Pharm - Antihistamines Flashcards
What are the sites of histamine storage?
Secretory granules of mast cells and basophils - turned over slowly
GI mucosa - rapid turnover
Nerve endings in brain - more rapid turnover
Cells of rapidly growing tissues - more rapid turnover
What are the functions of histamine?
Immediate hypersensitivity reactions
Gastric acid secretion
Neurotransmitter
How is histamine degraded?
Mainly methylation
Products inactive, secreted in urine
Disappears from serum in minutes
What is interesting about histamine receptors?
Receptors have significant basal activity
Approved antagonists are inverse agonists
What pathway do each of the histamine receptors use?
H1 - G protein –> PLC –> IP3 –> Ca and PLA2
H2 - Gs –> cyclase –> cAMP
H3 - Gi,o decreases Ca
H4 - Gi,o increases Ca by beta gamma paths, decrease cAMP
What are the main functions of specific histamine receptors?
H1 - antagonists block effects of histamine release in allergic rxns
H2 - antagonists modify gastric acid secretion
What are potential targets for therapy with H3 receptors?
Narcolepsy and Parkinson’s
ADHD
Alzheimer’s and schizophrenia
What are potential drug considerations with H4 receptors?
Allergic rhinitis
Atopic dermatitis
Inflammatory and autoimmune disorder
When are histamine AGONISTS used?
H1 - tests of bronchial reactivity, nerve integrity, positive control in skin tests for allergy
H2 - test gastric secretory function
What is an example of first generation and second generation H1 receptor antagonists and what are their side effects?
First - diphenhydramine - sedation, GI disturbance, anti cholinergic (muscarinic) activity
Second - loratadine - fewer side effects (poor ability to cross BBB)
Also some drug allergy, teratogenic effects and acute poisoning in children
What are the therapeutic uses of H1 antagonists?
Diseases of allergy - but ineffective in bronchial asthma and systemic anaphylaxis (but can be adjunct)
Motion sickness due to anti cholinergic
Urticaria
Nausea
Partial effectiveness in hypersensitivity rxns
What is cromolyn sodium?
Inhibits mast cell activation (esp pulm)
Inhaled for prophylactic treatment in bronchial asthma
May take weeks to develop effect, ineffective in many people, not useful for acute attacks
What is ranitidine?
H2 receptor antagonist
Absorbed from GI tract
Generally mild side effects - can have drug interxns due to p450 inhibition
What are the therapeutic uses of h2 receptor antagonists?
Treats peptic ulcers and GERD
Can prevent ulceration
Zollinger Ellison syndrome - elevated production of gastrin due to non beta cell tumor in pancreas
Any other states where increased acid production not desired
