Autocoids Flashcards
histamine
beta imidazolylethylamine
histamine metabolism
oxidation
methylation
histamine release inhibition
beta adrenergic agonist/ methylxanthines - increase cAMP - INHIBITION OF RELEASE
histamine release from exocytosed granules require
sodium
H4 agonist
4-methylhistamine
H4 receptors
on basophil, mast cell, eosinophils - chemotaxis- inflammation
Histamine
vasodilation - smaller vessels vasoconstriction - larger arteries and veins flushing capillary permeability increased increased co and heart rate
fall in bp
- persistent slow via h2
- fast short via h1
pulsatile headache
Histamine - vasodilation
H1 - EDRF mediated
H2 - directly
intradermal histamine
triple response
capillary dilation - red spot
increased permeability - wheal
arterioles dilate - flare
isolated heart
H2 mediated stimulation
H1 - negative dromotropic effect
histamine on bronchus
contraction
histamine on intestine
contraction
visceral smooth muscles
H1 - contraction
H2 - may cause relaxation
histamine on glands
increase acid, pepsin
h2 on parietal cells
h2 increase cAMP
activate H K ATPase pump
histamine on sensory nerves, autonomic ganglion, adrenal medulla
stimulated
intracerebral histamine
rise in BP, cardiac stimulation, behavioural arousal, hypothermia, vomiting and ADH release
LTD4 and PAF
asthma
anaphylactic fall in bp
Histamine - role
gastric secretion - H2
hypersensitivity - H1
appetite - brain H1
wakefulness
h2 mediated regulation of: body temperature, cvs, thirst inflammation tissue growth and repair vascular headache
beta histine
selective H1 agonist
meniere disease - vasodilation in ear
histamine liberators
ab:ag reaction
tissue trauma
polymers - dextran, pvp (polyvinyl pyrrolidine)
surface acting agents - tween 80
some bqsic drugs - even some antihistamines
counter acted by H1, (and H2) drugs
antihistamines - actions
blocks - bronchoconstriction, vasodilation of capillaries, vasoconstriction of larger vessels, intestine contraction, ttiple response, hypersensitivity i, motion sickness
sedative (older)
antitussive
anti muscarinic
local anesthesia (membrane stabilization)
fall in bp (iv injection)
antihistamines
route - oral, parenteral metabolism - liver excretion - urine duration of action - 4-6 hours penetrate brain (older ones)
antihistamines
Promethazine Chlorpheniramine Fexofenadine Diphenhydramine Hydroxyzine Dimenhydrinate Triprolidine Pheniramine Cyproheptadine Astemizole Loratadine Cetirizine Mizolastine
antihistamines side effects
Sedation, motor incoordination, fatigue
epigastric distress
anticholinergic side effects
headache
acute overdose of antihistamines
central excitation, tremors, hallucinations, muscular incoordination, flushing, convulsions, hypotension, fever, respiratory and cvs failure
2nd gen H1 antagonist
no sedation, no anticholinergic side effects
also inhibits paf and LTD4
poor antipruritic, antiemetics and antitussive effects
astemizole, terfenadine
inhibit delayed rectifier K channels - prolong qtc - torsades de pointes
fexofenadine
allergic rhinitis - 120mg OD
urticaria - 180 mg OD
rapid absorption
excreted - unchanged - urine, bile
half life - 11-16 hours
loratidine
metabolised by 3A4
t1/2- 17 hr
adr - seizures
urticaria, atopic dermatitis
active metabolite - desloratidine - half dose required; cardiac safety, non interference with psychomotor performance
citrizine
SGA H1
metabolite of hydroxyzine
mild sedation
not metabolised
antiallergy - inhibits release of cytotoxic mediators fro platelets and eosinophils
utricaria, allergic rhinitis, asthma
Levo cetrizine - half dose required
azelastine
topical inhibits histamine release triggered by paf LTD4 downregulate icam-1 t1/2- 24 hour active metabolite - 3A4 side effect- stinging, altered taste
mizolastine
non sedating
allergic rhinitis, utricaria
t1/2 - 10 hrs
SINGLE DOSE
ebastine
converted to carbastine cyp3A4
t1/2 - 10-16 hrs
nasal, skin allergies
some reports of arrhythmias
rupatidine
antihistaminic
paf antagonist
allergic rhinitis
antihistamines - uses
allergic disorders, pruritides (older), common cold, motion sickness, vertigo (cinnarizine, dimenhydrinate), preanesthetic, cough, parkinson, acute muscle dystonia, as sedative, hypnotic, anxiolytic
vertigo
Labyrinthine suppressant- inhibit cholinergic pathway
antihistamines - cinnarizine, dimenhydrinate, diphenhydramine, promethazine
anticholinergic- atropine, hyoscine
antiemetics phenothiazine- prochlorperazine, thiethylperazine
vasodilators- improve blood flow to labyrinthine- nicotinic acid, cidergocrine, betahistine
diuretics - decrease fluid pressure- acetazolamide, thiazide, amiloride
modify the sensation
anxiolytics - diazepam
antidepressants- amitriptyline
corticosteroids
common cold
antihistamines- anticholinergic, sedative action
