Pills Information Blog » Pharmacology

Answering liberal arguments #4: “We’re the richest nation in the world!”

administrator — Thu, 17 Sep 2009 13:02:02 +0000

Here’s one that I hear a lot: “We’re the richest country in the world, yet we don’t provide health care for all of our citizens. That’s unconscionable!”

Embedded in the “That’s unconscionable!” part of the argument is an implicit statement that health care is a right. But a right for whom? For Americans? Why Americans? Why not Mauritanians, Serbians, Cambodians, and so on and so forth? If “health care is a right” is taken to its logical conclusion, then every child in sub-Saharan Africa who isn’t getting the HIV medications he needs, every Southeast Asian who suffers from malaria, even every Briton and Canadian who is denied treatment because the government considers it unnecessary, is a living reproach to all of us Americans. If health care is a right, we ought to be providing it to them…shouldn’t we?

Even liberals have to realize that this isn’t possible. And if a so-called moral ideal is impossible, we need to reevaluate whether what we are glorifying — health care as a right — is indeed a proper moral ideal. Morality, after all, is a guide for how to live on this earth — and if morality suggests a goal that is physically impossible, then maybe it’s the morality being applied that needs to get tossed out.

In fact, health care is not a right, as so many others have eloquently argued. It would be impossible to live if health care were a right, because every dollar we earned would be “owed” to a child with AIDS, or a homeless person with tuberculosis, or prenatal care for a heroin addict. Health care is a need — but it’s every person’s responsibility to provide for that need himself, and if he cannot, to seek private charity, not to demand his care as a right from others.

reasonpharm.blogspot.com

Preclinical investigations

administrator — Tue, 17 Mar 2009 03:43:25 +0000

Development plans for new drugs should include screening for potential drug interactions at an early stage. Structural chemistry and other chemical properties will give a broad idea of how the drug may be absorbed, transported, metabolized and excreted. Mechanistic studies to elucidate the mechanism of action will give indications for possible interactions with other drugs acting at the same site. In vitro and in vivo investigations on hepatic enzyme systems can be carried out to investigate the substrate potential and/or capability for inhibition or induction of liver enzyme systems; this information can then be used to guide investigations of metabolic interactions that may be of eventual clinical significance. The animal toxicokinetics may also provide information about what can be expected in humans.
These batteries of preclinical tests will often generate questions that can only be answered by studying potential interactions in humans. Understanding whether a new drug will interact with other drugs that are likely to be co-prescribed for the disease of interest is essential for good product labeling. Oral contraceptives are used by about 50% of women in their reproductive years in the developed world, and must always be considered as a concomitant medication.

Drug distribution

administrator — Tue, 17 Mar 2009 03:40:56 +0000

Most of these drug interactions involve displacement of drug from plasma proteins, thus increasing the free/bound ratio for drug concentration. When the free moieties are those that are pharmacologically active, then unexpectedly exaggerated responses result from standard doses. Most (but not all) such interactions are unwanted. Almost any nonsteroidal anti-inflammatory drug (NSAID) displaces warfarin, thus enhancing its anticoagulant effect and rendering the patient liable to unexpected ecchymosis or more serious hemorrhagic adverse events. Similarly unwanted are the interactions between phenytoin and thyroxine (sedation and thyrotoxicosis), and salicylates with tolbutamide (hypoglycemia). Oral contraceptives compete for albumin-binding sites, and phenytoin doses may need to be adjusted when the former are introduced. A rare example of a beneficial drug interaction at this locus are the use of NSAIDs with some glucocorticoids, where enhanced anti-inflammatory effects of the latter can result, even though a relatively low dose has been administered.
Drug interactions at the site of action are manyfold and familiar. All receptor antagonists, when used in the face of an agonist challenge, are clinically desirable. Obvious examples include naloxone for opioid overdose and physostigmine for reversal of tubocurarine in anesthesia. Note that succinylcholine paralysis during anesthesia is only made worse with anticholinesterase administration (an adverse drug interaction at the receptor, beloved by multiple-choice question setting examiners!). Sequential biochemistry interactions also fall within this category. Sulfamethoxazole and trimethoprim inhibit different stages of the folate metabolism pathway. Concomitant administration reduces the probability that a bacterial strain can mutate in any single step to evade the antibiotic effects of both drugs.
Physiological interactions are a subset of site of action interactions. Adding spironoloactone to furosemide (frusemide) provides no extra diuresis, but does antagonize the potassium loss that occurs when the latter drug is used alone. Both progestagens and estragens (progesterones and estragens) such as ethinyl(o)estradiol and levonorgestrol inhibit ovulation and uterine deciduation, thus being positive or wanted interactions, albeit acting at different receptors.
Unwanted interactions at the site of action classically include the highly undesirable concomitant use of tetracyclines and penicillins. The latter are bacteriocidal when the organism is dividing because they obstruct cell wall manufacture, and thus expose the new bacterial membrane to osmotic destruction. Bacteriostatic compounds, such as tetracyclines, reduce the rate of bacterial division and thus reduce the effectiveness of penicillins. Other nonreceptor site of action interactions include MAOIs – pethidine (acute dystonias), ethanol – benzodiazepines (synergisitic sedation and respiratory depression), cocaine – amphetamines (hypertensive crisis) and dihydrocodeine –morphine (the former is a partial agonist and reduces the efficacy of the full agonist). As far as drug metabolism is concerned, it is essential to understand some of the basic biochemistry before being able to anticipate the interactions that can occur at this locus. Mobile omnivore mammals are constantly exposed to xenobiotics, many of which can be toxic. An efficient defence against these toxins resides in the gut and the liver, with the general aim of metabolizing such toxic molecules into smaller and less toxic metabolites; these are generally more water-soluble and thus more capable of excretion, thus reducing the exposure of the rest of the body to high concentrations of the parent toxin. Drugs fall foul of the same defence mechanisms.

