Histamine and anti-histamines

Question 1

What are the classes of the anti-histamines ?

Answer 1

1. H1 receptor antagonists - Split into first and second generations.
   Generation 1 = Hydroxyzine, chlopheniramine.
   Generation 2 = Cetrizine and loratadine.
2. H2 receptor antagonists

The difference of H1 generations is the fact that gen 1 is non polar and has CNS penetration, causes sedation. Gen 2 however is made polar by the addition of carboxyl groups, no CNS penetration and no side effect of sedation. These gen 2 H1 anti-histamines are specific for peripheral H1 receptors.

Question 2

H1 and H2 receptor actions ?

Answer 2

H1 receptors function to mediate smooth muscle contraction, increased capillary permeability and vasodilation ( endothelial Nitric Oxide secretion).

H2 receptors= stimulation gastric parietal cells function, increase production of the gastric acid.

Question 3

H1 anti-histamine function ?

Answer 3

Block “receptor mediated responses” of Histamine at the H1 receptor. These anti-histamines are not able to reverse conditions but rather prevent them before they occur e.g : motion sickness before travel.

Question 4

H1 anti-histamine therapeutic uses ?

Answer 4

1. Treatment of allergic/inflammatory reactions ( caused by antigen:IgE interaction ).
2. Motion sickness : Taken prior to travel to prevent symptoms before they have started, diminishing nausea and vomiting via blockage of central H1 and M1 receptors that mediate these symptoms.
3. Insomnia : 1st gen drugs have strong sedative properties.

Question 5

H1 anti-histamine Pharmacokinetics?

Answer 5

Good oral absorption, CYP-450 hepatic metabolism and urinary excretion. The first generation H1 anti-histamines are distributed to all body tissues, including the CNS.

Question 6

Adverse effects of H1 anti-histamines?

Answer 6

Sedation is the most common side effect of the H1 anti-histamines. However due to the blockage of the muscarinic receptors they may lead to anti-cholinergic symptoms such as xerostomia, urinary retention and blurred vision.

The most common AE of 2nd gen is headache.

Question 7

What are the drug interaction of the H1 anti-histamines ? (Not adverse effects of the drugs)

Answer 7

In combination with CNS depressants the first gen H1 inhibitors leads to a potentiation of the effects on the CNS (Sedation).

H1 anti-histamines combined with MAOI leads to exacerbation of sedative and anti-cholinergic effects.

Question 8

Explain the H2 anti-histamine drugs.

Answer 8

Function to inhibit parietal cell gastric acid secretion, to treat conditions such as ulcers or heart burn.