Summer 2005 – Q. 1b Write an essay on pharmacokinetic drug interaction, including mechanisms and clinical relevance. Illustrate your answer with specific examples

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Summer 2005 – Q.1b Write an essay on pharmacokinetic drug interaction, including mechanisms and clinical relevance. Illustrate your answer with specific examples.
Pharmacokinetics refers to, in simple terms, what the body does to the drug. It generally involves the following steps: absorption, distribution, metabolism and elimination of the drug. An important element within pharmacokinetics is drug interaction, this may prove useful or detrimental depending on the drug and the interaction involved. Interactions are often not easily predicted and commonly affect only a small minority of patients taking the two drugs. Drugs with steep dose-response curves (e.g. verapamil) and a low therapeutic index (e.g. digoxin) are most likely to cause unwanted drug interactions. Pharmacokinetic interactions are those which cause the following processes:

  • Altered absorption

  • Altered protein binding

  • Altered metabolism

  • Altered excretion


The rate of absorption and the total amount of absorbed drug can be affected in drug interactions. Reduction in the total amount absorbed may reduce the efficacy of the therapy. Drug absorption interactions are often avoided if an interval of 2-3 hours occurs before the administration of the interacting drug.

  • Some drugs increase (e.g. metoclopramide) and decrease (e.g. atropine, morphine) the rate of gastric emptying which subsequently affects absorption. Delayed absorption is a problem when a high peak plasma concentration is required for the drug to be effective (e.g. analgesics and hypnotics). Increased gastric emptying may be advantageous, for example metoclopramide increases the absorption rate of paracetamol – this effect is used in the treatment of migraine.

  • Drugs can affect the gastrointestinal pH which can subsequently alter the absorption of other drugs. The salicylates for example, are weakly acidic drugs which are best absorbed at a low pH when they are in an unionized form. Drugs which alkalinize the GI tract (e.g. antacids, omeprazole) can decrease their bioavailability significantly.

  • Certain drugs react within the GIT to form complexes or chelates which prevent their absorption. Examples of these drugs include the tetracyclines which can form complexes with metal cations such as iron and calcium. The formation of insoluble complexes results in reduced serum tetracycline concentrations.

  • Another example is that of anion-exchange resins (e.g. cholestyramine) reducing the absorption of warfarin and cardiac glycosides such as digoxin.

  • Some broad spectrum antibiotics (e.g. ampicillin) have adverse effects on the circulation of oral contraceptives (esp. low-dose oestrogen); they kill the bacterial flora in the large bowel which is required to release the steroid from the conjugated form in the bile, and thus reduce reabsorption of the active drug. This interaction could obviously have serious consequences i.e. pregnancy.


Most drugs are transported in the blood by binding to the plasma proteins (albumin or globulin). The extent to which they are bound depends on the drug. The risk with these drugs is that of displacement by a second drug, as protein-binding sites are non-specific. When a drug is displaced, it causes an increase in the proportion of free drug which can travel to the site of action, as bound drugs cannot exert their effects. In most drugs this peak is only transient however, as the rate of elimination is also increased – warfarin is an exception.

  • Warfarin is 98% protein bound. Its anti-coagulative effect is carried out by just 2% of the dose. When a 2nd drug displaces some of the bound drug into solution it can have serious consequences and the patient may bleed to death. Aspirin potentiates the effect of warfarin – this interaction is mainly pharmacodynamic i.e. platelet aggregation is inhibited, but there is also an element of displacement from protein binding.


Most clinically important interactions involve the effect of one drug on the metabolism of another. Drug metabolism involves phase I reactions (oxidation, reduction and hydrolysis) and phase II reactions (conjugation of the drug with other substances). Phase I reactions generally involve the CYP450 isoenzymes in the liver. Drug interaction can affect the action of CYP isoenzymes on a particular substrate. They do this by: acting as substrates, inhibiting the isoenzyme or inducing the isoenzyme. This is only of clinical relevance when a drug is metabolized primarily by a SINGLE isoenzyme, thus inhibition/induction of this enzyme would have a major effect on the plasma concentration of the drug.

Enzyme Induction requires the synthesis of new protein therefore the effect usually takes several days/weeks to materialize. Similarily, the effect may persist for a period following the cessation of the drug. Enzyme induction generally results in a decreased pharmacological effect of the specific drug. Examples of interactions due to enzyme induction are as follows:

  • CYP1A2: Warfarin and theophylline metabolism is induced by interaction with omeprazole and cigarette smoke.

