be MAO- Inhibitor

(Mono amino oxidase inhibitor)

Types:
Two distinct forms of MAO exists-

MAO A

MAO-B

Functions:
Metabolites the exogenous amines (NA, DP, 5-HT) MAO-A: For NA,5-HT,tyramine metabolism MAO-
B: Causes dopamine metabolism. Inactivation of endogenous and ingested amines.

Mechanism of action of MAO-I:

MAO-I forms stable complexes with MAO-enzyme, irreversibly in actives it, prevents oxidation
deamination of biogenic amines, such as nor-adrenaline, dopamine, serotonin and tramline.

There are two types of MAO-I .Type-A MAO-I, Type -B MAO-I. Type- A MAO-I delaminates serotonin
and nor-adrenaline but not phenyl-etolamine. Type -B MAO-I delaminates phenyl-etholamine better than
serotonin and nor-adrenaline. MAOI-B found in majority into CNS

The non-hydrazied, by its amphetamine like action, releases nor-adrenaline centrally. This probably
accounts for the relative rapidity of action of non-hydrazides in contrast to other MAO-I.

Flow chart

MAO-I

Irreversible inactivation of MAO

Inhibition of breakdown of nor-epinephrine, serotonin, dopamine

 Increase concentration of these4 biogenic amines in the brain, heart, and liver, intestine

Antidepressant action

Overview of the mechanism of action of MAO-I

Pharmacological action of MAO-I

Normal subject: Increase motor activity

Euphoria

Excitement

CNS: Antidepressant action

Reduced REM sleep

CVS: Orthostatic hypotension

Hypertensive crisis (if MAO-I is taken with tramline containing food)

Indication of MAO-I:
1. As anti- depressive agent when other drugs fail.
2. As anti-hypertensive agent
3. In the treatment of angina pectoris
4. Narcolepsy
5. Certain phobic anxiety state

Adverse effects of MAO-I:

1. Hypotension or hypertension
2. Excessive CNS stimulation:
Tremors
Insomnia
Excitement
Convulsions
3. Atropine like side effects:
Constipation
Dry mouth
Blurred vision

4. Weight gain
 5. Ankle edema

Psychotropic Drugs
Drugs that inhibit, sharpen or alter the emotional and behavioral response are called psychotropic drugs

Psychosis:
It is a condition where the patient thinks that he lives in the world of his own and he feels his all action
are major and rational.

Mechanism of action of chlorpromazine

Chlorpromazine

Block D2 D1 receptors

Theory-1:

Anti-psychotic action due to post synaptic inhibition of dopamine receptor in the mesolimbic system

Theory-2:

Extra-pyramidal syndrome due to blockage of post-synaptic receptor in nigrostriatai pathway.

Theory- 3 :

Endocrine effect due to blockage of dopamine receptors in tubero-infudibular dopamine pathway

Pharmacological action of chlorpromazine

CNS effects

1. Anti-psychotic effect:
Apathy
Reduced initiative
2. Extra-pyramidal effect:
Parkinson like symptoms
Tardive dyskinesia
3. Effects on CTZ:
Anti-emetic action
Anti-hiccup action
 4. Effects on hypothalamus:
Hypotension
Hypothermia
5. Endocrine effects

On ANS

1. Postural hypotension
2. Anti-cholinergic and anti-serotonin like action

On CVS

1. Postural or orthostatic hypotension

2. Reflex tachycardia
3. Anti-arrhythmic effect.

On Endocrine system

Chlorpromazine depress hypothalamus and decreases the release of GH,ACTH, oxytocin and
Gonadotropic hormone and increase release of prolactin.

Other effects

1. Analgesia
2. Antihistaminic effect
3. Local anesthetic effects
4. Diuretic effects

Anxiolytic Drugs

Drugs that reduce the physiological anxiety, tension & agitation but do not have
therapeutic effect on disturbance of cognition & perception are called anxiolytic drugs.

Classification of anxiolytic drugs :

1. Benzodiazepines.
- Diazepam.

-Oxazepam.

