Adverse effects on reproduction

Testing of new drugs on animals for their effects 13 Carcinogens that are effective as a single dose in animals are known, e.g. nitrosamines. on reproduction has been mandatory since the thalidomide disaster, even though the extrapolation of the findings to humans is uncertain (see Preclinical testing, p. 47). The placental transfer of drugs from the mother to the fetus is considered on page 98. Drugs may act on the embryo and fetus Directly (thalidomide, cytotoxic drugs, antithyroid drugs,...

Colonystimulating Factors

A number of cytokines (see p. 280) stimulate the growth, differentiation and functional activity of myeloid progenitor cells. As the name implies the function of these polypeptides was defined by in-vitro colony assays of bone marrow progenitors. They have effects on all myeloid cells including the multipotential stem cells (but probably not the more immature pluripotential cells), intermediate progenitors and circulating mature cells. Those in clinical use are described below. Granulocyte...

Drug Therapy In Relation To Psychologicaltreatment

No account of drug treatment strategies for psychiatric illness would be complete without consideration of psychological therapies. Psychotherapy is broad in content, ranging from simple counselling and 'supportive psychotherapy' sessions through ongoing formal psychoanalysis to newer techniques such as cognitive behavioural therapy. As a general rule, psychotic illnesses (e.g. schizophrenia, mania and depressive psychosis) require drugs as first-line treatment, with psychotherapeutic...

Guideto Further Reading

Blood Pressure Lowering Treatment Trialists Collaboration 2000. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs results of prospectively designed overviews of randomised trials. Lancet 355 1955-1964 Braunstein J B et al 2000 Unstable angina pectoris. New England Journal of Medicine 342 101-114 British Cardiac Society (and other Societies) 2000 Joint British recommendations on prevention of coronary heart disease in clinical practice summary. British...

Info

Penicillins are organic acids and their rapid clearance from plasma is due to secretion into renal tubular fluid by the anion transport mechanism in the kidney. Renal clearance therefore greatly exceeds the glomerular filtration rate (127 ml min). The excretion of penicillin can be usefully delayed by concurrently giving probenecid which competes successfully for the transport mechanism. Dosage of penicillins may should be reduced for patients with severely...

Initial Assessment And Resuscitation

The initial clinical review should include a search for known consequences of poisoning, which include impaired consciousness with flaccidity (benzodiazepines, alcohol, trichloroethanol) or with hypertonia (tricyclic antidepressants, antimuscarinic agents), hypotension, shock, cardiac arrhythmia, evidence of convulsions, behavioural disturbances (psychotropic drugs), hypothermia, aspiration pneumonia and cutaneous blisters, burns in the mouth (corrosives). Maintenance of an adequate oxygen...

Mode Of Action

Endogenous opioid peptides (endorphins, dynor-phins, enkephalins), have been termed 'the brain's own morphine'. Their discovery in 1972 explained why the brain has opioid receptors when there were no opioids in the body. These peptides attach to specific opioid receptors, mainly Li (mu), 5 (delta) or k (kappa) located at several spinal and multiple supraspinal sites in the CNS. Opioid receptors are part of the family of G-protein-coupled receptors (see p. 91) and act to open potassium channels...

Other Oralagents

Acarbose is an a-glucosidase inhibitor which reduces digestion of complex carbohydrates and slows their absorption from the gut in high doses it may cause actual malabsorption. Acarbose reduces glycaemia after meals, and may improve overall glycaemic control. The usual dose is 50-300 mg daily. Adverse effects are mainly flatulence and diarrhoea, which lead to a high discontinuation rate. The drug may be combined with a sulphonylurea. Dietary fibre and diabetes. The addition of gel-forming...

Oxytocics

Oxytocin is a peptide hormone of the posterior pituitary gland. It stimulates the contractions of the pregnant uterus, which becomes much more sensitive to it at term. Patients with posterior pituitary disease (diabetes insipidus) can, however, go into labour normally. Oxytocin is reflexly released from the pituitary following suckling (also by manual stimulation of the nipple) and causes almost immediate contraction of the myoepithelium of the breast it can be used to enhance milk ejection...

