Nicotinic acid derivatives

• Nicotinic acid (niacin) has proven cholesterol-lowering effects when given in daily doses exceeding 1 gram. However, such doses cause flushing and rashes. Treatment with nicotinic acid should be supervised by a doctor, who can advise on how to increase the dosage over three or four weeks and minimise the risk of side effects.
• Besides nicotinic acid/niacin preparations, there is a nicotinic acid derivative, acipimox (Olbetam). Side effects are less of a problem with this drug, and it may well be the drug of choice if dietary and lifestyle modifications prove ineffective, although safety in long-term use has not been established.

Fibrates
- These drugs can reduce LDL cholesterol levels by as much as 18%, and at the same time raise HDL cholesterol levels.

• – Bezafibrate (Bezalip). Its primary effect is to reduce triglyceride levels. It also increases the breakdown of LDL particles, thus lowering the LDL Cholesterol level in the bloodstream.
• – Clofibrate (Atromid-S) is gradually becoming obsolete. New derivatives have proved just as effective with fewer side effects.
• – Fenofibrate (Lipanthyl) lowers VLDL and LDL cholesterol levels and raises HDL levels.
• – Gemfibrozil (Lopid) reduces VLDL and LDL cholesterol by decreasing the synthesis of VLDL in the liver. It also raises low levels of HDL cholesterol.
• – Ciprofibrate (Modalim) reduces VLDL and LDL cholesterol levels.

The drugs in this group can be used to lower blood cholesterol levels but are more usually given in cases of raised triglyceride levels. Their long-term safety, although not fully established, looks good.

Bile acid sequestrates
Soluble fibre in the diet binds acids in the gut. Some of these bile acids are then excreted and not resorbed in the large intestine as would normally be the case. Cholesterol is then diverted into making more bile acids, thus reducing cholesterol levels. Bile acid sequestrates work in much the same way, but more effectively, binding the acids and then removing them in faeces.

Two bile acid sequestrates widely available are cholestyramine (Questran) and colestipol (Colestid).They are very successful when used correctly, lowering blood LDL levels by as much as 25%, in addition to any impact diet and lifestyle changes might have on blood cholesterol levels. Many patients use them daily to keep cholesterol levels within reasonable limits. The drugs also have the advantage of being confined to the gut; they don’t enter the body.

Bile acid sequestrates can interfere with the functioning of other prescribed drugs, so you should take them at quite different times. The long-term safety of bile-acid sequestrates is well established.

Probucol (Lurselle) has a poorly understood mode of action. It increases the loss of bile acids in faeces, so its effect is similar to the sequestrates. Long-term safety of the drug is not established. It sometimes causes nausea and diarrhoea and is not recommended during pregnancy and breastfeeding.

HMG CoA Reductase Inhibitors
The full term for this group of drugs is 3-hydroxy-3-methyl-glutaryl co-enzyme A reductase inhibitors. Despite the name, the action of these drugs is quite elegant. All body cells synthesise cholesterol; if the blood cholesterol level falls, cholesterol supply to the cells is reduced and the cells try to make up the deficit by stepping up cholesterol synthesis. The cellular manufacture of cholesterol is complex, but one of the key steps is governed by an enzyme called HMG CoA reductase. Block the action of this enzyme and you can block the manufacture of cholesterol in the cells.

Some of the more common inhibitors available are simvastatin (Zocor), pravastatin (Pravachol), fluvastatin (Lescol), atorvastatin (Lipitor) and cerivatatin (Lipobay). These drugs are generally considered the gold standard of lipid lowering therapy with a good record of clinical efficacy and long-term safety.

Warts are communicable from one part of the body to another part of the body and from one person to another as well. So, if any of the family member suffer from this health issue, the others should be careful. The warts can broadly be classified into four major categories; they are common warts, foot warts, flat warts and genital warts.

Some of the warts symptoms are as follows:

• One of the most common warts symptom found in all types of warts is the urge to scratch the affected area.
• The affected area will become rough.
• The bumps will be fleshy, small and grainy.
• The affected area might have a color change like tan, white or pink.

Types of warts:

• Common warts are called common hand warts, which grows around the nails on the back of the hands and on the fingers. This appears very often when the skin is broken due to biting of finger nails or peeling of skin from the finger.
• Flat Warts are known to grow in higher numbers and are smoother and smaller as compared to other warts. This can appear anywhere in the body like faces of children (commonly known as facial warts), legs of women, in the face of young adult males, who does shaving.
• Foot warts are also called as planter warts in medical terms. Foot warts normally appear as single or even as in clusters. Some of the areas in foot, which are prone to warts are the heel, the ball of the foot and the plantar part of the toes since these areas are often subject to pressure due to the body weight. People with diabetes are most prone to foot warts. So, they should be careful about this health issue.

