Histamine, Serotonin, and their antagonists

Question 1

Autocoids regulate aspects of GI, uterine, and renal function, and they are involved in what pathologic conditions?

Answer 1

Pain, fever, inflammation, allergic rxns, thromboembolic disorders.

Question 2

Histamine distribution. What cells is it stored in?

Answer 2

Skin, lungs, GI, nasal mucosa. Stored in mast cells and basophils, paracrine cells of gastric fundus and histaminergic neurons.

Question 3

Mast cell histamine release occurs in response to what?

Answer 3

Certain ANTIGENS and ANAPHYLATOXINS (IgE crosslinking mediates opening of Ca channels, activating enzymes leading to exocytosis, degranulation, and Hist release); certain basic DRUGS (i.e. codeine); chemical or mechanical INJURY.

Question 4

Histamine receptor subtypes H1, H2, H3, H4. For H1 and 2, what’s the distribution?

Answer 4

Smooth muscle, endothelium, brain;

Gastric mucosa, cardiac muscle, mast cells, brain.

Question 5

Physiologic actions of Histamine: Cardiovascular

Answer 5

Immediate bp drop (H1 and H2) due to peripheral vasodilation; inc vasc perm (endothelial cell contraction) causing edema and loss of plasma from circ (H1); direct cardiac effects that’s minor in humans (inc contractility, HR (H2)).

Question 6

Physiologic actions of Histamine: Bronchiolar smooth muscle

Answer 6

Bronchoconstriction (H1); hyperreaction in asthmatics

Question 7

Physiologic actions of Histamine: GI Tract

Answer 7

contraction of intestinal sm muscle, diarrhea (H1); stim’s gastric acid, pepsin, and intrinsic factor secretion (H2)

Question 8

Physiologic actions of Histamine: Nervous system

Answer 8

stimulant of sensory nerve endings, pain (dermis) and itching (epidermis) (H1).

Question 9

3 general ways to reduce the effects of histamine:

Answer 9

Physiologic antagonists (i.e. Epi has opposite sm muscle actions), release-inhibitors (reduce degranulation of mast cells), receptor antagonism.

Question 10

Diphenhydramine: Class, Action

Answer 10

Ethanolamine derivative. Antimuscarinic fx, sedation; popular antihistamines.

Question 11

Tripelennamine: Class, Action

Answer 11

Ethylenediamine derivative. Mod sedating, OTC sleep aid.

Question 12

Meclizine: Class, Action

Answer 12

Piperazine derivative. Anti-motion sickness

Question 13

Promethazine: Class, Action

Answer 13

Phenothiazine derivative. Antimuscarinic effects, marked sedation; antiemetic.

Question 14

Chlorpheniramine: Class, Action

Answer 14

Alkylamine derivatives. Less-sedating, cheap; component of cold meds

Question 15

Loratidine & fexofenadine: 1st or 2nd gen, which is significant how? Longer or shorter acting?

Answer 15

2nd gen antihistamines. Cross BBB poorly compared to first gens, so fewer central effects (no sedation). Longer action, more expensive.

Question 16

Azelastine: Uses, generation 1 or 2?

Answer 16

intranasal spray for allergic rhinitis, ophthalmic soln for allergic conjunctivitis. 2nd gen.

Question 17

Cetirizine: Gen 1 or 2? Rx’d in combo with what for what purpose?

Answer 17

2nd gen antihistamine. Rx’d in combo with decongestant pseudoephedrine hydrochloride.

Question 18

Clinical uses of H1 receptor antagonists

Answer 18

Allergic rxns (effective vs allergic rhinitis, urticaria, conjunctivitis) [largely ineffective for bronchial asthma and colds]. Motion sickness, n/v of pregnancy, sleep aids.

Question 19

Adverse effects of H1 receptor antagonists

Answer 19

Sedation, anti-muscarinic actions peripherally (blurred vision, dry mouth, urinary retention, constipation), convulsions in kids, allergy (topical use), local anesthesia, rare CV effects (v-tac with piperidines).

Question 20

H2 receptor antagonists: mech of action and clinical uses of Ranitidine and Nizatidine

Answer 20

Compete at H2R on basolateral memb of parietal cells, block gastric acid secretion in response to all stimuli. Used for dyspepsia, duo/gastric ulcers, and hypersecretory conditions (i.e. ZE Syndrome caused by gastrin-secreting tumor).

Question 21

Adverse effects of H2 receptor antagonists

Answer 21

CNS dysfunction (slurred speech, confusion), antiandrogen (Cimetidine), liver tox (Ranitidine), Inhibition of P450 enzymes (Cimetidine).

Question 22

Serotonin distribution

Answer 22

GI (90%), platelets (8%), raphe nuclei of brain stem (2%)

Question 23

Storage and release of serotonin is caused by what?

Answer 23

By mechanical and neuronal stimuli, and reserpine

Question 24

General actions of ergot alkaloids

Answer 24

Powerful hallucinations, powerful and prolonged blood vessel constriction, uterine sm muscle prolonged contracture.

Question 25

Ergotamine: Acts on which HT receptors? Agonist or antagonist? Given for what? S.E.s?

Answer 25

partial agonist at 5-HT1,2 and a-adrenergic receptors. Given for prodrome of migraine. Tox’s include n/v, prolonged vasoconstriction.

Question 26

Methylsergide: Acts on which HT receptors? Agonist or antagonist? Given for what? S.E.s?

Answer 26

partial agonist at 5HT1, antag at 5HT2. Prophy only. Tox’s include GI, inflamm fibrosis, and hallucinations.

Question 27

Triptans: Action. Agonize or antagonize what HT receptors? S.E.s?

Answer 27

Produce vasoconstriction or inhibit release of pro-inflamm neuropeptides from trigem to tx acute migraine. Selective 5HT1B,D agonists. Tox = coronary vasospasm.

Question 28

Ergonovine: Action and use

Answer 28

Sustain uterine stimulation to tx postpartum hemorrhage.

Question 29

Bromocriptine: Agonist or antagonist of what receptor? What does it suppress the secretion of?

Answer 29

D2 agonist, suppresses prolactin secretion from pituitary

Question 30

Pharm actions of 5-HT

Answer 30

Contraction of GI sm muscle (inc tone and facilitate peristalsis, severe diarrhea), carcinoid syndrome (high 5-HIAA in urine); powerful vasoconstrictor in sm muscle in CVS, vasodilator in skel musc and heart, platelet aggregation; nervous system (pain and itching, mood, food, sleep, pituitary secretions).

Question 31

Cyproheptadine: Class(es). Uses. S.E.s

Answer 31

antihistaminic and antiserotinergic. Used for skin allergies (anti H1) and diarrhea of carcinoid (anti-5HT2). S.E.s are sedation and antimuscarinic effects.

Question 32

Ketanserin (not in U.S.): Antag or agonist of 5-HT21,2C receptors? Uses.

Answer 32

selective antag of 5-HT2A,2C receptors. Antihypertensive (relaxes vascular and tracheal sm muscle), antagonizes platelet aggregation.

Question 33

Ondansetron: Receptor agonized or antagonized. Use?

Answer 33

5-HT3 antagonist. Prevention of n/v assoc’d with chemo.