![Therapeutic uses:
• Cocaine used as a local anesthetic.
• [Note: Cocaine is the only local anesthetic
that causes vasoconstriction].](https://image.slidesharecdn.com/8quyyhigeyf50oslzmog-230519153720-a299b9d4/85/8QuyYhigEyF50OSLZMog-pdf-27-320.jpg)
![Adverse effects:
• a. Anxiety: [Note: Little tolerance to the
toxic CNS effects of cocaine (for example,
convulsions) occurs with prolonged use.]
• b. Depression: cocaine stimulation of the
CNS is followed by a period of mental
depression.
Addicts withdrawing from cocaine exhibit
physical and emotional depression
• c. Toxic effects: Cocaine can induce
seizures as well as fatal cardiac
arrhythmias.](https://image.slidesharecdn.com/8quyyhigeyf50oslzmog-230519153720-a299b9d4/85/8QuyYhigEyF50OSLZMog-pdf-29-320.jpg)
![Mechanism of action:
• Methylphenidate is a dopamine transport
inhibitor.
• [Note: Methylphenidate may have 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.]](https://image.slidesharecdn.com/8quyyhigeyf50oslzmog-230519153720-a299b9d4/85/8QuyYhigEyF50OSLZMog-pdf-40-320.jpg)
8QuyYhigEyF50OSLZMog.pdf
- 1. CNS Stimulants Assistant Professor Dr.Qayssar Joudah Fadheel Ph.D. Pharmacology & Therapeutics Head of Department of Pharmacology & Toxicology Faculty of Pharmacy / University of Babylon
- 2. CNS Stimulents 1.psychomotor stimulants, cause excitement and euphoria, decrease feelings of fatigue (Analeptic Effect) increased nervousness and anxiety - convulsions. 2. hallucinogens, or psychotomimetic drugs, produce profound changes in thought patterns and mood
- 3. MOA of CNS Stimulants 1- Block neurotransmitters reuptake (Most reuptake inhibitors affect either NE or 5- HT(Serotonin) : Cocaine 2- Promote neurotransmitters release : Amphetamine 3- Block Metabolism - MAO inhibitors (monoamine oxidase):ex. Amphetamine 4. antagonize the effect of inhibitory neurotransmitter: Strychnine
- 4. 1. PSYCHOMOTOR STIMULANTS A. Methylxanthines I. theophylline, which is found in tea II. theobromine, found in cocoa III. caffeine, found in highest concentration in coffee, but it is also present in tea, cola drinks, chocolate candy, and cocoa.
- 5. Mechanism of action: • increase in cAMP and cGMP caused by inhibition of phosphodiesterase • blockade of adenosine receptors. • Alters intracellular calcium distribution
- 6. • Cyclic AMP is responsible for a abundant of cellular functions including, but not limited to 1.stimulation of cardiac function 2.relaxation of smooth muscle 3.reduction in the immune and inflammatory activity of specific cells
- 7. • adenosine has been shown to provoke 1.contraction of isolated airway smooth muscle 2.histamine release from airway mast cells
- 8. Actions: a. CNS: • 100–200 mg of caffeine causes a decrease in fatigue and increased mental alertness. • 1.5 g of caffeine produces anxiety and tremors. • Tolerance can rapidly develop to the stimulating properties of caffeine, and withdrawal consists of feelings of fatigue and sedation.
- 9. b. Cardiovascular system: A high dose of caffeine has positive inotropic and chronotropic effects on the heart. c. Diuretic action: Caffeine has a mild diuretic action. d. Gastric mucosa: stimulate secretion of HCL e. Effects on smooth muscle: bronchodilation f. Effects on skeletal muscle: improve contractility and reverse fatigue of the diaphragm in patients with COPD.
