CNS stimulants

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CNS Stimulants: 

CNS Stimulants Dr Sadia Batool Senior Lecturer Pharmacology Dept IMDC

CNS Stimulants: 

CNS Stimulants Have predominantly stimulant effect on the central nervous system Convulsants and respiratory stimulants Psychomotor stimulants Hallucinogens

CONVULSANTS AND RESPIRATORY STIMULANTS : 

CONVULSANTS AND RESPIRATORY STIMULANTS Little effect on mental function Act mainly on the brain stem and spinal cord Higher dosage causes convulsions Sometimes called analeptics

Slide 4: 

Strychnine Picrotoxin Pentylenetetrazol ( PTZ ) Doxapram Are of interest as experimental tools but have no clinical uses.

Strychnine: 

Strychnine Is an alkaloid found in the seeds of an Indian tree Has been used for centuries as a poison It is a powerful convulsant Acts throughout the CNS Particularly on the spinal cord causing violent extensor spasms triggered by minor sensory stimuli ( opisthotonus )t. Effects result from blocking receptors for glycine ( main inhibitory transmitter acting on motor neurons)

Bicuculline: 

Bicuculline A plant alkaloid, resembles strychnine in its effects Acts by blocking receptors for GABA Its main effects are on the brain rather than the spinal cord Is a useful experimental tool for studying GABA-mediated transmission; it has no clinical uses

Picrotoxin: 

Picrotoxin Obtained from the fishberry also blocks the action of GABA on chloride channels

Doxapram: 

Doxapram Similar to the above drugs Bigger margin of safety between respiratory stimulation and convulsions Causes nausea, coughing and restlessness, which limit its usefulness Occasionally used as an intravenous infusion in patients with acute respiratory

PSYCHOMOTOR STIMULANTS: 

PSYCHOMOTOR STIMULANTS Cause excitement and euphoria Decrease feelings of fatigue Increase motor activity

Psychomotor Stimulants: 

Psychomotor Stimulants Methylxnthines Nicotine Methylphenidate Cocaine Amphetamine Vareneciline

Methylxanthines: 

Methylxanthines Theophylline (tea) Theobromine (cocoa) Caffeine Caffeine, the most widely consumed stimulant in the world,is found in highest concentration in coffee Also present in tea, cola drinks, chocolate candy, and cocoa.

Mechanism of action: 

Mechanism of action Translocation of extracellular calcium Increase in CAMP and CGMP caused by inhibition of phosphodiesterase Blockade of adenosine receptors

System Effects: 

System Effects CNS: Decrease in fatigue and increased mental alertness as a result of stimulating the cortex and other areas of the brain. Consumption of 1.5 g of caffeine produces anxiety and tremors. The spinal cord is stimulated Tolerance can rapidly develop

Slide 14: 

CVS: A high dose of caffeine has positive inotropic and chronotropic effects on the heart.

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Diuretic action: Caffeine has a mild diuretic Gastric mucosa: Increase HCL production

Adverse effects:: 

Adverse effects: Moderate doses of caffeine cause insomnia, anxiety, and agitation High dosage required for toxicity manifested by emesis and convulsions The lethal dose is about 10 g of caffeine (about 100 cups of coffee)

Nicotine: 

Nicotine The active ingredient in tobacco Most widely used CNS stimulant and second only to alcohol as the most abused drug Tars,carbon monoxide smoke and nicotine are risk factors for lung, CVS disease, cancers Dependency on the drug is not easily overcome

Mechanism of action: 

Mechanism of action In low doses, nicotine causes ganglionic stimulation by depolarization At high doses, nicotine causes ganglionic blockade Nicotine receptors exist at a number of sites in the CNS, which participate in the stimulant attributes of the drug

Systemic Effects: 

Systemic Effects CNS: Nicotine is highly lipid soluble, readily crosses the blood-brain barrier Euphoria and arousal as well as relaxation Improves attention, learning, problem solving, and reaction time High doses result in central respiratory paralysis, severe hypotension caused by medullary paralysis

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Peripheral effects: Increases blood pressure and heart rate Vasoconstriction (can decrease coronary blood flow) Increased motor activity of the bowel

Pharmacokinetics-Nicotine: 

