Andrade: Stimulants and Migraine Drugs Flashcards
Amphetamines
MOA:
MOA: cause the release of monoamines (NE, DA etc.) though a non-exocytotic mechanism
- Displaces NE/DA from vesicles and causes it to be released in large quantities from the neuron
- Act at plasmalemal transporter and vesicular monoamine transporter
Amphetamines
Use in ADHD (Main Clinical Use of Stimulants):
Treat Core Symptoms: impulsivity, inattention and motor restlessness
Amphetamines
Effective:
Effective: medication alone (slightly better) or in combination with behavioral treatment most effective form of treatment for ADHD
Amphetamines
Effectiveness Important Point:
Important Point: although shown to be less effective, community care and behavioral treatment alone also result in noticeable improvements in ADHD symptoms (and effects may also be longer lived after the end of treatment)
Amphetamines
How does it help with ADHD?
Reduces activity, inattention and impulsivity (in both normal adults/children and children with ADHD)
Increases NE and DA
Amphetamines
Imaging Studies of Children with ADHD:
Show changes in the DA transporter levels in kids with ADHD
Some studies have suggested that DA transporter levels have normalized after treatment with methylphenidate (continues to be a contentious issue)
Drugs Used for ADHD: (5)
Drugs Used for ADHD: note that ER/controlled release formulations now dominate (more convenient, provide stable effect of stimulant throughout the day)
- Amphetamine (Adderall)
- Methylphenidate (Ritalin)
- Dextroamphetamine (Dexedrine)
- Dexmethylphenidate (Focalin)
- Pemoline (Cyclert)- should not be a first line drug because of side effects of liver damage*
Amphetamines
Side Effects
Mostly dose dependent: (4)
Decreased appetite
Insomnia
Increased anxiety/irritability
Mild stomach aches and headaches
Amphetamines
Side Effects
Concerns in children: (2)
Potential toxicity
Growth suppression
Other ADHD Medications (Non-Stimulant): (2)
Atomoxetine: NE reuptake inhibitor
Guanafacine/Clonidine: ER alpha2 adrenergic agonists
Other Uses of Stimulants: (2)
Treatment of Excessive Daytime Sleepiness
Historical use as appetite suppressants
Treatment of Excessive Daytime Sleepiness
Conditions:
Conditions: narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work sleep disorder etc.
Treatment of Excessive Daytime Sleepiness
Agents Used:(2)
Agents Used:
Modafinil: mechanism unknown (possible DA uptake inhibitor)
Sodium oxybate (Xyrem): especially for treatment of narcolepsy - Sodium salt of GHB (date rape drug)
Migraines
Headaches that are: (5)
o Unilateral
o Pulsatile or throbbing
o Associated with N/V (severe cases)
o Of sufficient intensity to interrupt daily activities
o Usually lasting 4-72 hours if left untreated
Migraines
Prodrome/Aura:
Epidemiology:
Triggers:
Prodrome/Aura: distinguishes it from other types of headaches (occurs in most cases)
Epidemiology: 18% of women and 6% of men affected
Triggers: often dietary (~20% of cases)
Migraines
Vascular Theory:
Vascular Theory: used to dominate
- Stated that it was purely a vascular disorder
- Vasodilation of blood vessels in the brain leading to pain
Migraines
Neurogenic Inflammation:
Neurogenic Inflammation: now seems to provide a better explanation
- Some stimulus (probably spread of cortical depression) results in aura (when it crosses the visual cortex)
- As cortical depression spreads, mediators get released that cause vasodilation of vessels (ie. NO, K+, AA, H+), resulting in activating of the trigeminal nerves and the sensation of pain
Migraines
Treatment of Non-Severe:
Non-Severe: no vomiting, use NSAIDs
Migraines
Treatment of severe: (2)
Triptans
Dihydroergotamine
Triptans
MOA:
MOA: 5HT 1B/1D receptor agonists
- Inhibit release of NTs that lead to vasodilation and extravasation
Triptans
Drugs in this Class: (2)
Sumatriptan (Imitrex)
Frovatriptan (longer acting)
Triptans
Efficacy:
Best when used in combination with:
Can also be combined with :
Early intervention:
Efficacy: very effective (mainstay of treatment for severe migraines)
Best when used in combination with an NSAID
Can also be combined with antiemetics (for N/V)
Early intervention is very important (ie. want to prevent release of mediators as early as possible to limit inflammatory process that causes pain)
Triptans
Contraindications:
Other Issues:
Contraindications: people with coronary disease
Other Issues: high cost
Dihydroergotamine:
Older drugs with more side effects and less efficacy than triptans
Preventative Therapy
Beta Blockers:
Propanolol
Timolol
Metoprolol
Preventative Therapy
Antiepiletic Drugs: (2)
Valproate
Topiramate
Preventative Therapy
TCAs:
Amitriptiline
Preventative Therapy
Non-Drug Therapy:
Behavioral therapies (relaxation training, EMG biofeedback, cognitive therapy)
Pharmacotherapeutic Future
CGRP Receptor Antagonists:
CGRP:
CGRP Receptor Antagonists: currently in phase III clinical testing
CGRP: released by cells that innervate the cranial vasculature (very important part of vasodilation and extravasation)
