugs). Exceptions include the transdermal or transmucosal routes, which are still commonly referred to as routes of administration.

The location of the target effect of active substances are usually rather a matter of pharmacodynamics (concerning e.g. the physiological effects of drugs). An exception is topical administration, which generally means that both the application location and the effect thereof is local.

Topical administration is sometimes defined as both a local application location and local pharmacodynamic effect, and sometimes merely as a local application location regardless of location of the effects.

By Application Location

Enteral/Gastrointestinal

through the gastrointestinal tract is sometimes termed enteral or enteric administration (literally meaning ‘through the intestines’). Enteral/enteric administration usually includes oral (through the mouth) and rectal (into the rectum) administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may also occur already in the stomach, and as such gastrointestinal (along the gastrointestinal tract) may be a more fitting term for this route of administration. Furthermore, some application locations often classified as enteral, such as sublingual (under the tongue) and sublabial or buccal (between the cheek and gums/gingiva), are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Strictly enteral administration (directly into the intestines) can be used for systemic administration, as well as local (sometimes termed topical), such as in a contrast enema, whereby contrast media are infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects.

Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy. Substances may also be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach.

The rectal route is an effective route of administration for many medications, especially those used at the end of life. The walls of the rectum absorb many medications quickly and effectively. Medications delivered to the distal one-third of the rectum at least partially avoid the “first pass effect” through the liver, which allows for greater bio-availability of many medications than that of the oral route. Rectal mucosa is highly vascularised tissue that allows for rapid and effective absorption of medications. A suppository is a solid dosage form that fits for rectal administration. In hospice care, a specialised rectal catheter, designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the distal rectum, giving health practitioners a way to leverage the established benefits of rectal administration. The Murphy drip is an example of rectal infusion.

Parenteral

The parenteral route is any route that is not enteral (par- + enteral).

Parenteral administration can be performed by injection, that is, using a needle (usually a hypodermic needle) and a syringe, or by the insertion of an indwelling catheter.

Locations of application of parenteral administration include:

  • Central nervous system:
    • Epidural (synonym: peridural) (injection or infusion into the epidural space), e.g. epidural anesthesia.
    • Intracerebral (into the cerebrum) administration by direct injection into the brain. Used in experimental research of chemicals and as a treatment for malignancies of the brain. The intracerebral route can also interrupt the blood brain barrier from holding up against subsequent routes.
    • Intracerebroventricular (into the cerebral ventricles) administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain.
  • Epicutaneous (application onto the skin). It can be used both for local effect as in allergy testing and typical local anaesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route.
  • Sublingual and buccal medication administration is a way of giving someone medicine orally (by mouth). Sublingual administration is when medication is placed under the tongue to be absorbed by the body. The word “sublingual” means “under the tongue.” Buccal administration involves placement of the drug between the gums and the cheek. These medications can come in the form of tablets, films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, opioid analgesics with poor gastrointestinal bioavailability, enzymes and, increasingly, vitamins and minerals.
  • Extra-amniotic administration, between the endometrium and foetal membranes.
  • Nasal administration (through the nose) can be used for topically acting substances, as well as for insufflation of e.g. decongestant nasal sprays to be taken up along the respiratory tract. Such substances are also called inhalational, e.g. inhalational anaesthetics.
  • Intra-arterial (into an artery), e.g. vasodilator drugs in the treatment of vasospasm and thrombolytic drugs for treatment of embolism.
  • Intra-articular, into a joint space. It is generally performed by joint injection. It is mainly used for symptomatic relief in osteoarthritis.
  • Intracardiac (into the heart), e.g. adrenaline during cardiopulmonary resuscitation (no longer commonly performed).
  • Intracavernous injection, an injection into the base of the penis.
  • Intradermal, (into the skin itself) is used for skin testing some allergens, and also for mantoux test for tuberculosis.
  • Intralesional (into a skin lesion), is used for local skin lesions, e.g. acne medication.
  • Intramuscular (into a muscle), e.g. many vaccines, antibiotics, and long-term psychoactive agents. Recreationally the colloquial term ‘muscling’ is used.
  • Intraocular, into the eye, e.g., some medications for glaucoma or eye neoplasms.
  • Intraosseous infusion (into the bone marrow) is, in effect, an indirect intravenous access because the bone marrow drains directly into the venous system. This route is occasionally used for drugs and fluids in emergency medicine and paediatrics when intravenous access is difficult.
  • Intraperitoneal, (infusion or injection into the peritoneum) e.g. peritoneal dialysis.
  • Intrathecal (into the spinal canal) is most commonly used for spinal anaesthesia and chemotherapy.
  • Intrauterine.
  • Intravaginal administration, in the vagina.
  • Intravenous (into a vein), e.g. many drugs, total parenteral nutrition.
  • Intravesical infusion is into the urinary bladder.
  • Intravitreal, through the eye.
  • Subcutaneous (under the skin). This generally takes the form of subcutaneous injection, e.g. with insulin. Skin popping is a slang term that includes subcutaneous injection, and is usually used in association with recreational drugs. In addition to injection, it is also possible to slowly infuse fluids subcutaneously in the form of hypodermoclysis.
  • Transdermal (diffusion through the intact skin for systemic rather than topical distribution), e.g. transdermal patches such as fentanyl in pain therapy, nicotine patches for treatment of addiction and nitroglycerine for treatment of angina pectoris.
  • Perivascular administration (perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery).
  • Transmucosal (diffusion through a mucous membrane), e.g. insufflation (snorting) of cocaine, sublingual, i.e. under the tongue, sublabial, i.e. between the lips and gingiva, nitroglycerine, vaginal suppositories.

Topical

The definition of the topical route of administration sometimes states that both the application location and the pharmacodynamic effect thereof is local.

In other cases, topical is defined as applied to a localised area of the body or to the surface of a body part regardless of the location of the effect. By this definition, topical administration also includes transdermal application, where the substance is administered onto the skin but is absorbed into the body to attain systemic distribution.

If defined strictly as having local effect, the topical route of administration can also include enteral administration of medications that are poorly absorbable by the gastrointestinal tract. One such medication is the antibiotic vancomycin, which cannot be absorbed in the gastrointestinal tract and is used orally only as a treatment for Clostridium difficile colitis.

Choice of Routes

The reason for choice of routes of drug administration are governing by various factors:

  • Physical and chemical properties of the drug. The physical properties are solid, liquid and gas. The chemical properties are solubility, stability, pH, irritancy etc.
  • Site of desired action: the action may be localised and approachable or generalised and not approachable.
  • Rate of extent of absorption of the drug from different routes.
  • Effect of digestive juices and the first pass metabolism of drugs.
  • Condition of the patient.

In acute situations, in emergency medicine and intensive care medicine, drugs are most often given intravenously. This is the most reliable route, as in acutely ill patients the absorption of substances from the tissues and from the digestive tract can often be unpredictable due to altered blood flow or bowel motility.

Convenience

Enteral routes are generally the most convenient for the patient, as no punctures or sterile procedures are necessary. Enteral medications are therefore often preferred in the treatment of chronic disease. However, some drugs can not be used enterally because their absorption in the digestive tract is low or unpredictable. Transdermal administration is a comfortable alternative; there are, however, only a few drug preparations that are suitable for transdermal administration.

Desired Target Effect

Identical drugs can produce different results depending on the route of administration. For example, some drugs are not significantly absorbed into the bloodstream from the gastrointestinal tract and their action after enteral administration is therefore different from that after parenteral administration. This can be illustrated by the action of naloxone (Narcan), an antagonist of opiates such as morphine. Naloxone counteracts opiate action in the central nervous system when given intravenously and is therefore used in the treatment of opiate overdose. The same drug, when swallowed, acts exclusively on the bowels; it is here used to treat constipation under opiate pain therapy and does not affect the pain-reducing effect of the opiate.

