Analeptic
ANALEPTICS
Analeptics are CNS Stimulant. They are used to treat CNS
depression, Attention deficit hyperactivity disorder.(ADHD) and respiratory
depression. They were used to counter
CNS depressant intoxication. They have very low therapeutic index thus they are
not preferred by physicians. They have little clinical use but they are
important as drug of abuse. They can be divided into two groups
1. Psychomotor Stimulants
a.
Methylxanthiene
(Caffeine, Theobromine and Theophyline),
b.
Amphetamine,
c.
Cocaine,
d.
Methylphenidate,
e.
Nicotine,
2. Psychotomimetic drug(Hallucinogens or psychedelic agents)
a.
Lysergic Acid
diethylamide (LSD),
b.
Phencyclidine (PCP),
c.
Tetra hydro cannabonol (THC)
Psychomotor Stimulant: They elevate
mood, sense of physical and metal well being, self esteem, euphoria and
alertness, decrease appetite and need for sleep, dull pain sensation. Over dose
produces anxiety and dysphoria. Their acute administration induces mydriasis,
diaphoresis, hypertension, tachycardia, anorexia. Their high dose causes mental
confusion and cardiac arrhythmias. Chronic use causes reversible psychosis.
Paranoid behaviour hallucination, delusion, aggressiveness, hyperactivity,
anxiety and irrational bizarre behaviour are some symptoms of chronic use of
psychomotor stimulants. They also unmask symptoms of latent schizophrenia.
Adverse effect: They have low therapeutic index. They induce
serious adverse effects like cardiac arrhythmias, myocardial infractions,
myocarditis, cerebrovascular spasm, hypertension, intracerebral hemerhage, respiratory
depression convulsion and hyperpyrexia. Long term use may cause hepatic and
renal failure.
Pharmacodynamics: They act as
noradrenergic and dopaminergic agonist.
METHYL XANTHINES: They are natural
analeptic agents. Ex. Caffeine (Present in Coffee seeds and tea leaves),
Theobromine (Present in Cocoa and coffee seeds) and Theophylline (Present in
tea leaves.) Caffeine is most widely used CNS
stimulant. Coffee has highest
concentration of caffeine. It is also found in tea, chocolate candy, cold
drinks, cocoa, and energy drinks etc.
Mechanism of Action: Methyl xantheines
act at cellular level to stimulate CNS.
1.
They inhibit enzyme Phosphodiestearase and
2.
Block adenosine
receptors
to increase concentration of c
AMP (Cyclo Adenosine monophosphate) and
c GMP (cyclo guanosine monophosphate).
Cyclo Adenosine monophosphate and cyclo guanosine monophosphate act as
chemical messanger for intracellular signal transduction (transmission) in CNS.
This helps to increase mental alertness.
3.
They increase
intracellular calcium ion in skeletal muscles and cardiac muscles to induce to
decrease fatigue.
Pharmacological Actions
1. Central nervous
System: Among all three caffeine is most
active and theobromine is least active CNS stimulant. Small dose decreases
fatigue and improve physical performance. High dose improves mental alertness,
sense of well being, thought process and sleep disturbance. Slightly high dose
produces anxiety, excitement, nervousness, tremor and confusion.
One to two cups of coffee contain
100 to 200 mg caffeine. This dose produces relief from skeletal muscle fatigue,
increases mental alertness by stimulating brain cortex and other parts. 10 to
15 cups of coffee contain about 1.5 gm caffeine It produces anxiety and tremor.
Very high dose 2 to 5 gm caffeine stimulate spinal cord
2. Cardiovascular
system: Caffeine induces inotropic and
chronotropic effect on heart in high dose. This inotropic and chronotropic
effect is harmful for patient suffering from angina pectoris and other heart
diseases.
3. Kidney: Among all three
theophulline is more potent than caffeine as diuretic. These drugs are mild
diuretic. They increase excretion of sodium, potassium and chloride by
increasing their glomerular filtration and inhibiting their renal reabsorption.
4. Smooth Muscles:
Among all three theophylline is more
effective smooth muscle relaxant. They have
muscle relaxant effect on smooth muscles especially on bronchial muscles. This
effect produces bronchodilation. It is used in treatment of asthma
5. Skeletal
muscle: Among all three caffeine is more
effective to increase tonicity of skeletal muscles. They increase contractile
power of skeletal muscles. This property is used to treat skeletal muscle
fatigue.
6. GIT: They stimulate secretion of hydrochloric acid and pepsin
into stomach. Due to this consumption of tea, coffee, caffeine containing
beverages etc in empty stomach promote peptic ulcer. Among all three
theophylline is more dangerous to produce peptic ulcer.
