CNS Stimulants

Dr. Nadeem akhtar

MBBS.M.Phil

Asst. Professor Pharmacology

Amna Inayat Medical College

Shaikhupura

CEREBRAL STIMULANTS

AND

HULLUCINOGENS

Cerebrostimulants

1. Caffeine

2. Nicotine

3. Amphetamines

4. Cocaine

Caffeine

• Caffeine is most widely consumed CNS stimulant.

• A cup of instant coffee or strong tea contains 50-70mg of caffeine

• Average daily consumption is about 200mg, in tea & coffee drinking countries

• Nuts of cola plant also contain caffeine• CNS stimulation & Diuresis are its

pharmacological actions• Main psychological effects are remove fatigue and

improve mental performance

Mode of action

• Antagonize adenosine receptors

• Activates nor-adrenaline neurons

• Effect the local release of dopamine & glutamate

Effects on different body function

• CVS: produce positive ionotrpic and chronotropic effects on heart.

• GIT: increase gastric secretions, therefore should be avoided in peptic or gastric ulcer

• Urinary system: produce mild diuretic action & increase urinary output of elctrolytes.

Clinical uses

• Caffeine relax the smooth muscle of bronchioles therefore effective in asthma

• It is included with aspirin or paracetamol in some preparations to treat headaches or other aches

Nicotine

• Nicotine is named after the tobacco plant Nicotiana tabacuma which acts as a nicotinic acetylcholine receptor agonist.

• Average 1 cigarette yields about 1 mg nicotine. As nicotine enters body it quickly distributed throughout blood stream and crosses BBB reaching brain within 10-20 seconds after inhalation.

• Eliminatin half life is 2 hrs

• Metabolized in liver by cytochrome P450 enzyme system mostly by CY2A6 & CY2B6

• Major metabolite is cotinine

• By binding to nicotinic acetylcholine receptors, it increases the level of several neurotransmitters in the brain.

• Tobacco smoke contains monamine oxidase inhibitors.

• Powerful interaction between MAOs and Nicotine are responsible for addictive effects of smoking

Withdrawal

• Nicotine withdrawal is mild as compared to opiods and involves irritability with insomnia .

• Nicotine is among the most addictive drugs and relapse after attempted cessation is common

Treatment

• Antidepressant BUPROPION is approved for nicotinic cessation therapy .

• It is most effective when combined with behavioral therapies

Amphetamines

• Amphetamines are group of synthetic, indirect acting sympathomi metic drugs that cause the release of endogenous biogenic amines such as dopamine and noradrenaline.

Mechanism of action

• It stimulate both alpha & beta adrenoreceptors through an indirect mechanism(by release of intracellular catecholamines and MAOs blockade)

Pharmacological effects

• CNS: Psychic stimulation resulting in feeling of euphoria, self confidence, wakefulness, alertness with increase mental and physical activities.

• It has anti-fatigue & analeptic action

• It has mild analgesic properties, also increase analgesic effect of opiod and decrease effect of nitric oxide

• It depress appetite by central action on hypothalamus feeding centers by reduction sense of smell and taste

• Chronic abuse leads to psychotic state with delusion and paranoia like schizophrenia.

• CVS: increase BP and reflex bradycardia with large doses may cause arythmias

Clinical uses

Narcolepsy (its derivative methylphenidate is more better).

Hyperkinetic syndrome(attention deficit disorder)

Nocturnal enuresis

As nasal decongestant

Adverse effects

• Dysphoria, confusion, headache, mental depressan, psychosis, confusion, , arythmia, anginal pain, dry mouth , anorexia, vomiting.

• Overdose is treated by CHLOROPROMAZINE

Cocaine

• Cocaine is alkaloid found in the leaves of Erythroxylon coca.

• A shrub endogenous to the Andes.

• For more than 100 years it has been used in clinical medicine as a local anesthetic agent and to dilate the pupil in ophthalmology.

Mechanism of action

• In CNS cocaine blocks the uptake of dopamine, noradrenaline, and serotonin through their respective transporters.

• The block of dopamine transporter by increasing dopamine concentration in the nucleolus accubens has been indicated in reward effect of cocaine.

Adverse effects

• Loss of appetite

• Hyperactivity

• Intracranial hemorrhage

• Ischemic stroke

• Myocardial infarction

• Seizure

• Hyperthermia, coma &death on high doses

HALLUCINOGENS

Hallucination: is a sense or perception(sight, touch, smell, sound or taste) that has no basis of external stimulation.

Hallucinogens are characterized as agents which produce hallucinations

Cannabinoids

• 1)Endogenous cannabinoids: these

• include 2-arachidonyl (2-AG) &

anandamide, both bind to CB1 receptors where they inhibit release of either Glutamate or GABA receptors.

• Due to this backward signaling they are called retrograde Messengers'

• Exogenous cannabinoids:

• These include Marijuna and other pharmacological active substances like Tetrahydrocannabinol (THC)

Tetrahydrocannabinol (THC)

• This is a powerful psychoactive substance like opiods

• Causes release of Dopamine neurons mainly by pre-synaptic inhibition of GABA neuron in the VTA

• Half life of THC is about 4 hrs

• The onset of effect of THC after smoking marijuna occur within minute

• The prominent effects are euphoria, relaxation , feelings of well being, grandiosity and altered perception of passage of time

• Dose dependant perceptual changes(vision distortion)

• Drowsiness, diminished coordination and memory impairment may occur

• Rarely Cannabinoids create dysphoric state with higher doses

• Hashish ------ produce visional hallucination, depersonalization and frank psychotic episodes

• Increase appetite, nausea, decrease intraocular pressure and relief of chronic pain

• Chronic use of marijuna produce dependency with mild withdrawal symptoms, like restlessness, irritability, mild agitation and insomnia.

Lysergic acid diethylamide(LSD)

• Multiple sites in CNS are affected by LSD

• It shows agonistic activity at presynaptic 5HTI receptors in the midbrain and stimulates 5H2 receptors

Physical effects

• LSD can cause pupil dilatation

• Reduce or increase appetite

• Increased wakefulness, numbness, hypo or hyperthermia, elevated blood sugar, increase heart rate, jaw clenching.

• LSD is not considered addictive drug

Psychological effects

• Vary greatly from person to person

• Some users cite the LSD experience causing significant change in life pattern

• Some perceive radiant bright colors behind the closed eye lids(imagery) and altered sense of time & space

• This intuitive quality may play a role in spiritual and religeous aspects of LSD

Clinical uses

• Alcoholism (diazepines are more better)

• Painful conditions

• Cluster headache

• End of life anxiety: study conducted in Switzerland (2008-2011)on patients who were in terminal illnesses and were counting their days. They were treated with LSD and showed promising results

• LSD is taken orally from 100- 500 micrograms.

• Adverse effects: hyperreflexia, nausea, muscular weakness

• With high doses psychotic changes occur which are relieved by haloperidol

Phencyclidine

• It is also called angel dust

• Inhibit the reuptake of dopamine, 5HT, and norepinephrine

• It causes dissociative anesthesia (insensitivity to pain without loss of consciousness)

• Tolerance often produce with continued use