Oral

The oral route is generally the most convenient and costs the least. However, some drugs can cause gastrointestinal tract irritation. For drugs that come in delayed release or time-release formulations, breaking the tablets or capsules can lead to more rapid delivery of the drug than intended. The oral route is limited to formulations containing small molecules only while biopharmaceuticals (usually proteins) would be digested in the stomach and thereby become ineffective. Biopharmaceuticals have to be given by injection or infusion. However, recent research (2018) found an organic ionic liquid suitable for oral insulin delivery (a biopharmaceutical) into the blood stream.

Oral administration is often denoted “PO” from “per os”, the Latin for “by mouth”.

The bioavailability of oral administration is affected by the amount of drug that is absorbed across the intestinal epithelium and first-pass metabolism.

Local

By delivering drugs almost directly to the site of action, the risk of systemic side effects is reduced.

Skin absorption (dermal absorption), for example, is to directly deliver drug to the skin and, hopefully, to the systemic circulation. However, skin irritation may result, and for some forms such as creams or lotions, the dosage is difficult to control. Upon contact with the skin, the drug penetrates into the dead stratum corneum and can afterwards reach the viable epidermis, the dermis, and the blood vessels.

Mouth Inhalation

Inhaled medications can be absorbed quickly and act both locally and systemically. Proper technique with inhaler devices is necessary to achieve the correct dose. Some medications can have an unpleasant taste or irritate the mouth.

In general, only 20-50% of the pulmonary-delivered dose rendered in powdery particles will be deposited in the lung upon mouth inhalation. The remainder of 50-70% undeposited aerosolised particles are cleared out of lung as soon as exhalation.

An inhaled powdery particle that is >8 μm is structurally predisposed to depositing in the central and conducting airways (conducting zone) by inertial impaction.

An inhaled powdery particle that is between 3 and 8 μm in diameter tend to largely deposit in the transitional zones of the lung by sedimentation.

An inhaled powdery particle that is ❤ μm in diameter is structurally predisposed to depositing primarily in the respiratory regions of the peripheral lung via diffusion.

Particles that deposit in the upper and central airways are generally absorbed systemically to great extent because they are only partially removed by mucociliary clearance, which results in orally mediated absorption when the transported mucous is swallowed, and first pass metabolism or incomplete absorption through loss at the faecal route can sometimes reduce the bioavailability. This should in no way suggest to clinicians or researchers that inhaled particles are not a greater threat than swallowed particles, it merely signifies that a combination of both methods may occur with some particles, no matter the size of or lipo/hydrophilicity of the different particle surfaces.

Nasal Inhalation

Inhalation by nose of a substance is almost identical to oral inhalation, except that some of the drug is absorbed intranasally instead of in the oral cavity before entering the airways. Both methods can result in varying levels of the substance to be deposited in their respective initial cavities, and the level of mucous in either of these cavities will reflect the amount of substance swallowed. The rate of inhalation will usually determine the amount of the substance which enters the lungs. Faster inhalation results in more rapid absorption because more substance finds the lungs. Substances in a form that resists absorption in the lung will likely resist absorption in the nasal passage, and the oral cavity, and are often even more resistant to absorption after they fail absorption in the former cavities and are swallowed.

Parenteral

The term parenteral is from para-1 ‘beside’ + Greek enteron ‘intestine’ + -al. This name is due to the fact that it encompasses a route of administration that is not intestinal. However, in common English the term has mostly been used to describe the 4 most well-known routes of injection.

The term injection encompasses intravenous (IV), intramuscular (IM), subcutaneous (SC) and intradermal (ID) administration.

Parenteral administration generally acts more rapidly than topical or enteral administration, with onset of action often occurring in 15-30 seconds for IV, 10-20 minutes for IM and 15-30 minutes for SC. They also have essentially 100% bioavailability and can be used for drugs that are poorly absorbed or ineffective when they are given orally. Some medications, such as certain antipsychotics, can be administered as long-acting intramuscular injections. The practice is often carried out through physical force in company of law-enforcement, and often against the will of the patient. However, all doses of long-acting antipsychotics injections are of at extreme risk to the health and well-being of the patient. Extreme ethical concerns should be considered. If the choice is made to use force, care should be taken to use only the smallest dose that is currently scientifically demonstrated to be efficacious for the specific drug. This is because, despite being injected, the drugs are designed with heavy esterifying molecular additions which can cause traces of the drugs to be found in circulation for up to one year. Ongoing IV infusions can be used to deliver continuous medication or fluids.

Disadvantages of injections include potential pain or discomfort for the patient and the requirement of trained staff using aseptic techniques for administration. However, in some cases, patients are taught to self-inject, such as SC injection of insulin in patients with insulin-dependent diabetes mellitus. As the drug is delivered to the site of action extremely rapidly with IV injection, there is a risk of overdose if the dose has been calculated incorrectly, and there is an increased risk of side effects if the drug is administered too rapidly.

Intranasal

Drug administration via the nasal cavity yields rapid drug absorption and therapeutic effects. This is because drug absorption through the nasal passages doesn’t go through the gut before entering capillaries situated at tissue cells and then systemic circulation and such absorption route allows transport of drugs into the central nervous system via the pathways of olfactory and trigeminal nerve.

Intranasal absorption features low lipophilicity, enzymatic degradation within the nasal cavity, large molecular size, and rapid mucociliary clearance from the nasal passages, which explains the low risk of systemic exposure of the administered drug absorbed via intranasal.

Sublingual

Sublingual administration is fulfilled by placing the drug between the tongue and the lower surface of the mouth. The sublingual mucosa is highly permeable and thereby provides access to the underlying expansive network composed of capillaries, leading to rapid drug absorption.

Buccal

Buccally administered medication is achieved by placing the drug between gums and the inner lining of the cheek. In comparison with sublingual tissue, buccal tissue is less permeable resulting in slower absorption.

Research

Neural drug delivery is the next step beyond the basic addition of growth factors to nerve guidance conduits. Drug delivery systems allow the rate of growth factor release to be regulated over time, which is critical for creating an environment more closely representative of in vivo development environments.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Route_of_administration >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Drug Delivery?

Introduction

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect.

Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimise efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug’s pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Drug delivery is a concept heavily integrated with dosage form and route of administration, the latter sometimes being considered part of the definition. While route of administration is often used interchangeably with drug delivery, the two are separate concepts. Route of administration refers to the path a drug takes to enter the body, whereas drug delivery also encompasses the engineering of delivery systems and can include different dose forms and devices used to deliver a drug through the same route. Common routes of administration include oral, parenteral (injected), sublingual, topical, transdermal, inhaled, rectal, and vaginal, however drug delivery is not limited to these routes and there may be several ways to deliver medications through each route.

Since the approval of the first controlled-release formulation in the 1950s, research into new delivery systems has been progressing, as opposed to new drug development which has been declining. Several factors may be contributing to this shift in focus. One of the driving factors is the high cost of developing new drugs. A 2013 review found the cost of developing a delivery system was only 10% of the cost of developing a new pharmaceutical. A more recent study found the median cost of bringing a new drug to market was $985 million in 2020, but did not look at the cost of developing drug delivery systems. Other factors that have potentially influenced the increase in drug delivery system development may include the increasing prevalence of both chronic and infectious diseases, as well as a general increased understanding of the pharmacology, pharmacokinetics, and pharmacodynamics of many drugs.

Current Efforts

Current efforts in drug delivery are vast and include topics such as:

Targeted Delivery

Targeted drug delivery is the delivery of a drug to its target site without having an effect on other tissues. Interest in targeted drug delivery has grown drastically due to its potential implications in the treatment of cancers and other chronic diseases. In order to achieve efficient targeted delivery, the designed system must avoid the host’s defence mechanisms and circulate to its intended site of action. A number of drug carriers have been studied to effectively target specific tissues, including liposomes, nanogels, and other nanotechnologies.