The expanding place of self-medication

administrator — Tue, 17 Mar 2009 03:37:00 +0000

In recent years, the role of over-the-counter (OTC)
medication in the overall health system has
increased dramatically. The increased interest in
and availability of OTC medications is being driven
by several factors:
1. There is a growing recognition of the capability of patients to treat themselves in a rational and safe manner. The older authoritarian model of medicine is being gradually replaced by a more participative model.
2. There is an increasing desire by patients to participate in their own medical care. This is not just a result of changes in philosophy but also of the dramatic increase in average educational level over the past half-century. Theworld increasingly possesses a well-informed and intellectually capable population that demands an active and inclusive role in its own healthcare.
3. The quantity of information now available to the average person, both through formal education and through the media, has increased substantially, giving increasing awareness of treatment options.
4. There is a growing need to contain medical costs. OTC drugs are not only cheaper than prescription drugs, due to their simpler and more efficient distribution channels, but they also eliminate the need for an expensive visit to the doctor for each episode of illness. The professional intervention required to prescribe pharmaceuticals represents the dominant cost in the handling of many common types of illness.
5. There is a need to increase treatment effectiveness, which is not ordinarily considered an advantage of self-medication. Increase in effectiveness depends on the generally more rapid availability of OTC medications compared to prescription medications, so that treatment may begin sooner. This can significantly shorten the total length of suffering, especially when the natural course of a disease is brief or when severe discomfort makes prompt therapy especially helpful.
An example of this last phenomenon is in the treatment of vaginal candidiasis. Prior to the OTC availability of topical anti-fungals, it was often necessary for a woman who had already recognized the symptoms of the disease to call and arrange a clinician’s appointment. This often took several days. Delaying treatment caused much unnecessary suffering and encouraged disease progression. Many clinicians, recognizing these difficulties, would prescribe over the phone, based solely on the woman’s description of symptoms. Research has shown that the accuracy of the clinician’s diagnosis in this setting is no better than that of the woman herself. This constituted an ideal situation for the switching of an important class of drugs from prescription to OTC status. The patient obtained equally accurate diagnosis and far more rapid treatment for a disease that is very uncomfortable. Severe cases of vaginal candidiasis with heavy discharge are now much less common. A second example is in the treatment of the common cold. Anticold medications have been available OTC for many years, because of the compelling need for rapid treatment. A cold evolves quickly, the entire illness lasting only a few days. A delay of only a day or two in seeing the clinician for a prescription may eliminate any possibility of obtaining effective treatment for half of the duration of the illness. The prompt availability of self-medication improves treatment efficacy while reducing costs and enhancing patient satisfaction with the medical system. The above factors have combined to greatly increase public awareness of the importance of self-medication in the total healthcare scheme. The Sponsor should recognize the opportunities for OTC use of medications and the advantages and pitfalls attendant upon such use. As self-medication becomes a central part of the healthcare system, the skillful and appropriate movement of pharmaceuticals from prescription to OTC availability will increasingly become a vital role of the Sponsor in optimizing the nation’s health.

Principles of pharmacology: Drug disposition

administrator — Tue, 17 Mar 2009 03:22:41 +0000

Chapter overview
If a drug is to have a therapeutic effect on the body, it first has to reach its site of action. In order to do this a drug has to be administered in some way. Unless the route of administration is directly into the blood stream, the drug has to be absorbed, usually by diffusion. Once absorbed, distribution of the drug to different parts of the body follows. This necessarily includes passage through the liver. Most drugs are treated as potentially toxic substances and are metabolized by the liver. This detoxifies them and some drugs are almost totally inactivated on first pass through the liver. Eventually a drug will be excreted from the body. This usually occurs via the kidneys, although some drugs can be lost in faeces or exhaled air. This chapter discusses the processes of administration, absorption, distribution, metabolism and excretion of drugs together with factors affecting these processes. Collectively, these processes describe drug disposition, the way in which the body handles drugs. The study of the fate of drugs in the body is known as pharmacokinetics.
Administration of drugs
In order to get to their site of action in the body, drugs have to be administered in some way. There are two major routes of drug administration: enteral and parenteral. Enteral means to do with the gastrointestinal tract and includes oral and rectal administration. The parenteral route includes all other means of drug administration. There are many routes of parenteral administration, some of which are intended for a drug to have a systemic effect and others for a local effect. See Figure 2.1.
(In some definitions, parenteral is synonymous with injection (for example in the Medicines Act), but here the term is used to describe all routes of administration that are not enteral.)