Precautions During Chronic Adrenal Steroid Therapy

The most important precaution during replacement and pharmacotherapy is to see the patient regularly with an awareness of the possibilities of adverse effects including fluid retention (weight gain), hypertension, glycosuria, hypokalemia (potassium supplement may be necessary) and back pain (osteoporosis) and of the serious hazard of patient noncompliance. Mild withdrawal symptoms (iatrogenic cortical insufficiency) include conjunctivitis, rhinitis, weight loss, arthralgia and itchy skin...

Pregnancy

As the pregnancy evolves, profound changes occur in physiology, including fluid and tissue composition. Absorption. Gastrointestinal motility is decreased but there appears to be no major defect in drug absorption except that reduced gastric emptying delays the appearance in the plasma of orally administered drugs, especially during labour. Absorption from an intramuscular site is likely to be efficient because tissue perfusion is increased due to vasodilatation. Distribution. Total body water...

Receptors

Most receptors are protein macromolecules. When the agonist binds to the receptor, the proteins undergo an alteration in conformation which induces changes in systems within the cell that in turn bring about the response to the drug. Different types of effector-response exist. (1) The most swift are the channel-linked receptors, i.e. receptors coupled directly to membrane ion channels neurotransmitters act on such receptors in the postsynaptic membrane of a nerve or muscle cell and give a...

Social Anxiety Disorder

The essential feature of social phobia is a marked and persistent fear of performance situations when patients feel they will be the centre of attention and will do something humiliating or embarrassing. The situations that provoke this fear can be quite specific, for example public speaking, or be of a much more generalised nature involving fear of most social interactions, for example initiating or maintaining conversations, participating in small groups, dating, speaking to anyone in...

Synopsis

In most cases, the cause of cancer is multifactorial. About 75 of cancers are due to environmental factors, some of which are within the control of the individual, e.g. tobacco smoking, exposure to sunlight. Growing understanding of cancer genetics and inherited disease suggests that fewer than 10 of cancers are familial.The different systemic modalities used to treat cancer patients are discussed. Immunosuppressive drugs are described here as they share many characteristics with cytotoxics....

Some Special Techniques

Dissociative anaesthesia is a state of profound analgesia and anterograde amnesia with minimal hypnosis during which the eyes may remain open (see ketamine, p. 353). It is particularly useful where modern equipment is lacking or where access to the patient is limited, e.g. at major accidents or on battlefields. Sedation and amnesia without analgesia are provided by midazolam i.v. or, less commonly nowadays, diazepam. These drugs can be used alone for procedures causing mild discomfort, e.g....

Types Of Asthma

Asthma associated with specific allergic reactions This extrinsic type is the commonest and occurs in patients who develop allergy to inhaled antigenic substances. They are also frequently atopic showing positive responses to skin prick testing with the same antigens. The hypersensitivity reaction in the lung (and skin) is of the immediate type (type 1) involving IgE-mediated mast cell activation. Allergen avoidance is particularly relevant to managing this type of asthma. Asthma not associated...

Treatment Of A Hypoglycaemic Attack

Prevention depends very largely upon patient education, but it is an unavoidable aspect of intensive glycaemic control. Patients should not miss meals, must know the early symptoms of an attack, and always carry glucose with them.7 Treatment is to give sugar, either by mouth if the patient can still swallow or glucose (dextrose) i.v. (20-50 ml of 50 solution, i.e. 10-25 g this concentration is irritant especially if extravasation occurs and the veins of diabetics are precious, so compress the...

The Various Aspects Of Pain

Pain is not simply a perception, it is a complex phenomenon or syndrome, only one component of which is the sensation actually reported as pain. Pain has four major aspects present to varying extent in any one case Nociception6 is a consequence of tissue injury (trauma, inflammation) causing the release of chemical mediators which activate nociceptors, defined as receptors that are capable of distinguishing between noxious and innocuous stimuli in the tissue. That said, it is widely assumed...

Anticholinesterases

At cholinergic nerve endings and in erythrocytes there is an enzyme that specifically destroys acetylcholine, true cholinesterase or acetylcholinesterase. In various tissues, especially plasma, there are other esterases which are not specific for acetylcholine but which also destroy other esters, e.g. suxamethonium, procaine (and cocaine) and bambuterol (a pro-drug that is hydrolysed to terbutaline). These are called nonspecific or pseudocholinesterases. Chemicals which inactivate these...