Controlled-release Formulations

Controlled or modified-release formulations alter the rate and timing at which a drug is liberated, in order to produce adequate or sustained drug concentrations. The first controlled-release (CR) formulation that was developed was Dexedrine in the 1950s. This period of time saw more drugs being formulated as CR, as well as the introduction of transdermal patches to allow drugs to slowly absorb through the skin. Since then, countless other CR products have been developed to account for the physiochemical properties of different drugs, such as depot injections for antipsychotics and sex hormones that require dosing once every few months.

Since the late 1990s, most of the research around CR formulations has been focused on implementing nanoparticles to decrease the rate of drug clearance.

Delivery of Biologic Drugs

Pharmaceutical preparations containing peptides, proteins, antibodies, genes, or other biologic components often face absorption issues due to their large sizes or electrostatic charges, and may be susceptible to enzymatic degradation once they have entered the body. For these reasons, recent efforts in drug delivery have been focused on methods to avoid these issues through the use of liposomes, nanoparticles, fusion proteins, protein-cage nanoparticles and many others. Intracellular delivery of macromolecules by chemical carriers is most advanced for RNA, as known from RNA-based COVID-19 vaccines, while proteins have also been delivered into cells in vivo and DNA is routinely delivered in vitro.

What is Liberation (in Pharmacology)?

Introduction

Liberation is the first step in the process by which medication enters the body and liberates the active ingredient that has been administered. The pharmaceutical drug must separate from the vehicle or the excipient that it was mixed with during manufacture. Some authors split the process of liberation into three steps: disintegration, disaggregation and dissolution. A limiting factor in the adsorption of pharmaceutical drugs is the degree to which they are ionised, as cell membranes are relatively impermeable to ionised molecules.

The characteristics of a medication’s excipient play a fundamental role in creating a suitable environment for the correct absorption of a drug. This can mean that the same dose of a drug in different forms can have different bioequivalence, as they yield different plasma concentrations and therefore have different therapeutic effects. Dosage forms with modified release (such as delayed or extended release) allow this difference to be usefully applied.

Dissolution

In a typical situation, a pill taken orally will pass through the oesophagus and into the stomach. As the stomach has an aqueous environment, it is the first place where the pill can dissolve. The rate of dissolution is a key element in controlling the duration of a drug’s effect. For this reason, different forms of the same medication can have the same active ingredients but different dissolution rates. If a drug is administered in a form that is not rapidly dissolved, the drug will be absorbed more gradually over time and its action will have a longer duration. A consequence of this is that patients will comply more closely to a prescribed course of treatment, if the medication does not have to be taken as frequently. In addition, a slow release system will maintain drug concentrations within a therapeutically acceptable range for longer than quicker releasing delivery systems as these result in more pronounced peaks in plasma concentration.

The dissolution rate is described by the Noyes-Whitney equation:

Where:

  • {\frac  {dW}{dt}} is the dissolution rate.
  • A is the solid’s surface area.
  • C is the concentration of the solid in the bulk dissolution medium.
  • C8 is the concentration of the solid in the diffusion layer surrounding the solid.
  • D is the diffusion coefficient.
  • L is the thickness of the diffusion layer.

As the solution is already in a dissolved state, it does not have to go through a dissolution stage before absorption begins.

Ionisation

Cell membranes present a greater barrier to the movement of ionised molecules than non-ionised liposoluble substances. This is particularly important for substances that are weakly amphoteric. The stomach’s acidic pH and the subsequent alkalization in the intestine modifies the degree of ionisation of acids and weak bases depending on a substance’s pKa. The pKa is the pH at which a substance is present at an equilibrium between ionised and non-ionised molecules. The Henderson-Hasselbalch equation is used to calculate pKa.

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What is a Dosage Form?

Introduction

Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a capsule shell, for example), and apportioned into a particular dose. For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250 mg chewable tablets.

The term unit dose can also sometimes encompass non-reusable packaging as well (especially when each drug product is individually packaged), although the US Food and Drug Administration (FDA) distinguishes that by unit-dose “packaging” or “dispensing”. Depending on the context, multi(ple) unit dose can refer to distinct drug products packaged together, or to a single drug product containing multiple drugs and/or doses. The term dosage form can also sometimes refer only to the pharmaceutical formulation of a drug product’s constituent drug substance(s) and any blends involved, without considering matters beyond that (like how it is ultimately configured as a consumable product such as a capsule, patch, etc.). Because of the somewhat vague boundaries and unclear overlap of these terms and certain variants and qualifiers within the pharmaceutical industry, caution is often advisable when conversing with someone who may be unfamiliar with another person’s use of the term.

Depending on the method/route of administration, dosage forms come in several types. These include many kinds of liquid, solid, and semisolid dosage forms. Common dosage forms include pill, tablet, or capsule, drink or syrup, among many others. In naturopathy, dosages can take the form of decoctions and herbal teas, as well as the more conventional methods previously mentioned. A liquid dosage form is the liquid form of a dose of a chemical compound used as a drug or medication intended for administration or consumption.

The route of administration (ROA) for drug delivery is dependent on the dosage form of the substance in question. Various dosage forms may exist for a single particular drug, since some medical conditions such as being unconscious can restrict ROA. For example, persistent nausea, especially with vomiting, may make it difficult to use an oral dosage form, and in such a case, it may be necessary to use an alternative route such as inhalational, buccal, sublingual, nasal, suppository or parenteral instead. Additionally, a specific dosage form may be a requirement for certain kinds of drugs, as there may be issues with various factors like chemical stability or pharmacokinetics. As an example, insulin cannot be given orally because upon being administered in this manner, it is extensively metabolized in the gastrointestinal tract (GIT) before reaching the blood stream, and is thereby incapable of sufficiently reaching its therapeutic target destinations. The oral and intravenous doses of a drug such as paracetamol will differ for the same reason.

Oral

  • Pills, i.e. tablets or capsules.
  • Liquids such as syrups, solutions, elixers, emulsions, and tinctures.
  • Liquids such as decoctions and herbal teas.
  • Orally disintegrating tablets.
  • Lozenges or candy (electuaries).
  • Thin films (e.g. Listerine Pocketpaks, nitroglycerin) to be placed on top of or underneath the tongue as well as against the cheek.
  • Powders or effervescent powder or tablets, often instructed to be mixed into a food item.
  • Plants or seeds prepared in various ways such as a cannabis edible.
  • Pastes such as high fluoride toothpastes.
  • Gases such as oxygen (can also be delivered through the nose).

Ophthalmic

  • Eye drops.
  • Lotions.
  • Ointments.
  • Emulsions.

Inhalation

  • Aerosolised medication.
  • Dry-powder Inhalers or metered dose inhalers.
  • Nebuliser-administered medication.
  • Smoking.
  • Vaporiser-administered medication.

Unintended Ingredients

Talc is an excipient often used in pharmaceutical tablets that may end up being crushed to a powder against medical advice or for recreational use. Also, illicit drugs that occur as white powder in their pure form are often cut with cheap talc. Natural talc is cheap but contains asbestos while asbestos-free talc is more expensive. Inhaled talc that has asbestos is generally accepted as being able to cause lung cancer if it is inhaled. The evidence about asbestos-free talc is less clear, according to the American Cancer Society.

Injection

  • Parenteral.
  • Intradermally-administered (ID).
  • Subcutaneously-administered (SC).
  • Intramuscularly-administered (IM).
  • Intraosseous administration (IO).
  • Intraperitoneally-administered (IP).
  • intravenously-administered (IV).
  • Intracavernously-administered (ICI).

These are usually solutions and suspensions.

Unintended Ingredients

Safe

Eye drops (normal saline in disposable packages) are distributed to syringe users by needle exchange programs.