Genital Warts:
Genital warts are also known as venereal warts or condylomata acuminate. These are growths in the genital area caused by a virus called Human papilloma virus or HPV. HPVs are about 80 different types and Genital warts are caused by HPV types 18, 16, 11, 6, 2 and 1. The genital warts symptoms include pain, bleeding and odor.

Different methods are being followed by people suffering from warts for treatment. The warts treatments can broadly be classified into Professional treatment and home/self treatment. Self treatment includes the common medications for warts being sold in medical stores like lotions, ointments or plasters. But, if you are not able to cure warts with the help of these lotions and ointments even after using them for months together, it is better to go for professional treatments, which will be of great use in treating the warts.

1. Critical illnesses are often associated with circulatory, respiratory, hepatic and/or renal dys­function that may alter the pharmacokinetics and/or pharmacodynamics of drugs.
2. Decisions about routes of administration and doses of drugs used during medical emergen­cies must consider the physiological status of the patient, the pharmacokinetic and pharmacodynamic characteristics of the particular drug, and how the two interact.
3. Adverse drug reactions and interactions are more likely in critically ill patients due to the effect of the disease on drug kinetics, the decreased toxic-therapeutic ratio due to severe under­lying illness, and the large number of medications that such patients receive. Adverse reactions to drugs should be considered when unexplained deterioration or failure to respond to therapy are encountered.
4. Preservation of function of vital organs is a fundamental concept of critical care therapeutics. Preservation of cardiovascular functions requires attention to fluid and electrolyte status, prompt correction of arrhythmias and shock, and measures to preserve the myocardium against ischaemic injury.
5. Preservation of respiratory function requires protection of the airway, cautious use of fluids and oxygen, and prompt recognition and management of infection.
6. Preservation of cerebral function requires maintaining cerebral blood flow with adequate oxygen and glucose sufficient to meet the metabolic demands of the brain. This entails main­taining adequate systemic circulation, control of intracranial hypertension, and prompt control of seizures and hyperthermia.



7. Critically ill patients are particularly susceptible to infections, gastric stress erosions and ulcers, adult respiratory distress syndrome, pulmonary emboli, and haemostatic disorders. The risks of such complications may be reduced by meticulous care of catheters, pulmonary toilet, cautious use of fluids, prompt treatment of infection when it occurs, and selective prophylactic drug therapies.
8. Shock can be produced by many different processes including myocardial infarction, hypovolaemia, sepsis, drug overdose, burns, hypothermia, spinal cord transsection and anaphylaxis. Optimum treatment of shock depends on knowledge of the pathophysiology of the shock state and the pharmacology of the drugs.
9. Features of acute drug intoxication include coma, agitated delirium, seizures, hypo- and hyperthermia, shock, arrhythmias, aspiration and pulmonary oedema. Successful therapy of acute drug intoxication depends on the integration and application of knowledge of the pharmacology of both the intoxicating drug and the drugs used in therapy, as well as the principles of supportive critical care.

The mechanism by which anaesthetic drugs produce unconsciousness is still unknown. Meyer in 1899 and Overton in 1901 noted that within any group of drugs, anaesthetic potency correlates well with lipid solubility, and most modern theories agree that the site of action is probably the lipid bilayer of nerve cell mem­branes, or possibly a protein receptor in this sit­uation, but further knowledge is limited.

Inhalational Agents

Anaesthetic practice is unique in that a high proportion of the drugs are administered by the inhalational route. Such agents must either be gaseous, or the vapour of volatile liquids (Vari­ous Authors 1984).
Of the original three inhalational agents – ni­trous oxide, ether and chloroform – the first two are still used widely.

The greatest disadvantage of many of the volatile liquids and gases has been their flammable nature; the main reason for the decline of cyclopropane, which enjoyed wide popularity until the advent of halothane in 1956. Halothane, which has been firmly es­tablished as the basis of many general anaes­thetic techniques over the past 25 years, is not without its drawbacks, and investigation of new compounds continues. None of these is better overall than halothane, but in recent years ha­lothane has been slowly yielding popularity to enflurane and more recently to isoflurane.