Guide To Further Reading

Criqui M H, Ringel B L1994 Does diet explain the French paradox Lancet 344 1719-1723 (A study of diet, alcohol and mortality from 21 affluent contries.) Doll R et al 1994 Mortality in relation to smoking 40 years' observations on male British doctors. British Medical Journal 309 901-911 Doll R1997 One for the heart. British Medical Journal 315 1664-1668 Gawin F H, Ellinwood E H 1988 Cocaine and other stimulants actions, abuse, and treatment. New England Journal of Medicine 318 1173-1182 Green A...

Passive involuntary smoking

Many nonsmokers are exposed to tobacco smoke, and environmental tobacco smoke has been classified as a known human carcinogen in the USA since 1992.20 Although the risks are, naturally, smaller, the number of people affected is large. One study estimated that breathing other people's smoke increases a person's risk of ischaemic heart disease by a quarter.21 Smoke drawn through the tobacco and taken in by the smoker is known as mainstream smoke. Smoke which arises from smouldering tobacco and...

H2 receptor antagonists

These drugs bind selectively and competitively to the histamine H2 receptor on the basolateral membrane of the parietal cell. As well as inhibiting gastric acid release from histamine they inhibit acetylcholine- and gastrin-mediated acid secretion. This inhibitory effect can be overcome, particularly when gastrin levels are high, as occurs postprandially. In addition, tolerance may develop, probably as a result of down-regulation of receptors. Peptic ulcer healing with H2 receptor antagonists...

Starting and stopping use

Contrary to popular belief it is not generally difficult to stop, only 14 finding it 'very difficult'. But ex-smoker status is unstable and the long-term success rate of a smoking withdrawal clinic is rarely above 30 . The situation is summed up by the witticism, 'Giving up smoking is easy, I've done it many times'. Though they are as aware of the risks of smoking as men, women find it harder to stop they consistently have lower success rates. This trend crosses every age group and occupation....

Hydroxyurea hydroxycarbamide in sickle cell anaemia

Section is required to maintain a normal haematocrit or if the platelet count continues high (added risk of thrombosis). Radiophosphorus (32P, sodium radiophosphate) is given i.v. Phosphorus is concentrated in bone and in cells that are dividing rapidly, so that the erythrocyte precursors in the bone marrow receive most of the P-irradiation. The effects are similar to those of whole-body irradiation, and in PRV, 32P is a treatment option for those > 65 years (accumulation in the gonads...

Nomenclature names

Any drug may have names in all three of the 2. A nonproprietary (official, approved, generic) name used in pharmacopoeias and chosen by official bodies the World Health Organization (WHO) chooses recommended International Nonproprietary Names (rINN). The harmonisation of names began 50 years ago, and 1 The ATC Classification System developed by the Nordic countries and widely used in Europe meets most classification requirements. Drugs are classified according to their Anatomical, Therapeutic...

Pulmonarytuberculosis

Drug therapy has transformed tuberculosis from a disabling and often fatal disease into one in which almost 100 cure is obtainable, although the recent emergence of multiple drug resistant strains of Mycobacterium tuberculosis (MDRTB) in developed countries will disturb this optimistic view. Chemotherapy was formerly protracted, but a better understanding of the mode of action of antituber-culous drugs has allowed the development of effective short-course regimens. Principles of...

Spasm Of Striated Muscle

This is often a cause of pain, including chronic tension headache. Treatment is directed at reduc tion of the spasm in a variety of ways, including psychotherapy, sedation and the use of a centrally-acting muscle relaxant as well as non-narcotic analgesics, e.g. baclofen, diazepam clinical efficacy is variable (see Other muscle relaxants, p. 357). Local infiltration with lignocaine (lidocaine) is sometimes appropriate. Hzanidine is an a2-adrenoreceptor agonist that may be used to relieve muscle...