Unsafe

The injection of talc from crushed pills has been associated with pulmonary talcosis in intravenous drug users.

Topical

  • Creams, liniments, balms (such as lip balm or antiperspirants and deodorants), lotions, or ointments, etc.
  • Gels and hydrogels.
  • Ear drops.
  • Transdermal and dermal patches to be applied to the skin.
  • Powders.

Unintended Use

  • It is not safe to calculate divided doses by cutting and weighing medical skin patches, because there’s no guarantee that the substance is evenly distributed on the patch surface. For example, fentanyl transdermal patches are designed to slowly release the substance over 3 days. It is well known that cut fentanyl transdermal consumed orally have cause overdoses and deaths.
  • Single blotting papers for illicit drugs injected from solvents in syringes may also cause uneven distribution across the surface.

Other

  • Intravaginal administration:
    • Vaginal rings.
    • Capsules and tablets.
    • Suppositories.
  • Rectal administration (enteral):
    • Suppositories.
    • Suspensions and solutions in the form of enemas.
    • Gels.
  • Urethral.
  • Nasal sprays.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Dosage_form >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is a Dose (Biochemistry)?

Introduction

A dose is a measured quantity of a medicine, nutrient, or pathogen which is delivered as a unit. The greater the quantity delivered, the larger the dose. Doses are most commonly measured for compounds in medicine. The term is usually applied to the quantity of a drug or other agent administered for therapeutic purposes, but may be used to describe any case where a substance is introduced to the body. In nutrition, the term is usually applied to how much of a specific nutrient is in a person’s diet or in a particular food, meal, or dietary supplement. For bacterial or viral agents, dose typically refers to the amount of the pathogen required to infect a host.

In clinical pharmacology, dose refers to dosage or amount of dose administered to a person, whereas exposure means the time-dependent concentration (often in the circulatory blood or plasma) or concentration-derived parameters such as AUC (area under the concentration curve) and Cmax (peak level of the concentration curve) of the drug after its administrationneeded]. This is in contrast to their interchangeable use in other fields.

Refer to Defined Daily Dose, Prescribed Baily Dose, Maintenance Dose, and Dosage Form.

Factors Affecting Dose

A ‘dose’ of any chemical or biological agent (active ingredient) has several factors which are critical to its effectiveness. The first is concentration, that is, how much of the agent is being administered to the body at once.

Another factor is the duration of exposure. Some drugs or supplements have a slow-release feature in which portions of the medication are metabolized at different times, which changes the impacts the active ingredients have on the body. Some substances are meant to be taken in small doses over large periods of time to maintain a constant level in the body, while others are meant to have a large impact once and be expelled from the body after its work is done. It’s entirely dependent on the function of the drug or supplement.

The route of administration is important as well. Whether a drug is ingested orally, injected into a muscle or vein, absorbed through a mucous membrane, or any of the other types of administration routes, affects how quickly the substance will be metabolized by the body and thus effects the concentration of the active ingredient(s). Dose-response curves may illustrate the relationship of these metabolic effects.

Medicines

Over-the-Counter Medications

In over-the-counter medicines, dosage is based on age. Typically, different doses are recommended for children 6 years and under, children aged 6 to 12 years, and persons 12 years and older, but outside of those ranges the guidance is slim. This can lead to serial under or overdosing, as smaller people take more than they should and larger people take less. Over-the-counter medications are typically accompanied by a set of instructions directing the patient to take a certain small dose, followed by another small dose if their symptoms don’t subside. Under-dosing is a common problem in pharmacy, as predicting an average dose that is effective for all individuals is extremely challenging because body weight and size impacts how the dose acts within the body.

Prescription Drugs

Prescription drug dosage is based typically on body weight. Drugs come with a recommended dose in milligrams or micrograms per kilogram of body weight, and that is used in conjunction with the patient’s body weight to determine a safe dosage. In single dosage scenarios, the patient’s body weight and the drug’s recommended dose per kilogram are used to determine a safe one-time dose. In drugs where multiple doses of treatment are needed in a day, the physician must take into account information regarding the total amount of the drug which is safe to use in one day, and how that should be broken up into intervals for the most effective treatment for the patient. Medication underdosing occurs commonly when physicians write prescriptions for a dosage that is correct for a certain time, but fails to increase the dosage as the patient needs (i.e. weight based dosing in children, or increasing dosages of chemotherapy drugs if a patient’s condition worsens).

Medical Cannabis

Medical cannabis is used to treat the symptoms of a wide variety of diseases and conditions. The dose of cannabis depends on the individual, the condition being treated, and the ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) in the cannabis. CBD is a chemical component of cannabis that is not intoxicating and used to treat conditions like epilepsy and other neuropsychiatric disorders. THC is a chemical component of cannabis that is psychoactive. It has been used to treat nausea and discomfort in cancer patients receiving chemotherapy treatment. For anxiety, depression, and other mental health ailments, a CBD to THC ratio of 10 to 1 is recommended. For cancer and neurological conditions, a CBD to THC ratio of 1 to 1 is recommended. The correct dosage for a patient is dependent on their individual reaction to both chemicals, and therefore the dosing must be continually adjusted once treatment is initiated to find the right balance.

There is limited consensus throughout the scientific community regarding the effectiveness of medicinal cannabis.

Cancer

Calculating drug dosages for treatment for more serious diseases like cancer is commonly done through measuring the patient’s body surface area. There are approximately 25 different formulae for measuring a patient’s body surface area, none of them exact. Studies show that selecting the best method for an individual patient is a difficult task; consequently, patient often receive too much or too little medication due to their particular physical anomalies. Therefore, these formulas are typically adjusted by what is known as ‘toxicity-adjusting dosing,’ whereby physicians monitor immune suppression and adjust dosing accordingly. Because this strategy of trial and error requires close monitoring, it is inefficient, risky, and cost ineffective. Research into the development of safer and more accurate dosing methods is ongoing.

Ongoing Research

Another approach that’s been investigated recently is dosing on a molecular level, either through conventional delivery systems, nanoparticle delivery, light-triggered delivery, or other less known/used methods. By combining these drugs with a system that detects the concentration of drug particles in the blood, proper dosing could be achieved for each individual patient. Research in this field was initiated with monitoring of small-molecule cocaine levels in undiluted blood serum with electrochemical aptamer-based sensing. DNA aptamers, which are peptides that have with specific target molecules that they search for, fold in response to the molecule when they find it, and this technology was used in a microfluidic detection system to create an electrochemical signal that physicians can read. Researchers tested it on cocaine detection and found that it successfully found trace amounts of cocaine in blood.

This research was expanded upon and led to the creation of a product called MEDIC (microfluidic electrochemical detector for in vivo continuous monitoring) developed by faculty at the University of California at Santa Barbara. MEDIC is an instrument that can continuously determine the concentrations of different molecules in the blood. The blood does not have to be mixed with anything prior to testing to create a ‘serum’ as the first device did. MEDIC can detect a wide variety of drug molecules and biomarkers. In trials, early models of the device failed after about half an hour because the proteins in whole blood clung to the sensors and clogged the components. This problem was solved via a second chamber that allowed a liquid buffer to flow over the sensors with the blood, without mixing or disturbing the blood, so the results remained unchanged. The device is still in clinical trials and actual implementation in medicine is likely years away, however in the interim, its creators estimate that it could also be used in the pharmaceutical industry to allow for better testing in Phase 3 clinical trials.

