Codeine (Sulphate or phosphate)

It is phenanthrene derivative-opiate agonist.

Mechanism of Action:
It lowers the cough reflex by direct effect on the cough center in medulla of the brain that appears to exert a drying effect on respiratory tract mucosa and increased viscosity of bronchial secretions.

Action:
It has less effect on cough than morphine if we consider treatment on weight basis.

Therapeutic uses:
1. Cough:
It can be used for the (symptomatic) treatment of non-productive cough.

2. Analgesic

Administration and dosage:
It is administered orally for anti-tussive effect. Its dosage is 10-20 mg every 4-6 hours for adults and children above 12 years age. The dosage is half for children between 6-12 years.

Pharmacokinetics:
1. It is well absorbed from G.I. Tract.
2. Peak anti-tussive effect occurs after 0.5 to 2 hours and remains for (may) up to 4-6 hours.
3. It can be distributed into milk.
4. It is metabolized in the liver and excreted in the urine.

Adverse effects:
Its side effect is rare, which may show nausea, vomiting, constipation with repeated doses, dizziness and sedation.

Classification of Drugs used to treat cough

1. Anti-tussives
Codeine, Hydrocodone, Hydromorphone, Benzonate, Dextromethorphan HCl, Carbetapentane

2. Expectorant:
Guaifenesin, Guaiacol, Terpene hydrate, Creosate

3. Mucolytic agents:
Acetylcysteine, Bromohexine, Proteolytic enzymes such as trypsin, Ambroxol

Cough

It is the process of releasing air through the windpipe and mouth in a sudden noisy manner. Cough is initiated when there is a mechanical or chemical irritation to bronchi and trachea or by pressure from adjacent structures. Larynx and carina are especially sensitive to chemical stimuli such as SO₂ gas or chlorine gas.

Useful aspects of cough:
It is a physiological mechanism which:
1. Clears the respiratory pathways from foreign materials and extra secretions
2. May help to prevent sudden collapse of lungs.

Capreomycin

It is obtained from Streptomyces capreolus. It is peptide protein synthesis.


Its 1 gm IM injection leads to 10μg/ml of blood level.

It is used for the treatment of tuberculosis.
It may cause nephrotoxicity, ototoxicity, tinnitus and deafness.

Ethionamide

It is chemically related to INH and therefore it blocks the production of mycolic acids.


Pharmacokinetics:
It is given orally. It is metabolized by liver. Its dosage of 1 gm/day gives 20μg/ml of serum concentrations in plasma and tissues.

Adverse effects:
It is hepatotoxic.

Para-aminosalicylic acid

It is structurally similar to para-aminobenzoic acid (PABA).


Mechanism of action:
It competes for the enzyme involved in the conversion of PABA to dihydrpteroic acid that results in the inhibition of Purine and as a result DNA synthesis is stopped.

Pharmacokinetics:
It is widely distributed in tissues and rapidly excreted in urine.

Dosage:
Its usual adult dose is 8-12 g/day orally in divided doses.

Adverse effects:
It may cause anorexia, nausea, fever and skin rashes. Furthermore, nephrotoxicity, hepatotoxicity and granulocytopenia.

Pyrazinamide

It is closely related to nicotinamide.


Mechanism of action:
Its exact mechanism of action is unknown but it is thought to be converted into pyrazinoic acid (active form of the drug) with the help of mycobacterial pyrazinamidase, which causes the inhibition of tubercle bacilli at concentration of 20 μg/ml at 5.5 pH.

Therapeutic uses:
In combination with isoniazid and rifampin. It is also used for tuberculosis for short course that is 6 months.

Pharmacokinetics:
It is well absorbed from GIT. It is widely distributed in body tissues. Its half life is 8-11 hours.