Histamine, Serotonin, and their antagonists Flashcards
Autocoids regulate aspects of GI, uterine, and renal function, and they are involved in what pathologic conditions?
Pain, fever, inflammation, allergic rxns, thromboembolic disorders.
Histamine distribution. What cells is it stored in?
Skin, lungs, GI, nasal mucosa. Stored in mast cells and basophils, paracrine cells of gastric fundus and histaminergic neurons.
Mast cell histamine release occurs in response to what?
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.
Histamine receptor subtypes H1, H2, H3, H4. For H1 and 2, what’s the distribution?
Smooth muscle, endothelium, brain;
Gastric mucosa, cardiac muscle, mast cells, brain.
Physiologic actions of Histamine: Cardiovascular
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)).
Physiologic actions of Histamine: Bronchiolar smooth muscle
Bronchoconstriction (H1); hyperreaction in asthmatics
Physiologic actions of Histamine: GI Tract
contraction of intestinal sm muscle, diarrhea (H1); stim’s gastric acid, pepsin, and intrinsic factor secretion (H2)
Physiologic actions of Histamine: Nervous system
stimulant of sensory nerve endings, pain (dermis) and itching (epidermis) (H1).
3 general ways to reduce the effects of histamine:
Physiologic antagonists (i.e. Epi has opposite sm muscle actions), release-inhibitors (reduce degranulation of mast cells), receptor antagonism.
Diphenhydramine: Class, Action
Ethanolamine derivative. Antimuscarinic fx, sedation; popular antihistamines.
Tripelennamine: Class, Action
Ethylenediamine derivative. Mod sedating, OTC sleep aid.
Meclizine: Class, Action
Piperazine derivative. Anti-motion sickness
Promethazine: Class, Action
Phenothiazine derivative. Antimuscarinic effects, marked sedation; antiemetic.
Chlorpheniramine: Class, Action
Alkylamine derivatives. Less-sedating, cheap; component of cold meds
Loratidine & fexofenadine: 1st or 2nd gen, which is significant how? Longer or shorter acting?
2nd gen antihistamines. Cross BBB poorly compared to first gens, so fewer central effects (no sedation). Longer action, more expensive.
Azelastine: Uses, generation 1 or 2?
intranasal spray for allergic rhinitis, ophthalmic soln for allergic conjunctivitis. 2nd gen.
Cetirizine: Gen 1 or 2? Rx’d in combo with what for what purpose?
2nd gen antihistamine. Rx’d in combo with decongestant pseudoephedrine hydrochloride.
Clinical uses of H1 receptor antagonists
Allergic rxns (effective vs allergic rhinitis, urticaria, conjunctivitis) [largely ineffective for bronchial asthma and colds]. Motion sickness, n/v of pregnancy, sleep aids.
Adverse effects of H1 receptor antagonists
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).
H2 receptor antagonists: mech of action and clinical uses of Ranitidine and Nizatidine
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).
Adverse effects of H2 receptor antagonists
CNS dysfunction (slurred speech, confusion), antiandrogen (Cimetidine), liver tox (Ranitidine), Inhibition of P450 enzymes (Cimetidine).
Serotonin distribution
GI (90%), platelets (8%), raphe nuclei of brain stem (2%)
Storage and release of serotonin is caused by what?
By mechanical and neuronal stimuli, and reserpine
General actions of ergot alkaloids
Powerful hallucinations, powerful and prolonged blood vessel constriction, uterine sm muscle prolonged contracture.
