Main clinical uses of CNS Stimulants
ADHD and Narcolepsy
Methylxanthine, competitive antagonist of Adenosine receptors
What does caffeine inhibit at higher doses?
cAMP Phosphodiesterase --> increases cAMP, induces the release of Ca from intracellular stores (responsible for benefit to asthmatics)
Pharmacological actions of caffeine
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
Weak base, potent inhibitor of reuptake of NE, serotonin and dopamine
What is cocaine's specific mechanism of action?
Binds transporter itself and inhibits the binding of ntm --> reinforcing effects from increased dopamine in synapse; Also increases activity of tyrosine and tryptophan hydroxylases
What are the pharmacological effects of cocaine?
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)
Toxic Effects of Cocaine
Tolerance/physical dependence Mild withdrawal symptoms Neurotoxicologic effects d/t damage of dopaminergic neurons OD --> seizures, CV effects Effects developing fetus Profound psychological dependance
Therapeutic use of cocaine
Local anesthetic in URT, also decreases BF
Structurally similar to NE, weak bases, well-absorbed orally, metabolized to benzoic acid and excreted unchanged, relatively long 1/2 life
Amphetamine and Methamphetamine
Mechanism of action of Amphetamines
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
Pharmacological Properties of Amphetamines
Arousal, wakefulness, decreased fatigue; Enhance athletic/intellectual performance; Elevated mood, increased self-confidence; Respiratory stimulant, decreases appetite, peripheral sympathomemetic
Clinical uses of amphetamines
Side Effects of amphetamines
Insomnia, abdominal pain, anorexia, weight loss, suppression of growth, high body temp, facial tics
Mixture of stereoisomiers; active form is dextroamphetamine
Not technically an amphetamine but structurally and mechanistically simliar
Gets into brain better; higher abuse liability
Prodrug of dextroamphetamine
Toxicity of Amphetamines (At much higher doses than used for ADHD)
Acute toxicity --> Psychosis --> Neurotoxicity --> Meth mouth --> Abuse Liability
Agonist of nicotinic cholinergic receptors
What are the two mechanisms of action of Nicotine?
NMJ: initially activates muscle contraction, but then desensitizes Autonomic ganglia: sympathetic --> release of epinephrine from adrenal; parasympathetic --> GI effects
Where are nicotinic receptors in the CNS?
Nucleus accumbens--> monovalent cation channels, activation leads to membrane depolarization and neuronal excitation
What are the pharmacological effects of Nicotine?
CNS stimulant, increases alertness, increases dopamine release in limbic reward centers, muscle relaxant, activates chemoreceptor zone--> nausea (1st exposure)
Withdrawal symptoms of Nicotine
Irritability, hostility, impatience, anxiety, depression, difficulty concentrating, increase appetite, weight gain
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)
Antidepressant; Reduces cravings and some of the nicotine withdrawal symptoms; SE: dry mouth, insomnia; moderately effective