Histamine/antihistamines Flashcards
Where is histamine stored?
3
(1) Vesicles
(2) Mast cells
(3) Basophils
Where is histamine synthesized on demand?
4
(1) Skin
(2) Gastric mucosa
(3) Intestinal mucosa
(4) CNS
When is histamine released?
3
(1) Antigen binding to IgE antibodies on mast cells
(2) Cell damage
(3) Selected drug action such as morphine and curare
Where are H1 receptors found?
3
(1) Smooth muscle
(2) Endothelium
(3) Brain
Where are H2 receptors found?
3
(1) Gastric mucosa
(2) Cardiac muscle
(3) Brain
Where are H3 receptors found?
Presynaptic membranes of the brain
Where are H4 receptors found?
Eosinophils and neutrophils
What are the H1 receptor-mediated effects?
6
(1) Vasodilation of arterioles and precapillary sphincters via NO release
(2) Increased permeability of postcapillary venule (edema)
(3) Bronchoconstriction
(4) Pain and itch
(5) Increased GI contractions
(6) Wakefulness
What are the H2 receptor-mediated effects?
(1) Vasodilation of arterioles and precapillary sphincters
(2) Positive inotropic effect (increased heart contractility)
(3) Positive chronotropic effect (increased heart rate)
(4) Increased gastric acid secretion
(5) Increased pepsin secretion
What is the most important use of therapeutic H2 receptor blockers?
Block gastric acid secretion
What is the histamine triple response?
(1) Vasodilation - localized red spot
(2) Wheal - increased permeability and local edema
(3) Flare or flush - axon reflex vasodilation
What are the major pharmacological actions of first generation antihistamines?
(5)
Desired:
(1) H1-receptor blockade
Undesired (due to nonselectivity):
(2) Muscarinic receptor blockade
(3) Alpha adrenoreceptor blockade (leading to orthostatic hypotension)
(4) Serotonin receptor blockade
(5) Local anesthesia
How is histamine synthesized?
Histidine is converted to histamine by histidine decarboxylase, requiring pyridoxal
What are the first generation antihistamines?
4
(1) Diphenhydramine
(2) Pyrilamine
(3) Hydroxyzine
(4) Promethazine
What is diphenhydramine*?
4
(1) First generation antihistamine
(2) Ethanolamine class
(3) Causes marked sedation
(4) Used to combat motion sickness
* one of two important 1st gen antihistamines
What is pyrilamine?
4
(1) First generation antihistamine
(2) Ethylenediamine class
(3) Causes moderate sedation
(4) Used as OTC sleep aid
What is hydroxyzine*?
3
(1) First generation antihistamine
(2) Piperazine class
(3) Causes marked sedation
* one of two important 1st gen antihistamines
What is promethazine?
3
(1) First generation antihistamine
(2) Phenothiazine class
(3) Causes marked sedation
(4) Used as an anti-emetic
What are the major adverse effects of 1st gen antihistamines?
(7)
(1) Sedation (H1 blockage)
(2) Blurred vision (muscarinic blockage)
(3) Dry mouth (muscarinic blockage)
(4) Excitation and convulsions in children
(5) Constipation
(6) Postural hypotension (α1 blockage)
(7) Drug allergy
What are the second generation antihistamines?
3
(1) Fexofenadine
(2) Loratadine
(3) Cetirizine
What histamine receptors do 2nd gen antihistamines target?
H1 receptors, little effect at other receptors
What is a major pharmacological difference between 1st and 2nd generation antihistamines?
2nd gen antihistamines cause minimal sedation because they do not enter the CNS
What are adverse effects of 2nd gen antihistamines?
2
Very few because of specificity
(1) Risk of QT prolongation
(2) Cardiac arrhythmias
What is terfenadine and why was it removed from the pharm market?
(2)
(1) 2nd gen antihistamine
2) Caused cardiac arrhythmias, so replaced with fexofenadine (metabolite of terfenadine with low risk of arrhythmia
What are therapeutic uses of H1 blockers?
5
(1) Treat allergic reactions (rhinitis and urticaria/hives)
(2) Treat motion sickness with diphenhydramine
(3) Antitussive - diphenhydramine
(4) OTC sleep aids - diphenhydramine and doxylamine
(5) Non-rational treatment of common cold
What are four H2 antagonists?
4
(1) Cimetidine
(2) Ranitidine
(3) Famotidine
(4) Nizatidine
What is the mechanism of action of H2 blockers?
4
Blockage of acid secretion due to (1) histamine, (2) gastrin, (3) vagal stimulation, and (4) cholinomimetics
What are adverse effects of H2 blockers?
6
(1) Diarrhea
(2) Dizziness
(3) Somnolence
(4) Headache
(5) Rash
(6) Liver toxicity with elevated liver enzymes
What are adverse effects of cimetidine?
3
(1) CNS delirium and confusion, particularly in the elderly
(2) Antiandrogenic effects - gynecomastia and galactorrhea, reduction in sperm count and reversible impotence
(3) Blood dyscrasias
What are potential drug interactions of antihistamines?
2
(1) Cimetidine inhibits CYP450-catalyzed drug metabolism pathway, leading to interaction with warfarin and other drugs
(2) Ethanol bioavailability also increased due to inhibition of gastric first-pass metabolism
Wat are H2 blockers used to treat?
4
(1) Peptic duodenal ulcers
(2) Gastric ulcers
(3) Erosive esophagitis (due to GERD)
(4) Hypersecretory conditions (Zollinger-Ellison syndrome - pancreatic tumor secretes excess gastrin, leading to acid production and ulceration)