- 10. Therapeutic uses: 1. Previously the mainstay of asthma therapy, theophylline and its salt(aminophylline) but has been largely replaced by other agents, such as β2 agonists and corticosteroids. 2. pentoxifylline, is promoted as a remedy for intermittent claudication; this effect is said to result from decreased viscosity of the blood
- 12. Pharmacokinetics: I. well absorbed orally. II.Caffeine distributes throughout the body, including the brain. III.metabolized in the liver IV.excreted in the urine.
- 13. Adverse effects: 1.Moderate doses cause insomnia, anxiety, and agitation. 2.A high doses cause emesis and convulsions. 3.The lethal dose is 10 g of caffeine, which induces cardiac arrhythmias. 4.Lethargy, irritability, and headache occur in users who routinely consumed more than 600 mg of caffeine per day and then suddenly stop.
- 14. B. Nicotine • Nicotine is the active ingredient in tobacco. • It is not currently used therapeutically (except in smoking cessation therapy), nicotine remains important because 1. it is second only to caffeine as the most widely used CNS stimulant, 2. it is second only to alcohol as the most abused drug.
- 15. • Nicotine represents a serious risk factor for lung and cardiovascular disease, various cancers, and other illnesses. • Dependency on the drug is not easily overcome.
- 16. Mechanism of action: 1. In low doses, nicotine causes ganglionic stimulation by depolarization. 2.At high doses, nicotine causes ganglionic blockade. 3.Nicotine receptors exist at a number of sites in the CNS, which participate in the stimulant attributes of the drug.
- 17. Actions: a. CNS: Nicotine is readily crosses the bbb. • low doses of nicotine produces some degree of euphoria and relaxation. It improves attention, learning, problem solving, and reaction time. • High doses of nicotine result in central respiratory paralysis and severe hypotension caused by medullary paralysis. • Nicotine is also an appetite suppressant.
- 18. b. Peripheral effects: • Stimulation of sympathetic ganglia as well as the adrenal medulla increases blood pressure and heart rate. • Stimulation of parasympathetic ganglia also increases motor activity of the bowel.
- 19. • At higher doses, blood pressure falls, and activity ceases in both the gastrointestinal (GI) tract and bladder musculature as a result of a nicotine-induced block of ganglia
- 20. Pharmacokinetics: • absorption readily occurs via the oral mucosa, lungs, GI mucosa, and skin. Nicotine crosses the placental membrane and is secreted in the milk of lactating women. • metabolism in the lung and the liver and urinary excretion. • Tolerance to the toxic effects of nicotine develops rapidly, often within days after beginning usage.
- 21. • Adverse effects: • The CNS effects of nicotine include irritability and tremors. • Nicotine may also cause intestinal cramps, • increased heart rate and blood pressure.
- 22. C. Varenicline • a partial agonist at neuronal nicotinic receptors in the CNS. • produces less euphoric effects than those produced by nicotine itself. • useful as an adjunct in the management of smoking. • Additionally, varenicline tends to attenuate the rewarding effects of nicotine if a person relapses and uses tobacco.
- 23. D. Cocaine is highly addictive drug. Mechanism of action: 1.blockade of reuptake of the monoamines (norepinephrine, serotonin, and dopamine) into the presynaptic terminals. • the prolongation of dopaminergic effects in the brain’s pleasure system (limbic system) produces the intense euphoria But chronic intake of cocaine depletes dopamine.
- 24. Effects of Cocaine on Dopaminergic Activity Normal (no cocaine) Postsynaptic receptors Reuptake carrier Dopamine in synapse Presynaptic neuron Postsynaptic neuron Dopamine release Chronic cocaine use Decreased postsynaptic receptors Reuptake carrier Normal amount of dopamine in synapse Presynaptic neuron Postsynaptic neuron Dopamine release Cocaine blockade Acute cocaine use Postsynaptic receptors Reuptake carrier Presynaptic neuron Postsynaptic neuron Dopamine release Cocaine blockade Increased dopamine in synapse Cocaine withdrawal Decreased postsynaptic receptors Reuptake carrier Presynaptic neuron Postsynaptic neuron Dopamine release Decreased dopamine in synapse
- 25. Actions: a. CNS: 1.Cocaine acutely increases mental awareness and produces euphoria. 2.Like amphetamine, cocaine can produce hallucinations and delusions of grandiosity. 3.at high doses, it causes tremors and convulsions, followed by respiratory and vasomotor depression.
