Drugs for Pain Flashcards
Symptoms and Causes of Migraines:
Can occur with or without aura
-Typical features include duration (4-72 hours), pulsating several to moderate pain, impair function, nausea/ vomiting, photo/ photophobia (sensitivity to light) and aura.
Pathophysiology of Migraines:
2 Major Issues:
1. Vascular Theory: Migraines begin with vasoconstriction of cerebral vessels. The subsequent reduction in blood flow causes aura, followed by compensatory dilation of vessels which generally leads to pain.
- Neurogenic Theory:
Attacks precipitated by excess excitation in the neocortex. Followed by “Cortical Spreading Depression”
–>Rapid and profound depolarization of neurons
-This CSD leads to the aura which then triggers the pain.
- Dilation/ inflammation of the cerebral arteries, as well as the release of pain mediators lead to the pain caused by migraines.
- -Serotonin (5-HT) seems to a play a role in both theories.
Sumatriptan
- A type of Triptan
- ->5-HT-1B & 5-HT-1D agonist
- Vasoconstrictor which leads to reduced release of pain transmitters.
- Onset varies depending upon route of administration:
- Oral, Nasal Spray, and SC Injection
Side Effects: Related to vasoconstriction (Chest & Neck Discomfort)
- Rare, but Serious: Myocardial schema/ infarction
- Avoid in patients with cardiovascular/ cerebrovascular diseases
5-HT Side Effects:
Caution– 5-HT syndrome
-Nausea
Dihydroergotamine:
–>A type of Ergot Alkaloid
-5-HT-1B, 5-HT-1D and an alpha-1 agonist
-Vasoconstrictor
-Reduced release of pain transmitters
Routes of administration include:
-Injectable and Nasal Spray
Treatment for Acute Migraines Include:
Anti-inflammatories
- NSAIDS
- Acetaminophen
- Opioids (Codeine containing products; Butorphanol)
What are the problems using Opioids for treating Migraines?
- ->Not addressing the underlying issue
- No vasoconstrictor effects
- No anti- inflammatory effects
- -Tolerance/ withdrawal dependence
- Episodic nature of acute migraines means patient will take opioids infrequently (HIGH addictive potential)
- OD can lead to Respiratory Depression
Opioid side effects include constipation, euphoria, sedation and high abuse potential
*The goal is to stimulate Mu receptors without causing euphoria.
Butorphanol:
- Partial Agonist/ Mixed Agonist/ Antagonist
- more likely to see dysphoria (dissatisfaction)
- Administered as a Nasal Spray
- Definite potential for dependence
Medication Overuse Headache (MOH):
-Occurs for people treating headaches frequently (>15 headaches/ month)
-Can occur with any drugs treating migraine
(The mechanism for MOH is unknown)
Effects of chronic drug use for headache:
- Changes in neurotransmitter levels (5-HT)
- Decreased threshold for developing a subsequent headache.
To treat: Stop taking headache medication and switch to prophylaxis
Main drugs for Migraine Prophylaxis Drugs (Inhibit the release of pain mediators)
- Re-uptake Inhibitors (TCAs)
- Na+ Channel Blockers
(Valproic Acid) - Ca2+ and Alpha-2-delta- Channel Blockers
(Gabapentin)
Pain targets: Enhance the activity of the inhibitory descending pathways (5-HT and NE pathways) and increase 5-HT/ NE with re-uptake inhibitors.
Other drugs used for Migraine Prophylaxis:
Beta Blockers- Propanolol
- Inhibit SNS activity (therefore may modulate hyper- excitability)
- Some beta blockers modulate 5-HT (Off target effect)
Ca2+ Channel Blockers (Verapamil- Last resort Drug)
-Best evidence for DHP’s/ mechanism in preventing migraine is unknown
NSAID Side Effects:
Lower risk GI side effects with COX-2 selective Drugs (COX-1 mediates mucus production and only COX-2 may compromise CV health.
-CV risk (ASA- anti-platelet)
Higher Risk: COX- 2 selectivity
Lower Risk: Naproxen
