CNS Stimulants

Question 1

Main clinical uses of CNS Stimulants

Answer 1

ADHD and Narcolepsy

Question 2

Methylxanthine, competitive antagonist of Adenosine receptors

Answer 2

Caffeine

Question 3

What does caffeine inhibit at higher doses?

Answer 3

cAMP Phosphodiesterase –> increases cAMP, induces the release of Ca from intracellular stores (responsible for benefit to asthmatics)

Question 4

Pharmacological actions of caffeine

Answer 4

CNS stimulant: increases alertness, attention, decreases fatigue/drowsiness, can cause nervousness, restlessness, tremors, at high doses stimulates medullary respiratory and CV centers, can get tachycardia Peripheral effects: Positive inotropic and chronotropic on myocardium, dilates coronary/systemic bv, constricts cerebral bv, diuretic, increases gastric secretions, modest bronchodilation

Question 5

Weak base, potent inhibitor of reuptake of NE, serotonin and dopamine

Answer 5

Cocaine

Question 6

What is cocaine’s specific mechanism of action?

Answer 6

Binds transporter itself and inhibits the binding of ntm –> reinforcing effects from increased dopamine in synapse; Also increases activity of tyrosine and tryptophan hydroxylases

Question 7

What are the pharmacological effects of cocaine?

Answer 7

1. Peripheral sympathomimetic effects –> Vasoconstriction, tachycardia 2. Increase alertness/vigilance 3. Euphoria, elation, feeling of well-being –> d/t inhibition of Dopamine reuptake in the mesolimbic circuit (high abuse liability)

Question 8

Toxic Effects of Cocaine

Answer 8

Tolerance/physical dependence Mild withdrawal symptoms Neurotoxicologic effects d/t damage of dopaminergic neurons OD –> seizures, CV effects Effects developing fetus Profound psychological dependance

Question 9

Therapeutic use of cocaine

Answer 9

Local anesthetic in URT, also decreases BF

Question 10

Structurally similar to NE, weak bases, well-absorbed orally, metabolized to benzoic acid and excreted unchanged, relatively long 1/2 life

Answer 10

Amphetamine and Methamphetamine

Question 11

Mechanism of action of Amphetamines

Answer 11

1. Release NE, DA and 5-HT from neurons 2. Block reuptake of NE, DA and 5-HT 3. Partial agonist of alpha-receptors 4. MAOI at high doses

Question 12

Pharmacological Properties of Amphetamines

Answer 12

Arousal, wakefulness, decreased fatigue; Enhance athletic/intellectual performance; Elevated mood, increased self-confidence; Respiratory stimulant, decreases appetite, peripheral sympathomemetic

Question 13

Clinical uses of amphetamines

Answer 13

ADHD, Narcolepsy

Question 14

Side Effects of amphetamines

Answer 14

Insomnia, abdominal pain, anorexia, weight loss, suppression of growth, high body temp, facial tics

Question 15

Mixture of stereoisomiers; active form is dextroamphetamine

Answer 15

Amphetamine

Question 16

Not technically an amphetamine but structurally and mechanistically simliar

Answer 16

Methylphenidate

Question 17

Gets into brain better; higher abuse liability

Answer 17

Methamphetamine

Question 18

Prodrug of dextroamphetamine

Answer 18

Lisdextroamfetamine

Question 19

Toxicity of Amphetamines (At much higher doses than used for ADHD)

Answer 19

Acute toxicity –> Psychosis –> Neurotoxicity –> Meth mouth –> Abuse Liability

Question 20

Agonist of nicotinic cholinergic receptors

Answer 20

Nicotine

Question 21

What are the two mechanisms of action of Nicotine?

Answer 21

NMJ: initially activates muscle contraction, but then desensitizes Autonomic ganglia: sympathetic –> release of epinephrine from adrenal; parasympathetic –> GI effects

Question 22

Where are nicotinic receptors in the CNS?

Answer 22

Nucleus accumbens–> monovalent cation channels, activation leads to membrane depolarization and neuronal excitation

Question 23

What are the pharmacological effects of Nicotine?

Answer 23

CNS stimulant, increases alertness, increases dopamine release in limbic reward centers, muscle relaxant, activates chemoreceptor zone–> nausea (1st exposure)

Question 24

Withdrawal symptoms of Nicotine

Answer 24

Irritability, hostility, impatience, anxiety, depression, difficulty concentrating, increase appetite, weight gain

Question 25

Partial agonist of Nicotinic receptors; reduces craving by activation nACh Receptor, will not desensitize like nicotine, also blocks effects of nicotine if the person smoked (partial antagonist)

Answer 25

Varenicline

Question 26

Antidepressant; Reduces cravings and some of the nicotine withdrawal symptoms; SE: dry mouth, insomnia; moderately effective

Answer 26

Bupropion