THERAPEUTIC USES:
1. Bronchodilator: Theophylline is widely used as bronchodilator to treat
bronchial asthma. All methyl xanthines have bronchodilator effect. But β agonists and corticosteroids have largely replaced
methylxanthines in management of asthma.
2. CNS Stimulant: Caffeine is usually mixed with analgesics to produce
relief from body pain and headache due to fatigue.
PHARMACOKINETICS: Methyl xanthenes
are well absorbed from GIT, well distributed throughout body, cross blood brain
barrier and placental barrier. They are metabolised in liver by demethylation
and oxidation. Active drug and their metabolites are excreted through urine and
breast milk.
Adverse effects: Moderate dose
causes insomnia. Slightly high dose causes anxiety, excitement, nervousness,
tremor and confusion. They have very high therapeutic index even very high dose
does not cause death. High dose shows vomiting and convulsion. About 10 gm
caffeine induces cardiac arrhythmias. Theophylline is more toxic than caffeine.
NICOTINE
Caffeine is most widely used CNS
stimulant. Nicotine is second most widely used CNS stimulant. Similarly alcohol
is most abused drug. Nicotine is second most abused drug. Nicotine is active
constituent of tobacco. It is not therapeutically used.
Pharmacodynamics: Nicotine
acts as ganglionic stimulant at low dose and ganglionic blockade at high dose.
Nicotinic receptor exists in CNS. Initially nicotine stimulates nicotinic
receptor then block it.
Pharmacological Actions:
1. Central Nervous
System: Nicotine is highly lipid
soluble. It crosses BBB rapidly. In low dose it stimulates CNS and produces
euphoria, improve attention, learning, problem solving, reaction time along
with relaxation. In high dose it depresses CNS, causes hypotension and
respiratory paralysis.
2. Cardiovascular
System: Nicotine stimulates autonomic
ganglia, adrenal medulla to produce vasoconstriction, increase blood pressure,
tachycardia and cardiac arrhythmias. It stimulates release of antidiuretic
hormone. This also causes constriction of peripheral and coronary blood vessel.
Thus use of tobacco by hypertensive and heart patient is very harmful.
3. Gastrointestinal
Tract effect: It stimulates salivary and
bronchial secretion. It stimulates chemoreceptor zone to produce nausea and
vomiting, It stimulates gastric acid secretion that delays peptic ulcer
healing. It increases motor activity in bowel.
4. Enzyme effect: It stimulates enzymes activity in intestine, liver that
alters metabolism of other drugs.
Pharmacokinetics: Nicotine is
highly soluble in lipid. It is absorbed from intact skin, oral mucosa, GIT
mucosa and lungs. It can cross blood brain barrier, placental barrier and
secreted through breast milk. It is metabolised in liver and excreted through
urine and breast milk both in free and metabolite form.
Tolerance: Nicotine has
several toxic effects. Tolerance to toxic effect of nicotine develops very
quickly. Ex. Nausea, vomiting, sweating, fall in blood pressure occurs in first
time smokers. Tolerance to these effects develops very rapidly. Tolerance to
bowel activity and tachycardia does not develop.
Withdrawal Symptoms: Nicotine is addictive drug. Dependence to nicotine
develops very quickly. Withdrawal symptoms are headache, irritability,
restlessness, anxiety, concentration difficulty and insomnia. Withdrawal
symptoms in smokers can be controlled by using nicotine transdermal patch or
nicotine chewing gum. Nicotine transdermal patch or nicotine chewing gum produces
concentration of nicotine in blood very less than cigarettes.
COCAINE
It is self administered by
chewing, intranasal snoring, smoking and intravenous injection. Cocaine is
highly addictive drug. It increases dopaminergic and noradrenergic activity. It
blocks serotonin, dopamine and nor-epinephrine reuptake blockade at pre-synaptic
terminals. This blockade enhances and extends duration of action of these
neurotransmitters. This affects limbic
system and produces euphoria. Chronic use of cocaine depletes dopamine. This
increases craving for cocaine and produces addiction.
Pharmacological Actions:
A. Behavioural effects: It
acts as psychostimulant. It elevates mood, self esteem, physical and mental
well being, Physical and mental alertness, euphoria, decreases appetite
(anorexia) and need of sleep. Acute
use produces mydriasis, diaphoresis, hypertension and tachycardia. High dose may cause mental confusion and
arrhythmias.
B. Sympathetic
nervous system: It stimulates
sympathetic nervous system and increases activity of norepinephrine to produce
“fight and flight” characteristics.