  • CYP3A4: Oral contraceptives are often affected by the antibiotic rifampicin, carbamazepine and phenytoin causing failure of contraception. Other precautions should be carried out and an increased oestrogen dose may be indicated. (These 3 drugs also induce warfarin, terfenadine, and corticosteroid metabolism via CYP3A4).

Enzyme Inhibition can cause reduced metabolism of drugs and their subsequent accumulation within the body. Interactions of this type are clinically important when the affected drug has a narrow therapeutic range, as plasma concentrations may be dramatically increased. Interestingly, the ability to inhibit an enzyme may be associated with a specific chemical structure as many enzyme inhibitors contain an imidazole ring (e.g. ketoconazole, metronidazole, omeprazole, and cimetidine).

  • Cimetidine can potentiate the effects of warfarin and may cause carbamazepine, phenytoin or theophylline toxicity.

  • Allopurinol is also known to potentiate the effects of warfarin.

  • Erythromycin and ketoconazole inhibit the CYP3A4 enzyme thereby affecting the metabolism of oral contraceptives, terfenadine (antihistamine), corticosteroids and warfarin.

  • Grapefruit juice is known to reduce the metabolism of terfenadine, ciclosporin and calcium channel blockers.


Most drugs are excreted in the bile or urine. Drug interactions involving excretion generally affect the kidneys. These interactions usually occur via the alteration of urinary pH or active transport systems.

Changes in tubule fluid pH can seriously affect the passive reabsorption of drugs which relies on the drug being in a non-ionized form. Thus the clearance of weakly acidic drugs is increased when the urine is alkaline and conversely, the renal clearance of weakly basic drugs is increased in acidic urine. This interaction is of minor clinical relevance as most weakly acidic or basic drugs are inactivated by hepatic metabolism and thus do not depend on renal excretion. However, these interactions are sometimes used therapeutically for drug elimination after poisoning (e.g. with salicylates or amphetamines).
Some drugs may share the same transport system in the proximal tubules of the kidney and therefore compete with one another for excretion. This interaction is sometimes a clinical advantage. For example, probenecid may be administered to decrease renal excretion and hence increase the serum concentration of penicillin.
Thiazide and loop diuretics are known to reduce sodium reabsorption in the proximal tubule, leading to increased reabsorption of monovalent ions. This method of interaction is critically important in patients receiving lithium therapy as lithium accumulation and severe toxicity result.

Summer 2005 - Q.2b Discuss the pharmacological management of cardiac arrhythmias.
The sinoatrial node in the heart acts as a pacemaker and determines its rhythm. This is altered by both parasympathetic (acetylcholine HR) and sympathetic (noradrenaline HR) nerves. Arrhythmias are essentially abnormalities of the cardiac rhythm which manifest due to alterations in impulse initiation or propagation, or both. They can generally be divided into two groups:

  • Bradycardia (<60bpm)

  • Tachycardia (>100bpm)

Arrhythmias may be asymptomatic but commonly they lead to palpitations, syncope, heart failure or sudden death. Tachycardia tends to be more symptomatic. Serious arrhythmias arise from scar tissue in the heart due to underlying structural heart disease. These especially occur after MI, in fact 85% of those who survive an MI experience arrhythmias in the following couple of days.
The arrhythmia must be classified before the correct treatment can be defined. An ECG should be carried out as it is a valuable aid in the diagnosis.

Bradycardia may occur due to a number of reasons. Sinus bradycardia frequently follows MI. This condition may be normal in some people such as athletes who have increased vagal tone. It may also manifest due to extrinsic causes which must be treated to resume normal cardiac rhythm e.g. hypothermia and hypothyroidism. Other causes of bradycardia include SA block, sinus pause and AV block. Treatment for the above involves review of the patient’s medication list and elimination of any provocative drugs i.e. antiarrhythmic drugs. IV atropine is commonly indicated to inhibit the parasympathetic innervation of the SA node. This has the effect of HR. In those who don’t respond to atropine or who have a complete heart block, insertion of a pacemaker is necessary.
Tachycardia is subdivided into supraventricular tachycardia or SVT (arises from the atrium or AV junction) and ventricular tachycardia (arises from the ventricles).


