p harmacology rhpt-365 by m ajid a hmad g anaie m. pharm., p h.d. assistant professor department of...
TRANSCRIPT
Pharmacology RHPT-365
ByBy
MMajid ajid AAhmad hmad GGanaie anaie MM. Pharm., . Pharm., PPh.D.h.D.Assistant ProfessorAssistant ProfessorDepartment of Pharmacology Department of Pharmacology E mail: E mail: [email protected]@gmail.com
ChapterChapter 6: 6:
Drugs used in CNS disordersDrugs used in CNS disorders
ANTIDEPRESSANTS
Drugs which can Elevate Mood (Mood Elevators)
ANTIDEPRESSANTS
1. MAO inhibitors:– Irreversible: Isocarboxazid, Iproniazid, Phenelzine and Tranylcypromine– Reversible: Moclobemide and Clorgyline
2. Tricyclic antidepressants (TCAs) NA and 5 HT reuptake inhibitors – Imipramine, Amitryptiline, Doxepin,
Dothiepin and Clomipramine NA reuptake inhibitors – Desimipramine, Nortryptyline, Amoxapine
3. Selective Serotonin reuptake inhibitors: – Fluoxetine, Fluvoxamine, Sertraline and Citalopram
4. Atypical antidepressants:– Trazodone, Mianserin, Mirtazapine, Venlafaxine, Duloxetine, Bupropion and
Tianeptine
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
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
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
Mechanism of Antidepressants
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
Effect of Antidepressants
Deficient Drive of MOOD to - Normal Rhythmic Drive on Prolonged Treatment
Antianxiety Drugs
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
Antianxiety Drugs – contd.
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.
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
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
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
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.
Anti-epileptic / anti-convulsant Drugs
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
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.
LamotriginePharmacological 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
Common Causes of Failure of Antiepileptics1. Improper diagnosis of the type of seizures
2. Incorrrect choice of drug
3. Inadequate or excessive dosage
4. 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.
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
Thank you