Pharmacology

Contents: Whats it all about? Where does it happen? What does it involve? 100 high-return facts to get you started What are the hard bits? What are the good bits? What relevance does this have when Im on the wards seeing patients? Resources to help you out

Written by James S Dawson Copyright 2002 fleshandbones.com

What is it all about?

Pharmacology is all about drugs: legal, illegal, natural, synthetic and theoretical. In its purer sense it is about their discovery, design, testing and administration, although pharmacology today is more concerned with drug administration and the mechanisms of drug action and interaction. For the medical student, pharmacology should be about learning the more common drug names and classes, and appreciating their modes and sites of action, their more common indications and contraindications for use, and their potential side-effects.

Where does it happen?

Pharmacology happens in all tissues of the body with very few exceptions. Drugs given by most routes will eventually become systemic and, over long periods of time, can have whole-body effects. Take, for example, the topical use of steroid creams; there have been case reports of topical steroid preparations being used to excess and making patients cushingoid. The reason locally applied drugs have such profound effects is that we have such an efficient blood system, which can transport agents from one end of the body to the other within minutes. This must never forgotten; lignocaine is used most frequently as a local anaesthetic for numbing skin, but in sufficient doses can travel to the heart and have disastrous consequences. Pharmacology mostly relies on ligandreceptor interaction and, initially, responses are at the cellular, then the tissue level. Some drugs have much less specific actions, such as emollient creams and the laxative lactulose.

What does it involve?

To get a good understanding of pharmacology it is essential to understand at what level specific drugs act, and upon which cells and tissues. Knowing this information is most useful because it allows you to foresee any obvious side-effects, and to plan potential steps to reverse or lessen these.

100 high-return facts to get you started

Basic pharmacology General principles

The half-life of a drug is the time taken for the plasma concentration of the drug to become half of its original level. Most drugs have a generic name (a simple chemical name, e.g. salbutamol) and a proprietary name (a trade name, e.g. Ventolin). Drugs are given topically (via the skin), enterally (via the mouth and gut) or parenterally (not via the gut, e.g. intravenously). Orally administered drugs undergo first-pass metabolism in the liver after they have been absorbed from the gut. They are transported to the liver via the hepatic portal vein. Drugs are excreted from the body by the kidneys (in the urine), the liver (in the faeces) or both.

How drugs act Ion channels: local anaesthetics act by inhibiting sodium channels, slowing electrical propagation within nerves. Carrier molecules: digoxin inhibits the carriage of sodium/potassium ATPase, disturbing the potential gradient across the cell membrane. Enzymes: sildenafil inhibits the phosphodiesterase enzyme, which elevates the cellular level of cyclic AMP. Receptors: insulin binds to receptors, which encourages glucose uptake into the cell. Non-specific: most general anaesthetics do not have a specific target.

Drugreceptor interactions An agonist is an agent that activates a receptor to bring about its physiological response. Efficacy is the degree to which an agonist activates a receptor. An antagonist is an agent that interacts with a receptor but does not bring about a physiological response. A competitive antagonist binds reversibly to a receptor but can be displaced by an agonist. A non-competitive antagonist binds to a receptor irreversibly and cannot be displaced by an agonist.

Autonomic nervous system (1): the parasympathetic nervous system Parasympathetic nerves arise from the cranial and sacral regions. Parasympathetic ganglia lie close to target organs. Preganglionic transmission relies on nicotinic-type acetylcholine receptors. Postganglionic transmission relies on muscarinic-type acetylcholine receptors. Atropine is a cholinergic antagonist.

Autonomic nervous system (2): the sympathetic nervous system Sympathetic nerves arise from the thoracic and lumbar spine. Sympathetic ganglia lie close to the spinal cord. Preganglionic transmission relies on nicotinic-type acetylcholine receptors. Postganglionic transmission relies on adrenoceptors and on both muscarinic- and nicotinic-type acetylcholine receptors. Adrenoceptors are either alpha- or beta- in type.

15 common drugs Aspirin Non-steroidal anti-inflammatory (NSAID) drug. Inhibits cyclo-oxygenase (COX) enzyme. Limits prostaglandin synthesis. Used as an analgesic and antipyretic. Has antiplatelet properties.

Atenolol Beta-adrenergic antagonist. Acts primarily by slowing heart rate and force of contraction. Used in the treatment of hypertension and angina. Can worsen asthma and acute heart failure. Overdose results in bradycardia and hypotension.

Benzylpenicillin Digoxin Cardiac glycoside. Inhibits the Na+/K+ ATP pump. Slows conduction through the atrioventricular node. Does not revert dysrhythmia back into sinus rhythm. Overdose results in bradycardia. Beta-lactam antibiotic. Inhibits bacterial cell wall synthesis. Used to treat most streptococcal, gonococcal and meningococcal infections. Inactivated by bacterial beta-lactamases. Side-effects include hypersensitivity reactions and diarrhoea.

Fluoxetine Selective serotonin reuptake inhibitor. Used to treat depression. Acts to increase serotonin levels within the brain. Side-effects include insomnia and sexual dysfunction. Safer in overdose than the tricyclic antidepressants.