Classes of cytotoxic chemotherapy drugs

Cytotoxic chemotherapy drugs exert their effect by inhibiting cell proliferation. All proliferating cells, whether normal and malignant, cycle through a series of phases of synthesis of DNA (S phase) mitosis (M phase) and rest (G phase). Noncycling cells are quiescent in G0 phase (Fig. 30.1). Cytotoxic drugs interfere with cell division at various points of the cell cycle, e.g. synthesis of nucleotides from purines and pyrimidines, of DNA and RNA, and interference with mitosis. They are...

Some poisonings

(for medicines see individual drugs) Many substances used in accidental or self- 7 Voltaire (pseudonym of Francios-Marie Arouet, French writer, 1694-1778). 8 Based on Kulig K1992 New England Journal of Medicine 326 1677-1681. poisoning cause dysfunction of the central or autonomic nervous systems and produce a variety of effects which may be usefully grouped to aid the identification of the agent(s) responsible. Antimuscarinic syndromes consist of tachycardia, dilated pupils, dry, flushed skin,...

Tetracyclines

Tetracyclines have a broad range of antimicrobial activity and differences between the individual members are in general small. Mode of action. Tetracyclines interfere with protein synthesis by binding to bacterial ribosomes and their selective action is due to higher uptake by bacterial than by human cells. They are bacteriostatic. Pharmacokinetics. Most tetracyclines are only partially absorbed from the alimentary tract, enough remaining in the intestine to alter the flora and cause...

Calcium Channel Blockers

Calcium is involved in the initiation of smooth muscle and cardiac cell contraction and in the propagation of the cardiac impulse. Actions on cardiac pacemaker cells and conducting tissue are described in Chapter 24. Vascular smooth muscle cells. Contraction of these cells requires an influx of calcium across the cell membrane. This occurs through ion channels 4 Useful, but not always safe. Defibrillator paddles and nitrate patches make an explosive combination, and it is not always in the...

Nonulcer Dyspepsia

Many patients with nonulcer dyspepsia have abnormalities of gastric emptying and increased pain perception in the gastrointestinal tract, suggesting that the condition is part of the spectrum of irritable bowel syndrome (see Chapter 32). Patients with predominant epigastric pain or reflux symptoms may improve with simple antacids taken as needed. More severe symptoms may require antisecretory drugs, particularly a proton pump inhibitor, although the response rate is lower (40-50 ) than in...

Adverse Effects

As most antidepressants have similar therapeutic efficacy, the decision regarding which drug to select often rests on adverse effect profiles and potential to cause toxicity. The commonest unwanted effects are those of the antimuscarinic action, i.e. dry mouth (predisposing to tooth decay), blurred vision and difficulty with accommodation, raised intraocular pressure (glaucoma may be precipitated), bladder neck obstruction (may lead to urinary retention in older males). Patients may also...

Rationale for cytotoxic chemotherapy

Cytotoxic chemotherapy began with sulphur mustards (oily vesicant liquids) which had been developed and used as chemical weapons in World War I (1914-18). Amongst their actions depression of haemopoiesis and of lymphoid tissues were observed. Preparations for World War II (1939 5) included research to increase the potency and toxicity ('efficacy') of these odious substances. Substitution of a nitrogen atom for the sulphur atom, i.e. making nitrogen mustards, had the desired result. The...

Composition

The principal components are tar and nicotine, the amounts of which can vary greatly depending on the country in which cigarettes are sold. Regulation and voluntary agreement by manufacturers aspires to achieve a 'global cigarette' containing at most 12 mg of tar and 1 mg of nicotine. The composition of tobacco smoke is complex (about 500 compounds have been identified) and varies with the type of tobacco and the way it is smoked. The chief pharmacologically active ingredients are nicotine...

Osmotic Laxatives

These are but little absorbed and increase the bulk and reduce viscosity of intestinal contents to promote a fluid stool. Some inorganic salts retain water in the intestinal lumen or, if given as hypertonic solution, withdraw it from the body. When constipation is mild, magnesium hydroxide will suffice but magnesium sulphate (Epsom4 salts) is used when a more powerful effect is needed. Both magnesium salts act in 2-4 h. The small amount of magnesium absorbed when the sulphate is frequently used...

