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P harmacology RHPT-365

Learn about the different types of drugs used in the treatment of CNS disorders, including antidepressants, antianxiety drugs, and anti-epileptic drugs. Understand their mechanisms of action and the effects they have on improving mood, reducing anxiety, and controlling seizures.

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P harmacology RHPT-365

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  1. ByMajid Ahmad Ganaie M. Pharm., Ph.D.Assistant ProfessorDepartment of Pharmacology E mail: majidsays@gmail.com Pharmacology RHPT-365 Chapter 6:Drugs used in CNS disorders

  2. ANTIDEPRESSANTS Drugs which can Elevate Mood (Mood Elevators)

  3. ANTIDEPRESSANTS • MAO inhibitors: • Irreversible: Isocarboxazid, Iproniazid, Phenelzine and Tranylcypromine • Reversible: Moclobemide and Clorgyline • Tricyclic antidepressants (TCAs) • NA and 5 HT reuptake inhibitors – Imipramine, Amitryptiline, Doxepin, Dothiepin and Clomipramine • NA reuptake inhibitors – Desimipramine, Nortryptyline, Amoxapine • Selective Serotonin reuptake inhibitors: • Fluoxetine, Fluvoxamine,Sertraline and Citalopram • Atypical antidepressants: • Trazodone, Mianserin, Mirtazapine, Venlafaxine, Duloxetine, Bupropion and Tianeptine

  4. Causes of Depression and Mechanism of antidepressants • The Monoamine Theory: • Adrenaline, Noradrenaline, Dopamine and 5-HT are neurotransmitters (Biogenic amines) • Called Noradrenergic, Serotonergic or Dopaminergic etc. neurones • Normally NA and 5 HT are in adequate numbers at post synaptic region • In DEPRESSION – Deficiency of NA or 5 HT or BOTH

  5. Mechanism of antidepressants – contd. • Drugs act by increasing the local availability of NA or 5 HT • MAO Inhibitors: MAO is a Mitochondrial Enzyme involved in Oxidative deamination of these amines • MAO-A: Peripheral nerve endings, Intestine and Placenta (5-HT and NA) • MAO-B: Brain and in Platelets and Mainly Serotonergic (Phenylalanine) • Selective MAO-A inhibitors (RIMA) have antidepressant property

  6. Mechanism of antidepressants – contd. • TCAs: • NA, 5 HT and Dopamine are present in Nerve endings • Normally, there are reuptake mechanism and termination of action • TCAs inhibit reuptake and make more monoamines available for action • SSRIs: • Serotonins also reuptaken by Nerve terminals • SSRIs inhibit the reuptake mechanism and make more 5 HT available for action

  7. Mechanism of Antidepressants

  8. MAO inhibitors • Drugs: Irreversible:Isocarboxazid, Iproniazid, Phenelzine and Tranylcypromine, Reversible:Moclobemide and Clorgyline • Not popular now except irreversible selective MAO-A inhibitors: • Strict dietary restrictions • Irreversible action • Drug-drug interactions • Safer drugs are available now • Major drawbacks: • Manic state or hypertensive crisis • Cheese reactions • Other drug interactions

  9. Effect of Antidepressants Deficient Drive of MOOD to - Normal Rhythmic Drive on Prolonged Treatment

  10. Antianxiety Drugs

  11. What is anxiety? • Anxiety is a normal reaction to stress • It helps one deal with a tense situation in the office, study harder for an exam, keep focused on an important speech • In general, it helps one cope • But when anxiety becomes an excessive, irrational dread of everyday situations, it has become a disabling disorder

  12. Antianxiety Drugs – contd.

  13. What are the Drugs? • Benzodiazepines: Alprazolam, Diazepam, Chlordiazepoxide, Oxazepam and Lorazepam • Older Drugs: Barbiturates, Chloral hydrate and Meprobamate • Azapirones: Buspirone, Gepirone and Isapirone • Others: Propranolol, Imipramine Fluoxetine and Zolpidem etc.

