Histamine, serotonin, & ergot alkaloids

Question 1

Diphenhydramine

Answer 1

• 1st gen H₁ antihistamine
• MOA
• competitive antagonism/inverse agonism at H₁ receptors
• Effects
• reduces or prevents histamine effects on smooth muscle, immune cells
• blocks muscarinic and α adrenoceptors
• highly sedative
• Clinical
• IgE immediate allergies, esp. hay fever, urticaria
• sedative, antiemetic, anti-motion sickness uses
• Kinetics, tox, int.
• oral, parenteral, duration 4-6h
• tox: sedation when used in hay fever, muscarinic blockade symptoms, orthostatic hypotension
• int: additive sedation with other sedatives including alcohol, some CYP2D6 inhibition, may prolong action of some β blockers

Question 2

Cetirizine, loratadine

Answer 2

• 2nd gen H₁ antihistamine
• MOA
• competitive antagonism/inverse agonism at H₁ receptors
• Effects
• reduces or prevents histamine effects on smooth muscle, immune cells
• Clinical
• IgE immediate allergies, esp. hay fever, urticaria
• Kinetics, tox, int.
• oral, duration 12-24h
• tox: sedation and arrythmias in overdose
• int: minimal

Question 3

Sumatriptan

Answer 3

• MOA
• partial agonist at 5-HT_1B/1D receptors
• Effects
• not fully understood, may reduce release of calcitonin gene-related peptide and perivascular edema in cerebral circulation
• Clinical
• migraine and cluster headache
• Kinetics, tox, int.
• oral, nasal, parenteral, duration 2h
• tox: paresthesias, dizziness, coronary vasoconstriction
• int: additive with other vasoconstrictors

Question 4

Ondansetron

Answer 4

• MOA
• 5-HT₃ antagonism in gut and CNS
• Effects
• extremely effective in preventing chemotherapy-induced and postop nausea & vomiting
• Clinical
• first-line agent in cancer chemotherapy, also useful for postop emesis
• Kinetics, tox, int.
• usually given IV, but orally active in prophylaxis, 4-9h duration
• very low toxicity but may slow colonic transit

Question 5

Ergotamine

Answer 5

• Vasoselective ergot alkaloid
• MOA
• mixed partial agonist effects at 5-HT₂ and α adrenoceptors
• Effects
• marked smooth muscle contraction but blocks α-agonist vasoconstriction
• Clinical
• migraine, cluster headache
• Kinetics, tox, int.
• oral, parenteral, duration 12-24h
• tox: prolonged vasospasm causing angina, gangrene; uterine spasm

Question 6

Ergonovine

Answer 6

• Uteroselective ergot alkaloid
• MOA
• mixed partial agonist effects at 5-HT₂ and α adrenoceptors
• Effects
• same as ergotamine, some selectivity for uterine smooth muscle
• Clinical
• postpartum bleeding, migraine headache
• Kinetics, tox, int.
• oral, parenteral, duration 2-4h
• tox: same as ergotamine