Postmenopausal hormone replacement therapy HRT

HRT refers to the use of oestrogen treatment in order to reverse or prevent problems due to the loss of ovarian hormone secretion after the menopause, 5 The mares are bred on 480 farms in the prairie provinces of Canada. The 80 000 foals that are produced each year have a less medicinal future than their mothers' urine they are weaned at 120 days and sold for meat. whether physiological or induced. The tissues sensitive to oestrogen include brain, bone, skin, cardiovascular and genitourinary....

Pulmonary hypertension

Therapy is determined by the underlying cause. When the condition is secondary to hypoxia accompanying chronic obstructive pulmonary disease, long-term oxygen therapy improves symptoms and prognosis anticoagulation is essential when the cause is multiple pulmonary emboli. Primary pulmonary hypertension verapamil may give symptomatic benefit, also continuous intravenous infusion of prostaglandin. Evidence suggests that endothelin, a powerful endogenous vasoconstrictor, may play a pathogenic...

Intravenous anaesthetics

Controlled infusion (TCI) provides a convenient method for giving a continuous infusion of propofol. Central nervous system. Propofol causes dose-dependent cortical depression and is an anticonvulsant. It depresses laryngeal reflexes more than barbiturates, which is an advantage when inserting a laryngeal mask airway. Cardiovascular system. Propofol reduces vascular tone, which lowers systemic vascular resistance and central venous pressure. The heart rate remains unchanged and the result is a...

Benefits And Risks

Benefits of drugs are manifest to doctor and patient and also, it might be thought, obvious to even the most unimaginative healthy people who find themselves dismayed by some aspects of modern technology. Modern technological medicine has been criticised, justly, for following the tradition of centuries by waiting for disease to occur and then trying to cure it rather than seeking to prevent it from occurring in the first place. Although many diseases are partly or wholly preventable by...

Stimulant Laxatives

These drugs increase intestinal motility by various mechanisms they may cause abdominal cramps, should used only with caution in pregnancy, and never where intestinal obstruction is suspected. Bisacodyl stimulates sensory endings in the colon by direct action from the lumen. It is effective orally in 6-10 h and, as a suppository, acts in 1 h. In geriatric patients, bisacodyl suppositories reduce the need for regular enemas. There are no important unwanted effects. Sodium picosulphate is similar...

Criticisms Of Modern Drugs

Extremist critics have attracted public attention for their view that modern drug therapy, indeed modern medicine in general, does more harm than good others, whilst admitting some benefits from drugs, insist that this is medically marginal. These opinions rest on the undisputed fact that favourable trends in many diseases preceded the introduction of modern drugs and were due to economic and environmental changes, sanitation, nutrition and housing. They also rest on the claim that drugs have...

Notes For Prescribing Insulin

There is no need to change a stabilised diabetic from animal to human insulin. Unexplained requirement of above 100 units d is usually due to noncompliance and less often to antibodies since the withdrawal of the older insulin preparations. Allergy still occurs to additives (protamine), to the preservative, e.g. phenol, cresol, or to insulin itself. It may take the form of local reactions (inflammatory or fat atrophy) or of insulin resistance. Antibodies to insulin, provided they are moderate...

Interference With Selfregulating Systems

When self-regulating physiological systems (generally controlled by negative feedback systems, e.g. endocrine, cardiovascular) are subject to interference, their control mechanisms respond to minimise the effects of the interference and to restore the previous steady state or rhythm this is homeostasis. The previous state may be a normal function, e.g. ovulation (a rare example of a positive feedback mechanism), or an abnormal function, e.g. high blood pressure. If the body successfully...

Classification Of Drugs

Drugs may be classified as producing Reduction of preload Diuretics increase salt and water loss, reduce blood volume and lower excessive venous filling pressure (see Ch. 26). The congestive features of oedema, in the lungs and periphery, are alleviated when the heart is grossly enlarged, cardiac output will also increase (see discussion of Starling curve, above). Nitrates (see also Ch. 23) dilate the smooth muscle in venous capacitance vessels, increase the volume of the venous vascular bed...

Fixeddose Drug Combinations

This section refers to combinations of drugs in a single pharmaceutical formulation. It does not refer to concomitant drug therapy, e.g. in infections, hypertension and in cancer, when several drugs are given separately. Fixed-dose drug combinations are appropriate for Convenience, with improved patient compliance. This is particularly appropriate when two drugs are used at constant dose, long term, for an asymptomatic condition, e.g. a thiazide plus a (3-adrenoceptor blocker in mild or...