Pharmacokinetics-Nicotine Highly lipid soluble Absorption readily occurs via the oral mucosa, lungs gastrointestinal mucosa, and skin Crosses the placental membrane Secreted in the milk of lactating women By inhaling tobacco smoke, the average smoker takes in 1 to 2 mg of nicotine per cigarette (most cigarettes contain 6 to 8 mg of nicotine) The acute lethal dose is 60 mg

Adverse effects: 

Adverse effects The CNS effects of nicotine include irritability and tremors Nicotine may also cause intestinal cramps, diarrhea, and increased heart rate and blood pressure Cigarette smoking increases the rate of metabolism for a number of drugs

Nicotine-Withdrawal: 

Nicotine-Withdrawal Nicotine is an addictive substance Physical dependence on nicotine develops rapidly and can be severe Withdrawal is characterized by irritability, anxiety, restlessness, difficulty concentrating, headaches, and insomnia Appetite is affected, and gastrointestinal pain often occurs

Transdermal patch: 

Transdermal patch The transdermal patch and chewing gum containing nicotine reduce nicotine withdrawal symptoms help quit smoking

Varenicline: 

Varenicline Partial agonist at a 4 b 2 neuronal nicotinic acetylcholine receptors in the CNS Because it is a partial agonist at these receptors, it produces less euphoric effects than those produced by nicotine itself (nicotine is a full agonist at these receptors) Useful as an adjunct in the management of smoking cessation in patients with nicotine withdrawal symptoms.

Cocaine: 

Cocaine Cocaine is a widely available and highly addictive drug

Mechanism of action: 

Mechanism of action Blockade of reuptake of the monoamines ( norepinephrine , serotonin, and dopamine) into the presynaptic terminals from which these neurotransmitters are released Cocaine binds to the monoaminergic reuptake transporters and, thus, potentiates and prolongs the CNS and peripheral actions of these monoamines

Slide 28: 

Dopaminergic effects in the brain's pleasure system (limbic system) produces the intense euphoria Chronic intake of cocaine depletes dopamine which triggers the vicious cycle of craving for cocaine

System effects: 

System effects CNS: Powerful stimulation of the cortex and brainstem. Acute increase in mental awareness Feeling of well-being and euphoria Can produce hallucinations and delusions Increases motor activity, High doses,causes tremors and convulsions, followed by respiratory and vasomotor depression

Slide 30: 

Sympathetic nervous system : Peripherally, potentiates the action of norepinephrine Associated with tachycardia, hypertension, pupillary dilation, and peripheral vasoconstriction. Recent evidence suggests inability of baroreceptor reflexes

Slide 31: 

Hyperthermia: Death can result from hyperthermia [Mortality rates for cocaine overdose rise in hot weather] Even a small dose of intranasal cocaine impairs sweating and cutaneous vasodilatation. Perception of thermal discomfort is also decreased.

Therapeutic uses:: 

Therapeutic uses: Cocaine has a local anesthetic Applied topically as a local anesthetic during eye, ear, nose, and throat surgery Local anesthetic action due to a block of voltage-activated sodium channels Only local anesthetic that causes vasoconstriction. This effect is responsible for necrosis Perforation of the nasal septum is seen with chronic inhalation of cocaine powder

Pharmacokinetics: 

Pharmacokinetics Cocaine is often self-administered by chewing, intranasal snorting, smoking The peak effect occurs at 15 to 20 minutes after intranasal intake of cocaine powder Rapid but short-lived effects are achieved following IV injection of cocaine or by smoking the freebase form of the drug

Adverse effects: : 

Adverse effects: Anxiety: Many users take cocaine with alcohol A product of cocaine metabolites and ethanol is cocaethylene which is also psychoactive and believed to contribute to cardiotoxicity . Depression: Depression is followed on after stimulation

Toxic effects: 

Toxic effects Cocaine can induce seizures as well as fatal cardiac arrhythmias Diazepam and propranolol may be required to control cocaine-induced seizures and cardiac arrhythmias, respectively The incidence of myocardial infarction in cocaine users is unrelated to dose, duration or to route

Amphetamine: 

Amphetamine Amphetamine is a noncatecholaminergic sympathetic amine Shows neurologic effects similar to cocaine.