Disposition and Pharmacological Properties

The uptake and distribution of inhalational anaesthetics is complex (Eger 1974). One must distinguish between an effective gas tension (partial pressure) and the total amount of drug dissolved in blood; it is the tension which de­termines the depth of anaesthesia. When a con­stant concentration of the anaesthetic is in­haled, the concentration in the alveoli rises gradually toward the inhaled level.

How quickly it rises will depend on the ventilation of the al­veoli (which may be reduced if the drug is ir­ritant or depresses respiration) and on the rate at which the drug is taken up into the blood from the alveoli. If the solubility (blood/gas sol­ubility coefficient) of the drug is high, then it will take longer for equilibrium to be attained, because (a) more of the drug needs to be dissolved in the blood for a given tension to be reached, and (b) the more rapid removal of the drug from the alveoli reduces the concentration here, and therefore reduces the gradient driving it from alveolus to capillary blood. A less sol­uble drug will likewise reach equilibrium more rapidly.

The rate of removal of drug into the blood will also depend on the cardiac output, which may be influenced by the drug itself; and finally the rate at which the tension of the drug in the blood rises toward that in alveoli will also depend on the rate at which it is distributed to other tissues, not only the target organ (brain), but also muscle, fat depots, etc. Such differences between infants and adults helps to explain the more rapid alveolar uptake of inhalational anaesthetics in the neonate. (Cook 1976; Eger et al. 1971).

The ability of the drug in the blood to pro­duce anaesthesia will depend on its anaesthetic potency. The minimal alveolar concentration (MAC) of the drug which will cause anaesthesia in 50% of patients is a measure often used to compare the potencies of different inhalational agents.

1. The main aim of anaesthesia is the prevention of pain during surgery and at other times.
2. Anaesthesia involves a balanced approach, in which the individual patient’s psyche and pathophysiology are taken into account and drugs are used to modify and control any aspect as required.
3. The decision to use a particular drug or technique must be made after careful consideration of the pathophysiological features of the individual case and how these may affect the phar­macokinetic handling and tissue response to the drugs available.
4. Any associated disease or pathophysiological abnormality should wherever possible be treated or corrected before operation, and potentially dangerous physiological disturbances avoided during and after anaesthesia.
5. Anaesthetic drugs are relatively non-toxic but there are some important effects. Halothane is occasionally associated with hepatitis and methoxyflurane with kidney damage. Malignant hyperpyrexia, the aetiology of which is uncertain, is a rare but often fatal condition which can be triggered off by several anaesthetic drugs in genetically susceptible individuals.
6. Drugs used in anaesthesia can be involved in significant unwanted interactions with other drugs.
7. The treatment of respiratory failure is usually the responsibility of the anaesthetist. Although ventilatory assistance, physiotherapy, etc. are often the mainstay of treatment, drugs of different pharmacological classes are used.
8. Pain perception is an individual sensation. Symptomatic treatment of acute pain should not therefore be based on a concept of the painfulness of certain conditions, although some anal­gesics may be more appropriate for pain of certain conditions.
9. Strong analgesics for severe chronic pain should preferably be given orally, in adequate dosage, and on a regular individualised dosage schedule.

General Considerations

Although achieving insensibility to pain and to unpleasant surroundings has been the goal of much human activity since prehistoric times, it is only since 1846 with the introduction of ether by Morton that this could be done with any re­liable chance of success. Anaesthesia has devel­oped and been refined considerably since that time, and several important milestones are re­cognized and worthy of recall. These include the discovery of the local anaesthetic action of co­caine by Koller in 1884 and its use to produce spinal anaesthesia by Bier in 1898, the perfec­tion of endotracheal anaesthesia by Magill and Rowbotham about 1920, the introduction of the first barbiturate for induction of anaesthesia in 1932, and the introduction of curare in 1942.
In recent years, the specialty of anaesthesia has been broadened, and its scope is well de­scribed in a definition for the US Department of Labor (Dripps 1966):

Anesthesiology is a practice of medicine dealing with:

• The management of procedures for ren­dering a patient insensible to pain during surgical procedures.
• The support of life functions under the stress of anesthetic and surgical manipu­lations.
• The clinical management of the patient unconscious from whatever cause.
• The management of problems in pain re­lief.
• The management of problems in cardiac and respiratory resuscitation.
• The application of specific methods of inhalational therapy.
• The clinical management of various fluid electrolyte and metabolic disturbances.

The modern concept is one of ‘balanced an­aesthesia’, in which the whole of the patient’s psyche and pathophysiology are taken into ac­count and drugs are used to modify and control any aspect as required. Thus, as well as general anaesthetic agents, drugs of many classes – tran­quillisers, analgesics, muscle relaxants, drugs af­fecting the autonomic system etc. – all fall within the sphere of interest of the anaesthetist. ( Some of the more important of these will be discussed further at later part – Drugs Used in Anaesthesia .)

