Antihistamines Flashcards
(27 cards)
1
Q
Histamine Overview
A
- Biologically active amine
- Hydrophilic
- Unevenly distributed in animal kingdom
2
Q
Histamine Synthesis
A
- Histidine converted to Histamine via L-histidine decarboxylase
3
Q
Histamine Metabolism
A
- Ring Methylation: form N-methylhistamine via histamine N-methyltransferase followed by oxidative deamination to N-methylimidazole acetic acid by MAO
- Oxidative Deamination and conjugation to ribose via nonspecific diamine oxidase yielding imidazoleacetic acid riboside
- Excreted in urine
4
Q
Major Source of Histamine
A
- Chief storage site = mast cells
- In blood: basophils: slow turnover rate
- Non-mast cells: epidermis, gastric mucosa, neurons within the CNS: rapid turnover rate
5
Q
Immunologic Histamine Release
A
- IgE bind and activate mast cells leading to immediate hypersensitivity reaction and allergic response
- Prostaglandins and leukotrienes are also mast cell mediators
6
Q
Non-immunologic Release of Histamine
A
- Organic bases
- Tubocurarine, succinylcholine, morphine
- Kallidin and substance P
- Polymyxin B
- Anaphylotoxins: C3a and C5a
- Inflammatory mediators
- Gastric Enterochromafin like cells: ACh and Gastrin mediate histamine release
7
Q
H1 Receptor
A
- Smooth muscle, endothelium, brain
- Gq
8
Q
H2 Receptor
A
- Gastric mucosa, cardiac muscle, mast cells, brain
- Gs
9
Q
H3 Receptor
A
- Presynaptic:brain, myenteric plexus
- Gi
10
Q
H4 Receptor
A
- Eosinophils, Neutrophils, and CD4 T-Cells
- Gi
11
Q
CV Effects of Histamine: Blood Vessels
A
- Vasodilation, Decreased BP, Flushing
- Reflex tachycardia
- Indirect: small doses of histamine—H1 receptor on endothelium = release of NO and Prostacyclin
- Direct: Higher dose of histamine—H2 receptor on VSMC
- Increased capillary permeability: H1 mediated, contraction of endothelial cells, and responsible for urticaria
12
Q
CV Effects of Histamine: Heart
A
- Increased HR and Contraction
- Indirect: vasodilation —> reflex
- Direct: H2 receptors on cardiac muscle
13
Q
Lung Effects of Histamine: Smooth Muscle
A
- Bronchoconstriction in asthmatics: H1 mediation on smooth muscle
14
Q
GI Effects of Histamine
A
- Increased gastric acid secretion
15
Q
Neural Effects of Histamine
A
- Sensory nerve stimulation: pruritus and pain and itching: H1 mediated
- Neurotransmitter in CNS: Increases wakefulness and inhibits appetite via H1
16
Q
Cutaneous Effects of Histamine
A
- Triple response
- Red Spot: Vasodilation (H1 and H2)
- Flare: Axon reflex and indirect vasodilation (H1)
- Wheal: edematous exudation and capillary permeability (H1)
17
Q
Histamine Antagonists
A
- Physiological antagonists
- Release inhibitors
- Histamine receptor antagonists
18
Q
H1 Receptor Antagonists
A
- First generation: Chlorpheniramine, Diphenhydramine, Tripelennamine, Hydroxyzine, Promethazine
- Second generation: Loratadine, Fexofenadine, Cetirizine, Azelastine
19
Q
Pharmacokinetics: H1 Antagonists
A
- Rapidly absorbed, peak blood concentrations in 1-2 hrs
- Widely distributed throughout body: 1st generation rapidly enters CNS
- Extensive metabolism by microsomal systems in liver
- Several 2nd generation agents metabolized by CYP3A4
20
Q
H1 Antagonist Effects
A
- Inhibit more rapid vasodilator effects mediated by H1 activation on endothelial cells
- Strongly block increased capillary permeability and formation of edema and wheal
- Partially block histamine induced increase in HR by blocking H1 receptor mediated arterial VD
- Little reduction in bronchoconstriction
- No gastric acid suppression
- Some relief from atopic and contact dermatitis
- Suppress both flare component of triple response and itching caused by intradermal injection
- Antimuscarinic Effects and motion sickness prevention
21
Q
H1 Antagonist 1st Generation ADR’s
A
- CNS Stimulation at conventional doses
- CNS depression at therapeutic doses, potentiated by alcohol and CNS depressants
- Antimuscarinic effects: dry mouth and urinary retention
- GI: nausea, vomiting, diarrhea or constipation, anorexia
22
Q
H1 Antagonist Indications
A
- Acute rhinitis, urticaria, conjunctivitis
- Systemic anaphylaxis
- Motion sickness prophylaxis (1st Generation: dimenhydrinate, promethazine)
- Sedation
23
Q
H2 Receptor Antagonists
A
- Ranitidine, Famotidine, Nizatidine, Cimetidine
24
Q
H2 Receptor Antagonists: GI Effects
A
- Decreased Gastric Acid Secretion by inhibition of H2 receptors on parietal cells
25
H2 Receptor Antagonists: Pharmacokinetics
1. Significant renal excretion
2. Cimetidine inhibits CYP450
3. Increased gastric pH may alter vitamin/mineral absorption
26
H2 Receptor Antagonists: ADR’s
1. HA, GI, Fatigue, Drowsiness
2. Cytopenias and CNS (rare)
27
H2 Receptor Antagonists: Indications
1. Promote peptic and duodenal ulcer healing
2. Treat uncomplicated GERD
3. Prophylaxis of stress ulcers
