Acetazolamide in acute mountain sickness- the probable mechanism

 Acute mountain sickness is triggered by low oxygen at high altitudes. The ensuing hypoxia leads to adaptive changes by the human body.

In the brain, the adaptive response is vasodilatation. The objective is to improve perfusion. Overtime, this leads to carbon dioxide retention, increase in intracranial tension and oedema. The condition is known as high altitude cerebral oedema.

In the lungs, the adaptive response is vasoconstriction because of ventilation perfusion mismatch. Overtime, this leads to tissue damage and oedema. The condition is known as high altitude pulmonary oedema. 

The respiratory centre senses the hypoxia and in response hyperventilation occurs. Hyperventilation washes away carbon dioxide from blood leading to alkalosis.

So, in the pathophysiology of acute mountain sickness, hypoxia, oedema and alkalosis co-exist.

The treatment aims to alleviate hypoxia, oedema and alkalosis.

Hypoxia is corrected by giving supplemental oxygen.

Oedema is corrected by giving diuretics and steroids.

Alkalosis is corrected by giving acetazolamide.

The only diuretic which is able to cause acidosis is acetazolamide.

So, acetazolamide becomes the diuretic of choice in acute mountain sickness because it corrects alkalosis.

The steroid of choice is dexamethasone.

Multi drug therapy- the new weapon against cancer

 We all know that multi-drug therapy is a key way to prevent the emergence of resistance in infectious diseases. It not only provides rapid cure but also stamps out those strains of the infective organism which would have easily survived the onslaught of a single drug. Like the infectious organisms, cancer cells are also rapidly dividing cells, the growth and spread of which can be stopped using chemotherapy. There is astonishing similarity between drug resistance seen in infectious diseases and cancer. Infectious organisms have learnt to evade killing by antimicrobials by developing multiple mechanisms. In recent times, the problem of resistance in infectious organisms has become rampant and we find ourselves in very difficult situation to combat the infectious organisms. Similarly, in cancers which were sensitive to single drug of chemotherapy has over a period of time become more and more resistant. To overcome this problem multiple drug therapy with multiple anti-cancer drugs acting at multiple levels have been developed which not only kills the cancer cells in a shorter period of time but also prevents the development of resistance. Use of multiple drugs also decreases the chances of adverse effects associated with use of high dose of a single drug in cancer chemotherapy The doses of the respective drugs can be reduced such that the toxicity profile is much better. Nowadays we have an armamentarium of drugs against cancer-cytotoxics, biologicals, monoclonal antibodies, hormonal therapy. These drugs acts by different mechanisms and are effective in remission of cancer which otherwise would not have been possible with a single drug. In a classical example of drug resistance associated  with PGP (P glycoprotein) or MDR (multi-drug resistance protein), the cancer chemotherapeutic agent is extruded out of the cancer cells by the PGP resulting in decreased efficacy of the agent. In such conditions multiple drugs enables the remission of cancer even when one of the drugs is extruded out from the site of its action.

Seizure, epilepsy and convulsion-Are they same.

 People use “seizure” and “epilepsy” interchangeably, but they are not some. To understand better, I will put it like this, “ All epilepsy patients have seizures but all seizure patients are not epileptic” which means that there are non-epileptic causes of seizures also like hypoglycaemia, brain tumours, hypoxia, metabolic derangements, brain infections, cerebrovascular accidents etc. In other words, epilepsy is seizure without any organic cause or lesion. Sometimes, another terminology ‘convulsion’ is also used. It refers to the involuntary contraction/relaxation that occurs in seizure patients. ‘Convulsion’ is rather a layman’s term and you will find them referred to frequently in news and general discussion. It is to be remembered that some seizure disorder like absence seizure may not be manifested as ‘convulsions’

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Differential action of cortisol on tissues- the cellular checkpoints at the tissue level

 

·       Cortisol (and some amount of cortisone) is produced by the adrenal cortex in response to stress

·       Like all hormones, cortisol is secreted directly into the circulation and distributed uniformly throughout the body.

·       Most tissues of the body (mainly the liver and the adipose tissues) are rich in glucocorticoid receptors and poor in mineralocorticoid receptors. They have the enzyme HSD-11β Type 1 which converts cortisone into cortisol and promotes glucocorticoid action.

·       Some tissues of the body (kidneys, liver, lungs, colon, salivary glands) are rich in mineralocorticoid receptors and poor in glucocorticoid receptors. They are very sensitive to mineralocorticoid action of cortisol. They have the enzyme HSD-11β Type 2 which converts active cortisol into inactive cortisone and prevent excessive mineralocorticoid action of cortisol.