Furosemide (frusemide) Loop diuretic. Used to treat acute pulmonary oedema and chronic heart failure. Acts by inhibiting Na+/K+/Cl pump in the loop of Henle. Common side-effects include hypotension, hypokalaemia and hyponatraemia. Can precipitate hyperuricaemia and cause gout.

Lansoprazole Proton pump inhibitor. Irreversibly inhibits H+/K+ ATP pump in the stomach. Used to treat gastro-oesophageal reflux, ulcer disease and in Helicobacter pylori eradication. Can cause diarrhoea. Can be used to protect gastric mucosa from NSAID use.

Lidocaine (lignocaine) Local anaesthetic. Blocks slow sodium channels in nerves. Used as local anaesthetic and as antiarrhythmic. Perioral paraesthesia is a feature of overdose. Should be avoided in heart block.

Lisinopril Angiotensin-converting enzyme (ACE) inhibitor. Acts to decrease synthesis of angiotensin II. Used in the treatment of hypertension and heart failure. Side-effects include hypotension and hyperkalaemia. ACE inhibitors are also used after myocardial infarction and to slow the onset of diabetic nephropathy.

Metoclopramide Dopamine antagonist. Acts centrally in the chemoreceptor trigger zone. Acts peripherally to increase rate of gastric motility. Used to treat nausea and vomiting. Can cause Parkinsonism.

Morphine Opiate. Acts on endogenous opiate receptors. Used to treat severe pain. Overdose results in sedation and respiratory depression. Action can be reversed by naloxone.

Phenytoin Anticonvulsant. Blocks voltage-gated Na+ channels. Used to treat most forms of epilepsy and trigeminal neuralgia. Side-effects include insomnia, nausea and gum hypertrophy. Interacts with warfarin and the oral contraceptive pill.

Salbutamol Beta-adrenergic agonist. Acts by relaxing respiratory tract smooth muscle. Used in asthma and chronic obstructive pulmonary disease (COPD). Side-effects include tachycardia and tremor. Can also be employed to delay onset of premature labour.

Simvastatin HMG CoA reductase inhibitor. Inhibits the rate-limiting enzyme in endogenous cholesterol synthesis. Used to treat hypercholesterolaemia. Should be taken at night when the enzyme most expressed. Side-effects include nausea and abdominal cramps.

Warfarin Coumarin, oral anticoagulant. Vitamin K analogue. Inhibits synthesis of factors II, VII, IX and X. Used to prevent thromboembolic events. Interacts with antibiotics and the oral contraceptive pill.

What are the hard bits?

There are hundreds of drugs and it would be silly to contemplate knowing all their names and pharmacological profiles; even the most knowledgeable professor of therapeutics does not know everything about every drug. Clinical trials that compare the effects of competing drugs are often reported and it can become confusing when there is conflicting information about which drug is better or safer. For the majority of drugs, stick to the largest clinical trials, which are well established and reported in modern textbooks. Many students dread pharmacology exams. Dont. If you know the more common drug classes then you will be able to easily list indications, contraindications, mechanisms of action and sideeffects. Pharmacology is very logical most of the time, just put your logical brain on and think about the question and you will come up with a sensible answer.

What are the good bits?

One of the best aspects of pharmacology is that no-one will ever frown on you or think you are stupid if you look a drug up in a local formulary. That is the purpose of drug formularies to offer the prescriber (and the student) sound, reliable and up-to-date information on each and every drug. Use it now, and when you qualify. Drugs often make very rapid changes in patients and drug therapy can be most rewarding to watch. For example, furosemide (frusemide) can clear pulmonary oedema within minutes, and opiate analgesics can minimise agonising pain even more quickly. Remember, though, that adverse events can also happen as quickly, so be sure to keep an eye on patients.

What relevance does this have when Im on the wards seeing patients?
Drug therapy is often one of the main forms of treatment and it is the doctors responsibility to decide which drugs should be given and which should be avoided in each and every situation. Side-effects of drugs also account for many consultations both in the community and in hospital and for this reason a sound knowledge of pharmacology can allow a rapid diagnosis to be made and simple steps taken to remedy problems. Drugs are prescribed in each and every speciality within medicine and surgery, so there is no doubt you will encounter drug names and be expected to know a little about the more commonly used drugs. When you qualify and start working on the wards, you will be expected by nurses and patients to have been taught all about drugs and drug prescribing, but in reality you will probably only know about the pharmacology of individual drugs. Spend time with junior medical staff when they prescribe medicines and appreciate that there is much more to it that than just writing paracetamol.

Resources to help you out

Textbooks C Page, Curtis M J, Sutter M C et al 2002 Integrated pharmacology, 2nd edn. Mosby Rang H P, Dale M, Ritter J M 1999 Pharmacology, 4th edn. Churchill Livingstone British Medical Association 2002 British National Formulary (BNF). BMA/Pharmaceutical Press Revision books Dawson J 2002 Crash course: pharmacology, 2nd edn. Mosby Websites http://www.bnf.org/ http://www.pharmweb.net/pwmirror/pwb/pharmwebb.html

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