CNS Stimulants

Question 1

Caffeine

Answer 1

Blocks adenosine receptors (blocks postsynaptic IPSP by adenosine R, blocks inhibition of glutamate release by presynaptic R)
Inhibition of phosphodiesterase so increased cAMP
Release of Ca from intracellular stores
Action: CNS stimulant, stimulate myocardium, dilate coronary vessels and constricts cerebral, diuretic, increase gastric secretion, bronchodilator
Therapeutic: stay awake and treat headache
Toxicity: nervousness, insomnia, excitement
Chronic: Tolerance developers and physical dependent (withdrawal= fatigue, headaches, nausea)

Question 2

Adenosine

Answer 2

The receptors which caffeine acts on and blocks to cause CNS stimulation
Postsynaptic adenosine receptors cause IPSP
Presynaptic adenosine receptors inhibit glutamate release
Caffeine blocks both of these inhibitor effects resulting in CNS stimulation

Question 3

Methylphenidate

Answer 3

Enhance catecholaminergic Neuro-transmission

Question 4

Cocaine

Answer 4

Psychoactive alkaloid present in the coca plant
Chemistry: weak base so unprotonated is neutral
Well absorbed through mucous membranes including the lungs
Metabolized primarily by serum and liver esterase said–> cocaine (metabolites in urine)
MOA: cocaine is potent inhibitor of the reuptake of NE, dopamine, serotonin
Cocaine receptor on transporter for dopamine, compete for binding of endogenous ligand resulting in increased ligand in the synapse
Effects: peripheral sympathomimetic due to increased NE, (vasoconstriction, tachycardia) increased alertness; vigilant, produces euphoria and feelings of elation due to to dopamine increase in Mesolimbic circuit
Toxicity: withdrawal is mild, tolerance and physical dependence, overdose cause seizures and CV effects, fetal effects more significant with low birth weights and learning and emotional problems
Therapeutic uses: local anesthetic in upper respiratory track

Question 5

Amphetamine

Answer 5

Alpha methyl phenethylamine derivatives and weak base
Orally absorbed with longer duration of action (4-6 hours)
Metabolism: deamination to benzoic acid and also excreted unchanged as amphetamine base excretion increased in acid urine
MOA: release NE, dopamine, and serotonin and blocks transmitter uptake into presynaptic terminals
Direct partial agonist of alpha adrenergic receptors at high
Properties: wakefulness, alertness, decreased fatigue, enhance athletic and intellectual performance, elevation of mood; increased self confidence nad increase in motor and speech activities, respiratory stimulation, decrease in appetite, peripheral sympathomimetic effects
Use: Naracolepsy, ADHD
Side effects: insomnia, abdominal pain, anorexia, weight loss, suppression of growth
Toxicity: sympathomimetic effects with restless, dizziness, tremor
Psychosis
Neurotoxicity
Abuse liability

Question 6

Methamphetamine

Answer 6

Better CNS bioavailability and more effect and higher abuse liability than amphetamines

Question 7

Methylphenidate

Answer 7

Not actually an amphetamine but structurally and mechanically very similar
Uses: ADHD
Toxicity: acute (sympathomimetic and restless, dizziness, tremor), psychosis, abuse liability, neurotoxicity

Question 8

Nicotine

Answer 8

MOA: against nicotine cholinergic receptors at NM junction not as affected but at autonomic ganglia (sympathetic ganglia activation results in release of epinephrine and parasympathetic results in GI effects)
CNS receptors: brain regions
Effects: CNS stimulant (increased alertness, activates dopamine in nucleus accumbens) and muscle relaxant
Tolerance: nicotine absorbed readily through mucous membranes and nicotine is reinforcing because it activates neuronal systems designed to maintain behaviors for survival
Tolerance throughout the day
Nicotine withdrawal symptoms- irritability, impatience, hostility, anxiety, depression, difficulty concentration, increased appetite; weight gain

Question 9

Bupropion

Answer 9

Treatment for nicotine dependence
Seems to enhance nor adrenergic and dopaminergic signaling
Adverse effects: dry mouth, insomnia
Moderately effective; reduces craving and nicotine withdrawal symptoms

Question 10

Varenicline

Answer 10

Partial agonist of CNS nicotinic receptors–> activate nicotinic receptors enough to reduce cravings and withdrawal
Significant increase in abstinence
Adverse effects: nausea, insomnia, headache, constipation