Vaccines

Vaccinations are typically administered as liquids and dosed in millilitres. Each individual vaccine comes with constraints regarding at what age they should be administered, how many doses must be given, and over what period of time. There are 15 vaccines that the Centres for Disease Control and Prevention recommend every person (in the United States and Canada) receive between birth and 18 years of age to protect against various infectious agents that may affect long-term health. Most vaccines require multiple doses for full immunity, given in recommended intervals depending on the vaccine. There are several typical vaccination routes:

  • Intramuscular: the needle is inserted perpendicular to the skin into the muscle, beneath the skin and (subcutaneous) tissues that rest on top.
  • Subcutaneous: the needle is inserted at a 45-degree angle into the (subcutaneous) tissue between the outer layer of the skin and the muscle.
  • Intranasal: the vaccine is sprayed into the nose and absorbed through the nasal passage.
  • Oral: the vaccine is swallowed and ingested.

Nutrition

For healthy humans, experts recommend daily intake quantities of certain vitamins and minerals. The Food and Nutrition Board, Institute of Medicine, and National Academy of Sciences sets a recommended Dietary Reference Intake (DRI) in several forms:

  • Recommended Dietary Allowance (RDA): average daily intake which adequately meets the nutrient requirements of 97-98% of healthy individuals.
  • Adequate Intake (AI): established when the evidence gathered for an RDA is inconclusive, An AI is assumed to recommend a daily amount to meet nutritional adequacy.
  • Tolerable Upper Intake Level (UL): maximum amount of a nutrient which can be consumed without causing adverse impacts to an individual’s health.

DRIs are established for elements, vitamins, and macronutrients. Common elemental and vitamin dosages are milligrams per day (mg/d) or micrograms per day (μg/d). Common macronutrient dosages are in grams per day (g/d). Dosages for all three are established by both gender and age.

Individuals take vitamin and mineral supplements to promote healthier lifestyles and prevent development of chronic diseases. There is no conclusive evidence linking continued vitamin and mineral supplement intake with longevity of life.

Infectious Dose

The infectious dose of a pathogen is the number of cells required to infect the host. All pathogens have an infectious dose typically given in number of cells. The infectious dose varies by organism and can be dependent on the specific type of strain. Some pathogens can infect a host with only a few cells, while others require millions or billions.

Examples of infectious doses, ranked loosely in increasing order:

  • Enterohemorrhagic E. coli (causes haemorrhaging of the intestines): 10 bacteria cells.
  • Hepatitis A: 10-100 virus particles.
  • Norovirus (commonly called ‘a stomach bug’): 10-100 virus particles.
  • Rotavirus (severe diarrhoea, can be fatal): 10-100 virus particles.
  • Shigella (shigellosis): 500 bacteria cells.
  • Streptococcus pyogenes (Group A strep throat): 1000 bacteria cells.
  • Salmonella: varies by strain, 100-1 billion bacteria cells.
  • Vibrio cholerae (Cholera): 1000-100,000,000 bacteria cells.

Typically, stomach acids can kill bacteria below the infectious dosing range for a given pathogen and keep the host from feeling symptoms or falling ill. Complexes constructed by fat can protect infectious agents from stomach acid, making fatty foods more likely to contain pathogens that successfully infect the host. For individuals with low or reduced stomach acid concentrations, in infectious dosage for a pathogen will be lower than normal.

Rather than being administered by a physician or individual, infectious dosages are transmitted to a person from other persons or the environment, are generally accidental, and result in adverse side effects until the pathogen is defeated by the individual’s immune system or flushed out of the individual’s system by excretory processes.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Dose_(biochemistry) >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is a Medical Prescription?

Introduction

A prescription, often abbreviated ℞ or Rx, is a formal communication from a physician or other registered health-care professional to a pharmacist, authorising them to dispense a specific prescription drug for a specific patient.

Historically, it was a physician’s instruction to an apothecary listing the materials to be compounded into a treatment – the symbol ℞ (a capital letter R, crossed to indicate abbreviation) comes from the first word of a medieval prescription, Latin: Recipere (“Take thou”), that gave the list of the materials to be compounded.

Brief History

The idea of prescriptions dates back to the beginning of history. So long as there were medications and a writing system to capture directions for preparation and usage, there were prescriptions.

Modern prescriptions are actually extemporaneous prescriptions (from the Latin ex tempore, “at/from the time”), meaning that the prescription is written on the spot for a specific patient with a specific ailment. This is distinguished from a non-extemporaneous prescription that is a generic recipe for a general ailment. Modern prescriptions evolved with the separation of the role of the pharmacists from that of the physician. Today the term extemporaneous prescriptions is reserved for compound prescriptions that requires the pharmacist to mix or compound the medication in the pharmacy for the specific needs of the patient.

Predating modern legal definitions of a prescription, a prescription traditionally is composed of four parts: a superscription, inscription, subscription, and signature.

The superscription section contains the date of the prescription and patient information (name, address, age, etc.). The symbol “℞” separates the superscription from the inscriptions sections. In this arrangement of the prescription, the “℞” is a symbol for recipe or literally the imperative “take!” This is an exhortation to the pharmacist by the medical practitioner, “I want the patient to have the following medication” – in other words, “take the following components and compound this medication for the patient.”

The inscription section defines what is the medication. The inscription section is further composed of one or more of:

  • A basis or chief ingredient intended to cure (curare).
  • An adjuvant to assist its action and make it cure quickly (cito).
  • A corrective to prevent or lessen any undesirable effect (tuto).
  • A vehicle or excipient to make it suitable for administration and pleasant to the patient (jucunde).

The subscription section contains dispensing directions to the pharmacist. This may be compounding instructions or quantities.

The signature section contains directions to the patient and is often abbreviated “Sig.” or “Signa.” It also obviously contains the signature of the prescribing medical practitioner though the word signature has two distinct meanings here and the abbreviations are sometimes used to avoid confusion.

Thus sample prescriptions in modern textbooks are often presented as:

  • Rx: medication.
  • Disp.: dispensing instructions.
  • Sig.: patient instructions.

Format and Definition

For a communication to be accepted as a legal medical prescription, it needs to be filed by a qualified dentist, advanced practice nurse, physician or veterinarian, for whom the medication prescribed is within their scope of practice to prescribe. This is regardless of whether the prescription includes prescription drugs, controlled substances or over-the-counter treatments.

Prescriptions may be entered into an electronic medical record system and transmitted electronically to a pharmacy. Alternatively, a prescription may be handwritten on pre-printed prescription forms that have been assembled into pads, or printed onto similar forms using a computer printer or even on plain paper according to the circumstance. In some cases, a prescription may be transmitted from the physician to the pharmacist orally by telephone. The content of a prescription includes the name and address of the prescribing provider and any other legal requirement such as a registration number (e.g. DEA Number in the United States). Unique for each prescription is the name of the patient. In the United Kingdom and Ireland the patient’s name and address must also be recorded. Each prescription is dated and some jurisdictions may place a time limit on the prescription. In the past, prescriptions contained instructions for the pharmacist to use for compounding the pharmaceutical product but most prescriptions now specify pharmaceutical products that were manufactured and require little or no preparation by the pharmacist. Prescriptions also contain directions for the patient to follow when taking the drug. These directions are printed on the label of the pharmaceutical product.

The word “prescription”, from “pre-” (“before”) and “script” (“writing, written”), refers to the fact that the prescription is an order that must be written down before a drug can be dispensed. Those within the industry will often call prescriptions simply “scripts”.

Contents

Every prescription contains who prescribed the prescription, who the prescription is valid for, and what is prescribed. Some jurisdictions, drug types or patient groups require additional information as explained below.

Drug Equivalence and Non-Substitution

Many brand name drugs have cheaper generic drug substitutes that are therapeutically and biochemically equivalent. Prescriptions will also contain instructions on whether the prescriber will allow the pharmacist to substitute a generic version of the drug. This instruction is communicated in a number of ways. In some jurisdictions, the pre-printed prescription contains two signature lines: one line has “dispense as written” printed underneath; the other line has “substitution permitted” underneath. Some have a pre-printed box “dispense as written” for the prescriber to check off (but this is easily checked off by anyone with access to the prescription). In other jurisdictions, the protocol is for the prescriber to handwrite one of the following phrases: “dispense as written”, “DAW”, “brand necessary”, “do not substitute”, “no substitution”, “medically necessary”, “do not interchange”. In Britain’s National Health Service, doctors are reminded that money spent on branded rather than generic drugs is consequently not available for more deserving cases.