Mode Of

Since the potency (therapeutic efficacy in relation to weight) of antipsychotic agents varies markedly between compounds, it is useful to think of the effective antipsychotic dose of classical agents in terms of 'chlorpromazine equivalents' (see Table 19.5). For example, haloperidol has a relatively high antipsychotic potency, such that 2-3 mg is equivalent to chlorpromazine 100 mg, whereas sulpiride 200 mg (low potency) is required for the same antipsychotic effect. Patients who are...

Moderate Efficacy Diuretics

Thiazides depress sodium reabsorption at site 3 which is just proximal to the region of sodium-potassium exchange. These drugs thus raise potassium excretion to an important extent. Thiazides lower blood pressure, initially due to reduction in intravascular volume but chronically by a reduction in peripheral vascular resistance. The latter is accompanied by diminished responsiveness of vascular smooth muscle to noradrenaline (norepinephrine) they may also have a direct action on vascular smooth...

Skin Infections

Superficial bacterial infections, e.g. impetigo, eczema, are commonly staphylococcal or streptococcal. They are treated by a topical antimicrobial for less than 2 weeks and applied twice daily after removal of crusts that prevent access of the drug, e.g. by a povidone-iodine preparation. Very extensive cases need systemic treatment. Topical fusidic acid and mupirocin are preferred (as they are not ordinarily used for systemic infections and therefore development of drug resistant strains is...

Safe Limits For Chronic Consumption

But both patients and nonpatients justifiably expect some guidance, and doctors and government departments will wish to be helpful. They may reasonably advise as a 'safe' or prudent maximum (there being no particular individual contraindication) men, not more than 21 units per week (and not more than 4 units in any one day), and women, 14 units per week (and not more than 3 units in any one day).33 Consistent drinking more than these amounts carries a...

Pregnancy Hypertension

Effective treatment of pregnancy-induced hypertension improves fetal and perinatal survival. There is a lack of good clinical trial evidence on which to base recommendations of one agent over another. Instead, drug usage reflects longevity of use without obvious harm to the fetus. Hence methyldopa is still the drug of choice for many obstetricians.35 Calcium-channel blockers (especially nifedipine) are common second-line drugs parenteral hydralazine is reserved for emergency reduction of blood...

Drugtherapy

Blood pressure may be reduced by any one or more 32 DASH-Sodium Collaborative Research Group 2001 Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet. N Engl J Med 344 3-10. of the actions listed at the beginning of this chapter (p. 46). The large number of different drug classes for hypertension reduces, paradoxically, the likelihood of a randomly selected drug being the best for an individual patient. Patients and drugs can broadly...

Treating Hypertension

A simple stepped regimen in keeping with the 1999 British Hypertension Society guidelines30 is the AB CD schema illustrated in Figure 23.2 33 1. Depending on the patient's age (see above) use either a p Blocker or thiazide Diuretic as firstline therapy, unless there is a compelling reason to avoid these (e.g. asthma and gout, respectively). If the first drug is effective but not tolerated, switch to the other member of the pair i.e. ACE inhibitor (or AIIRA) instead of P-blocker, Calcium blocker...

Drugs used in hypertension and angina

Two groups of drugs, (3-adrenergic blockers and calcium channel blockers, are used in both hypertension and angina. Several drugs for hypertension are used also in the treatment of heart failure. Diuretics, particularly the thiazides, are useful antihypertensives. They cause an initial loss of sodium with a parallel contraction of the blood and extracellular fluid volume. The effect may reach 10 of total body sodium but it is not maintained. After several months of treatment, the main blood...

Changing And Stopping Antidepressants

When an antidepressant fails through lack of efficacy despite an adequate trial or due to unacceptable side effects, it is generally advisable to change to a drug of a different class. For a patient who does not respond to an SSRI it is logical to try a TCA or a novel compound such as venlafaxine, reboxetine or mirtazapine. Any of these options may offer a greater increase in synaptic noradrenaline than the ineffective SSRI. There is also evidence to suggest that patients failing on one SSRI...