-Lorazepam,

2. Propyl alcohol : Meprobamate.

 3. Barbiturate : Phenobarbitone.
4. Miscellaneous: Benzoctamine.

Benzodiazepines (BDZs) : The term Benzodiazepine refers the portion of the

structure composed of a benzene ring fused to a seven membered diazepine ring. All
important benzodiazepines contain a 5-aryl substituent. They have sedative, hypnotic,
anti-convulsant & muscle relaxant properties.

Classification of Benzodiazepines:
A. Short acting (t1/2 < 5 hours):
Midazolam
Triazolam
B. Intermediated acting (t1/2 8-15 hours):
Lorazepam
Oxazepam
Temazepam
C. Long acting (t1/2 up to 200 hours):
Diazepam
Halazepam
Nitrazepam
Flurazepam

Site of action of Benzodiazepine:

Limbic system.
Thalamus.
Midbrain reticular formation.
Hypothalamus.

Mechanism of action of BDZs (e.g. Diazepam):

Benzodiazepines

Binds with specific regulatory site on GABA receptor in Brain

Enhance GABA activity

Opening of Cl- channel

Enhance of Cl- conductance



Hyperpolarization of cells

Depression of CNS.

Overview of the mechanism of action of Benzodiazepines

Pharmacological action of BDZs (Diazepam):

CNS effect:
1) Anxiolytic & tensiolytic effects.
2) Sedative & hypnotic effect.
3) Anti-convulsing effect.
4) Skeletal muscle relaxant effect.
5) Anterograde amnesia.

Peripheral action:

1) Neuromuscular blockade (high dose)

2) Coronary vasodilation.

Indication of BDZs (Diazepam):

1) Treatment of anxiety.
2) As sedative-Hypnotics.
3) Preanaesthetic medication.
4) Nightmares, somnambulism (in children).
5) For sedation before medical or surgical procedure.

Contraindication of Diazepam: Myasthenia gravis.

Dose of Diazepam:
Hypnotic dose : 5-15 mg
Lethal dose : 750 mg

Adverse effects of BDZs (Diazepam):

a) Normal therapeutic dose:

Dry mouth.
Light headache.
Lassitude.
 Confusion, etc.
b) Acute overdose: prolong sleep.

c) Tolerance & dependency.

Ganglion Blocking Agents

Ganglion blockers are the agents which block the nicotinic receptors at autonomic
ganglia, including adrenal medulla & neuromuscular junction.

Classification of Ganglion blockers:

a. Competitive ( non-depolarizing)
1) Quaternary ammonium compounds:
Methodism group
- Penta-methonium
- Hexa-methonium
Sulfonium group: Trimethophan.
2) Tertiary amines:
Pempidine
Trimethophan
3) Secondary amines: Mecamylamine.
b. Non-competitive (polarizing)
Gelsenium.
Nicotine
Lobelline

Mechanism of action of Ganglion blockers:

1. They compete with Ach. For nicotinic receptor on the post-synaptic membrane.
2. They produce persistence depolarization of post-synaptic membrane, which can
stabilize the membrane to the action of Ach.

Cholinergic Drugs

Drugs, which act on acetylcholine receptors and evoke response similar to those , which result
from cholinergic nerve stimulation, are called cholinergic drugs.

Classification of cholinergic drugs:

 Direct acting
1 Choline esters
Acetylcholine
Methacholine
Carbachol
2 Natural cholinomimetic alkaloids
Pilocarpine
Arecoline
Nicotine
Indirect acting
1 Reversible
Physostigmine
Neostigmine
Endrophonium
2 Irreversible (OPC)
Chlorothion
Malathion
Diainon

Acetylcholine

Acetylcholine is a major neurohormonal transmitter at autonomic, somatic, as well as central

site.

Pharmacological action of acetylcholine:

Muscarinic action:
On cardiac muscle:
Depress the cardiac muscle by stimulating vagus nerve & produce-
1 -v inotropic action: Decrease force of contraction
2 -ve chronotropic action: Decrease heart rate (bradycardia)
3 -ve Bathmotropic action: Decrease conductivity.
4 -ve dromotropic action: Decrease automaticity.
5 Decrease stroke volume & cardiac output.

