HISTAMINE & ANTIHISTAMINES (Part #3) 

Pharmacokinetics Of H-1 Anti-histamines:

H-1 receptor blockers are well absorbed via oral administration with maximum serum level reach within one to two hours.

Average plasma half-life is four to six hours except Meclizine and second generation drugs which have 12 to 24 hours; so, only once daily dose allowed to given.

All first generation and second generation drugs are metabolized by Hepatic Cytochrome p450 system.

Cetrizine and Levocetrizine are excreted largely in urine

while Fexofenadine excreted largely in feces

Adverse Effects of H-1 Anti-histamines:

     Sedation:

The first generation drugs such as Chlorpheniramine, Diphenhydramine, hydroxyzine, promethazine, bind to H-1 receptor and block the effective histamine in CNS.

Most frequent adverse effects of first generation is sedation

Diphenhydramine may cause Paradoxical Hyperactivity in young children. Other actions includes fatigue, dizziness, lack of co-ordination, tremors, etc

Mostly elder patients are sensitive to these effects

Sedation is less common in second generation drugs because they can't enter in CNS while first generation drugs enter in CNS

2   Other Effects:

Due to first generation drugs adverse effects occur due to anticholinergic effects

The effects includes dryness in nasal passage, dryness in oral cavity, blurred vision, retention of urine, etc

While, due to second generation drugs, the effect occur is headache

The Diphenhydramine may cause local hypersensitivity reactions, such as dermatitis

3   Drug Interactions:

H-1 blockers also interacts with other drugs causes serious problems

Example:

Phenilizine should not take as antihistamine because Monoamine Oxidase Inhibitors increases the sedative and anticholinergic effects

Also the first generation drugs when taken along with anticholinergic drugs it may decease the cholinesterase inhibitor's activity in Alzheimer’s disease

4   
Overdoses:

Margin of safety of H-1 blockers is high

Chronic toxicity is rare

Acute poisoning usually common in young children. The dangerous effects of acute poisoning are those on the CNS including hallucinations, excitement, ataxia and Convulsions. If these effects untreated, the patient may suffer deep coma and make collapse of cardiovascular system

H-2 Anti-histamines:

They have little affinity for H-1 blockers

The effect produced by H-2 blockers are inhibition of gastric acid secretion especially in case of ulcers and heartburn

Example:

Cimetidine

Ranitidine

Fexofenadine

Nizatadine