Pharmacology of Headache/Migraine Flashcards Preview

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Flashcards in Pharmacology of Headache/Migraine Deck (13):
1

What is serotonin synthesized from?
What are the steps of synthesis and which is the rate limiting step (RLS)?
How is serotonin's action terminated?

 

Synthesized from Tryptophan

First step, tryptophan hydroxylase is RLS
Second step is L-aromatic amino acid decarboxylase: 5-HO-Tryptophan to 5-HT

Reuptake by SERT then converted 5-hydroxyindoleacetic acid via MAO and aldehyde DH
Conversion to melatonin in pineal gland

2

What is the location of serotonin in the body?

In the CNS specifically where is it?

90% - GI system
8% - Platelets (No synthesis)
2% - CNS

Cell bodies in midbrain raphe nuclei
Projection: Hypothalamus, neostriatum, limbic forebrain, neocortex, medulla, spinal cord

3

What are the serotonin receptors?

5-HT1(A-E) – Inhibition of adenylate cyclase
5-HT1A – K+ channel opens
5-HT2(A-C) – PI hydrolysis
5-HT3 – Ligand-gated cation channels
5-HT4-7 – Activation of adenylate cyclase or unknown
Auto-receptors – Decreased serotonin release (1A and 1D like)

4

What is the cardiovascular role of serotonin?

Potent vasoconstriction of large arteries and veins; cranial (5-HT1D) blood vessels
Vasodilation in coronary, skeletal muscle and cutaneous blood vessels
Bezold-Jarisch reflex – Coronary chemoreceptors; Bradycardia, hypotension, and hypoventilation
Platelet aggregation – Active uptake of serotonin from circulation

5

What is the CNS role of 5-HT

Sensory Perception
Sleep
Temperature regulation
Neuroendocrine regulation
Learning and memory, particularly short-term
Pain perception – spinal and brain sites of action
Drug abuse
Emesis – 5-HT3 receptors

6

What is the role of 5-HT in mental illness?

Affective disorders – SSRIs and SNRIs
Schizophrenia – Atypical antipsychotics
OCD – SSRIs
Anxiety – 5-HT1A receptors
Aggressive behavior

7

Lysergic Acid Diethylamide (MoA, Indication)

Nonspecific – 5-HT2 receptors
Potent hacllucinogen

8

Buspirone (MoA, Indication)

5-HT1A Partial Agonist – Antianxiety

9

Sumatriptan (Delivery, MoA, Indication)

Delivery: Oral, nasal spray, SC
Combination with naproxen

5-HT1B/D receptors on cerebral blood vessels (Vasoconstriction promoting)
CGRP – Inhibition of vasoactive peptides
NT inhibits of the trigeminal and cortical nerves
Block brainstem pain pathways

Treatment of migraine headaches, stop existing ones – Major abortive

10

Sumatriptan (Side Effects, Contraindications)

Peripheral vasoconstriction
Nausea and vomiting
Angina
Dizziness
Flushing

Stroke/MI
Uncontrolled HTN, IHD

11

Sumatripitan (Drugs in same class, and any details in delivery)

Almotriptan, eletriptan, frovatriptan (long half-life), naratriptan (long half-life), rizatriptan, zolmitripitan (oral, nasal spray)

12

What are some other abortives?

Ergots – DHE
Many routes
Ergotamine – Oral

NSAIDS w/ caffeine (Excedrin)

Steroids

Butalbital/Caffeine/APAP (Fioricet)
Butalbital – Mild barbiturate
Bad choice

13

What are some prophylactic drugs for headache?

Tricyclic Antidepressents: Amitryptyline, Nortriptyline
Sedating
Anti-ACh
Effective for variety of sources

Antiseizure agents
Divalproex sodium/valproic acid
Topiramate
Others – Gabapentin, pregabalin, lamotrigine

Vasoactive Agents
Beta blockers – Propranolol, atenolol
Calcium channel blockers – Verapamil, diltiazem
Variable efficacy – Side effects