- 26. b. Sympathetic nervous system: potentiates the action of norepinephrine. This is associated with tachycardia, hypertension, pupillary dilation, and peripheral vasoconstriction c. Hyperthermia: Cocaine is unique among illicit drugs in that death can result not only as a function of dose, but also from the drug’s propensity to cause hyperthermia.
- 27. Therapeutic uses: • Cocaine used as a local anesthetic. • [Note: Cocaine is the only local anesthetic that causes vasoconstriction].
- 28. Pharmacokinetics: Cocaine is often self-administered by chewing, intranasal snorting, smoking, or intravenous (IV) injection. Cocaine is rapidly de-esterified and demethylated to benzoylecgonine, which is excreted in the urine.
- 29. Adverse effects: • a. Anxiety: [Note: Little tolerance to the toxic CNS effects of cocaine (for example, convulsions) occurs with prolonged use.] • b. Depression: cocaine stimulation of the CNS is followed by a period of mental depression. Addicts withdrawing from cocaine exhibit physical and emotional depression • c. Toxic effects: Cocaine can induce seizures as well as fatal cardiac arrhythmias.
- 30. E. Amphetamine • Amphetamine is a sympathetic amine that shows neurologic and clinical effects quite similar to those of cocaine. • Dextroamphetamine is the major member of this class of compounds. • Methamphetamine is also available.
- 31. Mechanism of action: • Indirect by elevation of the level of catecholamine neurotransmitters in synaptic spaces. 1.Amphetamine, however, achieves this effect by releasing intracellular stores of catecholamines. 2.Because amphetamine also inhibits monoamine oxidase (MAO), high levels of catecholamines are readily released into synaptic spaces.
- 32. Actions: a. CNS: • increased alertness, decreased fatigue, depressed appetite, and insomnia. • At high doses, psychosis and convulsions b. Sympathetic nervous system: amphetamine acts on the adrenergic system, indirectly stimulating the receptors through norepinephrine release.
- 33. Therapeutic uses: Factors that limit the therapeutic usefulness of amphetamine include psychological and physiological dependence and, with chronic use, the development of tolerance to the euphoric and anorectic effects.
- 34. a. Attention deficit hyperactivity disorder (ADHD): • Atomoxetine is a nonstimulant drug approved for ADHD in children and adults. Unlike methylphenidate, which blocks dopamine reuptake, atomoxetine is a norepinephrine-reuptake inhibitor. Therefore, it is not habit forming and is not a controlled substance. b. Narcolepsy: Recently, a newer drug, modafinil and its derivative, armodafinil, have been used
- 35. Pharmacokinetics: • Amphetamine is completely absorbed from the GI tract, • metabolized by the liver, • and excreted in the urine.
- 36. Adverse effects: The amphetamines may cause addiction, leading to dependence, tolerance, and drug-seeking behavior. In addition, they have the following undesirable effects.
- 37. CNS effects: • insomnia, irritability, weakness, dizziness, tremor, and hyperactive reflexes. • Amphetamine can also cause confusion, delirium, panic states, and suicidal tendencies.
- 38. b. Cardiovascular effects: palpitations, cardiac arrhythmias, hypertension, anginal pain, and circulatory collapse. Headache, chills, and excessive sweating may also occur. c. GI system effects: causing anorexia, nausea, vomiting, abdominal cramps, and diarrhea. d. Contraindications: Neither patients with cardiovascular disease, hyperthyroidism, or glaucoma should be treated with this drug, nor should patients with a history of drug abuse, nor anyone taking MAO inhibitors
- 39. F. Methylphenidate • Methylphenidate has CNS-stimulant properties similar to those of amphetamine and may also lead to abuse. It is presently one of the most prescribed medications in children.
