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.

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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.

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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 .)

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• Anaesthetic Agents – Drugs Used in Anaesthesia
• Methods for Enhancement of Drug Elimination
• Treatments Usage and Effects of Dronabinol Drug (Or Marinol )
• Gastric Aspiration and Lavage

• Anxiety,
• tension,
• symptoms of acute alcohol withdrawal,
• partial seizures,
• fatigue,
• agitation,
• irritable bowel syndrome,
• and panic attacks.

General Information of the drug

• Clorazepate dipotassium is a benzodiazepine, which directly affect the brain. This drug is a central-nervous-system depressant, and can relax you and make you more tranquil or sleepier, or they can slow nervous system transmissions in such a way as to act as an anticonvulsant.
• Many doctors prefer benzodiazepines to other drugs that can be used to similar effect because they tend to be safer, have fewer side effects.
• Clorazepate may increase blood levels of digoxin and the chances of digoxin toxicity.
• Don’t mix it with alcohol, other sedatives, narcotics, barbiturates, monoamine oxidase inhibitor and other antidepressants, and antihistamines.
• Taking clorazepate with other similar effects drugs may result in excessive depression, tiredness, sleepiness, breathing difficulties, or related symptoms.
• Combining clorazepate with phenytoin may increase phenytoin blood concentrations and the chances of phenytoin toxicity.
• Smoking may reduce clorazepate’s effectiveness by increasing the rate at which it is broken down by the body.
• Clorazepate’s effects may be prolonged when it is mixed with cimetidine, contraceptive drugs, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, probenecid, propoxyphene, propranolol, rifampin, or valproic acid.
• If you have to take Tranxene for a prolong period of time, your doctor will need to monitor your blood counts and liver function to be sure of your health state.
• Theophylline may reduce clorazepate’s sedative effects.
• If you take antacids, separate them from your clorazepate dose by at least 1 hour to prevent them from interfering with the absorption of clorazepate into the bloodstream.
• The effect of levodopa + carbidopa may be decreased if it is taken together with clorazepate.

Cautions ( This drug may be addictive ! )

• Clorazepate may be addictive. It should be used with caution in people with a history of drug dependence.
• Do not take clorazepate if you are allergic or sensitive to any of its ingredients or to another benzodiazepine drug, including clonazepam.
• Clorazepate can aggravate narrow-angle glaucoma, but you may take it if you have open-angle glaucoma and are receiving therapy for it.
• Clorazepate should not be taken by psychotic patients because it is not effective for them and can trigger unusual excitement, stimulation, and rage.
• Clorazepate is not intended to be used for more than 3-4 months at a time. Your doctor should reassess your condition before continuing your prescription beyond that time.
• Your dosage should always be reduced gradually to prevent drug withdrawal symptoms, which may develop if you stop taking it after as few as 4 weeks of regular use but is more likely after longer use.
• Drug withdrawal symptoms may start with anxiety and progress to tingling in the hands or feet, sensitivity to bright light, sleep disturbances, cramps, tremors, muscle tension or twitching, poor concentration, flu-like symptoms, fatigue, appetite loss, sweating. and changes in mental state.
• Other conditions in which clorazepate should be avoided are: severe depression, severe lung disease, sleep apnea (intermittent cessation of breathing during sleep), liver disease, drunkenness, and kidney disease. In each of these conditions, the depressive effects of clorazepate may be enhanced or could be detrimental to your overall condition.

Note

• This drug is for Adult Only ! It is not recommended for child.
• Clorazepate is best taken on an empty stomach, but if it upsets your stomach then it may be taken with food. Consult your doctor on this.
• Clorazepate can cause tiredness, drowsiness, inability to concentrate, or similar symptoms. Be careful if you are driving, operating machinery, or performing other activities that require concentration.
• People taking clorazepate for more than 3 or 4 months at a time may develop drug withdrawal reactions if the medication is stopped suddenly (see “Cautions” section above). Do not stop taking clorazepate or increase or decrease your dosage without first consulting your doctor.
• Do not take a double dose. If you forget a dose of clorazepate, take it as soon as you remember. If it is almost time for your next dose, skip the dose you forgot and continue with your regular schedule.

Pregnancy/Breast-feeding period :

• Clorazepate may cause birth defects if taken during the first 3 months of pregnancy.
• Avoid this drug if you are or might be pregnant, as Clorazepate may pass into breast milk. Nursing mothers who must take clorazepate should switch to use infant formula.