Prescriptions for Children

In some jurisdictions, it may be a legal requirement to include the age of child on the prescription. For paediatric prescriptions some advise the inclusion of the age of the child if the patient is less than twelve and the age and months if less than five. In general, including the age on the prescription is helpful, and adding the weight of the child is also helpful.

Label and Instructions

Prescriptions in the USA often have a “label” box. When checked, the pharmacist is instructed to label the medication and provide information about the prescription itself is given in addition to instructions on taking the medication. Otherwise, the patient is simply given the instructions. Some prescribers further inform the patient and pharmacist by providing the indication for the medication; i.e. what is being treated. This assists the pharmacist in checking for errors as many common medications can be used for multiple medical conditions. Some prescriptions will specify whether and how many “repeats” or “refills” are allowed; that is whether the patient may obtain more of the same medication without getting a new prescription from the medical practitioner. Regulations may restrict some types of drugs from being refilled.

Writing Prescriptions

Legal Capacity to Write Prescriptions

National or local (i.e. US state or Canadian provincial) legislation governs who can write a prescription. In the United States, physicians (either M.D., D.O. or D.P.M.) have the broadest prescriptive authority. All 50 US states and the District of Columbia allow licensed certified Physician Assistants (PAs) prescription authority (with some states, limitations exist to controlled substances). All 50 US states and the District of Columbia, Puerto Rico and Guam allow registered certified nurse practitioners and other advanced practice registered nurses (such as certified nurse-midwives) prescription power (with some states including limitations to controlled substances). Many other healthcare professions also have prescriptive authority related to their area of practice. Veterinarians and dentists have prescribing power in all 50 US states and the District of Columbia. Clinical pharmacists are allowed to prescribe in some US states through the use of a drug formulary or collaboration agreements. Florida pharmacists can write prescriptions for a limited set of drugs. In all US states, optometrists prescribe medications to treat certain eye diseases, and also issue spectacle and contact lens prescriptions for corrective eyewear. Several US states have passed RxP legislation, allowing clinical psychologists who are registered as medical psychologists and have also undergone specialised training in script-writing, to prescribe drugs to treat emotional and mental disorders.

In August 2013, legislative changes in the UK allowed physiotherapists and podiatrists to have independent prescribing rights for licensed medicines that are used to treat conditions within their own area of expertise and competence. In 2018 this was extended to paramedics.

Standing Orders

Some jurisdictions allow certain physicians (sometimes a government official like the state Secretary of Health, sometimes physicians in local clinics or pharmacies) to write “standing orders” that act like a prescription for everyone in the general public. These orders also provide a standard procedure for determining if administration is necessary and details of how it is to be performed safely. These are typically used to authorise certain people to perform preventive, low-risk, or emergency care that would be otherwise logistically cumbersome to authorise for individual patients, including vaccinations, prevention of cavities, birth control, treatment of infectious diseases, and reversal of drug overdoses.

Legibility of Handwritten Prescriptions

Doctors’ handwriting is a reference to the stereotypically illegible handwriting of some medical practitioners, which sometimes causes errors in dispensing. In the US, illegible handwriting has been indirectly responsible for at least 7,000 deaths annually.

There are several theories about the causes of this phenomenon. Some sources say the extreme amount of writing doctors employ during training and at work leads to bad handwriting, whereas others claim that doctors neglect proper handwriting due to medical documents being intended to be read solely by medical professionals, not patients. Others simply classify the handwriting of doctors as a handwriting style. The issue may also have a historical origin, as physicians from Europe-influenced schools have historically used Latin words and abbreviations to convey prescriptions; many of the abbreviations are still widely used in the modern day and could be a source of confusion.

Some jurisdictions have legislatively required prescriptions to be legible – Florida, US specifies “legibly printed or typed” – and the Institute for Safe Medication Practices advocated the elimination of handwritten prescriptions altogether. There have been numerous devices designed to electronically read the handwriting of doctors, including electronic character recognition, keyword spotters, and “postprocessing approaches,” though the gradual shift to electronic health records and electronic prescriptions may alleviate the need for handwritten prescriptions altogether. In Britain’s NHS, remaining paper prescriptions are almost invariably computer printed and electronic (rather than paper) communication between surgery and pharmacy is increasingly the norm.

Conventions for Avoiding Ambiguity

Over the years, prescribers have developed many conventions for prescription-writing, with the goal of avoiding ambiguities or misinterpretation. These include:

  • Careful use of decimal points to avoid ambiguity:
    • Avoiding unnecessary decimal points and trailing zeros, e.g. 5 mL rather than 5.0 mL, 0.5 rather than .50 or 0.50, to avoid possible misinterpretation as 50.
    • Always using leading zeros on decimal numbers less than 1: e.g. 0.5 rather than .5 to avoid misinterpretation as 5.
  • Directions written out in full in English (although some common Latin abbreviations are listed below).
  • Quantities given directly or implied by the frequency and duration of the directions.
  • Where the directions are “as needed”, the quantity should always be specified.
  • Where possible, usage directions should specify times (7 am, 3 pm, 11 pm) rather than simply frequency (three times a day) and especially relationship to meals for orally consumed medication.
  • The use of permanent ink.
  • Avoiding units such as “teaspoons” or “tablespoons”.
  • Writing out numbers as words and numerals (“dispense #30 (thirty)”) as in a bank draft or cheque.
  • The use of the apothecaries’ system or avoirdupois units and symbols of measure – pints (O), ounces (℥), drams (ℨ), scruples (℈), grains (gr), and minims (♏︎) – is discouraged given the potential for confusion. For example, the abbreviation for a grain (“gr”) can be confused with the gram, abbreviated g, and the symbol for minims (♏︎), which looks almost identical to an ‘m’, can be confused with micrograms or metres. Also, the symbols for ounce (℥) and dram (ℨ) can easily be confused with the numeral ‘3’, and the symbol for pint (O) can be easily read as a ‘0’. Given the potential for errors, metric equivalents should always be used.
  • The degree symbol (°), which is commonly used as an abbreviation for hours (e.g., “q 2-4°” for every 2-4 hours), should not be used, since it can be confused with a ‘0’ (zero). Further, the use of the degree symbol for primary, secondary, and tertiary (1°, 2°, and 3°) is discouraged, since the former could be confused with quantities (i.e. 10, 20 and 30, respectively).
  • Micrograms are abbreviated mcg rather than µg (which, if handwritten, could easily be mistaken for mg (milligrams). Even so, pharmacists must be on the alert for inadvertent over- or under-prescribing through a momentary lapse of concentration.

Abbreviations

Many abbreviations are derived from Latin phrases. Hospital pharmacies have more abbreviations, some specific to the hospital. Different jurisdictions follow different conventions on what is abbreviated or not. Prescriptions that do not follow area conventions may be flagged as possible forgeries.

Some abbreviations that are ambiguous, or that in their written form might be confused with something else, are not recommended and should be avoided. These are flagged in the table in the main article. However, all abbreviations carry an increased risk for confusion and misinterpretation and should be used cautiously.

Non-Prescription Drug Prescriptions

Over-the-counter medications and non-controlled medical supplies such as dressings, which do not require a prescription, may also be prescribed. Depending upon a jurisdiction’s medical system, non-prescription drugs may be prescribed because drug benefit plans may reimburse the patient only if the over-the-counter medication is taken at the direction of a qualified medical practitioner. In the countries of the UK, National Health Service (NHS) prescriptions are either free or have a fixed price per item; a prescription may be issued so the patient does not have to purchase the item at commercial price.

Some medical software requires a prescription.

