Antihistamine

Question 1

Histamine function

Answer 1

Histamine will contract smooth muscle and dilate blood vessels. Agents that increase cAMP formation (e.g. beta-adrenoreceptor agonist) inhibit histamine secretion.

Question 2

Histamine receptors and their pathway

Answer 2

H1 and H3 (Gs) – increase cAMP
H2 and H4 (Gq) – stimulate PLC

Question 3

1st generation H1 antagonists

Answer 3

Promethazine: H1 antagonist, but relatively unspecific (so actually targets all histamine receptors as well as the muscarinic receptors).
MOA: (crosses the BBB):
- Anti-inflammatory (H1).
- Sedative (H1).
- Antiemetic (H1)
- Inhibits gastric acid secretion (H2)
- Antimuscarinic effect (M1)

Question 4

2nd generation H1 antagonists

Answer 4

MOA: do not cross the BBB:
- Non-sedative
- Anti-inflammatory (H1)

Question 5

H2 antagonist

Answer 5

MOA: inhibits HCL secretion from parietal cells.

Question 6

H3 antagonist

Answer 6

CNS use.
MOA: autoreceptor inhibition  increase histamine signaling.
Stimulatin, nootropic effects (treatment of eg. Alzheimers.

Question 7

Bronchodilators (drug to treat asthma)

Answer 7

Beta2-agonists, xanthine drugs, muscarinic receptor antagonists, leukotriene receptor antagonists.

Question 8

Beta2-agonists

Answer 8

Dilates bronchi. Gs coupled -> AC -> cAMP -> PKA -> phosphorylates myosin-light chain phosphatase (MLPC) -> MLCP is an enzyme that normally dephosphorylate myosin light chains in SM cells. When MLCP is phosphorylated, its activity is inhibited, leading to a decreased dephosphorylation of myosin light chain kinase, which promotes relaxation of the SM cells.

Side-effects: tremor (beta2-receptor activation, increased muscle discharge), mild tachycardia (reflex mechanism), Dysrhythmias (hypokalemia), Drop in blood pressure (β2-R activation also leads to vasodilation), Desensitization (extensive use).

Question 9

Xanthine drugs

Answer 9

Actions:
By inhibiting phosphodiesterase enzyme, xanthines prevent the breakdown of cAMP and cGMP in cells. Elevated levels of cAMP and cGMP lead to relaxation of smooth muscle, bronchodilation, and inhibition of mediator release.
Also acts as a non-selective antagonist of adenosine receptors, particularly the A1 and A2 subtypes. Adenosine can normally cause bronchoconstriction, vasodilation and inflammation.

Side-effects: very narrow therapeutic window, alertness, tremor nervousness (CNS), interfere with sleep (CNS), tachycardia and dysrhythmia (fatal), cause generalized vasodilation, but constrict cerebral blood vessels (headache), weak diuretics.

Question 10

Muscarinic receptor antagonists

Answer 10

Inhibits bronchoconstriction by Ach. (M3 receptor -> Gq coupled).
Inhibits augmentation of mucus secretion (beneficial for COPD patients).

Side-effects: Inhibits M2 auto receptors (augments ACh release), dry mouth and other glands (can’t see, pee, spit, shit), mild tachycardia from M2 antagonism.

Question 11

Leukotriene receptor antagonists

Answer 11

They block the action of leukotrienes by binding to leukotriene receptors. Leukotrienes are lipid mediators produced by inflammatory cells, such as mast cells, eosinophils, and basophils, during allergic and inflammatory response. By preventing binding, their inflammatory effects on target cells are prevented, such as bronchoconstriction.

Side-effects: few but can include headache, GI disturbance.