  14. Classifications of Benzodiazepines - Short acting: (3-5 hours): triazolam - Intermediate: (6-24 hours) Alprazolam, Lorazepam, Oxazepam Estazolam, Temazepam - Long acting: ( 24-72 hours) Clonazepam , Chlordiazepoxide ,Diazepam Flurazepam

  15. Mechanism of Action Benzodiazepines act by binding to BZ receptors in the brain enhance GABA action on brain  chloride channels opening   chloride influx to the cell  hyper- polarizationinhibition of brain. GABA (γ-aminobutyric acid): is an inhibitory neurotransmitter

  16. Antianxiety Drugs - Buspirone • Partial agonist action on presynaptic auto receptor 5-HT1A – reduces serotonergic activity in dorsal raphe • Antagonist of certain 5-HT1A post synaptic receptors • Weak D2 action but no antipsychotic effect • Adaptive changes after chronic treatment – reduction in 5-HT2 receptors in cortex • Given orally, absorbed rapidly – high 1st pass metabolism, active metabolite – urine and faeces • Dose: 5-15 mg dose

  17. Antianxiety Drugs - Propranolol • Reduces symptoms of anxiety • Symptoms: Sympathetic overactivity – palpitation, tachycardia, rise in BP, sweating, tremor, GIT hurrying etc • No action on psychological symptoms – fear, tension etc. • Useful in examination fear, public appearance etc.

  18. Anti-epileptic / anti-convulsant Drugs

  19. Definition of Epilepsy It is a Chronic medical condition produced by sudden changes in the electrical function of the brain. A group of chronic CNS disorders characterized by recurrent seizures First generation AED Phenytoin, Carbamazepine, Valproic acid Second generation AED Lamotrigine, Gabapentin, Vigabatrin, Topiramate, In general, the newer AEDs have less CNS sedating effects than the classical AEDs

  20. Phenytoin Pharmacokinetics Well absorbed when given orally, however, it is also available as iv. (for emergency) Mechanism of Action: Membrane stabilization by blocking Sodium & Calcium influx into the neuronal axon. or inhibits the release of excitatory amino acids via inhibition of Calcium influx Clinical Uses: Used for partial Seizures & generalized tonic-clonic seizures. But not effective for absence Seizures . Also can be used for treatment of ventricular fibrillation.

  21. Lamotrigine Pharmacological effects Resembles phenytoin in its pharmacological effects Well absorbed from GIT Mechanism of Action: Inhibits excitatory amino acid release (glutamate & aspartate ) by blockade of Na channels. Uses: As add-on therapy or as monotherapy

  22. Common Causes of Failure of Antiepileptics Improper diagnosis of the type of seizures Incorrrect choice of drug Inadequate or excessive dosage Poor compliance Antiepeliptics and Pregnancy: • Seizure very harmful for pregnant women. • Monotherapy usually better than drugs combination. • Folic acid is recommended to be given for every pregnant women with epilepsy • Phenytoin, sodium valproate are absolutely contraindicated and oxcarbamazepine is better than carbamazepine. • Experience with new anticonvulsants still not reliable to say that are better than old ones.

  23. Possible Mechanism of Action 1) By acting on the neuronal membrane action potential: Membrane Stabilization: Phenytoin; Carbamazepine: Phenobarb; Lamotrigine; Topiramate, Zonisamide. Prolong refractory period: e.g: Ethosuximide; Valproate 2) By inhancement of GABA neurotransmissions: Inhibit GABA catabolism (inhibit GABA transaminase) e.g: Valproate; Vigabatrin Inhibit re-uptake of GABA: benzodiazepines Analog of GABA: e.g: Gababentin Increase the activity of GABA: phenobarbitone; Topiramate; Gabapentin 3) By antagonizing the action of Aspartate and Glutamate: e.g: Lamotrigine

  24. Thank you

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