Legislation may define certain equipment as “prescription devices”. Such prescription devices can only be used under the supervision of authorised personnel and such authorisation is typically documented using a prescription. Examples of prescription devices include dental cement (for affixing braces to tooth surfaces), various prostheses, gut sutures, sickle cell tests, cervical cap and ultrasound monitor.

In some jurisdictions, hypodermic syringes are in a special class of their own, regulated as illicit drug use accessories separate from regular medical legislation. Such legislation often allows syringes to be dispensed only with a prescription.

Use of Technology

As a prescription is nothing more than information among a prescriber, pharmacist and patient, information technology can be applied to it. Existing information technology is adequate to print out prescriptions. Hospital information systems in some hospitals do away with prescriptions within the hospital. There are proposals to securely transmit the prescription from the prescriber to the pharmacist using smartcard or the internet. In the UK a project called the Electronic Transfer of Prescriptions (ETP) within the National Programme for IT (NPfIT) is currently piloting such a scheme between prescribers and pharmacies.

Within computerised pharmacies, the information on paper prescriptions is recorded into a database. Afterwards, the paper prescription is archived for storage and legal reasons.

A pharmacy chain is often linked together through corporate headquarters with computer networking. A person who has a prescription filled at one branch can get a refill of that prescription at any other store in the chain, as well as have their information available for new prescriptions at any branch.

Some online pharmacies also offer services to customers over the internet, allowing users to specify the store that they will pick up the medicine from.

Many pharmacies now offer services to ship prescription refills right to the patient’s home. They also offer mail service where you can mail in a new, original prescription and a signed document, and they will ship the filled prescription back to you.

Pharmacy information systems are a potential source of valuable information for pharmaceutical companies as it contains information about the prescriber’s prescribing habits. Prescription data mining of such data is a developing, specialised field.

Many prescribers lack the digitised information systems that reduce prescribing errors. To reduce these errors, some investigators have developed modified prescription forms that prompt the prescriber to provide all the desired elements of a good prescription. The modified forms also contain predefined choices such as common quantities, units and frequencies that the prescriber may circle rather than write out. Such forms are thought to reduce errors, especially omission and handwriting errors and are actively under evaluation.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Medical_prescription >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is a Prescription Drug?

Introduction

A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of what constitutes a prescription drug.

In North America, ℞, usually printed as “Rx”, is used as an abbreviation of the word “prescription”. It is a contraction of the Latin word “recipe” (an imperative form of “recipere”) meaning “take”. Prescription drugs are often dispensed together with a monograph (in Europe, a Patient Information Leaflet or PIL) that gives detailed information about the drug.

The use of prescription drugs has been increasing since the 1960s.

Regulation

Australia

In Australia, the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) governs the manufacture and supply of drugs with several categories:

  • Schedule 1 – Defunct Drug.
  • Schedule 2 – Pharmacy Medicine.
  • Schedule 3 – Pharmacist-Only Medicine.
  • Schedule 4 – Prescription-Only Medicine/Prescription Animal Remedy.
  • Schedule 5 – Caution/Poison.
  • Schedule 6 – Poison.
  • Schedule 7 – Dangerous Poison.
  • Schedule 8 – Controlled Drug (Possession without authority illegal).
  • Schedule 9 – Prohibited Substance (Possession illegal without a license legal only for research purposes).
  • Schedule 10 – Controlled Poison.
  • Unscheduled Substances.

As in other developed countries, the person requiring a prescription drug attends the clinic of a qualified health practitioner, such as a physician, who may write the prescription for the required drug.

Many prescriptions issued by health practitioners in Australia are covered by the Pharmaceutical Benefits Scheme, a scheme that provides subsidised prescription drugs to residents of Australia to ensure that all Australians have affordable and reliable access to a wide range of necessary medicines. When purchasing a drug under the PBS, the consumer pays no more than the patient co-payment contribution, which, as of 01 January 2022, is A$42.50 for general patients. Those covered by government entitlements (low-income earners, welfare recipients, Health Care Card holders, etc.) and or under the Repatriation Pharmaceutical Benefits Scheme (RPBS) have a reduced co-payment, which is A$6.80 in 2022. The co-payments are compulsory and can be discounted by pharmacies up to a maximum of A$1.00 at cost to the pharmacy.

United Kingdom

In the United Kingdom, the Medicines Act 1968 and the Prescription Only Medicines (Human Use) Order 1997 contain regulations that cover the supply of sale, use, prescribing and production of medicines. There are three categories of medicine:

  • Prescription-only medicines (POM), which may be dispensed (sold in the case of a private prescription) by a pharmacist only to those to whom they have been prescribed.
  • Pharmacy medicines (P), which may be sold by a pharmacist without a prescription.
  • General sales list (GSL) medicines, which may be sold without a prescription in any shop.

The possession of a prescription-only medicine without a prescription is legal unless it is covered by the Misuse of Drugs Act 1971.

A patient visits a medical practitioner or dentist, who may prescribe drugs and certain other medical items, such as blood glucose-testing equipment for diabetics. Also, qualified and experienced nurses and pharmacists may be independent prescribers. Both may prescribe all POMs (including controlled drugs), but may not prescribe Schedule 1 controlled drugs, and 3 listed controlled drugs for the treatment of addiction; which is similar to doctors, who require a special license from the Home Office to prescribe schedule 1 drugs. Schedule 1 drugs have little or no medical benefit, hence their limitations on prescribing. District nurses and health visitors have had limited prescribing rights since the mid-1990s; until then, prescriptions for dressings and simple medicines had to be signed by a doctor. Once issued, a prescription is taken by the patient to a pharmacy, which dispenses the medicine.

Most prescriptions are NHS prescriptions, subject to a standard charge that is unrelated to what is dispensed. The NHS prescription fee was increased to £9.15 per item in England on 01 April 2020; prescriptions are free of charge if prescribed and dispensed in Scotland, Wales and Northern Ireland, and for some patients in England, such as inpatients, children, those over 60s or with certain medical conditions, and claimants of certain benefits. The pharmacy charges the NHS the actual cost of the medicine, which may vary from a few pence to hundreds of pounds. A patient can consolidate prescription charges by using a prescription payment certificate (informally a “season ticket”), effectively capping costs at £29.60 per quarter or £105.90 per year.

Outside the NHS, private prescriptions are issued by private medical practitioner and sometimes under the NHS for medicines that are not covered by the NHS. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS.

Survey results published by Ipsos MORI in 2008 found that around 800,000 people in England were not collecting prescriptions or getting them dispensed because of the cost, the same as in 2001.

United States

In the United States, the Federal Food, Drug, and Cosmetic Act defines what substances require a prescription for them to be dispensed by a pharmacy. The federal government authorises physicians (of any specialty), physician assistants, nurse practitioners and other advanced practice nurses, veterinarians, dentists, and optometrists to prescribe any controlled substance. They are then issued unique DEA numbers; many other mental and physical health technicians, including basic-level registered nurses, medical assistants, emergency medical technicians, most psychologists, and social workers, for example, do not have the authority to prescribe any legend drugs or controlled drugs. Legend drugs are another name for drugs requiring a prescription.

The Controlled Substances Act (CSA) was enacted into law by the US Congress of the United States in 1970. It is the federal drug law that regulates manufacture, importation, possession, use, and distribution of controlled substances. The legislation classes these substances into five schedules, with varying qualifications for each schedule. The schedules are designated schedule I, schedule II, schedule III, schedule IV, and schedule V. Many drugs require a prescription, even though they are not a controlled substance.

The safety and the effectiveness of prescription drugs in the US are regulated by the 1987 Prescription Drug Marketing Act (PDMA). The Food and Drug Administration (FDA) is charged with implementing the law.

Misuse or abuse of prescription drugs can lead to adverse drug events, including those due to dangerous drug interactions.

