Histamines

Question 1

Histamine metabolites

Answer 1

N-methylhistamine and imidazole acetic acid

Need MAO to metabolize

Question 2

H1 receptor

Answer 2

Found in smooth muscle and endothelium; increases IP3 (Gq protein)

-Chlorpheniramine is a partial agonist

Question 3

H2 receptor

Answer 3

Found in gastric mucosa, cardiac cells, mast cells; increases cAMP (Gs protein)

Ranitidine is an agonist

Question 4

Triple Response to Histamine

Answer 4

Wheal (increased capillary permeability from H1)

Red spot (vasodilation from H1 and H2)

Flare (axon reflex from H1; indirect)

Question 5

Chlorpheniramine, Diphenhydramine, Promethazine

Answer 5

1st generation H1 receptor antagonists

Inhibits vascular permeability, vasodilation, and heart fnxn; has little effect on bronchoconstriction and gastric fnxn

ADRs: CNS stimulation, sometimes CNS depression if combined w/ alcohol, antimuscarinic effects (dry mouth, constipation)

Uses: Tx for exudative allergies (rhinitis, asthma), systemic anaphylaxis (epinephrine first line tho), bronchial asthma, motion sickness (promethazine)

Question 6

Promethazine

Answer 6

1st generation H1 antagonist that has strongest anti-muscarinic effects and strongest anti-emetic

Question 7

Ceftirizine, Loratidine

Answer 7

2nd Generation HT-1 receptor antagonists; same uses as 1st generation but w/ less side effects

• Ceftirizine can have CNS depression tho
• Enter the CNS much slower than 1st generation; metabolized by CYP3A4

Question 8

Cimetidine, Ranitidine

Answer 8

HT-2 receptor antagonists that decrease gastric acid secretion; used to promote healing of ulcers, GERD, and prophylactic for stress ulcers

ADRs: N/V, headache

*Cimetidine=CYP inducer

Renal excretion so lower dose in renal disease

Question 9

Gastric ECL cells

Answer 9

Contain histamine and can release it in response to Ach or gastrin