Antipsychotic drugs, Anti-Depressants, Anti-Anxiety Agents, AntiManics And Hallucinogens

Classify Antipsychotic drugs. How do antipsychotic drugs differ from antimaniac drugs? Discuss mode of action and pharmacological actions of chlorpromazine.

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Classify Antipsychotic agents. Write in detail therapeutic uses and adverse effects of Chlorpro- mazine(CPZ).

Ans: PSYCHOPHARMACOLOGICAL AGENTS

The psychotropic drugs act on the psyche. These drugs may be grouped as:

1. Antipsychotics
2. Anti Anxiety
3. Antidepressant
4. Antimanic
5. Psychotomimetics

 * ANTIPSYCHOTIC DRUG OR NEUROLEPTICS

Drugs used for the treatment of psychosis. they reduce agitation and disturbed behaviors seen in schizophrenia. These produce calming effect with out marked drowsiness,

Classification

A.Penothiazines

1. Aliphatic side chain
2. Chlorpromazine
3. Triflupromazine.

2. Piperdine side chain

Thioridazine

3.Piperdine side chain

1. Trifluoperazine
2. Fluphenazine

B.Butyrophenones

1. Haloperidol
2. Trifluperidol
3. c) Droperidol
4. Penfluridol.

C.Thioxanthenes

1. Thiothexene
2. Flupenthixol.

D.Other heterocyclics

1. Pimozide
2. Lixapine
3. Reserpine.

E. Atypical neuroleptics

1. Clozapine
2. Risperidone
3. Olanzapine.

 CHLORPROMAZINE

It is the first neuroleptic introduced. It can be described as the prototype.

Mechanism of Action of Chlorpromazine

1. They block the post synaptic monoaminergic (Nor adrenaline, dopamine and 5-HT) transmission in the brain, thus leading to a decrease in the central sympathetic activity.
2. brain It reduces the incoming sensory stimuli by acting stem reticular formation.

3.They modify the function of Limbic system.

Pharmacological actions

1.Central nervous system :- When chlorpromazine is given to patients with psychosis, it produces:

a.Psychomotor slowing

b.Emotional quitening

c. decreased initiative

d. decreased anxiety.

Phenothiazines do not have an analgesic effect. But they potentiate the analgesic effect of morphine. They do not have anticonvulsant effect.

2.Antiemetic action

Chlorpromazine has a powerful antiemetic effect.

3. Autonomic nervous system

Chlorpromazine has an alpha adrenergic blocking effect. It also blocks the actions of acetylcholine and 5hydroxytryptamine.

4.Cardiovascular system

Chlorpromazine has a hypotensive, myocardial depressant and anti-fibrillatory effect.

5. Endocrine system

Chlorpromazine produces inhibition of ovulation, amenorrhea and lactation in females. In males, it produces loss of these effects are produced by blocking the action of dopamine on hypothalamus and pituitary.

6. Miscellaneous actions

They are:

1. a.Inhibition of hiccough
2. Local anaesthetic effect
3. Skeletal muscle relaxant effect.

Dose: 200-800 mg orally , 25-50 mg I.M.

Adverse effects

1.CNS effects

Drowsiness, lethargy and confusion.

2.Adrenergic block

Postural hypotension, palpitation.

 3.Anticholinergic effect

Dry mouth, blurred vision, constipation.

4.Endocrinal effect

Infertility, amenorrhoea, gynaecomastia.

5.Ocular toxicity

Granular deposits in cornea and lens.

 6.Extrapyramidal disturbances

Iatrogenic parkinsonism, acute muscular dystonias (oculogyric crisis, face grimacing), akathesia.

 Uses

1. In the treatment of major psychosis. 2. To control aggressiveness in children 3. As an anti emetic. 4. Pre anaesthetic medication. 5. To potentiate hypnotics and analgesics. 6. In tetanus to achieve muscle relaxation. 7. Intractable hiccough.

 

ANTI-ANXIETY OR ANXIOLYTIC AGENTS

Antianxiety or Anxiolytic-sedative, formerly called minor tranquillizers drugs. These control tension and anxiety.

Classification

1.Benzodiazepine

1. Diazepam
2. Chlordiazepoxide
3. Oxazepam
4. Lorazapam
5. Alprazolam.

2. Azapirones

a.Buspirone b. Gepirone C. Ispapirone.

3. Sedative antihistaminic :- Hydroxyzine

4.ß blocker

Propranolol.

1. Benzodiazepine.

Benzodiazepines cause sedation, hypnosis, decreased anxiety muscle relaxation and anti-convulsant action. Clinically the sleep induced by benzodiazepines is more refreshing with less hangover than those produced by barbiturates. In therapeutic doses they do not produce any significant action on respiration, gut and cardiovascular system.

