CNS Drugs

1. CNS Drugs Dr. Felix Hernandez M.D.

2. Neurotransmitters of the Brain • Dopamine • Synthesized from Dopa • Over stimulation leads to psychoses • Too little dopamine is seen in Parkinson’s Disease • Impaired transmission is implicated in depression, ADD, and narcolepsy • Serotonin • Synthesized from the AA tryptophan • Is released from inhibitory neurons • LSD stimulates the same receptors as serotonin • Imbalances are associated with depression, ADD and headaches • GABA • An inhibitory NT • Cause hyperpolarization of neurons making it harder for them to fire • Low levels have been implicated in anxiety and seizures

3. Tricyclic Antidepressants • MOA: • Block the reuptake of monoamine NT (Dopamine) thus increasing their levels in the synapse. • Possible that a subsequent downregulation of the receptors is the actual MOA • Interactions: Potentiate the effects of other CNS depressants and anticholinergic drugs • Amitriptyline • Indications: major depressive disorder, enuresis, agoraphobia, OCD, migraines • Side Effects: severe anticholinergic effects, sedation • Imipramine • Indications: Enuresis in children. Was the TCA DOC but is no longer used due to its side effects • Side Effects: similar to others but can induce arrhythmias

4. Selective Serotonin Reuptake Inhibitors • Mechanism of action: Selectively inhibit the reuptake of serotonin • Fluoxetine (Prozac) • Inidications: depression, OCD, bulimia nervosa • Side Effects: altered platelet function, increased suicide rate • Interactions: life-threatening reaction with cisapride (promotes the release of ACH in the GI) • Sertraline (Zoloft) • Indications: depression, OCD, panic disorder • Side Effects: dry mouth, insomnia, altered platelet function • Interactions: Similar to fluoxetine

5. Selective Serotonin Reuptake Inhibitors • Paroxetine (Paxil) • Indications: depression, OCD, panic disorder • Side Effects: somnolence, insomnia, weakness, abnormal ejaculation, altered platelet function • Interactions: cimetidine (Histamine blocker used for ulcers) increases its levels. Warfarin levels are increased. Digoxin levels are decreased. • Trazodone • Indications: depression, aggressive disorders, cocaine withdrawl • Side Effects: Rash, HTN, Tachycardia, SOB, priapism

6. Benzodiazepines • Alprazolam (Xanax) • MOA: Increase levels of GABA thus making it harder for neurons to fire • Indications: Used together with TCA to treat depression and panic attacks • Side Effects: Has no anitcholinergic effects. Causes sedation and lethargy • Interactions: additive with other CNS depressants

7. Buproprion (Wellbutrin) • MOA: Unknown • Indications: depression and smoking cessation • Side Effects: seizures, hepatotoxicity, anticholinergic effects • Interactions: don’t use with drugs that lower seizure threshold

8. Stimulants • D-Amphetamine (Adderall and Dexedrine) • MOA: releases biogenic amines (NE, dopamine and serotonin) from storage vesicles • Indications: narcolepsy, ADD • Side Effects: restlessness, insomnia, HTN, arrhythmia, anorexia, psychotic episodes • Interactions: TCA potentiates the CNS effects by inhibiting the metabolism of amphetamine • Special Notes: to treat OD you acidify the urine, give chlorpromazine (Thorazine-sedation) to reduce CNS effects and an alpha blocker for the HTN • Methylphenidate • Same thing but milder stimulation

9. Stimulants • Caffeine • MOA: Adenosine receptor blocker. Stimulates CNS, constricts cerebral artreioles, induces diuresis • Indications: prolonged apnea in pre-term infants, headache analgesics • Side Effects: insomnia, restlessness, tachycardia, diuresis • Interactions: oral contraceptives and cimetidine inhibit its metabolism, smoking enhances elimination

10. Antiemetic • Promethazine (Phenegran) • MOA: dopamine and histamine antagonist • Indications: motion sickness, N&V (Post anesthesia) • Ondansetron (Zofran) • MOA: serotonin receptor blocker (not dopamine) • Indications: control chemo induced N&V