Although the use of cathartics and enemas is traditional, these measures are most unlikely to reduce absorption since this usually occurs rap­idly in the upper small intestine. They can only add to the misery and discomfort of the patient Efficacy in removal of drug has never been es­tablished. In one recent study, saline catharsis had no beneficial effect whatsoever on the ab­sorption of aspirin taken with charcoal (Sketris et al. 1982).

Whole Gut Lavage

One situation where attempts to empty the bowel may be helpful is in poisoning with ‘slow’ or ‘timed release’ formulations. The number of such preparations on the market is increasing and since they usually contain a much larger dose of drug than ordinary tablets, intoxication may be severe and prolonged.

In such circumstances, rapid emptying of the bowel might limit in absorption. The preferred technique is ‘whole gut lavage’ in which normal saline is given by nasogastric tube at a rate of 2 litres an hour (Woo et al. 1976). Although this technique is readily controlled and rapidly effective in emptying the bowel in conscious patients being prepared for abdominal surgery, its efficacy in removing un-absorbed drug has yet to be established. It may not be effective and could possibly be dangerous in poisoned patients with grossly depressed gas­trointestinal motility.

Activated Charcoal

Activated charcoal has great adsorptive ca­pacity and can reduce the absorption of many compounds if taken orally at the same time (Neuvonen 1982; Pond 1986). The charcoal must be given in great excess (at least 10 times the weight of the drug) and efficacy falls off rap­idly as the time interval between ingestion of the poison and administration of the charcoal increases. After 1 hour, there is little inhibitory effect on the absorption of most drugs, although a significant reduction has been reported with phenytoin.

The time interval during which ac­tivated charcoal can significantly reduce ab­sorption following overdosage may be increased by the presence of food in the stomach (Olkkola & Neuvonen 1984). Oral activated charcoal ap­pears to be as effective as emesis induced by syrup of ipecac in limiting absorption (Neuvo­nen et al. 1983), but its administration after gas­tric lavage is of little or no benefit (Comstock et al. 1982).

Although the delay between inges­tion of the drug and arrival in hospital is usually such that significant reduction in absorption by oral activated charcoal is unlikely, there is no contraindication to its use and repeated admin­istration greatly increases the elimination of some drugs.

Never­theless, poisoned patients are often unnecessar­ily subjected to these potentially harmful meas­ures, and the literature is full of anecdotal accounts of miraculous recovery attributed to such treatment (Winchester et al. 1977). Prop­erly controlled clinical trials are difficult to carry out, and very few have been published. With the possible exception of forced alkaline di­uresis for poisoning with salicylate and long act­ing barbiturates such as phenobarbitone, none of these methods for enhancement of drug re­moval has ever been shown to reduce morbidity or mortality in poisoned patients (Todd 1984).

Indeed, some studies suggest the opposite result. This is not to say that such measures are never necessary, or indeed sometimes life saving, but a more critical appraisal of their role is required.

In some cases, the drug presumed to have been taken has never been chemically identi­fied, while, in others, haemodialysis has been carried out in patients with less than therapeutic plasma concentrations of the drug in question. Other studies have shown removal of only a very small and insignificant fraction of the ingested dose, sometimes amounting to the equivalent of less than 1 tablet or capsule (see, for example, Comstock et al. 1983; Heath et al. 1983). A mis­leading impression of efficacy may be gained by the use of nonspecific analytical methods for drug assay (Prescott 1974).

Other Binding Agents

Other agents have been used in attempts to bind unabsorbed drug in the gastrointestinal tract. Paraquat, a lethal weedkiller for which there is no known antidote, binds very strongly to Fuller’s earth and bentonite, and these ad­sorbents are used routinely in the treatment of paraquat poisoning.

Although bentonite may re­duce the normally slow absorption of paraquat in pure aqueous solution in rats (Smith et al. 1974), ail the evidence points to extremely rapid absorption of paraquat from commercial weed­killers in man. Our experience of paraquat poi poi­soning has been disastrous, with no apparent benefit from the early use of bentonite.

Cholestyramine binds acidic drugs and can reduce the absorption of paracetamol (aceta­minophen) taken at the same time. Like acti­vated charcoal, however, it is virtually useless when the delay between ingestion and admin­istration exceeds 1 hour (Dordoni et al. 1973).