Druginduced liver damage

Sedatives, antidepressants and antiepilepsy drugs should be avoided or used with extreme caution in patients with advanced liver disease, and particularly those with current or recent hepatic encephalopathy. Enhanced sensitivity of the CNS to such drugs is well documented and adds to the pharmacokinetic changes. Treatment of alcohol withdrawal in patients with established liver disease using chlormethiazole is hazardous, especially given i.v. The temptation to give initial...

Unwanted Interactions With Antihypertensive Drugs

Specific interactions are described in the accounts of individual drugs. The following are general examples for this diverse group of drugs. Alcohol intake is the commonest contributing factor, or even cause of hypertension, and should always be considered as a cause of erratic or failed 36 The Magpie Trial Collaborative Group 2002 Lancet 359 1877-1890. 37 The Eclampsia Trial Collaborative Group 1995 Which anticonvulsant for women with eclampsia Evidence from the Collaborative Eclampsia Trial....

Dose And Usage

The total daily output of endogenous insulin from pancreatic islet cells is 30-40 units determined by the needs of completely pancreatectomised patients , and most insulin-deficient diabetics will need 30-50 unit day 0.5-0.8 units kg of insulin two-thirds in the morning and one-third in the evening . Initial treatment for a Type 1 IDDM patient, who does not present with ketoacidosis, will usually be outside hospital with two injections of intermediate-acting insulin, or a mixed insulin. Other...

Bile Salt Malabsorption

Failure of the terminal ileum to reabsorb bile salts may result from Crohn's disease, or ileal resection, and it occurs in many patients with microscopic colitis. Bile salts in the colon cause diarrhoea which is relieved by colestyramine. The dose required is titrated against symptoms, starting with 8 g bd. Colestyramine can also bind to many drugs and reduce their bioavailability see p. 131 . This condition affects 20 of the population and is the commonest reason for referral to a...

Low Efficacy Diuretics

Spironolactone Aldactone is structurally similar to aldosterone and competitively inhibits its action in the distal tubule exchange of potassium for sodium excessive secretion of aldosterone contributes to fluid retention in hepatic cirrhosis, nephrotic syndrome and congestive cardiac failure see specific use in chapter 24 , in which conditions as well as in primary hypersecretion Conn's syndrome spironolactone is most useful. Spironolactone is also useful in the treatment of resistant...

Effects of prolonged administration chronic organ toxicity

While the majority of adverse events occur within days or weeks after a drug is administered, some reactions develop only after months or years of exposure. In general, pharmacovigilance programmes reveal such effects once recognised, they demand careful monitoring during chronic drug therapy for their occurrence may carry serious consequences for the patient and the nonvigilant doctor, medico-legally . Descriptions of such types C and D reactions appear with the accounts of relevant drugs some...

Vehicles For Presenting Drugs To The Skin

The formulations are described in order of decreasing water content. All water-based formulations must contain preservatives, e.g. chlorocresol, but these rarely cause allergic contact dermatitis. Water is the most important component. Wet dressings are generally used to cleanse, cool and relieve pruritus in acutely inflamed lesions, especially where there is much exudation, e.g. atopic eczema. The frequent reapplication and the cooling effect of evaporation of the water reduce the inflammatory...

Choice Between Drugs And Electroconversion

Direct current DC electric shock applied externally is often the best way to convert cardiac arrhythmias to sinus rhythm. Many atrial or ventricular arrhythmias start as a result of transiently operating factors but, once they have begun, the abnormal mechanisms are self-sustaining. When a successful electric shock is given, the heart is depolarised, the ectopic focus is extinguished and the SA node, the part of the heart with the highest automaticity, resumes as the dominant pacemaker....

Advantages And Disadvantages Of Parenteral Administration

An i.v. bolus, i.e. rapid injection, passes round the circulation being progressively diluted each time it is delivered principally to the organs with high blood flow brain, liver, heart, lung, kidneys . Advantages are that the i.v. route gives swift, effective and highly predictable blood concentration and allows rapid modification of dose, i.e. immediate cessation of administration is possible if unwanted effects occur during administration. The route is suitable for administration of drugs...

