Caffeine• Caffeine is most widely consumed CNSstimulant.• A cup of instant coffee or strong teacontains 50-70mg of caffeine• Average daily consumption is about200mg, in tea & coffee drinking countries• Nuts of cola plant also contain caffeine• CNS stimulation & Diuresis are itspharmacological actions• Main psychological effects are remove
Mode of action• Antagonize adenosine receptors• Activates nor-adrenaline neurons• Effect the local release of dopamine &glutamate
Effects on different bodyfunction• CVS: produce positive ionotrpic andchronotropic effects on heart.• GIT: increase gastric secretions, thereforeshould be avoided in peptic or gastriculcer• Urinary system: produce mild diureticaction & increase urinary output ofelctrolytes.
Clinical uses• Caffeine relax the smooth muscle ofbronchioles therefore effective in asthma• It is included with aspirin or paracetamol insome preparations to treat headaches orother aches
Nicotine• Nicotine is named after the tobacco plantNicotiana tabacuma which acts as anicotinic acetylcholine receptor agonist.• Average 1 cigarette yields about 1 mgnicotine. As nicotine enters body it quicklydistributed throughout blood stream andcrosses BBB reaching brain within 10-20seconds after inhalation.• Eliminatin half life is 2 hrs
• Metabolized in liver by cytochrome P450enzyme system mostly by CY2A6 &CY2B6• Major metabolite is cotinine
• By binding to nicotinic acetylcholinereceptors, it increases the level of severalneurotransmitters in the brain.• Tobacco smoke contains monamineoxidase inhibitors.• Powerful interaction between MAOs andNicotine are responsible for addictiveeffects of smoking
Withdrawal• Nicotine withdrawal is mild as compared toopiods and involves irritability withinsomnia .• Nicotine is among the most addictivedrugs and relapse after attemptedcessation is common
Treatment• Antidepressant BUPROPION is approvedfor nicotinic cessation therapy .• It is most effective when combined withbehavioral therapies
Amphetamines• Amphetamines are group of synthetic,indirect acting sympathomi metic drugsthat cause the release of endogenousbiogenic amines such as dopamine andnoradrenaline.
Mechanism of action• It stimulate both alpha & betaadrenoreceptors through an indirectmechanism(by release of intracellularcatecholamines and MAOs blockade)
Pharmacological effects• CNS: Psychic stimulation resulting infeeling of euphoria, self confidence,wakefulness, alertness with increasemental and physical activities.• It has anti-fatigue & analeptic action• It has mild analgesic properties, alsoincrease analgesic effect of opiod anddecrease effect of nitric oxide
• It depress appetite by central action onhypothalamus feeding centers byreduction sense of smell and taste• Chronic abuse leads to psychotic statewith delusion and paranoia likeschizophrenia.• CVS: increase BP and reflex bradycardiawith large doses may cause arythmias
Cocaine• Cocaine is alkaloid found in the leaves ofErythroxylon coca.• A shrub endogenous to the Andes.• For more than 100 years it has been usedin clinical medicine as a local anestheticagent and to dilate the pupil inophthalmology.
Mechanism of action• In CNS cocaine blocks the uptake ofdopamine, noradrenaline, and serotoninthrough their respective transporters.• The block of dopamine transporter byincreasing dopamine concentration in thenucleolus accubens has been indicated inreward effect of cocaine.
Adverse effects• Loss of appetite• Hyperactivity• Intracranial hemorrhage• Ischemic stroke• Myocardial infarction• Seizure• Hyperthermia, coma &death on highdoses
HALLUCINOGENSHallucination: is a sense or perception(sight,touch, smell, sound or taste) that has nobasis of external stimulation.Hallucinogens are characterized as agentswhich produce hallucinations
Cannabinoids• 1)Endogenous cannabinoids: these• include 2-arachidonyl (2-AG) &anandamide, both bind to CB1 receptorswhere they inhibit release of eitherGlutamate or GABA receptors.• Due to this backward signaling they arecalled retrograde Messengers
• Exogenous cannabinoids:• These include Marijuna and otherpharmacological active substances likeTetrahydrocannabinol (THC)
Tetrahydrocannabinol (THC)• This is a powerful psychoactive substancelike opiods• Causes release of Dopamine neuronsmainly by pre-synaptic inhibition of GABAneuron in the VTA• Half life of THC is about 4 hrs• The onset of effect of THC after smokingmarijuna occur within minute
• The prominent effects are euphoria,relaxation , feelings of well being,grandiosity and altered perception ofpassage of time• Dose dependant perceptualchanges(vision distortion)• Drowsiness, diminished coordination andmemory impairment may occur
• Rarely Cannabinoids create dysphoricstate with higher doses• Hashish ------ produce visionalhallucination, depersonalization and frankpsychotic episodes• Increase appetite, nausea, decreaseintraocular pressure and relief of chronicpain
• Chronic use of marijuna producedependency with mild withdrawalsymptoms, like restlessness, irritability,mild agitation and insomnia.
Lysergic acid diethylamide(LSD)• Multiple sites in CNS are affected by LSD• It shows agonistic activity at presynaptic5HTI receptors in the midbrain andstimulates 5H2 receptors
Physical effects• LSD can cause pupil dilatation• Reduce or increase appetite• Increased wakefulness, numbness, hypoor 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 experiencecausing significant change in life pattern• Some perceive radiant bright colorsbehind the closed eye lids(imagery) andaltered sense of time & space• This intuitive quality may play a role inspiritual and religeous aspects of LSD
Clinical uses• Alcoholism (diazepines are more better)• Painful conditions• Cluster headache• End of life anxiety: study conducted inSwitzerland (2008-2011)on patients whowere in terminal illnesses and werecounting their days. They were treatedwith LSD and showed promising results
• LSD is taken orally from 100- 500micrograms.• Adverse effects: hyperreflexia, nausea,muscular weakness• With high doses psychotic changes occurwhich 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 ofconsciousness)• Tolerance often produce with continueduse