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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• 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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Parkinson’s disease

• Chronic (persistent) disorder of part of the brain, which affects the way the brain co-ordinates the movements of the muscles in various parts of the body.

General Information of the drug
Entacapone is always used in combination with levodopa + carbidopa. It is prescribed For Parkinson’s disease patients for whom levodopa + carbidopa loses its effectiveness between doses.

Entacapone enhances the effect of levodopa + carbidopa by reversing the action of an enzyme known as catechol-O-methyltransferase (COMT), which is primarily responsible for breaking down levodopa in the body.

Some patients experience signs and symptoms of an end-of-dose “wearing-off” effect with these drugs.

Cautions

• If you are allergic or sensitive to any of its ingredients -> Do not take entacapone !
• People with liver disease should use entacapone with caution as they may accumulate twice as much of this drug in their blood as people with normal liver function.
• Entacapone may cause kidney toxicity.
• Entacapone may increase the risk of dizziness or fainting when rising from a sitting or lying down position.
• Do not take entacapone with phenelzine or tranyleypromine -> Serious reaction may occur.
• Hallucinations have been reported with other Parkinson’s disease drugs.
• Entacapone has been rarely associated with the formation of fibrous tissues in unusual places such as the urinary tract and lungs. It has also caused fluid in the lungs.

Intake and Dosage

• Adult Dose Intake :- 200 mg with each levodopa + carbidopa dose, up to 1600 mg a day.
• Entacapone may be taken with or without food. However, Do Not Mix entacapone with the monoamine oxidase inhibitor (MAGI) antidepressants phenelzine or tranylcypromine.
• Entacapone may be taken with the MA01 selegiline.
• Other drugs broken down by COMT will also be affected by entacapone.
• lsoproterenol, epinephrine, ephedrine, norepinephrine, isoetharine, and others will interact with entacapone, even when taken by inhalation. The result may be increased heart rate, arrhythmias, and excessive changes in blood pressure.
• Cholestyramine, probenecid, erythromycin, rifampin, ampicillin, and chioramphenicol may interfere with the elimination of entacapone from the body.
• Entacapone may enhance the effects of sedatives and other nervous system depressants.
• Although there have been no reports of significant entacapone overdose as of publcation. But theoretically, a massive entacapone overdose could prove lethal by completely inhibiting COMT throughout the body.
• Doses up to 800 mg have been taken and side effects were mainly abdominal pain and loose stools.
• Other effects that might be expected include difficulty breathing, loss of muscle coordination, reduced level of activity, and convulsions.
• Overdose victims should be taken to a hospital emergency room as soon as possible ( ALWAYS bring along the prescription bottle or container. )
  

Important Note

• This drug can cause dizziness, nausea, sweating, or fainting when rising quickly from a sitting or lying position, especially at the beginning of treatment.
• Always take your entacapone dose together with your levodopa + carbidopa dose. If you forget a dose. take it as soon as you remember. ( If it is within 2 hours of your next dose. skip the dose you forgot and continue with your regular schedule. )
• If you experience an increased body movements and twitching, twisting, or uncontrolled tongue, lip, face, arm, or leg movement, consult your doctor as he may need to adjust your dose of levodopa + carbidopa.
• Until your body has become accustomed to the effects of entacapone, it’s highly advisable to be caution when performing tasks, such as driving, that require coordination and concentration.
• Gradually reducing the dose of entacapone decreases some drug side effects.
• Patients who stop using entacapone should be monitored as rapid withdrawal of the drug can cause high fever, sweating, unstable blood pressure, stupor, and muscular rigidity.
• If your urine to turn a brownish-orange color after taking Entacapone,  it is usually harmless.

Possible Side Effects

Most of the common effects after taking this drugs are :-

• difficulty performing voluntary muscle functions,
• excessive muscle activity,
• nausea,
• urine discoloration,
• diarrhea,
• reduced muscle activity,
• dizziness,
• fatigue,
• constipation,
• abdominal pain.

Less common side effects or rarely occurs side effects ( Consult your doctor immediately ) :-

• low blood pressure and fainting ( especially when rising from a sitting or lying position ),
• hallucinations,
• anxiety,
• agitation,
• gastritis or other stomach disorders,
• dry mouth,
• vomiting,
• increased sweating,
• back pain,
• taste changes,
• shortness of breath,
• easy bruising,
• weakness,
• bacterial infection,
• muscle damage or death,
• high fever,
• confusion.

Pregnancy/Breast-feeding period :

• When this drug is considered crucial by your doctor, its potential benefits must be weighed against its risks.
• Entacapone causes birth defects, miscarriage and abortion in pregnant animals. It has been known that Entacapone passes into the breast milk of animals, but at the moment if publication, there is no information on humans is available. Nursing mothers who must take this drug should use infant formula.

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