- 40. Mechanism of action: • Methylphenidate is a dopamine transport inhibitor. • [Note: Methylphenidate may have 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.]
- 41. Therapeutic uses: • treatment of ADHD in children ages 6 to 16 years. • It is also effective in the treatment of narcolepsy. Unlike methylphenidate, dexmethylphenidate is not indicated in the treatment of narcolepsy.
- 42. • Pharmacokinetics: • Both methylphenidate and dexmethylphenidate are readily absorbed upon oral administration. • The de-esterified product, ritalinic acid, is excreted in urine.
- 43. Adverse reactions: • abdominal pain and nausea. Other reactions include anorexia, insomnia, nervousness, and fever. • Methylphenidate is contraindicated in patients with glaucoma.
- 44. G. Strychnine is a source of accidental poisoning. Also used to study CNS mechanism because of its relatively specific action as a glycine antagonist. • Adverse Reactions: Convulsion is characterized by opisthotonos, i.e., tonic extension of body and all limbs. Back is arched and only the back of the head and the heels are touching the surface. All sensory stimuli produce exaggerated response and slight sensory stimulation may trigger convulsion.
- 46. 2. HALLUCINOGENS (psychotomimetic) • produce profound changes in thought patterns and mood • The individual under the influence of these drugs is incapable of normal decision- making because the drug interferes with rational thought.
- 47. A. Lysergic acid diethylamide • Multiple sites in the CNS are affected by lysergic acid diethylamide (LSD). • The drug shows serotonin (5-HT) agonist activity at presynaptic 5-HT1 receptors in the midbrain, and it stimulates 5-HT2 receptors.
- 48. • Lysergic acid diethylamide • Activation of the SNS occurs, which causes papillary dilation, increased blood pressure, piloerection, and increased body temperature. • Tolerance and physical dependence have occurred, but true dependence is rare. • Adverse effects include hyperreflexia, nausea, and muscular weakness. High doses may produce long-lasting psychotic changes in susceptible individuals.
- 49. B. Tetrahydrocannabinol • The main psychoactive alkaloid contained in marijuana is tetrahydrocannabinol • (THC), which is available as dronabinol. This product is prescribed to treat emesis and to stimulate the appetite. • THC can produce euphoria, followed by drowsiness and relaxation.
- 50. • Its wide range of effects includes appetite stimulation, xerostomia, visual hallucinations, delusions, and enhancement of sensory activity. • THC receptors, designated CB1 receptors, have been found on inhibitory presynaptic nerve terminals
- 51. • Dronabinol • is administered orally. • It is highly lipid soluble. • THC itself is extensively metabolized by the mixed-function oxidases. • Elimination is largely through the biliary route.
- 52. • Dronabinol is indicated as an appetite stimulant for patients with acquired immunodeficiency syndrome who are losing weight. • It is also sometimes given for the severe emesis caused by some cancer chemotherapeutic agents. • The CB1-receptor antagonist • Rimonabant :- is effective in the treatment of obesity and has been found to decrease appetite and body weight in humans.
- 53. • Adverse effects • include increased heart rate, decreased blood pressure, and reddening of the conjunctiva. • At high doses, a toxic psychosis develops. • Tolerance and mild physical dependence occur with continued, frequent use of the drug.
- 54. C. Phencyclidine • Phencyclidine (also known as PCP, or “angel dust”) inhibits the reuptake of dopamine, 5-HT, and norepinephrine. • Phencyclidine has anticholinergic activity but, surprisingly, produces hypersalivation. • Phencyclidine, an analog of ketamine, causes dissociative anesthesia . • At increased dosages, anesthesia, stupor, and coma may result but the eyes may remain open.
- 55. • Tolerance often develops with continued use. • Phencyclidine has no therapeutic applications, and manufacture of the drug in the United States is illegal.