Isoniazid

It is also referred to as INH as its full name is “Isonicotinic acid hydrazide”.
Mechanism of action:
It causes a decreased synthesis of mycolic acid. Mycolic acid is a constituent of mycobacterial cell wall that is thought to be responsible for the acid fastness of the bacteria.

Where,

KatG is mycobacterial catalase (peroxidase),

AcpM is Acyl carrier protein,

KaSA is Beta ketoacyl carrier protein synthetase.

Here in the above diagram, mycolic acid synthesis is blocked as mycolic acid is produced by the incorporation of cyclopropane ring near the centre of acyl chain.

Pharmacokinetics:
It is readily absorbed by GIT. 300 mg of oral dose achieves peak plasma concentration of 3-5μg/ml in 1-2 hours. The drug diffuses easily into bodily fluids and cells.

It is metabolized by liver N-acetyltransferase (in which its acetylation occurs).

Average half life in peoples with rapid acetylation is 1 hour and in peoples with slow acetylation it is 3 hours.

Elimination is done via urine.

Therapeutic uses:
It is used in the prophylaxis as well as treatment of tuberculosis.

Dosage:
The usual adult dose is 5mg/kg/day to a maximum of 300 mg/day.

Adverse effects:
It may cause fever, skin rashes, Insomnia and restlessness. It may also induce hepatitis characterized by loss of appetite, nausea and vomiting. Hepatitis is thought to be associated to the metabolite monoacetylhydrazine.

Sometimes peripheral neuropathy (neuropathy is caused by pyridoxine deficiency and isoniazid causes an increased pyridoxine excretion) is also observed.

Resistance:

Resistance is found to be due to chromosomal alterations resulting in change in genetic material of KatG or due to over expression of enoyl acyl carrier protein reductase.

Classification of anti-tuberculosis

First line drugs:

Isoniazid, Rifampin, Ethambutol, Streptomycin, Pyrazinamide

Second line drugs:
Ethionamide, Cycloserine, Tetracycline, para-aminosalicylic acid, Amikacin, Fluoroquinolones

Tuberculosis

Symptoms of tuberculosis:


Early symptoms:
Usually no symptoms develop but sometimes influenza is present.

Symptoms in second stage:
1. Low fever
2. Weight loss
3. Chronic fatigue
4. Heavy sweating especially at night

Later stages:
1. Cough with sputum that becomes progressively bloody, yellow, thick or grey
2. Chest pain
3. Shortness of breath
4. Reddish or cloudy urine

Mycobacteria

Characteristic features of mycobacteria are:

1. Slender rod shaped bacteria
2. Lipid rich cell wall
3. Acid fast

Major diseases caused by mycobacteria:
1. Leprosy
2. Tuberculosis

An Interview with Mr. Pharmaceutics

Jeepakistan Team (J. T.): Tell something shortly about yourself.

Mr. Pharmaceutics (P): I am an art from patient’s and customer’s point of view and science from doctor and scientist’s point of view.

J. T.: Your family members!

P: I’ve many brothers, children and grand children. My powerful brothers are biotechnology, medicine, chemistry and botany. My most favourite children are Hospital pharmacy, industrial pharmacy, forensic pharmacy and retail pharmacy. My grand children are computer education, biostatistics, quality control and many others.

J. T.: Some thing about your life!

P: Peoples love me. In most cases you’ll find me present everywhere from urban to rural areas, from jungles to desert, from air to water and from east to west. Even I love peoples very much. That’s why, I try to give them not only healthy life but also good employment opportunities.

J. T.: The hidden reality you want to tell peoples!

P: The best cure for every pain are not NSAIDs nor any other type of painkillers. But many types of pain can only be cured by the world’s best medicine, that’s love.

J. T.: I can’t understand, what you have said!

P: For example, in very old age the pain felt in the body is due to loneliness, if the children don’t leave their parents alone then the severity of the pain will be reduced.Even that pain will not be felt in many cases if the children give their parents much happiness.

J. T.: Your interview will be published. Do you want to give your readers some message?

P: I can’t do anything for disable peoples, genetically ill peoples and many peoples, who are in very poor or far off areas. Please, for the sake of God, help those peoples as much as you can.

J. T.: Thank you.

Sulfinpyrazone

It is a derivative of phenylbutazone.


Mechanism of Action:
Same as that of probenecid.

Therapeutic Uses:
It is used for the treatment of Uric acid.
Pharmacokinetics:
It shows renal excretion.

Adverse effects:
Same as that of probenecid.

Probenecid

Action:

It acts generally as an inhibitor of the tubular secretion of organic acids.

Mechanism of action:
It causes blockage of resorption of uric acid by proximal tubular resorption.

Therapeutic Uses:
It is used for the treatment of Uric Acid.
Pharmacokinetics:
It is well absorbed by renal tubules. Its plasma half life is about 5-8.5 hours.

Adverse effects:
It may show gastric discomfort.

Interaction:
Probenecid stops tubular secretion of penicillin and that is why it sometimes is used for increasing the levels of the antibiotic.

It also inhibits excretion of naproxen, ketoprofen and indomethacin.