Mode of action of benzodiazepines

Antianxiety effect may be due to stimulation of GABA and glycine (inhibitory transmitters) in limbic system, muscle relaxation is due to inhibition of poly-synaptic reflexes in spinal cord.

 

Clinical uses

1. For anxiety: diazepam, chlordiazepoxide
2. As hypnotic: nitrazepam, flurazepam 4.
3. Asantiepileptic: clonazepam
4. 4.For status epilepticus: I. V. diazepam
5. As anticonvulsant: diazepam I. V., chlordiazepoxide
6. I.M. or 1. V. in tetanus, atropine poisoning, delirium tremens, strychnine poisoning.
7. As premedicament:diazepam
8. As muscle relaxant in chronic spastic disorders : diazepam.

 

Adverse effects

1. Sedation 2. Confusion 3. Lethargy 4. Paradoxical aggression 5. Drug dependence.

 

Other antianxiety drugs

Buspirone

It is the first azapirone, a new class of intensity drugs, distinctly different from BZDs.

1. Does not produce significant sedation or cognitive /functional impairment.
2. Does not interact with BZD receptor or modify GABA ergic transmission.
3. Does not produce tolerance.
4. Does not suppress B Z D or barbiturate withdrawal syndrome.
5. Has no muscle relaxant or anticonvulsant activity.
6. Buspirone relieves mild to moderate generalized anxiety, but is ineffective in severe cases.

Dose: 5-15 mg OD-TDS

Adverse effect

Side effects are minor: dizziness, nausea, ache, light head-edness, rarely excitement.

Hydroxyzine

It is a H, antagonist with sedative, anti emetic and anti cholinergic, antispasmodic and local anaesthetic properties.

Dose

100-200 mg/d; 10-25 mg tablet; 10mg/5 ml syrup; 6 mg/ml drops and 25 mg/2ml injection.

Propranolol and other non selective beta blocker relieve symptoms of anxiety due to sympathetic over activity.

 

Q3. What are antidepressants? Classify them.

Ans: ANTIDEPRESSANT DRUGS

These are drugs used for the treatment of mental depression. They are also called as psychoanaleptics’ or ‘mood elevators.

Classification

• Reversible inhibitors of MAO-A(RIMAS)
• a.Maclobemide
• Clorgyline
• Tricyclic Antidepressants (TCAS)
• Na +5-HT reuptake inhibitors

1. .Imipramine
2. Amitriptyline
3. Trimipramine
4. Doxepin
5. Dothiepin
6. Clomipramine.

B.Predominantly NAreuptake inhibitors

a.Desipramine b. Nortriptyline c. Amoxapine.

 3.Selective serotonin reuptake inhibitors (SSRIs)

1. Fluoxetine b. Fluvoxamine
2. Paroxetine d. Sertraline

4. Atypical antidepressants

• a.Trazodone
• Mianserin,
• Mirtazapine.

1. Reversible inhibitors of MAO-A (RIMAs)

The deficiency of the monoamine neurotransmitter serotonin, dopamine and noradrenaline has been proposed as the cause of depression. MẠO is the major metabolizing enzyme of these neurotransmitters. Thus the MAO inhibitors lead to increase intra neuronal concentration of monoamine transmitters and thereby act as antidepressants.

Types

The MAOIs can be classified as:

A. Non-selective

Hydrazines e.g. phenelzine, isocarboxazide

Nonhydrazines e.g. pargyline, tranylcypromine.

B. Isoenzyme selective

1.Chlorgyline, 2. Deprenyl.

Mechanism of action

Biogenic amines like 5-hydroxy tryptamine, noradrenaline and dopamine are inactivated by the enzyme monomania oxidase (MAO). MAOI inhibit the enzyme MAO. This leads to accumulation of these amines in brain. This produces antidepressant effect.

 Pharmacological actions

1.Behaviour

In case of mental depression, these compounds elevate the mood. The patient feels more energetic and fresh.

 2. Reserpine reversal

In animals pretreated with MAOI, reserpine does not produce drowsiness. Instead, it produces agitation and excitement. This is called as ‘reserpine reversal’.

3. Cardiovascular system

No effect on heart or circulation at normal dose.

4.Potentiation of sympathomimetic amines

These compounds potentiate the action of sympthomimetic amines like amphetamine and tyramine.

 

Pharmacokinetics

These compounds are well absorbed after oral administrate The are quickly metabolised. But they produce long lasting effects.

 

Adverse reactions

1. Behavioural effects

Headache, excitement and disturbed sleep.

2. CNS effects: Twitching, ataxia and tremors.
3. ANS effects: Dry mouth, constipation and blurred vision.

4. Hypertensive crisis

Tyramine is met abolished by the enzyme MAS Food products like cheese contain tyramine. In presence of MAOI tyramine is not metabolised. This leads to accumulation of tyramine. Tyramine produces rise in blood pressure by releasing noradrenaline.

