Histamine and Serotonin Flashcards
What is the source of natural histamine?
Histidine and L-histidine decarboxylase
Where is most histamine in the body found?
~90% is in secretory granules of basophils and mast cells; also GI tract
What are the two major clinical sources of histamine degranulation?
Antigens and anaphylaxitoxins
What kind of protein are histamine receptors? How many subtypes are there?
7TM receptors; 4 subtypes (H1, H2, H3, H4)
Asthma-like symptoms in the lungs are mediated in part by what histamine receptor subtype?
H1
Hypotension due to PCV dilation and edema due to vascular permeability are modified by what histamine receptor subtype?
H1
Itchiness and pain due to sensitization of afferent nerve terminals involves what histamine receptor subtype?
H1
What two effects are mediated by the H2 receptor?
Increased gastric acid secretion and (minor) increase in heart rate/contractility
What are the three major strategies to counteract histamine’s effects?
Direct drug administration (epinephrine), prevent mast cell degranulation, deliver a histamine receptor antagonist
What general properties are common to antihistamines?
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
What other receptors are affected by antihistamines?
Cholinergic, alpha-adrenergic, and serotonin
What is the oldest/classic antihistamine? What is its major side effect?
Diphenhydramine, heavily sedating
What antihistamines are most commonly sold as sleep aids?
Tripelennamine (an ethylenediamine derivative)
The motion sickness action of cyclizines is due to activity on what receptor type?
Muscarinic
What antihistamine has significant anti-alpha-adrenergic activity?
Promethazine
What ‘daytime’ antihistamine is used in many cold medicines?
Chlorpheniramine
What 1st generation property of antihistamines is lost in the second generation? What side effect does this limit?
CNS entry is minimized, limiting or removing sedative effects
What is the first line therapy for allergic rhinitis and conjunctivitis? What form of drug is it?
azelastine; 2nd generation antihistamine prodrug metabolized by P450
What are the major clinical uses for antihistamines?
Allergic reactions (allergies, insect stings, but not colds), XXXXXXXXXXXXXX
What are the major adverse effects of antihistamines?
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)
What are the 4 major H2 receptor antagonists? What are the two major indications?
Cimetidine (1st, Tagamet), ranitidine, famotidine, and nizatidine; dyspepsia and ulcer formation
What H2 receptor antagonist inhibits cytochrome P450s?
Cimetidine
What side effects are common with H2 receptor antagonists?
cytP450 inhibition, CNS dysfunction, cimetidine antiandrogen (gynecomstaia, male impotence), and ranitidine liver toxicity
What is the major precursor to serotonin? The major product found in the pineal gland?
Tryptophan -> Serotonin -> Melatonin
Most serotonin receptors are what type of protein? Which is a ligand-gated channel?
7TM receptors; 5HT3
What 3 systems are most affected by serotonin? How?
GI: contraction/peristalsis; CV: vasoconstriction, platelet aggregation; CNS: afferent receptor sensitization, mood, sleep, etc
What 3 compounds are serotonin receptor antagonists?
Ketanserin (anti-hypertensive), Ondansetron (5HT3, nausea/vomiting preventive), Cyproheptadine (5HT2 and H1, skin allergies and carcinoid symdrome diarrhea)
What two compound families are mixed agonist/antagonists of serotonin?
Rye ergots,
What are the three clinically useful ergots?
Ergonovine, Ergotamine, and Bromocriptine/pergolide
What is the major use of bromocriptine?
Hyperprolactinemia?
What are the 4 major non-ergot alkylaoids? What is their class?
Sumatriptan, naratriptan, rizatriptan, and zolmitriptan; Triptans
What is the major indication for a triptan prescription?
Migraine; 70-80% have relief in 1-2 hours
What is the role of a non-histaminergic neuron in histamine signaling?
It has H3 receptors that regulate neurotransmitter release , geneerally inhibitory to NE, Ach, 5HT, DA, etc
What is the effect of histamine on a histaminergic neuron?
Histamine uptake regulates histamine synthesis and release within the same neuron
What histamine receptor subtypes are found in neurons? What are their general effects?
H1, H2, H3; increased vigilance/attention/working memory/sensory gating and decreased feeding