The package insert for a prescription drug contains information about the intended effect of the drug and how it works in the body. It also contains information about side effects, how a patient should take the drug, and cautions for its use, including warnings about allergies.

As a general rule, over-the-counter drugs (OTC) are used to treat a condition that does not need care from a healthcare professional if have been proven to meet higher safety standards for self-medication by patients. Often, a lower strength of a drug will be approved for OTC use, but higher strengths require a prescription to be obtained; a notable case is ibuprofen, which has been widely available as an OTC pain killer since the mid-1980s, but it is available by prescription in doses up to four times the OTC dose for severe pain that is not adequately controlled by the OTC strength.

Herbal preparations, amino acids, vitamins, minerals, and other food supplements are regulated by the FDA as dietary supplements. Because specific health claims cannot be made, the consumer must make informed decisions when purchasing such products.

By law, American pharmacies operated by “membership clubs” such as Costco and Sam’s Club must allow non-members to use their pharmacy services and may not charge more for these services than they charge as their members.

Physicians may legally prescribe drugs for uses other than those specified in the FDA approval, known as off-label use. Drug companies, however, are prohibited from marketing their drugs for off-label uses.

Large US retailers that operate pharmacies and pharmacy chains use inexpensive generic drugs as a way to attract customers into stores. Several chains, including Walmart, Kroger (including subsidiaries such as Dillons), Target, and others, offer $4 monthly prescriptions on select generic drugs as a customer draw. Publix Supermarkets, which has pharmacies in many of their stores, offered free prescriptions on a few older but still effective medications to their customers, the programme ended in 2022. The maximum supply is for 30 days.

Some prescription drugs are commonly abused, particularly those marketed as analgesics, including fentanyl (Duragesic), hydrocodone (Vicodin), oxycodone (OxyContin), oxymorphone (Opana), propoxyphene (Darvon), hydromorphone (Dilaudid), meperidine (Demerol), and diphenoxylate (Lomotil).

Some prescription painkillers have been found to be addictive, and unintentional poisoning deaths in the United States have skyrocketed since the 1990s according to the National Safety Council. Prescriber education guidelines as well as patient education, prescription drug monitoring programs and regulation of pain clinics are regulatory tactics which have been used to curtail opioid use and misuse.

Expiration Date

The expiration date, required in several countries, specifies the date up to which the manufacturer guarantees the full potency and safety of a drug. In the United States, expiration dates are determined by regulations established by the FDA. The FDA advises consumers not to use products after their expiration dates.

A study conducted by the U.S. Food and Drug Administration covered over 100 drugs, prescription and over-the-counter. The results showed that about 90% of them were safe and effective far past their original expiration date. At least one drug worked 15 years after its expiration date. Joel Davis, a former FDA expiration-date compliance chief, said that with a handful of exceptions – notably nitroglycerin, insulin, some liquid antibiotics; outdated tetracyclines can cause Fanconi syndrome – most expired drugs are probably effective.

The American Medical Association (AMA) issued a report and statement on Pharmaceutical Expiration Dates. The Harvard Medical School Family Health Guide notes that, with rare exceptions, “it’s true the effectiveness of a drug may decrease over time, but much of the original potency still remains even a decade after the expiration date”.

The expiration date is the final day that the manufacturer guarantees the full potency and safety of a medication. Drug expiration dates exist on most medication labels, including prescription, over-the-counter (OTC) and dietary (herbal) supplements. US pharmaceutical manufacturers are required by law to place expiration dates on prescription products prior to marketing. For legal and liability reasons, manufacturers will not make recommendations about the stability of drugs past the original expiration date.

Cost

Prices for prescription drugs vary widely around the world. Prescription costs for biosimilar and generic drugs are usually less than brand names, but the cost is different from one pharmacy to another.

Prescription drug prices including generic prices are rising faster than the average rate of inflation. To lower prescription drug costs, some US patients buy medicine in Canada or online.

Generics undergo strict scrutiny to meet the equal efficacy, safety, dosage, strength, stability, and quality of brand name drugs. Generics are developed after the brand name has already been established, and so generic drug approval in many aspects has a shortened approval process because it replicates the brand name drug.

Brand name drugs cost more due to time, money, and resources that drug companies invest in in order to repeat research clinical trials that the FDA requires for the drug to remain in the market. Because drug companies have to invest more in research costs to do this, brand name drug prices are much higher when sold to consumers.

When the patent expires for a brand name drug, generic versions of that drug are produced by other companies and are sold for lower price. By switching to generic prescription drugs, patients can save significant amounts of money: e.g. one study by the FDA showed an example with more than 50% savings of a patient’s overall costs of their prescription drugs.

Drug Cost Containment Strategies in the US

In the United States there are many resources available to patients to lower the costs of medication. These include co-payments, coinsurance, and deductibles. The Medicaid Drug Rebate Programme is another example.

Generic drug programs lower the amount of money patients have to pay when picking up their prescription at the pharmacy. As their name implies, they only cover generic drugs.

Co-pay assistance programmes are programmes that help patients lower the costs of specialty medications; i.e., medications that are on restricted formularies, have limited distribution, and/or have no generic version available. These medications can include drugs for HIV, hepatitis C, and multiple sclerosis. Patient Assistance Programme Centre (RxAssist) has a list of foundations that provide co-pay assistance programmes. It is important to note that co-pay assistance programmes are for under-insured patients. Patients without insurance are not eligible for this resource; however, they may be eligible for patient assistance programmes.

Patient assistance programmes are funded by the manufacturer of the medication. Patients can often apply to these programs through the manufacturer’s website. This type of assistance programme is one of the few options available to uninsured patients.

The out-of-pocket cost for patients enrolled in co-pay assistance or patient assistance programmes is $0. It is a major resource to help lower costs of medications – however, many providers and patients are not aware of these resources.

Environment

Traces of prescription drugs – including antibiotics, anti-convulsants, mood stabilisers and sex hormones – have been detected in drinking water. Pharmaceutically active compounds (PhACs) discarded from human therapy and their metabolites have been found to not be eliminated by sewage treatment plants and have been found at low concentrations in surface waters downstream from those plants. The continuous discarding of incompletely treated water may interact with other environmental chemicals and lead to uncertain ecological effects. Due to most pharmaceuticals being highly soluble, fish and other aquatic organisms are susceptible to their effects. The long term effects of pharmaceuticals in the environment may affect survival and reproduction of such organisms. However, levels of medical drug waste in the water is at a low enough level that it is not a direct concern to human health. However, processes, such as biomagnification, are potential human health concerns.

On the other hand, there is clear evidence of harm to aquatic animals and fauna. Recent advancements in technology have allowed scientists to detect smaller, trace quantities of pharmaceuticals in the ng/ml range. Despite being found such low concentrations, female hormonal contraceptives have been documented to cause feminising effects on male vertebrate species, such as fish, frogs and crocodiles. A promising model has been developed to further study the effects on the aquatic environment. The biological read across model combines the concepts of the mechanism of action (MoA) and adverse outcomes pathway (AOP). In other words, the species being studied needs to have similar mechanisms by which the pharmaceutical acts on the species and reach similar concentrations that would be enough to cause an effect in humans. Studying these relations may give us more quantifiable information on the effects of pharmaceuticals in the environment.

Currently, research is being done on various methods of reducing chemical waste in the environment. In addition, FDA established guidelines in 2007 to inform consumers should dispose of prescription drugs. When medications do not include specific disposal instructions, patients should not flush medications in the toilet, but instead use medication take-back programmes. This aims to reduce the amount of pharmaceutical waste that gets into sewage and landfills. If no take-back programs are available, prescription drugs can be discarded in household trash after they are crushed and/or dissolved and then mixed in a separate container or sealable bag with undesirable substances like cat litter or other unappealing material (to discourage consumption).

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Prescription_drug >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.