Example

1. Maclobemide

It is a reversible and selective MAO-A inhibitor with short duration of action; full MAO activity is restored within 1-2 days of stopping the drug.

2. Tricyclic Antidepressants (T CAS)

Tricyclic antidepressants chemically related to the phenothiazine tranquillizers and like phenothizanes most of than exert a sedatives effect during the first few days of their use.

 

Mechanism of action of tricyclic antidepressants and related antidepressants.

1. Potentiate the action of biogenic amines, by blocking the inactivating reuptake of amines.
2. They possess antihistaminic (H -receptor blocking) and alpha-adrenergic properties.
3. Possess antimuscarinic action and block reuptake of serotonin Tertiary amines imipramine, amitriptyline) are more effective in blocking serotonin uptake.

 Adverse effects

These include urinary retention, constipation, dry mouth (anticholinergic effects), tremors, hallucinations, excitement convulsions, and hypertension. Postural hypotension, cardiac arrhythmias, aggravation of epilepsy and jaundice have also been reported.

Therapeutic use of TCAS

1. Treatment of endogenous depression
2. Obsessive compulsive and phobic state.
3. Peptic ulcer
4. Enuresis
5. In attention deficit
6. In migraine (headache
7. In pruritus
8. In chronic painful state.

 

Pharmacological action

1.Cardiovascular system

No effect at normal dose. But toxic show cardiac arrhythmias.

2.Autonomic nervous system

Imipramine produces anticholinergic effects like dry mouth, constipation palpitation and blurted vision.

Drugs

Some clinically important tricyclic antidepressants are:

 Imipramine : 75-300 mg it closely related to phenothiazines;

Desipramine : 75-300 mg, less sedative than imipramine;

Nortriptyline : 75-300mg produces less sedation than its parent compound amitriptyline.

 

3. Selective serotonin reuptake inhibitors (SSRIs)

Fluoxetine is a selective inhibitor of serotonin uptake in the CNS. It has little effect on central NE or dopamine function. It has less adverse effects because of minimal binding to cholinergic, histaminic, and alpha-adrenergic receptors.

Pharmacokinetics : It is well absorbed from G 1 T, undergoes extensive hepatic biotransformation to the active metabolite ngrfluoxetine. The inactive metabolites are excreted in the urine.The onset of action is within 1-3 weeks after beginning treatment. The elimination half-life for fluoxetine is 1-3 days and for norfluoxetine 7-15 days.

Uses

It is used for the treatment of mild to moderate endogenous depression,

Adverse effects

Adverse effects include anorexia, nausea, nervousness, headache, and insomnia occur more frequently than with tricyclics. It may precipitate mania or hypomania.

Drugs

1.Paroxetine : It is another short acting SSRI (1,2 20 hours) which does not produce active metabolite. A higher incidence of G. I.

 

4. antidepressants :- A. Trazodone

It is the first atypical anti-depressant; selectively but less efficiently blocks 5-HT uptake and has prominent a blocking well as weak 5-HT, antagonistic action.

B. Tianeptin

It has shown efficacy in antidepressive states particularly with psychosomatic symptoms as well as in endogenous depression. Side effects are dry mouth, epigastric pain, flatulence, drowsiness/insomnia, tremor and body ache.

 

      Q4. What are Antimaniac drugs?

Ans: ANTIMANIC DRUGS

Antimanic (mood stabiliser) used to control mania and to break into cyclic affective disorders. Antidepressants and antimonic drugs are sometimes collectively referred as ‘Drugs for Affective Disorders.

 Drugs

1.Lithium carbonate

Lithium is a monovalent cation. It was found to be sedative in animals ant to exert beneficial effects in manic patients. They are failed to gain popularity because:

1. Response was slow and poorly mensurable.
2. Use without monitoring serum levels was associated with unacceptable toxicity.

 

  Q5. Classify Psychotomimetics.

PSYCHOTOMIMETIC OR HALLUCINOGEN

Hallucinogen is defined as the drugs or agents which alter mood, behavior, thought and perception in a manner similar to that seen is psychosis called hallucinogen. It is also known as psychotomimetic, psychedelics, psychodysleptics and psychotogens.

 

Classification

1. Indole amines

Lysergic acid diethylamide

Lysergic acid amide.

2. Phenylakylamines

Mescaline

3. Cannabinoids

Tetra hydrocannabinol (A’THC)

 

1.Indole amines

1. Lysergic acid diethylamide(LSD)

It is the most potent psychedelic, 25-50 u g produces all the effects.

2. Lysergic acid amide

A close relative of LSD but less potent, found in morning glory (Ipomoea violace) seeds.