Histamine and Serotonin

Question 1

What is the source of natural histamine?

Answer 1

Histidine and L-histidine decarboxylase

Question 2

Where is most histamine in the body found?

Answer 2

~90% is in secretory granules of basophils and mast cells; also GI tract

Question 3

What are the two major clinical sources of histamine degranulation?

Answer 3

Antigens and anaphylaxitoxins

Question 4

What kind of protein are histamine receptors? How many subtypes are there?

Answer 4

7TM receptors; 4 subtypes (H1, H2, H3, H4)

Question 5

Asthma-like symptoms in the lungs are mediated in part by what histamine receptor subtype?

Answer 5

H1

Question 6

Hypotension due to PCV dilation and edema due to vascular permeability are modified by what histamine receptor subtype?

Answer 6

H1

Question 7

Itchiness and pain due to sensitization of afferent nerve terminals involves what histamine receptor subtype?

Answer 7

H1

Question 8

What two effects are mediated by the H2 receptor?

Answer 8

Increased gastric acid secretion and (minor) increase in heart rate/contractility

Question 9

What are the three major strategies to counteract histamine’s effects?

Answer 9

Direct drug administration (epinephrine), prevent mast cell degranulation, deliver a histamine receptor antagonist

Question 10

What general properties are common to antihistamines?

Answer 10

rapid absorption (1-2 hrs), systemic dispersion, ready entry to CNS (1st gen especiially), rapid microsomal metabolism in liver, actions not specific to H1-receptor blockade, non-prescription analgesic/decongestant use

Question 11

What other receptors are affected by antihistamines?

Answer 11

Cholinergic, alpha-adrenergic, and serotonin

Question 12

What is the oldest/classic antihistamine? What is its major side effect?

Answer 12

Diphenhydramine, heavily sedating

Question 13

What antihistamines are most commonly sold as sleep aids?

Answer 13

Tripelennamine (an ethylenediamine derivative)

Question 14

The motion sickness action of cyclizines is due to activity on what receptor type?

Answer 14

Muscarinic

Question 15

What antihistamine has significant anti-alpha-adrenergic activity?

Answer 15

Promethazine

Question 16

What ‘daytime’ antihistamine is used in many cold medicines?

Answer 16

Chlorpheniramine

Question 17

What 1st generation property of antihistamines is lost in the second generation? What side effect does this limit?

Answer 17

CNS entry is minimized, limiting or removing sedative effects

Question 18

What is the first line therapy for allergic rhinitis and conjunctivitis? What form of drug is it?

Answer 18

azelastine; 2nd generation antihistamine prodrug metabolized by P450

Question 19

What are the major clinical uses for antihistamines?

Answer 19

Allergic reactions (allergies, insect stings, but not colds), XXXXXXXXXXXXXX

Question 20

What are the major adverse effects of antihistamines?

Answer 20

Sedation, anti-muscarinic (blurred vision, dry mouth, urinary retention), poisoning in children (high CNS activity), Allergy (esp. topicals), Local anesthesis, and ventricular tachycardia (piperidines only)

Question 21

What are the 4 major H2 receptor antagonists? What are the two major indications?

Answer 21

Cimetidine (1st, Tagamet), ranitidine, famotidine, and nizatidine; dyspepsia and ulcer formation

Question 22

What H2 receptor antagonist inhibits cytochrome P450s?

Answer 22

Cimetidine

Question 23

What side effects are common with H2 receptor antagonists?

Answer 23

cytP450 inhibition, CNS dysfunction, cimetidine antiandrogen (gynecomstaia, male impotence), and ranitidine liver toxicity

Question 24

What is the major precursor to serotonin? The major product found in the pineal gland?

Answer 24

Tryptophan -> Serotonin -> Melatonin

Question 25

Most serotonin receptors are what type of protein? Which is a ligand-gated channel?

Answer 25

7TM receptors; 5HT3

Question 26

What 3 systems are most affected by serotonin? How?

Answer 26

GI: contraction/peristalsis; CV: vasoconstriction, platelet aggregation; CNS: afferent receptor sensitization, mood, sleep, etc

Question 27

What 3 compounds are serotonin receptor antagonists?

Answer 27

Ketanserin (anti-hypertensive), Ondansetron (5HT3, nausea/vomiting preventive), Cyproheptadine (5HT2 and H1, skin allergies and carcinoid symdrome diarrhea)

Question 28

What two compound families are mixed agonist/antagonists of serotonin?

Answer 28

Rye ergots,

Question 29

What are the three clinically useful ergots?

Answer 29

Ergonovine, Ergotamine, and Bromocriptine/pergolide

Question 30

What is the major use of bromocriptine?

Answer 30

Hyperprolactinemia?

Question 31

What are the 4 major non-ergot alkylaoids? What is their class?

Answer 31

Sumatriptan, naratriptan, rizatriptan, and zolmitriptan; Triptans

Question 32

What is the major indication for a triptan prescription?

Answer 32

Migraine; 70-80% have relief in 1-2 hours

Question 33

What is the role of a non-histaminergic neuron in histamine signaling?

Answer 33

It has H3 receptors that regulate neurotransmitter release , geneerally inhibitory to NE, Ach, 5HT, DA, etc

Question 34

What is the effect of histamine on a histaminergic neuron?

Answer 34

Histamine uptake regulates histamine synthesis and release within the same neuron

Question 35

What histamine receptor subtypes are found in neurons? What are their general effects?

Answer 35

H1, H2, H3; increased vigilance/attention/working memory/sensory gating and decreased feeding