Histamine, Serotonin and their agonists

Question 1

physiologic actions of HA

Answer 1

• immediate fall in BP due to peripheral vasodilation (most imporant vascular effect in humans!) –> extensive systemic release can produce sharp drop in BP and anaphylactic shock
• endotheial cell contraction –> increase in vascular permeability –> edema
• bronchoconstriction (hyper-rxn in asthmatics
• diarrhea
• secretion of gastic acid, pepsin and intrinsic factor
• stimulant of sensory nerve ending –> pain and itching
• circadian rhythms, wakefulness

Question 2

diphenydramine (benadryl)

Answer 2

• H1 receptor antagonist
• popular antihistamines (excedrin PM, tylenol PM, dramamine)
• anti-muscarinic effects, sedating

Question 3

tripelennamine (PBZ)

Answer 3

• H1 receptor antagonist
• OTC sleep aid

Question 4

cyclizine (dramamin II, antivert)

Answer 4

• H1 antagonist
• anti motion sickness

Question 5

promethazine

Answer 5

• H1 antagonist
• antiemetic
• antimuscarinic effects, marked sedation

Question 6

chlorpheniramine (Chlor-Trimeton, Dimetane)

Answer 6

• H1 antagonist
• component of “cold” meds
• less sedating

Question 7

Loratidine (claritin) and fexofenadine (Allegra)

Answer 7

• 2nd generation antihistamines that don’t cross BBB and have few CNS effects (no sedation)
• allergic rhinitis

Question 8

H1 receptor antagonists (clinical uses and adverse effects)

Answer 8

Clinical Uses

• allergies (allergic rhinitis, urticaria, conjunctivitis)
• **largely ineffective for bronchial asthama or colds
• motion sickness
• nausea and vomiting of pregnancy
• sleep aids

Adverse effects

• sedation, impaired cognitive function
• anti-muscarinic effects (blurred vision, dyr mouth, urinary retention, constipation)
• poisoning (esp kids), convulsions
• local anesthesia
• ventricular tachy

Question 9

Cimetidine

Answer 9

• H2 receptor antagonist
• blocks gastric acid secretion
• used for dyspepsia, duodenal and gastric ulcers, hypersecretory conditions
• adverse side effects:

inhibits P450 oxidative enzymes –>potentiates the actions of other drugs

antiandrogen (gynecomastia in men; impotence)

CNS dysfuncion possible

Question 10

Ranitidine

Answer 10

• H2 receptor antagonist
• blocks gastric acid secretion
• used for dyspepsia, duodenal and gastric ulcers, hypersecretory conditions
• liver toxicity
• CNS dysfunction possible (slurred speech, confusion)

Question 11

Famotidine

Answer 11

• H2 receptor antagonist
• inhibits gastric acid secretion
• used for dyspepsia, gastric and duodenal ulcers, hypersecretory conditions
• CNS dysfunction possible

Question 12

Nizatidine

Answer 12

• H2 antagonist
• inhibits gastic acid secretion
• used to treat dyspepsia, gastric and duodenal ulcers, hypersecretory conditions
• CNS dysfunction possible

Question 13

pharmocologic actions of 5-HT (serotonin)

Answer 13

• contraction of GI smooth mm
• carcinoid syndrome (enterochromaffin cell tumors that release large amounts of 5-HT) –> diarrhea
• vasodilation in skeletal mm and heart
• platelet aggregation
• peripheral NS: stimulates nociceptive nerve endings (pain and itching)
• central NS: involved in food intake, mood, sleep
• pre-synaptic activation of receptors inhibits raphe cell firing/serotonin release

Question 14

cyproheptadine

Answer 14

• antihistaminic and antiserotinergic
• used for skin allergies (anti-H1: urticaria), diarrhea of carcinoid (anti-5HT)
• side effects: anti-muscarinic and sedation

Question 15

Ketanserin

Answer 15

• selective 5HT2A,2C antagonist, also alpha1 adrenorecptor and H1 receptors
• used as antihypertensive and antagonizes platelet aggregation

**think Ke= Kellsey –> cardio stuff

Question 16

Odansetron

Answer 16

• 5HT3 antagonist
• prevents nausea and vomiting associated with chemo

**think Odansetron –> Onco

Question 17

physioloic actions of ergot alkaloids

Answer 17

• powerful hallucinogens
• blood vessel constriction of vascular smooth muscle
• contraction of uterine smooth muscle

Question 18

Ergotamine

Answer 18

• ergot alkaloid
• partial agonist of 5HT1,2 receptors, antagonist and agonist at alpha-adrenergic receptors
• used to treat migraines
• toxicities: N and V, vasoconstriction

Question 19

methysergide

Answer 19

• ergot alkaloid
• agonist/antagonist of 5HT receptors
• prophalyxis for migraines
• toxicities = GI disturbances, inflammatory fibrosis of chronic use, PTs must have drug holidas

Question 20

ergonovine

Answer 20

• ergot alkaloid
• used for postpartum hemorrhage (sustains uterine stimulation)

Question 21

bromocriptine

Answer 21

• ergot alkaloid
• dopamine agonist
• used for hyperprolactinemia

Question 22

Triptans

Answer 22

• non-ergot 5HT analogs
• selective 5HT1B,D agonists
• used to treat acute migraines

Question 23

Physiologic actions of HA on lungs, vascular smooth muscle, vascular endothelial cells, nerves, stomach, CNS

Answer 23

• lungs: bronchoconstriction –> allergic asthma
• vascular smooth mm: dilation –> rubor
• vascular endothelium: contraction and separation –> edema, wheal response
• nerves: sensitization of afferent terminals –> itchiness, pain
• stomach: gastric acid secretion –> heartburn, peptic ulcer disease (H2)
• CNS: wakefulness