  • Sinus tachycardia

  • Atrial flutter

  • Atrial fibrillation

  • AV node re-entry tachycardia

  • Multifocal atrial tachycardia


  • Premature vent. Contractions

  • Ventricular tachycardia

  • Torsade de Pointes

  • Ventricular fibrillation

Supraventricular tachycardia:
Supraventricular tachycardia can present with severe symptoms indicating haemodynamic instability e.g. hypotension, angina etc. These patients require immediate cardioversion and stabilization. All other patients should have an ECG recording carried out.

[SVT treatment: 1. adenosine 2. digoxin 3. verapamil]

Adenosine is frequently the treatment of choice for SVT. It stimulates the opening of K+ channels in the cell membrane of the AV node leading to hyperpolarization. This inhibits the calcium channels resulting in a slower conduction in the AV node. Adenosine can cause side effects including dyspnoea, bronchospasm and nausea but due to its short half life these are usually short lived.
Cardiac glycosides (e.g digoxin) slow the ventricular response in cases of atrial fibrillation and atrial flutter. They achieve this by stimulating vagal activity - thereby Ach. This leads to a slower conduction and prolonged refractory period in the AV node. IV digoxin can be used in the treatment of atrial flutter and fibrillation although it is rarely effective for rapid control. In chronic atrial fibrillation however, digoxin is often given orally.
Verapamil – a calcium channel blocker (class IV in Vaughan-Williams classification), can also be indicated in the treatment of SVT, initially by IV and then orally. It primarily affects the cells of the AV node where conduction is entirely dependent on calcium spikes. It carries out its effect by  conduction velocity and  the refractory period. Verapamil has a negative inotropic action therefore it should not be used in ventricular tachycardia or together with β-blockers or quinidine (Na+ channel blocker) because of cumulative effects. In patients with asthma, verapamil may be preferable to adenosine (which may cause bronchospasm). Verapamil toxicity can present with flushing, constipation, hypotension, sinus node depression or AV block.

SVT and ventricular arrhythmias:
[SVT/Vent Arr. treatment: 1. Class IA (quinidine, disopyramide - Na+CB) 2. Class IC (flecainide - Na+CB) 3. Class III (amiodarone, sotalol - K+CB) CB=channel blocker]
Some drugs are effective in treating both SVT and ventricular arrhythmias. Class IA agents (e.g. Quinidine, Disopyramide) are an example of these. They are Na+ channel blockers and therefore slow phase 0 of the cardiac action potential and prolong the refractory period. Disopyramide has a negative inotropic effect and therefore may cause side effects such as hypotension; it may also cause urinary retention in men due to its anticholinergic effects. Quinidine also has potentially dangerous side effects as it can cause thrombocytopenia, torsades de pointes and cinchonism (def= poisoning caused by an overdose of cinchona or the alkaloids quinine, quinidine or cinchonine derived from it. The symptoms include tinnitus, dizziness, blurring of vision and hypotension. Treat with diuretics in order to increase the rate of excretion of the toxic compounds from the body).
Flecainide (class IC) is often used in the prophylaxis of arial fibrillation. It also acts as a Na+ channel blocker, and works by dissociating very slowly (10-20secs). However it is usually used only as a last resort as it can have severe pro-arrhythmic side effects.
Class III agents (e.g. Amiodarone, Sotalol) are essentially K+ channel blockers however they also have a blocking effect on inactivated Na+ channels and β-receptors. They carry out their effects by slowly repolarizing therefore  the duration of the action potential and refractory period. Class III agents are often effective when other antiarrhythmics fail. Amiodarone has serious side effects including pulmonary fibrosis, corneal deposits, hepatotoxicity, skin deposits, bradycardia, and hypo- or hyper-thyroidism. Sotalol can cause hypotension and new arrhythmias.
Ventricular arrhythmia:
[Vent. Arr. treatment: Class IB (lidocaine - Na+CB)]
Class IB drugs (e.g. Lidocaine) are used to treat ventricular arrhythmias only. They act by blocking inactivated Na+ channels. These inactivated channels are plentiful in ischaemic or depolarized (due to anoxia) Purkinje and ventricular tissue; therefore lidocaine is particularly useful in ventricular arrhythmias post MI. In normal cardiac tissue it dissociates rapidly and hence has little effect. It is relatively safe when given slowly by IV, but high doses may cause convulsions, and CNS/CVS depression in patients with cardiac or hepatic failure.

[Arrhythmias are commonly treated with non-pharmacological therapy which is often more reliable. For example SVT can be treated with radiofrequency ablation and ventricular tachycardia is often overcome by an implanted cardioverter defibrillator (ICD). These options are more popular due to the poor efficacy of drugs, their severe side effects and also the long term expense incurred by the daily administration of drugs.]