11. Parkinson’s Disease Drugs • Levodopa (L-Dopa) • MOA: is decarboxylated to dopamine (DA) • Improves neuro, motor and psych s/sx of parkinson’s • Indications: parkinson’s disease • Side Effects: N&V, modest ortho hypo, arrhythmias in elderly, involuntary movements, increased sexual activity • Interactions: pyridoxine (B6) reduces its effects, antipsychotics block dopamine receptors, anticholinergics delay absorption • Special notes: always used with carbidopa which inhibits its decarboxylation

12. Parkinson’s Disease Drugs • Carbidopa • MOA: deminishes the decarboxylation of L-Dopa in peripheral tissues therefore increasing the effect of L-Dopa • Indications: Parkinson’s Dz • Side Effects: reduces the N&V associated with L-dopa • Interactions: None • Has no MOA when given alone • Amantadine • MOA: releases dopamine from intact terminals • Side Effects: at high doses hallucinations, confucion and nightmares • Interactions: anticholinergic drugs enhances the CNS side effects • Is less effective than L-Dopa but more effective than anticholinergics

13. Parkinson’s Disease Drugs • Bromocriptine • MOA: powerful dopamine receptor agonist • Indications: Parkinson’s with tolerance to L-Dopa, hyperprolactinemia, pituitary tumors • Side Effects: N, hallucinations, hypotension • Interactions: can be used with L-Dopa and carbidopa

14. Opioid Analgesics • Morphine • MOA: opiate receptor agonist. Induces analgesia, sedation, respiratory depression • Indications: severe pain not alleviated by non-narcotics. DOC for severe pain in MI • Side Effects: respiratory depression, constipation, orthostatic hypotension, cholestasis, constipation • Tolerance can develop to the analgesic effects but not the constipating effects • Analgesia is threefold: • Increased threshold, unpleasant psych response is reduced, sleep is induced

15. Opioid Analgesics • Oxycodone (Oxycontin) • MOA: Same as morphine • Indications: moderate to severe pain • Side Effects: same as morphine • Used because it has a better oral absorption than morphine • Methadone • MOA: full morphine actions with less sedative effects • Indications: detox of narcotic addiction (Heroin), severe pain in hospitalized patients • Is less psychologically addictive than morphine • You detox by replacing heroin addiction with methadone addiction and then you slowly lower the dose of methadone to zero

16. Opioid Analgesics • Fentanyl • MOA: same MOA as morphine but is more potent with a lower likelihood of respiratory depression • Indications: preoperative uses • Side Effects: muscle rigidity, mild bradycardia • Has no tolerance or dependence • Can be used to treat chronic pain by using the transdermal preparations • Codeine • MOA: is a prodrug  10% of the drug is converted to morphine. So the MOA is the same as morphine • Indications: minor pain relief and antitussive • Side Effects: similar to morphine but less intense, but if given in high doses it’s toxicity is as severe as morphine • Included in several cough meds

17. Opioid Antagonists • Naloxone • MOA: blocks opiod receptors but only has an effect on a person that has narcotics in their system • Indications: treatment of narcotic OD, diagnostic agent to evaluate narcotic addiction, reduces postoperative respiratory depression • Side Effects: induces narcotic withdrawal syndrome including LOA, muscle contractions, fever/chills, restlessness

18. Benzodiazepines • MOA: bind to GABA receptors and enhances GABA mediated neuronal inhibition. Causes sedation, skeletal muscle relaxation and barbiturate fast waves on EEG • Indications: anxiety, DT’s, seizures, relaxation of Skeletal muscles • Side Effects: drowsiness, clouding of consciousness, ataxia, behavioral disinhibition, dermatitis • Interactions: effects are additive with ETOH

19. Benzodiazepines • Diazepam (Valium) • Is long acting • Indicated for anxiety disorder • Midazolam (Versed) • Is short acting • Used in anesthesia • Alprazolam (Xanax) • Short acting • Used as an antidepressant and an anxiolytic • Used to treat panic attacks • Does not cause daytime drowsiness

20. Migraine Headache Therapy • Sumatriptan (Imitrex) • MOA: serotonin receptor agonists • Causes vasoconstriction of the basilar artery and dura matter vessels • Onset of relief is 10 minutes – two hours • Side Effects: dizziness, tingling, flushing, chest discomfort, weakness and neck pain • Used to treat a migraine that is already occuring • Propranolol and timilol are used to prevent the onset of a migraine