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.

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 .)

General Information

• Amiodarone works by decreasing the sensitivity of heart tissue to nervous impulses within the heart. It should be prescribed only in situations where the abnormal rhythm is so severe as to be life-threatening and does not respond to other drug treatments.
• It has not been proven that people taking this drug will live longer than those with similar conditions who do not take it.
• Amiodarone may exert its effects 2-5 days after you start taking it, but often takes 1-3 weeks to affect your heart.
• Amiodarone’s antiarrhythmic effects can last for weeks or months after you stop taking it.

How does the drug Interact ?

• Amiodarone increases the effects of metoprolol and other beta blockers, calcium channel blockers such as verapamil and dittiazem, cyclosporine, dextromethorphan, digoxin, disopyramide, flecainide, fentanyl, lidocaine, methotrexate, procainamide, quinidine, theophylline, and warfarin and other anticoagulants. These interactions can take from 2 or 3 days to several weeks to develop. Some can be life threatening, and for others, drug dosage adjustments may be enough to avoid a serious problem.
• Fluoroquinolones, azole antifungals, and macrolide antibiotics increase the effects of amiodarone. which can cause life-threatening abnormal heart rhythms.
• When amiodarone and phenytoin are taken together, both drugs can be affected. Amiodarone can be antagonized by phenytoin and other hydantoin anticonvulsants, and the effect of phenytoin can be increased by amiodarone.
• Cholestyramine interferes with the absorption of amiodarone into the bloodstream.
• Cimetidine and ritonavir interfere with the breakdown of amiodarone, leading to high drug blood levels and the increased possibility of side effects.
• Azithromycin can interfere with the effectiveness of amiodarone. This interaction may lead to dizziness and cardiac instability.

Cautions ( This drug has fatal effects ! )

• Amiodarone can cause potentially fatal drug side effects too ! At high doses, 10% or more of people taking this drug can develop potentially fatal lung and respiratory effects, beginning with cough and progressive breathing difficulties.
• Do not take amiodarone if you are allergic or sensitive to any of its ingredients or if you have heart block or a very slow heart rate.
• Amiodarone can also cause heart block, a drastic slowing of electrical impulse movement between major areas of the heart, or extreme slowing of the heart rate. Amiodarone heart block occurs about as often as heart block caused by some other antiarrhythmic drugs, but its effects may last longer than those of the other drugs.
• Amiodarone can also worsen existing abnormal heart rhythms in 2-5% of people who take the drug. These effects can be fatal.
• Liver damage caused by amiodarone is usually mild. In rare cases. amiodarone has been associated with liver failure that resulted in death.
• People taking amiodarone may develop optic nerve irritation, leading to partial or complete loss of vision. Most adults who take amiodarone for 6 months or more develop tiny deposits in the corneas of their eyes. These deposits may cause blurred vision or halos in up to 10% of people taking amiodarone. Some people develop dry eyes and sensitivity to bright light.
• One in ten people taking amiodarone can experience unusual sensitivity to the effects of the sun. Use an appropriate sunscreen product and reapply it frequently.
• Amiodarone can cause thyroid abnormalities. It may worsen an already sluggish thyroid gland in 2-10% of people taking the drug, and increase thyroid activity in 2% of people taking it.
• Amiodarone has also been associated with an increase in risk of thyroid tumors.
• Antiarrhythmic drugs are less effective and cause abnormal rhythms if blood potassium is low.

Other Possible Side Effects

• Side effects are very common with amiodarone. About 75% of people taking 400 mg or more of amiodarone a day develop some drug side effects. As many as 18% have to stop taking the drug because of a side effect.
• Amiodarone stays in the body for months, so side effects may remain even after the drug is stopped.
• Unusual sun sensitivity is the most common skin reaction to amiodarone, but people taking this drug can develop a blue skin discoloration that may not go away completely when the drug is stopped.
• Other skin reactions are sun rashes, hair loss, and black-and-blue spots.
• Amiodarone can cause heart failure, reduced heart rate, and abnormal rhythms.
• Up to 9% of people taking amiodarone develop abnormalities in liver function

See your doctor for an eye exam if your vision changes at all while taking amiodarone.

Call your doctor if you develop chest pain. breathing difficulties, spitting up blood, nausea, vomiting, abnormal heartbeat, bloating in your feet or legs. tremors, fever, chills, sore throat, unusual bleeding or bruising, changes in skin color, unusual sunburn, or any other unusual side effect.

Common Side Effects of the drug :-

• fatigue,
• not feeling well,
• tremors,
• unusual involuntary movements,
• loss of coordination,
• an unusual walk,
• muscle weakness,
• low blood pressure,
• dizziness,
• tingling in the hands or feet,
• reduced sex drive,
• sleeplessness,
• headache,
• nervous-system problems,
• nausea,
• vomiting,
• constipation,
• appetite loss,
• abdominal pain,
• dry eyes,
• unusual sensitivity to bright light,
• seeing halos around bright lights.

Rare Side Effects :-

• inflammation of the lung or fibrous deposits in the lungs,
• changes in thyroid function,
• changes in taste or smell,
• bloating,
• unusual salivation,
• changes in blood clotting.

Note

• Amiodarone can make you dizzy or lightheaded. Take care while driving a car or performing complex tasks.
• If you take amiodarone once a day and forget to take a dose, but remember within 12 hours, take it as soon as possible.
• If you do not remember until later, skip the dose you forgot and continue with your regular schedule.
• If you take amiodarone twice a day and remember within 6 hours of your regular dose, take it as soon as you remember.
• Call your doctor if you forget to take 2 or more doses in a row, ask for doctor advise on what to do next – Do not take a double dose.
• Pregnancy and/or Breast-feeding : In high doses, amiodarone has been found to be toxic to animal fetuses. Women of childbearing age should use an effective contraceptive while taking amiodarone. If you are or might be pregnant and this drug is considered crucial by your doctor, its potential benefits must be weighed against its risks.
  Amiodarone passes into breast milk. Nursing mothers who must take this drug should use infant formula.
• Seniors : Dosage reduction may be needed in seniors with poor liver function.

Usual Dose ( Doctor Instruction Should Be followed Closely )

• Starting dose 800-1600 mg a day, taken in 1 or 2 doses, usually for 1-3 weeks. Then, 600-800 mg a day for approximately a month. Maintenance dose 400 mg a day.
• You should take the lowest effective dose in order to minimize side effects.
• Amiodarone should be taken on an empty stomach, as food delays its absorption into your bloodstream.
• If amiodarone upsets your stomach, however, you may take it with food but then always take it with food to be consistent.
• Do not drink grapefruit juice during treatment with amiodarone because grapefruit juice affects how amiodarone is absorbed in the stomach.

Over Dosage Effect(s)

• The effects of amiodarone overdose include low blood pressure. shock, slow heartbeat, and liver toxicity.
• Overdose victims should be taken to a hospital emergency room for treatment.
• ALWAYS bring the prescription bottle or container.