Summer 2005 - Q.3b Discuss the basic and clinical pharmacology of drugs used to manage insomnia.
Insomnia is a condition characterized by the inability to fall asleep or to remain asleep for an adequate period of time. Up to one third of adults suffer from insomnia, of which there are many causes. Factors such as noise and jet lag may affect those who normally sleep well (transient insomnia). A therapeutic drug may be indicated in these cases but only one or two doses should be given. Short-term insomnia can last for up to a few weeks and has a tendency to recur – it is often associated with an emotional problem or a serious medical illness. Therapeutics may be useful but should not be administered for more than three weeks. Chronic insomnia can occur due to psychiatric disorders (e.g. depression, anxiety), or drug/alcohol abuse. In these cases it is vital that the underlying cause is treated rather than the insomnia. Other causes of insomnia include primary sleep disorders (e.g. sleep apnoea), and physical disorders (e.g. pain, dyspnoea).
Hypnotics are indicated to help insomnia. These include:

  1. benzodiazepines

  2. non-benzodiazepine hypnotics

  3. barbiturates

  4. antihistamines

  5. antidepressants

(1) Benzodiazepines (e.g. nitrazepam, lormetazepam, temazepam, diazepam) have anxiolytic, hypnotic, muscle relaxant, anticonvulsant and amnesic actions. It is suggested that benzodiazepines mediate their effects by binding to their specific receptor resulting in a structural change. This change subsequently enhances the effect of the inhibitory neurotransmitter GABA in the CNS. Their effects decline after 1-2 weeks of regular use.

The benzodiazepines are active orally and are usually metabolized via oxidation in the liver. They do not induce hepatic enzymes. Although they are generally safer than other hypnotics (the lethal dose being 300+ times the therapeutic dose), they have some side effects which include drowsiness, agitation and ataxia (esp. in the elderly). They may also cause respiratory depression in those with underlying bronchopulmonary disease or when administered by IV. If a long acting drug is used (e.g. diazepam T1/2=32hrs) the side effects may persist into the following day – this fact should be addressed when prescribing. A shorter acting drug such as temazepam (T1/2=8hrs) may be more suitable. Dependency and withdrawal symptoms are a common manifestation in patients given benzodiazepines for even short periods. These occur when the drug is stopped and are more likely to occur with short-acting drugs. The symptoms include anxiety, insomnia, depression, nausea and convulsions. Benzodiazepines are known to interact with other central depressants (alcohol, barbiturates, and antihistamines) in a synergistic manner causing additive effects – this fact must be addressed before prescribing.
(2) Recently introduced non-benzodiazepine hypnotics (e.g. zopiclone, zolpidem) are said to cause less dependence and tolerance than the benzodiazepines. However they should still not be indicated for long-term use. They act on the same receptor as the benzodiazepines. Contra-indications include severe hepatic impairment and those who suffer from sleep apnoea.

(3) Barbiturates (e.g. chlomethiazole, thiopental) have a more potent depressant effect than the benzodiazepines. This is due to the fact that they act directly on chloride ion channel sites. They were extensively used in the past but have now been largely superseded by benzodiazepines due to their psychological and physical dependence, induction of microsomal enzymes and narrow therapeutic index. Chlomethiazole is indicated as a hypnotic for the elderly only where it may cause less hangover, and occasionally to treat alcohol withdrawal or status epilepticus in younger adults. The short-acting barbiturate thiopental however, is still widely used to induce anaesthesia.

(4+5) Some antihistamines (e.g. diphenhydramine, promethazine) and antidepressants (e.g. amitriptyline) are not addictive and may have hypnotic properties when administered in low doses. Interestingly, they also have the added bonus of improving slow wave sleep. However, their prolonged duration of action may lead to drowsiness the following day and their sedative effects also wear off after a few days of continued administration. Antihistamines are also associated with some adverse effects including headache, psychomotor impairment and antimuscarinic effects.

Summer 2005 – Q.4b Give an account of the pharmacological management of hormone-sensitive tumours.
The growth of some tumours is partly dependent on hormones, such as carcinoma of the breast, and prostate. Other tumours including those of the ovary, neuroendocrine system and pituitary may also be hormone sensitive. Hormone therapy is used in three situations, described as follows:

  1. Secondary or adjuvant therapy – to slow down the growth and development of metastases

  2. Palliative therapy – to ease the pain caused by cancer spread

  3. Neoadjuvant therapy – to shrink the tumour, generally before a procedure to remove it.

There are many drugs which are useful to antagonize hormone-sensitive tumours, for example – anti-oestrogens, aromatase inhibitors, anti-androgens, LHRH analogues, progestogens.

