Autocoids and therapy of migraines Flashcards
histamine releasers
Morphine, d-tubocurarine, vancomycin, succinylcholine
Heat, cold, exposure to sunlight & X-rays
Insect bites/ stings, venoms
*** may lead to anaphylaxis, side effects, allergies
anaphylactic shock
bronchospasms, angioneurotic edema, and hypotension (due to release, and effects of histamine)
drug of choice against anaphylactic shock
epinephrine
Histamine release inhibitors
β2 agonist- Albuterol, Epinephrine
Mast cell membrane stabilizers- sodium cromoglycate
***Used in bronchial asthma
H1 blockers are used in
allergic conditions
H2 blockers are used in
peptic ulcer
H1 receptor mediated actions
Smooth muscles: bronchoconstriction
Exocrine glands: ↑ secretion
** Postsynaptic H1 in CNS: maintenance of wakefulness
H1 & H2 receptor mediated actions
fall i BP, ↑ cap permeability, headache: due to release of EDRF (NO)**
flush, wheel, flare
H2 receptor mediated actions
H2 receptor on gastric parietal cells
H3 receptor mediated actions
feedback inhibitors
release of histamine, NE & Ach
First generation H1 receptor antagonists
High permeability to BBB
More sedating
antimuscarinic side effects (dry mouth, urinary retention, constipation)
Second generation H1 receptor antagonists
selective H1 antagonism
Poor permeability to BBB (non-/less sedating)
First generation H1 receptor antagonist examples
Dimenhydrinate Diphenhydramine
HIGHLY SEDATIVE, antimotion sickness, antiemetic, sleep aid
Second generation H1 receptor antagonist examples
Fexofenadine
Cetrizine
Loratadine Desloratadine
(NON-SEDATING, more potent, longer acting, no/minimal anticholinergic effects )
Vertigo (Meniere’s disease)
cinnarizine
COX 1
constitutive
COX 2
inducible
PGI2 causes
vasodilation and inhibits platelet aggregation
TXA2 causes
vasoconstriction and platelet aggregation
PGE2 keeps
the ductus arteriosus patent
PGE2 in the hypothalamus causes
pyrogen induced fever
Medical termination of pregnancy (up to 56 days of pregnancy)
Misoprostol (PGE1 analogue)
Induction/ augmentation of labor/mid term abortion/ softening or ripening of cervix
Dinoprostone (PGE2 analogue)
Gemeprost (PGE1 analogue)
Post-partum hemorrhage
Carboprost (PGF2α analogue)
Peptic ulcer due to NSAIDs use
Misoprostol (PGE1 analogue)
Glaucoma
Latanoprost
To avoid platelet damage
PGI2 (Epoprostenol)
Impotence
sildenafil/ tadalafil
aspirin in low dose
used to inhibit platelets in MI patients
aspirin in high dose
inhibits TXA2 in platelets (anti-platelet effect)
NSAIDs
relieve musculoskeletal inflammatory pain very well (↓ inflammation, ↓ sensitization)
useful in bronchial asthma
Zilueton and LTC4 and D4 receptor blockers (Zafirlukast & montelukast)
classical migraine
migraine with aura
common migraine
migraine without aura
The Vascular theory
initial vasoconstriction -> cerebral ischemia -> vasodilation
Buspirone
partial agonist of 5-HT1A receptor
anti-anxiety drug
sumatriptan
selective 5-HT1D/1B agonist
antimigraine drug
induce vasoconstriction
Side effect:
• Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina)
Cisapride and renzapride
selective 5-HT4 agonists
prokinetic drugs
metoclopramide
5-HT4 agonist,
5-HT3 & D2 antagonist
antiemetic
Ondansetron
selective 5-HT3 antagonist
** antiemetic in cancer chemotherapy induced nausea & vomiting
Clozapine
5-HT2A/2C antagonist
antipsychotic
SSRIs
fluoxetine
antidepressants
Ergotamine, Dihydroergotamine
partial agonists at α adrenergic and 5-HT1, and 5HT2 receptors
Propranolol
β blockers
Amitriptyline
tricyclic antidepressants
Flunarizine
Ca2+ channel blockers