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• Synopsis of Important Principles – Drugs in Anaesthetic Practice
• Drug Overdosage and Poisoning – Synopsis of Important Principles
• Angiotensin-Converting Enzyme Inhibitor – Vasotec Enalapril
• Gastric Aspiration and Lavage

1. Specific antidotal therapy is available for very few poisons. The mainstay of treatment of severe poisoning is intensive supportive therapy and good nursing care.

2. The great majority of poisoned patients recover with intensive supportive therapy alone, and enthusiastic claims for the success of other treatment often cannot be justified.

3. With some important exceptions, the management of poisoning is not altered by knowledge of plasma drug concentrations. There are many pitfalls in the interpretation of drug concen­trations in poisoned patients, especially when nonspecific analytical methods are used.

4. Gastric lavage and induction of nemesis soon after ingestion may be effective in removing unabsorbed drug, but are unreliable. Adsorbents such as activated charcoal are usually ineffec­tive in limiting absorption when given more than 1 hour after ingestion.

5. Poisoned patients are often subjected to unnecessary and potentially harmful haemodialysis, haemoperfusion and diuresis. The efficacy of these measures has been established for relatively few substances in terms of reduction in morbidity and mortality or removal of toxicologically significant amounts of active drug or poison.

6. The efficacy of methods for extracorporeal removal can be predicted from pharmacokinetic principles. It depends primarily on the volume of drug distribution, plasma protein binding, rate of transfer from peripheral to central compartments, and dialysis clearance relative to the endogenous total body clearance.

7. Haemoperfusion with activated charcoal or exchange resins is more effective than haemo­dialysis in removing drugs from the blood. Peritoneal dialysis is less effective than haemodi­alysis. Drugs with large volumes of distribution cannot be removed rapidly by any of these techniques, and indications for their use are limited.

8. Forced diuresis can only increase the renal clearance of reabsorbed compounds, and clearance may be dramatically increased by appropriate manipulation of urine pH. However, the renal excretion of most drugs is insignificant in relation to the metabolic clearance. Forced alkaline diuresis is largely restricted to salicylate and phenobarbitone poisoning.

9. Repeated oral activated charcoal effectively increases the body clearance of a number of drugs. It probably acts by irreversibly binding drug diffusing from the circulation to the gut lumen and may also interrupt the enterohepatic circulation.

10. The toxicity of a few drugs and poisons can be reversed by specific antidotal therapy. Mechanisms include pharmacological antagonism, inhibition of conversion to toxic metabolites, inactivation of highly reactive alkylating intermediates, chelation and binding with drug-specific antibodies.

• Drugs Usage during Critical Medical Emergencies – Synopsis of Important Principles
• Generalized Anxiety Disorder Treatment with Clorazepate ( Tranxene )
• Methods for Enhancement of Drug Elimination
• Anaesthetic Agents – Drugs Used in Anaesthesia
• Synopsis of Important Principles – Drugs in Anaesthetic Practice
• Gastric Aspiration and Lavage
• Treating Diabetes Type2 with Miglitol ( Glyset, Acarbose, Precose )
• Collaboration Between Healthcare Provider and Clinical Labora­tory on Therapeutic Drug Monitoring
• Cathartics, Enemas and Activated Charcoal
• Treatments Usage and Effects of Dronabinol Drug (Or Marinol )

• Hypertension ( high blood pressure ),
• heart failure,
• diabetic kidney disease,
• and heart attack treatment ( when the function of the left ventricle has been affected),
• kidney failure,
• kidney hypertension,
• managing people with a high risk of heart disease,
• chronic kidney disease,
• preventing a second stroke.

General Information of the drug

• Enalapril begins working about 1 hour after you take it and continues to work for 24 hours.
• Enalapril maleate and other ACE inhibitors work by preventing the conversion of a hormone called ‘Angiotensin I‘ to another hormone called ‘Angiotensin II‘ , a potent blood-vessel constrictor. Preventing this conversion relaxes blood vessels, thus reducing blood pressure and relieving symptoms of heart failure.
• Enalapril also affects the production of other hormones and enzymes that participate in the regulation of blood-vessel dilation.