Breast cancer
Oestrogen receptors can be detected in varying amounts in approximately 75% of breast cancers. Progesterone receptors are also present in about 50%. Tumours which include both types of receptor respond more readily to hormone therapy. This suggests that these hormones are important in the growth and development of breast carcinoma.
Anti-oestrogens are competitive partial antagonists of oestrogen. They work by  IGF-1 levels in the serum and upregulating TGFβ production. An example of this type of drug is tamoxifen.
Tamoxifen (20mg daily) delays the growth of metastases and increases survival in women with breast cancer. It should ideally be continued for 5yrs if it is tolerated well. It also has the added advantage of  the risk of cancer in the other breast. Tamoxifen is contra-indicated in pregnancy. It should also be noted that it  the risk of thromboembolic events when administered with cytotoxics. It is reported that it may contribute to endometrial pathologies including hyperplasia, polyps and cancer. Therefore, patients on tamoxifen should be alert for the development of symptoms such as menstrual irregularities, vaginal discharge and pelvic pain.
Aromatase inhibitors may be indicated in women who are unable to take tamoxifen. This is common in post menopausal women who need to avoid the  risk of thromboembolism, or endometrial abnormalities. Aromatase inhibitors (e.g. anastrozole) act by inhibiting the conversion of androgens to oestrogens in the peripheral tissues. It should be noted that they don’t inhibit oestrogen synthesis in the ovaries and therefore should not be used in pre-menopausal patients. They are just as effective as tamoxifen as a first line treatment of metastatic breast cancer in post-menopausal women however it is unknown whether their benefits persist for the long-term. They are contraindicated in pregnancy (and pre-menopausal women as mentioned earlier) and in moderate or severe hepatic/renal impairment.

In pre-menopausal women with hormone sensitive breast cancer, ovarian ablation or a gonadorelin analogue (e.g. goserelin) should be considered as the basis for treatment. Gonadorelin analogues are essentially synthetic gonadotrophin-releasing hormone (GnRH) analogues. They cause initial stimulation of luteinizing hormone and a subsequent increase in testosterone release for the first 1-2 weeks before inhibiting LH and therefore suppressing testosterone release, therefore signs and symptoms of breast cancer may worsen initially.

Prostate Cancer
In the treatment of metastatic prostate cancer hormonal treatment is aimed at androgen depletion. This is achieved in a number of ways including bilateral orchidectomy or the use of a gonadorelin analogue (as explained above). Oestrogens (e.g. diethylstilbestrol) used to be widely used but have now been largely replaced by other drugs. Toxicity was common in the administration of oestrogens often leading to severe side effects such as thrombosis, impotence and gynaecomastia. Unfortunately, the effects of hormones usually last only 12-18 months as hormone-independent cells eventually predominate.
Gonadorelin analogues are generally expensive and require parenteral administration initially. During the first 1-2 weeks, when they stimulate testosterone release there may be an associated progression of the prostate cancer. This may cause spinal cord compression, ureteric obstruction or bone pain in some patients. If this is anticipated, concomitant use of an anti-androgen (e.g. flutamide) may be helpful. Other adverse effects include hot flushes, sweating, sexual dysfunction and gynaecomastia.
Leuprolide and triptorelin are other examples of gonadorelin analogues which are used in the treatment of prostate cancer. The latter may also be indicated in the treatment of ovarian cancer.
Anti-androgens are indicated together with gonadorelin analogues to prevent the transient ‘flare’ in symptoms initially. They act by blocking the testosterone produced by the adrenal glands. They may also be administered to patients before a radical prostatectomy or trans-urethral resection of the prostate is carried out in order to cause shrinkage of the tumour and therefore prevent peri-operative complications e.g. TURP syndrome.

