CNS Stimulants Flashcards
What can all stimulants cause in sufficient doses?
Convulsions/Seizures
- What is the mechanism of action of Caffeine?
- There are pre- and post- synaptic receptors. What do each do?
- Competitive antagonist of adenosine receptors causing dis-inhibition of CNS
- Postsynaptic cause inhibitory postsynaptic potential. (Hyperpolarization)
Pre-synaptic receptors inhibit glutamate release.
What two effects does caffeine have at higher doses?
- Inhibits cAMP phosphodiesterase: results in increased cAMP
- Induces release of calcium from intracellular stores
(Responsible for beneficial effects in asthma)
What are 5 unique peripheral effects of caffeine?
- Positive inotropic and chronotropic effects
- Dilates coronary and systemic blood vessels. Constricts cerebral blood vessels.
- Produces diuresis
- Increases gastric secretions
- Modest bronchodilation
How much coffee per day can create physical dependence?
2 cups per day
What are the three sympathomimetic stimulants for this course?
- Cocaine
- Amphetamines
- Methylphenidate
- Cocaine has what kind of pH/pKa profile?
- What are the two major forms?
- It is a weak base and therefore unionized in the unprotonated form (B)
- It is used as a Hydrochloride salt and a free base.
Why is the free base form of cocaine more desireable?
It is volatile and can be smoked
- How well is Cocaine absorbed?
- Where is it metabolized?
- What is the plasma half-life?
- It is well absorbed through any mucous membrane
- It is metabolized in plasma and liver
- Short half life (50 min). Shorter in CNS (10-30 min)
What is the mechanism of action for Cocaine?
- Potent inhibitor of reuptake of NE, D, 5-HT
- It binds to the transporter itself.
- Reinforcing effects due to increased dopamine in synapse.
- Increases activity of tyrosine and tryptophan hydroxylases
- What are the primary concerns with Cocaine overdose?
- What happens from cocaine use during pregnancy?
- Seizures, MI, Arrhythmias
- Similar to Fetal Alcohol but more significant. Low birth weight, learning and emotional problems, attachment disorder.
What increases the abuse potential and psychological dependence of Cocaine?
Dosage forms that deliver drug rapidly to the CNS
- What are Amphetamine and methamphetamine similar to?
- What is their acid/base status?
- What are they metabolized to?
- What is their relative half-life?
- Norepinephrine
- They are weak bases
- Metabolized to benzoic acid and excreted unchanged
- Relatively long half-life (much longer than cocaine)
What is the mechanism of action for amphetamine and methamphetamine?
- Release of NE, DA, 5-HT from neurons
- Block reuptake of NE, DA and 5-HT
- Partial agonist of alpha receptors
- MAO inhibitor at high doses
- What is the active form of Amphetamine?
- How is methylphenidate associated with amphetamine/methamphetamine?
- What has the highest abuse potential of the group?
- What is a prodrug of dextroamphetamine?
- Dextroamphetamine
- Methylphenidate is not technically an amphetamine but structurally and mechanistically similar.
- Methamphetamine because it gets into the brain better.
- Lisdextroamfetamine
What are the two primary clinical uses for amphetamine and methylphenidate?
Narcolepsy and Attention-deficit disorder
What are some side effects of amphetamine and methylphenidate? (6 possible)
- Insomnia
- Abdominal pain
- Anorexia/Weight loss
- Suppression of growth
- High body temperature
- Facial tics
What are the 5 major concerns at abuse level doses of amphetamines and methylphenidate?
- Acute toxicity: Profound sympathomimetic effects
- Psychosis due to excess DA
- Neurotoxicity: permanent intellectual problems
- “Meth mouth”
- More addictive long term than cocain (especially if smoked or IV)
What is the mechanism for Nicotine?
Agonist of nicotinic cholinergic receptors
What are the pharmacologic effects of nicotine:
- On the CNS
- On muscles
- On GI system
- It is a CNS stimulant and increases alertness. It increases dopamine in the limbic system and nucleus accumbens.
- It causes muscle relaxation
- It can cause nausea (primarily first exposure), supresses appetite
- How long does it take Nicotine to reach the brain?
- Why is smoking so “rewarding”?
- Why is smoking just as much as/if not more addicting than cocaine?
- 7 seconds
- It increases dopamine in the nucleus accumbens
- Each puff is a separate opportunity for the brain to associate smoking with reward. Individual “dose” of nicotine not as rewarding as single dose of cocain.
What is tachyphylaxis?
It is the rapid increase in tolerance to nicotine. “The first cigarette of the day is the best”
What does a nicotine withdrawal syndrome look like?
- Irritability
- Anxiety
- Depression
- Difficulty concentrating
- Increased appetite & weight gain
- What antidepressant is used for smoking cessation?
- What other medication is used for smoking cessation?
- Bupropion
- Varenicline
- What is the mechanism for Varenicline?
- What are the benefits of its use?
- How successful is it compared to buproprion?
- Partial agonist of nicotinic receptors
- Will not desensitize like nicotine itself
- Blocks the effects of nicotine if person smokes
- More efficacious at 12 and 24 weeks
