Histamine, Serotonin, and the Ergot Alkaloids

Question 1

what are autacoids?

Answer 1

endogenous molecules with powerful pharmacologic effects that do NOT fall into traditiona autonomic groups

Question 2

Triple Response of Lewis

Answer 2

wheal, flush, flare

mediated mainly by H1 and H2 receptors
involves a small red spot at the center of an intradermal injection of histamine surrounded by a red edematous wheal

Question 3

histamine receptors and effects

H1 vs. H2

Answer 3

H1
found in smooth muscle
Gq, increase IP3/DAG
prototype antagonist: diphenhydramine
effect: pain and itching, bronchoconstriction, vasodilation, local edema

H2
found in stomach, heart, mast cells
Gs, increase cAMP
prototype antagonist: cimetidine
effect: gastric acid secretion, cardiac stimulation

H3
found in nerve endings, CNS
Gi, decrease in cAMP
prototype antagonist: clobenpropit
effect: modulation of other NTs

H4
found in leukocytes
Gi, decrease cAMP
effect: leukocyte chemotaxis

Question 4

H1 receptor antagonist
1st generation
competitive pharmacologic block of peripheral and CNS H1 receptors plus alpha- and M-receptor block
anti-motion sickness effect
used for hay fever, angioedema, motion sickness, insomnia, dystonia
side effect: DROWSINESS, blurred vision, dry mouth, urinary retention, anorexia, orthostatic hypotension

Answer 4

diphenhydramine
brompheniramine, chlorpheniramine, cyclizine, meclizine, buclizine, carbinoxamine, dimehydrinate, hydroxyzine, promethazine (anti-emetic), cyproheptadine (for serotonin syndrome)

Question 5

adjunct for Parkinson’s because of significant anti-cholinergic effect

Answer 5

diphenhydramine
brompheniramine, chlorpheniramine, cyclizine, meclizine, buclizine, carbinoxamine, dimehydrinate, hydroxyzine, promethazine (anti-emetic), cyproheptadine (for serotonin syndrome)

Question 6

H1 receptor antagonist
2nd generation
competitive pharmacologic block of peripheral H1 receptors
no autonomic or anti-motion sickness effects
used for hay fever, angioedema, urticaria

Answer 6

cetirizine
loratadine, fexofenadine, desloratadine, terfenadine, astemizole, ebastine

FATAL ARRHYTHMIAS from interaction between azoles/erythromycin and terfenadine/astemizole

Question 7

prodrug of hydroxyzine (carboxylated form)

Answer 7

cetirizine

loratadine, fexofenadine, desloratadine, terfenadine, astemizole, ebastine

Question 8

H2 receptor antagonist
competitive pharmacologic block of H2
used for PEPTIC ULCER DISEASE, Zollinger-Ellison Syndrome, gastroesophageal reflux
side effects: CYP450 INHIBITOR

Answer 8

Cimetidine (side effect: GYNECOMASTIA)

ranitidine, famotidine, nizatidine

Question 9

produced from tryptophan

metabolized by monoamine oxidase

Answer 9

serotonin (5 hydroxytryptamine/5-HT)

Question 10

5 HT1D receptor agonist
causes vasoconstriction
modulates NT release
DRUG OF CHOICE FOR ACUTE MIGRAINE, CLUSTER HEADACHE
side effect: paresthesia, dizziness, chest pain, coronary vasospasm

Answer 10

sumatriptan

almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, zolmitriptan