Headache Drugs Flashcards
(41 cards)
How is kallidin formed? Bradykinin?
LMW kinogen –> kallidin via tissue kallikrein
HMW kinogen –> bradykinin via plasma kallikrein
How is kallidin converted to bradykinin?
Aminopeptidase
How is bradykinin formation linked to the clotting cascade?
- XIIa increases the formation of plasma kallikrein
- plasma kallikrein induces conversion of XII –> XIIa
positive feedback loop
By what (2) enzymes are kinins metabolized?
Kininase 1 (carboxypeptidase M/N) converts to active metabolites
Kininase 2 (ACE) converts to inactive metabolites
The prefix “des-arg” denotes?
An active kinin metabolite
Effect of ACEi on bradykinin?
INCREASES Bradykinin by preventing metabolism to inactive compounds via kininase 2 (ACE).
Differences between B1/2 kinin receptors:
+ (2) commonalities
Both are G protein coupled
Both cause ^NO/PG/EDHF
B1: binds active metabolites; present only in damaged tissue
B2: binds native kinins; always expressed
In what three ways do bradykinins induce pain? (3)
- ^ CGRP = Trigeminal vasodilation (migraine***)
- ^ neurokinins
- ^ substance P
How do bradykinins effect
1) microcirculation
2) pulmonary system
3) blood pressure
Microcirculation increased permeability = edema
Bronchospasm
Vasodilation = hypotension
Bradykinins increase prostaglandins.
What are two very common drugs that DECREASE prostaglandins?
What are their MOAs?
NSAIDs: inhibit COX (AA –> PG)
Corticosteroids: increase lipocortin (inhibits PL –> AA)
Kinins:
Classification
+ 3 general effects
Autocoids
Inflammation, pain, vasodilation
Serotonin is stored in platelets.
Why can serotonin be stored without appreciable metabolism?
In what (2) ways does serotonin mediate platelets’ effects?
- Serotonin is metabolized by MAO-A; platelets selectively express MAO-B
- Promotes vasoconstriction + aggregation
Effects of serotonin on CV and GI systems:
What GI system cells release serotonin?
^^ activity in both systems (increased HR; increased motility)
*enterochromaffin cells express serotonin in GI tract
2 Common symptoms assc with serotonin secreting carcinomas:
Diarrhea, abdominal cramping b/c serotonin causes increased GI motility
Urinary metabolite of serotonin?
When is it elevated?
5-hydroxyindolacetic acid (5HIAA)
Increased during active migraine episode
Effects of 5HT1b and 5HT1d receptors?
What drug class selectively targets these serotonin receptors?
For what are they most commonly used?
1d: vasoconstriction of cranial vessels (undoes vasoDilation)
1b: decreased Trigeminal nociception
Triptans select 5HT1b/d; used in acute migraine rescue
What does the pneumonic POUND stand for?
P-pulsatile O- 4-72 hOurs U- unilateral N- nauseating D- debilitating
4 stages seen in migraine attack?
What does the first stage involve?
Prodrome (GI/mood changes)
Aura
Attack
Postdrome
Propranolol/ Atenolol
1) MOA
2) Use in HA treatment
3) Contraindication
B1 AND 2 blockers
Migraine Px
Asthma (B2 = bronchodilator)
Amitriptylline/ Nortryptilline
1) MOA
2) Use in HA treatment
3) Common ADR
4) Contraindication
1) TCAs ( ^NE, 5HT)
2 )Migraine Px especially in patients that w/ frequent HA or trouble sleeping
3) anti-muscarinic fx (dry mouth, constipation, etc)
4) never use in patient with risk of suicide
Levitiracetam drug class?
Anti-epileptic
Valproic Acid, Levitiracetam, Gabapentin, Topirimate
1) Drug Class
2) MOA
3) Use in HA treatment
4) Which is a pregnancy X drug?
1) Anticonvulsants
2) ^ GABA
3) Migraine Px esp in cases of comorbid anxiety/epilepsy
4) never use valproic acid in pregnancy. Strong teratogen.
Verapamil
1) MOA
2) 3 uses
Ca Channel Blocker
HTN; migraine Px; cluster Px
Cyproheptadine
1) MOA
2) Uses (2)
3) Common ADR
1) histamine, serotonin and Ach antagonist
2) Migraine Px and Seasonal allergies
3) sleepiness
