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32 Cards in this Set
- Front
- Back
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What are the 8 general principles of Histamines?
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1. Ubiquitous autocoid (Local hormone)
2. No clinical app in treatment of disease 3. Important mediator of immediate allergic and inflammatory reaction 4. Important role in the stimulation of gastric acid secretion 5. Neurotransmitter/ Neuromodulator of brain/gut (Excitatory) 6. Concentrated in blood basophils 7. Concentrated in mast cells 8.Enterochromaffin-like cells in stomach |
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What type of hypersensitivity is histamine most associated?
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Type I - allergen - IgE
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What are the four types of release?
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1. Immunological
2. Chemical - Drugs like morphine and curare stimulate release of histamine (not degranulation) 3. Mechanical Injury - non-specific tissue injury 4. Gastric Stimulation - ECL reslease - swallowed food entering stomach causes this in anticipation |
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Four MOA's of histamine? Four receptors
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H1 - smooth muscle, endothelium, brain
H2 - gastric mucosa, cardiac muscle, mast cells, brain H3 - presynaptic in brain and myenteric plexus (modulates reslease of neurotransmitters) H4 - eosinophils/neutrophils/Tcells |
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Specific Systems: Cardiovascular
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Peripheral vasodilatation
*decrease in blood pressure (H1/H2) *Enhanced vascular permeability (H1) indirect - reflex tachycardia direct - increased contractility and pacemaker activity (H2) - high dose Decreased atrial contractility (H1) - low dose |
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GI
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-Smooth Muscle contraction (H1)
-Gastric Acid Secretion (H2) |
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Bronchiolar Smooth Muscle
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Histamine induced bronchoconstriction
-Bronchial asthma (H1) -Cystic Fibrosis (H1) |
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Other smooth muscles
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Uterine in women susceptible to anaphylacic rxns (H1)
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Nerve Endings
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*Sensory mediated in pain/itching (H1/3)
Modulation of NT relseas in CNS and ENS (H3) with a role in: -ALERTNESS and ATTENTIVENESS |
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Triple Response
(If Histamine is injected) |
Local red spots (vasodilitation)
Wheal due to edema Red irregular flare surrounding wheal (due to stimulation of axon reflex and causing vasodilatation indirectly) |
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Histamine Antagonists
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Epinephrine
Cromolyn Nedocromil |
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Clinical use of Anti-Histamines (histamine H1 receptor blockers)
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Allergic: Rhinitis, Urticaria(hives)
Motion sickness and vestibular disturb (First more effective than second gen) N&V - Pregnancy - Teratogen |
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Toxicity
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-Sedation and anitmuscarinic effets
(newer less than older: periph selectiv) -Paradocical excitation and convulsions in kids with high doses -Postural HTN in older -Allergic responses -Cardiac arrhythmias (2nd gen) -Teratogens (doxylamine/piperazines) |
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Serious Drug Interactions
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Terfenadine/Astemizole (prolonged QT)
in combo iwth ketoconazole, itraconazole, erythromycin Block K channels |
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Diphenhydramine
(H1 antagonist first gen) |
-Urticaria, hay fever, motionsickness
-short half life -VERY SEDATING -inexpensive |
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PromethazineAc
(H1 antag - first gen) |
-Motion sickness
-Antiemetic -MARKED sedation (hypotension) -PO or Suppository |
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Fexofenadine
(H1 antagonist - second gen) |
Product of TERFENADINE, but lacking heart problem
-Little or no sedation (no CNS) -NOT taken with AL/MG antiacids - decrease in bioavalitibity -seasonal allergies/uticaria |
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Loratidine
(H1 antagonist - second gen) |
-Mild sedation
OTC - Claritin -Relief of season allergies |
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Desloratidine
(H1 antagonist - second gen) |
Active metabolite of loratadine
Mild Sedative No difference from loratidine |
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Cetirizine
(H1 antagonist - second gen) |
-Indicated for the relieft of seasonal allergies
-MILD sedation - caution when operating machinery/driving cars |
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Selecting appropriate H1
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-people react differently to each one
-try a few to check em out -first gen - more sedative -second gen - same effectiveness, less sedating |
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H1 - Anticholinergic Activity
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Dimenhydrinate
Diphenhydramine Promethazine (Phenergan) |
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H2 - Antagonists Clinical Uses
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-Gi distrubances, gastric parietal cells
-reduces gastric acid secretion due to histamine, gastrin, and cholinrgic stimulation -Erosive - GERD -Being replaced by PPI for ulcers |
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Four H2 - OTC
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Cimetidine
Ranitidine Famotidine Nizatidine Highly selective for H2, not H1/3 |
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Highest H2 Bioavalibility?
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NIzatidine (75-100%)
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Longest Halflife H2
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Famotidine (2-4 hours increased with renal failure)
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Side effects (5% cimitidine - 1-2 for others) CNS
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CNS - Seen more in elderly, and renal dysfunciton
Cimetidine>others Slurred speech, Delirium, Confused Headache |
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SE: Endocrine
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Gynecomastia(men)
Galactorrhea (women) decreased sperm count reversible impotnce |
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SE: Blood Dyscrasias (Cim>Raniti)
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Granulocytopenia (decreased PMN's nutrophils, basophils, eosinophils)
Thrombocytopenia Neutropenia (most important WBC) Aplastic Anemia (Bone marrow) |
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SE: Liver Toxicity
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reversible cholestasis - cimetidine
reversible hepatitis - ranitidine reversible liver enzymes - famotidine/nizatidine |
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SE: Preg/Nursing
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no harm, but present in breast milk
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Drug Interactions
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Cimetidine - inhibits p450
Increase toxicity of theyphylline, phenytoin and warfarin Famotidine - only durg that does not inhibit first-pass gastirc metabolism of alcohol |