Cautions

• Enalapril occasionally causes very low blood pressure.
• Do not take enalapril if you are allergic or sensitive to any of its ingredients. Severe sensitivity reactions can occur in hemodialysis patients taking enalapril or those undergoing venom immunization.
• Swelling of the face, extremities, or throat has been known to occur with enalapril, which can be dangerous (see below section on “Important Notes” ).
• Enalapril may affect your kidney function, especially if you have congestive heart failure. Your doctor should check your urine for protein content during the first few months of treatment. Dosage adjustment of enalapril is necessary if you have reduced kidney function.
• Enalapril can affect white-blood-cell counts, possibly increasing your susceptibility to infection. Your doctor should monitor your blood counts periodically.
• Enalapril may cause serious injury or death to the fetus if taken during pregnancy. Pregnant women should not take enalapril.
• ACE inhibitors may be less effective in some black patients with high blood pressure, especially when dietary salt intake is high. Nevertheless, they should still be considered useful blood pressure treatments. Swelling beneath the skin to form welts is more common among black patients.

How the Drug works ?

• Antacids and enalapril should be taken at least 2 hours apart.
• The blood-pressure-lowering effect of enalapril is additive with diuretic drugs and beta blockers. Any other drug that causes a rapid drop in blood pressure should be used with caution if you are taking enalapril.
• Enalapril may increase the effects of lithium; this combination should be used with caution.
• Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the blood-pressure-lowering effects of enalapril and other ACE inhibitors. The combination may cause reductions in kidney function.
• Enalapril may increase blood-potassium levels, especially when taken with dyazide or other potassium-sparing diuretics.
• Capsaicin may trigger or aggravate the cough associated with enalapril therapy.
• Rifampin may reduce the effects of enalapril.
• The combination of allopurinol and enalapril increases the chance of side effects. Avoid this combination as severe sensitivity reactions can occur in those taking allopurinol.
• Enalapril affects blood levels of digoxin. More digoxin in the blood increases the chance of digoxin-related side effects, while less digoxin in the blood can compromise its effectiveness.
• Indomethacin may reduce the blood-pressure-lowering effects of enalapril.
• Phenothiazine sedatives and antiemetics may increase the effects of enalapril.

Important Note

• Enalapril can cause swelling of the face, lips, hands, or feet. This swelling can also affect the larynx (throat) or tongue and interfere with breathing. If this happens, go to a hospital emergency room at once.
• Call your doctor if you develop a sore throat, mouth sores, abnormal heartbeat, chest pain, persistent rash, or loss of taste perception.
• Some people who start taking enalapril after they are already on a diuretic (an agent that increases urination) could experience a rapid drop in blood pressure after their first doses or when their dosage is increased. To prevent this from happening, inform your doctor before hand ( that you are taking diuretic ) , as your doctor may tell you to stop taking your diuretic 2 or 3 days before starting enalapril or to increase your salt intake during that time. Upon your doctor advise, you may then restart on taking diuretic gradually.
• You may get dizzy if you rise to your feet too quickly from a sitting or lying position when taking enalapril.
• Avoid strenuous exercise or very hot weather because heavy sweating or dehydration can cause a rapid drop in blood pressure.
• While taking enalapril, avoid over-the-counter diet pills, decongestants, and other stimulants that can raise blood pressure.
• Do not take potassium supplements or salt substitutes containing potassium without consulting your doctor.
• Never take a double dose. If you take enalapril once a day and forget to take a dose, take it as soon as you remember. If it is within 8 hours of your next dose, skip the one you forgot and continue with your regular schedule. If you take enalapril twice a day and miss a dose, take it right away. If it is within 4 hours of your next dose, take 1 dose immediately and another in 5 or 6 hours, then go back to your regular schedule.

Possible Side Effects

Refers to Side Effects on Lexxel Drug , as these drugs works in combination in most treatments condition. However, if you experience unusual effects, do consult your doctor for advise.

Pregnancy/Breast-feeding period :

• ACE inhibitors can cause fetal injury or death. Women who are or might become pregnant should not take ACE inhibitors.
• Sexually active women of childbearing age who must take enalapril must use an effective contraceptive method to prevent pregnancy.
• If you become pregnant, stop taking the medication and call your doctor immediately.
• Nursing mothers who must take this drug should use infant formula as small amounts of enalapril pass into breast milk.

For Seniors who needs to take this drug :-

Seniors may be more sensitive to the effects of enalapril drug due to age-related losses in kidney or liver function.

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• Treating Hypertension with Lexxel Generic Drug
• Generalized Anxiety Disorder Treatment with Clorazepate ( Tranxene )
• Drugs Usage during Critical Medical Emergencies – Synopsis of Important Principles
• Synopsis of Important Principles – Drugs in Anaesthetic Practice
• Treatments Usage and Effects of Dronabinol Drug (Or Marinol )
• Using Entacapone in Parkinson’s Disease Treatment
• Symptoms, Types and Treatment Options for Warts
• Pathophysiology of Circulatory Failure and Cardiopulmonary Resuscitation
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