Histamine Flashcards
Omalizumab
MOA: decrease amount of antigen specific IgE that normally binds to and sensitized mast cells
It is an IgG antibody for which the antigen is the FC region of IgE
“Anti-body antibody” and binds tight to free IgE in ciruclation to form omalizumab IgE complex
Administration: Subq
Adverse effects: injection site reaction and anaphylaxis after first dose and in some cases> 1 year after treatment initiation
Therapeutic use: patients which severe poorly controlled asthma and severe concomitant allergic rhinitis
Pharmacology of H1 Antagonists
Reversible competitive antagonism of H1 receptors in periphery and CNS and inverse agonist because reduce activity of receptor and compete with histamine
Effects:
Inhibit capillary permeability
Suppress immediate hypersensitivity reaction
No effect on blood pressure
No effect on bronchoconstriction
Suppress itching
CNS: 1st generation cause sedation and sometimes stimulation in children and treat motion sickness
Peripheral and central anticholinergic effect–> 1st gen cause dry mucus membranes and urinary retention and atropine like effects (inhibit response to Ach via blockade of muscarinic receptors)
Local anesthetic effect–> block nerve conduction with first generation
Pharmacokinetics of H1 antagonist
Oral administration- rapid absorption and peak at 1-2 hours, topical preparations, nasal preparations
Widely spread–> 2nd generation less likely to Exeter brain
Extensive liver metabolism:
2nd gen—> CYP45s and have active metabolites (Terfenadine to fexofenadine, Loratadine to desloratadine, Hydroxyzine to Cetirizine)
Toxicity of H1 antagonist
Sedation—> CNS effect due to inhibition of central H1 effect and central anticholinergic effect
2nd generation with most sedative effect is Cetirizine but most have none
First generation can elicit paradoxical NS stimulation in children with high doses
GI Side effects: loss of appetite, nausea, vomiting, GI distress and rare cases cause increased appetite and weight gain (H1 effect blocked)
Anti-cholinergic side effects–> peripheral muscarinic receptors with 1st generation like dry mouth and respirator passagesand urinary retention
Major CV toxicity: second generation (Terfenadine and astemizole)- cause prolonged QT interval and polymorphic ventricular contractions and most likely to occur with increased dosage and in combination with other drugs that inhibit P450 metabolism
General uses of H1 Antagonist
Allergies- acute types that present with symptoms of rhinitis, urticaria, conjunctivitis
Seasonal allergies but drugs are less effective if–> allergens abundant and exposure prolonged and nasal decongestion prominent
First generation H1 antagonists
Chlorpheniramine- less prone to cause drowsiness
Diphenhydramine- profound sedation
Second generation H1 antagonist
Fexofenadine (Allegra)
Loratadine( Claritin)
Desloratadine (Clarinex)
Cetirizine (Zyrtec) higher incidence of sedation compared to other 2nd generation
Motion sickness treatment
Involve muscarinic cholinergic transmission
Promethazine
Dimenhydrinate
Diphenhydramine (Benadryl)
Other clinical uses
Diphenhydramine- non prescription sleeping tablets
Vestibular disturbance- dimenhydrinate
Chemotherapy induce nausea- promethazine
Early stage of Parkinson’s Disease- diphenhydramine
H2 Receptor Antagonist Uses
Relief of symptoms of peptic ulcer disease
Prevent occurrence of stress ulcers and promote healing of gastric and duodenal ulcers
GERD (Major use)
peptic ulcer secondary to Helicobacter pylori infection
Gastric injury caused by NSAID
Goals: relieve symptoms, enhance ulcer healing in affected mucosa and prevention of recurrence
H2 Antagonist Pharmacology
Reversible competitive inhibitors on basolateral membrane of parietal cells
Act as inverse agonist (binds to receptor and produces opposite effect of agonist but receptor must have constitutive activity for drug to be inverse agonist)
Inhibit basal gastric acid secretion and nocturnal gastric acid secretion
Reduce volume of gastric acid and H+ concentration
Oral administration-rapid
Small amount metabolized by liver and excreted by kidney
H2 Antagonist Side Effects
Low incidence (except Cimetidine)
More common minor side effects- diarrhea, headache, drowsiness
Less Common- CNS effects of confusion, slurred speech, delirium and happens with IV administration in elderly patient
Drugs that inhibit gastric acid secretion alter bioavailability of other drugs
Cimetidine inhibits P450 metabolism
Ranitidine also inhibits P450 but with 10% of affinity of cimetidine
This prolongs half-life of other drugs like warfarin with, phenytoin, theophylline, propranolol
Cimetidine
H2 antagonist
Long term uses at high doses decrease testosterone binding and inhibits a CYp enzyme that hydroxylates estradiol
Gynacomastia and reduced sperm count and impotence
Potency of H2 Antagonists
Potency:
Famotidine> Nizatidine= Ranitidine> Cimetidine
Side effects for first three are much less than Cimetidine
All block stimulatory effects of histamine on acid secretion from parietal cells
Chromolyn Sodium
Inhaled anti-inflammatory agent used in asthma (inhibit mast cell release of histamine)
MOA: stabilize mast cell membrane to prevent release of histamine and degranulation
ROute of Administration: inhalation, oral, nasal, opthalmic
Therapeutic uses: chronic control of asthma and prophylaxis of bronchospasm, opthalmic for conjunctivitis, nasal for allergies, organ for systemic mastocytosis, Off label use for food allergy and irritable bowel syndrome