Mechanism of action: 

Mechanism of action Indirect effects on the CNS and peripheral nervous system, depend upon an elevation of the level of catecholamine neurotransmitters in synaptic spaces Amphetamine achieves this effect by releasing intracellular stores of catecholamine Also inhibits monoamine oxidase (MAO)

Systemic Effects: 

Systemic Effects CNS: Dopamine and norepinephrine release-enhancing properties Stimulates the entire cerebrospinal axis, cortex, brainstem, and medulla Leads to increased alertness, decreased fatigue, depressed appetite, and insomnia At high doses, psychosis and convulsions can ensue

Slide 39: 

Sympathetic nervous system: Acts on the adrenergic system, indirectly stimulating the receptors through norepinephrine release.

Therapeutic uses: 

Therapeutic uses Factors that limit the therapeutic usefulness of amphetamine include psychological and physiological dependence and the development of tolerance to the euphoric and anorectic effects

Therapeutic uses:: 

Therapeutic uses: Attention deficit hyperactivity disorder ( ADHD ): Some young children are hyperkinetic and lack the ability to be involved in any one activity for longer than a few minutes Dextroamphetamine and the amphetamine derivative methylphenidate are used

Slide 42: 

Narcolepsy : Is a relatively rare sleep disorder that is characterized by uncontrollable bouts of sleepiness during the day Sometimes accompanied by catalepsy, a loss in muscle control, or even paralysis brought on by strong emotions, such as laughter.

Adverse effects: 

Adverse effects The amphetamines may cause addiction, leading to dependence, tolerance, and drug-seeking behavior.

Slide 44: 

Central effects: Insomnia, irritability, weakness, dizziness, tremor, and hyperactive reflexes,confusion , delirium, panic states, and suicidal tendencies, especially in mentally ill patients Chronic amphetamine use produces a state of amphetamine psychosis

Slide 45: 

Cardiovascular effects : Palpitations, cardiac arrhythmias, hypertension, anginal pain, and circulatory collapse Headache, chills, and excessive sweating may also occur

Slide 46: 

Gastrointestinal system effects: Amphetamine acts on the gastrointestinal system, causing anorexia, nausea, vomiting, abdominal cramps, and diarrhea

Methylphenidate: 

Methylphenidate Methylphenidate is a more potent dopamine transport inhibitor than cocaine, thus making more dopamine available Methylphenidate has less potential for abuse than cocaine, because it enters the brain much more slowly than cocaine and, thus, does not increase dopamine levels as rapidly

Adverse reactions: 

Adverse reactions Gastrointestinal effects are the most common Include abdominal pain and nausea, anorexia Insomnia,nervousness

Drug interactions: 

Drug interactions Can interfere in the metabolism of warfarin , diphenylhydantoin , phenobarbital , primidone , and the tricyclic antidepressants

HALLUCINOGENS: 

HALLUCINOGENS Have ability to induce altered perceptual states reminiscent of dreams Altered states are accompanied by bright, colorful changes in the environment and plasticity of constantly changing shapes and color The individual is incapable of normal decision making, because the drug interferes with rational thought

Hallucinogens: 

Hallucinogens LSD Tetrahydrocannabinol Phencyclidine

Lysergic acid diethylamide: 

Lysergic acid diethylamide Multiple sites in the CNS are affected by lysergic acid diethylamide (LSD) Serotonin (5-HT) agonist activity at presynaptic 5-HT 1 receptors in the midbrain Stimulates 5-HT 2 receptors Activation of the sympathetic nervous system occurs( pupillary dilation, inc. BP, piloerection,inc . body temperature

LSD: 

LSD Taken orally, low doses of LSD can induce hallucinations with brilliant colors Mood alteration also occurs High doses may produce long-lasting psychotic changes in susceptible individuals

Tetrahydrocannabinol: 

Tetrahydrocannabinol Main psychoactive alkaloid contained in marijuana is tetrahydrocannabin (THC) which is available as dronabinol

THC: 

THC Can produce euphoria, followed by drowsiness and relaxation Affecting short-term memory and mental activity Decreases muscle strength and impairs highly skilled motor activity Appetite stimulation, xerostomia , visual hallucinations, delusions, and enhancement of sensory activity.

Phencyclidine: 

Phencyclidine Phencyclidine (also known as PCP, or angel dust) Inhibits the reuptake of dopamine, 5-HT, and norepinephrine Major action is to block the ion channel regulated by the NMDA subtype of glutamate receptor Also has anticholinergic activity but, surprisingly, produces hypersalivation Phencyclidine is an analog of ketamine