Granuloma Inguinale

Calymmatobacterium granulomatis infection is treated with ampicillin or co-trimoxazole or a tetracycline for 2 weeks. BACTERIAL VAGINOSIS BACTERIAL VAGINITIS.ANAEROBIC VAGINOSIS Bacterial vaginosis is a common form of vaginal discharge in which neither Trichomonas vaginalis nor Candida albicans can be isolated and inflammatory cells are not present. There is evidence to associate the condition with overgrowth of several normal commensals of the vagina including Gardnerella vaginalis,...

Advantages And Disadvantages Of Enteral Administration

For systemic effect Advantages are convenience and acceptability. Disadvantages are that absorption may be delayed, reduced or even enhanced after food or slow or irregular after drugs that inhibit gut motility antimuscarinic, opioid . Differences in presystemic elimination are a cause of variation in drug effect between patients. Some drugs are not absorbed gentamicin and some drugs are destroyed in the gut insulin, oxytocin, some penicillins . Tablets taken with too small a quantity of liquid...

Mucolytics And Expectorants

Normally about 100 ml of fluid is produced from the respiratory tract each day and most of it is swallowed. Respiratory mucus consists largely of water and its slimy character is due to glycoproteins cross-linked together by disulphide bonds. In pathological states much more mucus may be produced an exudate of plasma proteins which bond with glycoproteins and form larger polymers results in the mucus becoming more viscous. Patients with chest diseases such as cystic fibrosis and bronchiectasis...

Morphine On Smooth Muscle

Morphine activates receptors on the smooth muscle of the stomach antrum and of both large and small bowel, causing it to contract. Peristalsis propulsion is reduced and segmentation increased. Thus, although morphine 'stimulates' smooth muscle, delayed gastric emptying and constipation occur, with gut muscle in a state of tonic contraction. Delay in the passage of the intestinal contents results in greater absorption of water and increased viscosity of faeces, which contribute...

Drugspecific Rashes

Despite great variability, some hints at drug-specific Drugs applied locally or taken systemically often bardie R A, Savin J A1979 British Medical Journal 1935, to cause rashes. These take many different forms and whom we are grateful for this quotation and classification. or characteristic rashes from drugs taken systemically, can be discerned, as follows Acne and pustular e.g. corticosteroids, androgens, Ciclosporin, penicillins. Allergic vasculitis e.g. sulphonamides, NSAIDs, thiazides,...

Amfetamines

Amfetamine has had multifarious uses. It is now obsolete for depression and as an appetite suppressant, and its use in sport is abuse see before . There is concern that its illicit use as a psychostimulant is widespread. Amfetamine is a racemic compound the laevo-form is relatively inactive but dexamphet-amine the dextro- isomer finds use in medicine. Amfetamine will be described, and structurally-related drugs only in the ways in which they differ. Mode of action. Amfetamine acts by releasing...

Organic Nitrates

Organic nitrates and nitrite were introduced into medicine in the 19th century.1 Denitration in the smooth muscle cell releases nitric oxide NO , which is the main physiological vasodilator, normally produced by endothelial cells. Nitrodilators a generic term for drugs that release or mimic the action of NO activate the soluble guanylate cyclase in vascular smooth muscle cells and cause an increase in intracellular cyclic GMP guanosine monophosphate con 1 Murrell, W 1879 Nitroglycerin as a...

Physical Dependence And Tolerance

Physical dependence and tolerance imply that adaptive changes have taken place in body tissues so that when the drug is abruptly withdrawn these adaptive changes are left unopposed, resulting generally in a rebound overactivity. The discovery that the CNS employs morphine-like substances endomorphins, dynorphins as neurotransmitters offers the explanation that exogenously administered opioid may suppress endogenous production of endorphins by a feedback mechanism. When administration of opioid...

Adrenergic Neuron Blocking Drugs

Adrenergic neuron blocking drugs are selectively taken up into adrenergic nerve endings by the active, energy-requiring, saturable amine noradrenaline pump mechanism uptake-1 . They accumulate in the noradrenaline storage vesicles from which they are released in response to nerve impulses, diminishing the release of noradrenaline and so all sympathetic function. They do not adequately control supine blood pressure and are prone to interactions with other drugs affecting adrenergic function,...