(The net effect: fall of blood pressure.)

 On smooth Muscles:
** On eye:
1 Miosis (due to contraction of circular muscle)
2 Accommodation of near vision
3 Decrease intraocular pressure.
4 Increase lacrimal secration.
** On lungs:

1 Bronchoconstriction
2 Increase bronchial secretion.

** On GIT:
1 Increase HCL secretion.
2 Increase intestinal secretion.
3 Increase motility.
4 Sphincter relaxation.
Nicotinic action:
On autonomic ganglia:
CVS:
Tachycardia
Increase blood pressure
GIT:

Increase motility
Increase secretion

ON CNS:
Insomnia
Restlessness
Anxiety
Therapeutic value of Acetylcholine:

Acetylcholine has a very little therapeutic value, because:

It is rapidly hydrolyzed by cholinesterase, so it has very short duration of action.

It has very less selective activity and more toxic effect.
Clinical uses of acetylcholine:

Treatment of glaucoma
Urinary bladder agony
Supraventricular tachycardia
Cerebrospinal diseases
 After bowel surgery
Contraindication of Acetylcholine:

Bronchial asthma
Peptic ulcer diseases
Myocardial infarction
Hyperthyroidism
Obstructive urinary retention
Adverse effect of Acetylcholine:

Mild:

Lacrimation
Salivation
Bradycardia
Sever:

Hypotension
Bronchospasm
Cardiac arrhythmia

Tricyclic Antidepressants
Amitriptyline is widely used anti-depressant, because it is most effective and less toxic than
MAO inhibitors.

Tricyclic anti-depressant (TCA) are so called because their structure contain three benzene rings.

Mechanism of action of TCA:

Tricyclic antidepressant

Inhibit the reuptake pump of biogenic amines (norepinephrine,

Serotonin,dopamine)
 Increase concentration of amines in the brain

Longer duration of action of amines at the receptor site

Antidepressant action

Pharmacological action of TCA:

CNS : Normal subject:

Sleepiness
Light headache
Anti-cholinergic effects
(Dry mouth,blurred vision)

Depressed patient: Blurred

Elevation of mood

ANS : Antimuscarinic (atropine like) action

Dry mouth
Blurred vision
Constipation
Urinary retention
Postural hypotension

CVS : Orthostatic hypotensis, Arrythmia, mild sinus tachycardia .

ECG: inversion / flattening of T waves

Advers Effect:
1. Anti-cholinergic effect:
Drynesss of mouth
Blurred vision
constipation
Urinary retention

2. CNS effect:
 Sedation
Tremor
Agitation
Confusion
Parkinsonism

3.CVS effect:

Tacycardia
Hypertension
Arrythmia

4.Agranulocytosis

5.Choleastic jaundice

Indication of Amitriptyline (TCA)

1. As antidepressant
2. Nocturnal enuresis
3. Chronic pain
4. Multiple sclerosis
5. Phobic anexiety syndrome
6. Hyperkinesis in children
7. Peptic ulcer
8. Minimal brain damage
9. Alcoholism
10. Neurosis , Neuraglia, Migranine

Contraindication of TCA:

Ischemic heart disease

Cardiac arrhythmia
Pregnancy and lactation
Severe liver damage
Following MAO-I within last two weeks

Acute toxicity of TCA:

Overdose of TCA causes toxicity. The main effects are on the CNS and heart.

On CNS: Excitement, Delirium , Convulsions, Coma

ON heart: cardiac arrhythmia ,hypertension

Treatment of acute TCA toxicity:

 Activated charcoal
Gastric lavage
Physostigmine
Anti- arrhythmic drugs
Anti- convulsants:Diazipum

Anti choliaesterase:
Drugs which inhibit the inzyme choliaestrerase and so increase the cholinergic
activity are called anti cholinesterase .

Mechanism of anti CHE .