Neuroendocrine and Pituitary tumours
Somatostatin analogues (e.g. octreotide, lanreotide) are frequently indicated in the treatment of neuroendocrine and pituitary tumours. Somatostatin acts as a hypothalamic release-inhibiting hormone and therefore its analogues work along the same means. These are very effective drugs when used to relieve the symptoms of carcinoid tumours in the neuroendocrine network or acromegaly due to a growth hormone-secreting pituitary tumour. Their adverse effects are generally mild but may include GI disturbances and the formation of gall stones.
Summer 2005 – Q.5b Discuss the issues to be considered in choosing between a new drug and the existing drug that it replaces.
New drugs are the result of years of research and stringent clinical trials conducted by the pharmaceutical industry. It costs approximately $1billion to discover and develop a new drug, and can take as long as 12 years. As we become more aware of the mechanisms behind diseases we have more opportunity for the development of drugs. Drugs are now available that imitate naturally occurring compounds e.g. levodopa. Even more recently is the development of drugs that associate with specific receptors e.g. β-agonists or antagonists. New targets for drugs are being discovered every day, and these may result in huge advances in the therapeutic industry. Usually new drugs, however, are just variations on existing drugs and not true innovative complexes. It is important therefore to entertain the idea of administering a new drug over its less recent counterpart. When choosing between new agents and existing drugs a number of issues should be addressed. These include:

  • Cost – is the new drug cost effective?

  • Quality – is it well manufactured?

  • Safety – is it safe or is it more toxic than the existing therapy?

  • Efficacy – is it more likely to work or cause a better response?


The cost of a drug is important to address before prescribing. There is a 12% increase in expenditure on medicines each year in the UK. On average, each person spends 115 pounds on therapeutic items. A doctor should keep in mind that any money spent unnecessarily on more expensive drugs is wasted and may deprive his/her patients from other care. As a general rule where efficacy and safety are equal then the least expensive drug should be recommended. More expensive drugs may be indicated if their efficacy or safety is reputed to be of a higher standard.

If a new treatment is claimed to be ‘cost effective’, the comparative studies should have been carried out together with a reasonable competitive drug or ideally the best current treatment. A drug that is no longer commonly used or in a sub-optimal dose will give a biased result, indicating that the new treatment is more cost effective than it actually is.

The quality of the new drug should be unquestionable. The clinical trials should have established that the raw materials used are of a high standard. They should be analyzed and also undergo impurity testing on a continual basis. Effective testing will ensure that the content of the drug remains the same and is stable from batch to batch. The quality of the biopharmaceutics should also have been scrutinized. In other words, the physical and chemical properties of drugs and their proper dosage should have been studied within the clinical trials.


The clinical trials of the new drug should have included comprehensive safety testing to include ‘acute toxicity’ and ‘chronic toxicity’. Acute toxicity explores the effects of large doses up to the lethal level. It establishes the ‘no effect dose’ which represents the maximum dose at which a toxic effect is not seen. Ideally, this should be 10 to 100 times the initial dose tried in humans. A ‘minimum lethal dose’ should also be established – this is the minimum dose needed to kill any animal. Chronic toxicity studies the effect of multiple dosages. It also addresses which organs are particularly at risk of toxicity.

Reproductive toxicity should be evaluated. All aspects should be tested including fertility, teratology, peri- and post-natal development, and lactation.
Carcinogenicity should be comprehensively examined. Whether the drug resembles a carcinogen or has a very long half life in humans should be made clear. As part of the trials two species should be administered the drug for a period of two years. Their haematology, histology and autopsy results should be studied to see if there has been any carcinogenic type effect. Genotoxicity is also an important element of safety testing and addresses the genetic stability of the cells whilst being treated with the drug.
The adverse effects of a new drug are often unclear initially, as these may only become apparent with time. Some may not be uncovered due to: small incidence, susceptibility factors, drug interactions and different diagnoses. Before prescribing a new drug however, the common side effects should be addressed with the patient. These may or may not affect the patient’s choice of therapy but they should still be made aware of them. There may be a significant increase in morbidity associated with adverse drug effects. For example the antibiotic gentamycin can cause severe nephrotoxicity.

Testing of the efficacy of the drug involves dose response studies and should also address intra-individual (gastric emptying, GI motility, state of health) and inter-individual (age, sex, ethnicity, genetic) variability. The concentration needed to achieve therapeutic success and therapeutic failure (due to no efficacy or adverse effects) should be ascertained. Drug interactions should also be tried and tested, keeping in mind that some may be useful and some detrimental.

The above issues – cost, quality, safety and efficacy, should all be addressed to some degree before choosing between a new drug and its existing competitor.

{Guys….that was a tough essay to write, as in I didn’t really know what they were looking for. Tried my best – it seems to me that you could waffle your way through it anyway on the day!}

{Also, I’m absolutely sick of these essays now so I didn’t bother proof reading them – hope they’re a little bit more legible than Dedge’s first few!}

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