Therapeutic Uses: Cocaine is used as local anesthetic during nose, ear, eye
and throat surgery. It blocks activated sodium channel and interact with
potassium channel to produce anesthetic effect. It also acts as
vasoconstrictor.
Adverse effects: It has very rapid onset of action and short lived effect.
Thus there is great chance of over dose and drug dependence. It produces
following adverse effects:
1. Anxiety: Hypertension,
tachycardia, sweating and paranoia (psychosis), Hyperpyrexia, Convulsion.
2. Depression: CNS stimulation followed by mental depression.
Respiratory depression,
3. Cardiac
Disease: Myocardial infarction,
Myocarditis, fatal cardiac arrhythmias
4. Rhabdomyolysis:
It is rapid break down of damaged skeletal
muscles. Symptoms are muscle pain, weakness, vomiting and confusion. It may be
associated with kidney and liver failure.
AMPHETAMINE: Amphetamine is
adrenergic CNS stimulant. It produces action by increasing release of
intracellular catecholamines (Norepinephrine, Serotonin and dopamine) and
inhibiting Monoamine Oxidase (MAO).
Pharmacokinetics: It is
completely absorbed from GIT, metabolised in liver and excreted through kidney.
Pharmacological Actions:
1. Central Nervous
System: It stimulates CNS. It is potent drug. It produces
euphoria i.e. 4 to 6 times longer than effect euphoric effect of cocaine. It
shows addiction, dependence, tolerance and drug seeking behaviour.
CNS stimulant effect depends upon
dose of amphetamine.
a. In low dose:10 to 30 mg dose, It produces
i.
increases alertness, mental concentration,
wakefulness and physical performance
ii.
reduces fatigue,
apetite
iii.
Insomnia
b. In high dose more than 30 mg it produces
i.
Respiratory
stimulation
ii.
Convulsion and
coma.
2. Sympathetic
nervous system: It stimulates adrenergic
system.
Therapeutic Uses: Several safe and more selectively acting drugs has
reduced its use. However it has following therapeutic uses:
1. Hyperkinetic
syndrome: It is hyper activity and attention
deficit syndrome (lack of ability to concentrate on one activity for more than
few minutes). Usually it occurs in children. Amphetamine reduces hyper kinesis
and prolongs attention.
2. Narcolepsy: It is uncontrollable desire for sleep or sudden desire
of sleep in appropriatesituation. It can be treated by Amphetamine or its
derivative methylphenidate.
3. Anorexiant: To treat obesity.
Adverse effect:
1. Central nervous
System: Insomnia, irritability,
weakness, dizziness, tremor, hyperactive reflex. Confusion, delirium, panic
state, suicidal tendency. Chronic use causes amphetamine psychosis. Overdose of
amphetamine can be treated by chlorpromazine.
2. Cardivascular
effects: Palpitation, cardiac arrhythmias, hypertension angina
pain, circulatory collapse. Cardiovascular effect also produces headache,
chills and sweatinh
PSYCHOTOMIMETIC
DRUG (HALLUCINOGENS OR PSYCHEDELIC AGENTS):
Hallucinogens cause profound destortion in peroson’s
perception of reality. It is accompanied by bright, colourful changes in
perception along with constantly change in colour and shapes. It interferes in
normal thought process and person will not be able to take rational decision.
It elevates mood, behaviour and perception. Thus it is called psychomimetic
drug,
1. Lycergic acid
diethylamide (LSD): It is very potent drug. It produces action in very low
dose. It is rapidly absorbed from GIT and effects last for 2-4 hours that
disappear in 6 hours. Extent of effect varies from person to person and time to
time. Tolerance develops to dose but it does not produce addiction or
dependence.
It acts as serotonin (5 HT)
agonist. It activates sympathetic nervous system to produce papillary dilation,
increase in blood pressure and temperature, flushing. Tachycardia, lacrrmation,
hyperreflexia
In low dose, 25 to 50 µg, it produces hallucination, perceptual changes and mood
change, Mood change may be euphoric (ecstasy) fear or depression. Occasionally
feeling of panic, severe anxiety, intense depression, suicidal thoughts and
visual disturbance may appear. These symptoms are termed as bad trip. It can be treated by
diazepam.
2. Phencyclidine (PCP): PCP
acts as dissociative anesthesia (insensitive to pain, remain consciousness, flat
face, rigid muscle, slurred speech, staggered gait, numbness in extremities and
staring gaze) and analgesic. In very low dose, it induces emotional withdrawal, strange response,
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