Anti-ChE

Inhibits enzyme ChE

 Prevent hydrolysis of cholinester

Increase conc of cholinest

Prolonging action of cholinester

Pharmacological action of anti ChE :

Eye : congitival hyperaemia

Decreasa intraocular pressure

GI tract: Increase gastric HCl secretion

Increase gastric contraction

Skeletal NMJ: Therapeutic dose :increase strength of muscle contraction

Highdose :fibrillation of muscle fibre

Other actions:

CVS: Decrease hert rat

BP: No change or a modest fall

Indication of anti-ChE:
Physostigmine:

1 Glaucoma
2 Atropine poisoning
Neostigmine:

1.Paralytic ileus

2.Urinary retention

3.Paroxysmal tachycardia

Endrophonium:

1.Paroxysmal supravantricular tachycardia

2.Myasthenia gravis
 Tricyclic
Antidepressants
Amitriptyline is widely used anti-depressant, because it is most effective and less
toxic than MAO inhibitors.

Tricyclic anti-depressant (TCA) are so called because their structure contain three
benzene rings.

Mechanism of action of TCA:

Tricyclic antidepressant

Inhibit the reuptake pump of biogenic amines

(norepinephrine,

Serotonin,dopamine)

Increase concentration of amines in the brain

Longer duration of action of amines at the receptor site

Antidepressant action

Pharmacological action of TCA:

CNS : Normal subject:

Sleepiness
Light headache
Anti-cholinergic effects
(Dry mouth,blurred vision)
 Depressed patient: Blurred

Elevation of mood

ANS : Antimuscarinic (atropine like) action

Dry mouth
Blurred vision
Constipation
Urinary retention
Postural hypotension

CVS : Orthostatic hypotensis, Arrythmia, mild sinus tachycardia .

ECG: inversion / flattening of T waves

Advers Effect:

3. Anti-cholinergic effect:
Drynesss of mouth
Blurred vision
constipation
Urinary retention

4. CNS effect:
Sedation
Tremor
Agitation
Confusion
Parkinsonism

3.CVS effect:

Tacycardia
Hypertension
Arrythmia

4.Agranulocytosis
 5.Choleastic jaundice

Indication of Amitriptyline (TCA)

11.As antidepressant
12.Nocturnal enuresis
13.Chronic pain
14.Multiple sclerosis
15.Phobic anexiety syndrome
16.Hyperkinesis in children
17.Peptic ulcer
18.Minimal brain damage
19.Alcoholism
20.Neurosis , Neuraglia, Migranine

Contraindication of TCA:

Ischemic heart disease

Cardiac arrhythmia
Pregnancy and lactation
Severe liver damage
Following MAO-I within last two weeks

Acute toxicity of TCA:

Overdose of TCA causes toxicity. The main effects are on the CNS
and heart.

On CNS: Excitement, Delirium , Convulsions, Coma

ON heart: cardiac arrhythmia ,hypertension

Treatment of acute TCA toxicity:

Activated charcoal
Gastric lavage
Physostigmine
Anti- arrhythmic drugs
Anti- convulsants:Diazipum
 Prazosin
Mini-Press

It is very potent and selective alpha-1 adrenoreceptor antagonist.

a) It has thousand folds greater affinity for alpha-1 receptor than alpha-2
receptor.
b) Rout of administration oral.
c) Plasma half-life:3 hours

Mode of action of prazosin

Direct action: Vasodialation,so decrease B.P.

Blocks alpha-1receptor (vascular smooth muscle): vasodialation

Pharmacological action of prazosin

Relaxes vascular smooth muscles

Decrease T.P.R
Decrease venous return
Reduce B.P(mainly diastolic)
Conserves Na+ and water
Plasma volume increase
Relieves pulmonary congestion
Reduces both left ventricular end diastolic volume and aortic impedance to
left ventricular ejection in CCF

Indication` of prazosin

Mild to moderate hypertension

 CCF
Raynauds disease
Prinzmetal angina

Adveres effects

First dose effect (severe postural hypotension sufficient to cause loss of

consciousness)
Synocope, headcache, dizziness, and palpitation.

To overcome first dose effect of prazosin

Treatment should be start with a low dose ,with food.

First dose should be given at night on going to bed.
Dose gradually increase.