Drug names

administrator — Tue, 17 Mar 2009 03:20:22 +0000

All drugs have at least three names: the chemical name, the generic name and the proprietary name. Chemical names can be complicated and difficult to remember and are not used in this book. A generic name is a drug’s official name and the majority of drugs in this book are referred to by their generic names. The proprietary name is the name given to a drug by the manufacturing company. As the same drug can be manufactured by several different companies, a drug can have multiple proprietary names and this can be confusing. Hence, proprietary names have been avoided in this book except where the proprietary name is in common usage. In the United Kingdom, the generic name is known as the British approved name (BAN ). Following European Directive 92/27/EEC, European Law requires the use of the recommended International Non-proprietary Name (rINN). This ensures that all countries, in Europe at least, recognize the same drug. In most cases, the BAN and the rINN were the same, but some British names have been changed. For example, amphetamine is now spelt amfetamine and lignocaine is now lidocaine. Where this has happened, both names are listed in the BNF. Wherever possible, drugs should be prescribed by their generic name; this allows any suitable product to be dispensed and in many cases, it saves the health service money. The only exception to this rule is when a patient must always receive the same brand of a drug because different preparations can result in different blood levels of the drug. No details of dosages are given in this book (except in some of the case studies), because these are subject to change and often have to be varied to suit individual patients. In practice, the BNF or MIMS should be used as a guide to dosages. Examples of individual drugs have been kept to a minimum in the text, with usually just one or two examples given in each section. It would be impractical to try to remember the names of all drugs available. In practice, health care professionals quickly become familiar with drugs commonly used in their area.

Patient compliance

administrator — Tue, 17 Mar 2009 03:18:58 +0000

Patient compliance is important for successful drug therapy. Compliance in this context is defined as the extent to which the patient follows the clinical prescription. Non-compliance and reasons why patients do not always take drugs as prescribed should be appreciated. Some common reasons for non-compliance are that the patient has doubts about a drug’s effectiveness, they believe they are cured, they misunderstand instructions, dosage regimes are too complicated, or they experience unacceptable side effects. Health care professionals play an important role in improving compliance. This is particularly important if a drug is for serious conditions like epilepsy, glaucoma or hypertension, or is for infection because of the problem of drug resistance. Well-informed patients are more likely to be compliant.
It is worth spending time explaining what the medication is, how it is taken and why, how long it is to be used for, what adverse effects to look out for and any alternatives if appropriate. The importance of the drug therapy can be explained and what might happen if the patient did not comply. Aids to help compliance can be suggested, for example packaging of daily doses can be arranged with pharmacists, special containers can be obtained, the help of relatives can be sought, suitable time of day for administration can be chosen and provision of written information can all help. Patient information leaflets must be included in packaging of medicines.

Introduction

administrator — Tue, 17 Mar 2009 03:13:28 +0000

Pharmacology is the science of drugs and their effects on biological systems. A drug can be defined as a chemical that can cause a change in a biological system; the important biological system to be considered in this book is the human body. A drug is the active ingredient in a medicine; a medicine is the formulation of a drug into a tablet, capsule or other delivery system. The Medicines Act 1968 refers to drugs as medicinal products. Drugs can be naturally occurring substances, for example hormones; everyday substances, for example caffeine and alcohol; synthetic chemicals marketed for therapeutic activity, for example aspirin; or substances used for recreation.
Pharmacology as a science encompasses the following:
• the action of natural chemicals in the body;
• the origins and sources of drugs;
• their chemical structure and physical characteristics;
• their mechanisms of action;
• their metabolism and excretion;
• studies of their action on whole animals, isolated organs, tissues and cells, enzymes, DNA and other components of cells;
• ultimately studies of their actions in humans and their therapeutic uses.
Pharmacology is also the study of the toxic effects of drugs and chemicals in the environment. All drugs are capable of being toxic and all drugs can produce unwanted effects at high doses, or if used incorrectly. The difference between a medicine and a poison is often merely a matter of concentration. In therapeutics, the treatment of disease is intended to have a beneficial effect with adverse effects kept to an acceptable minimum. The science of modern pharmacology is a relatively recent development. Prior to the 1930s, there were very few medicines available, and those that were available came from natural sources. Examples of drugs originally from natural sources and still in use today are quinine (from the bark of the cinchona tree and used to treat malaria), digitalis (from the foxglove and used for heart failure) and aspirin (extracted from the bark of willow tree and originally used to treat fever).
Development of new drugs can happen in many ways. Drugs have been developed following observation of side effects when being used for other purposes. It is now known Pharmacology for the Health Care Professions that the site of action of many drugs is a cellular receptor. As knowledge of receptor structures has developed, this has allowed drugs to be designed to fit with receptors. The human genome project and mapping of genes has led to work on the development of drugs to alter genes.