3. CNS stimulants lecture for pharmacy students.pptx

describes drug stimulants used in the field of pharmacy

1. CNS stimulants David Musoke PhD

2. Introduction Psychomotor stimulants- cause excitement and euphoria, decrease feeling of fatigue and increase motor activity Psychotomimetic or hallucinogens- produce changes in thought patterns and mood, with little effect on the brainstem and spinal cord CNS stimulants have few clinical uses but are important as drugs of abuse along with the CNS depressants and the narcotics

3. Psychomotor stimulants Theophylline, theobromine & caffeine ( methylxanthines ) Mechanism of action : several i.e. translocation of extracellular calcium; increase in cAMP & cGMP caused by inhibition of phosphodiesterase; and blockade of adenosine receptors Actions: CNS : decrease in fatigue & increased mental alertness by stimulating the cortex and other areas of the brain (100-200mg); 1.5gm produces anxiety and tremors; spinal cord is stimulated only by very high doses (2-5gm) CVS- high dose of caffeine has positive inotropic & chronotropic effects on heart Mild diuretic effect, increased output of Na, Cl and K Stimulate secretion of hydrochloric acid

4. Methylxanthines cont. PK- Well absorbed orally; caffeine distributes through out body including the brain; cross the placenta to the fetus and are secreted in the mothers milk; metabolized in the liver and metabolites excreted in urine Adverse effects : moderate doses cause insomnia, anxiety and agitation; high doses cause emesis and convulsions; higher doses may cause cardiac arrhythmias; lethargy Irritability and headache occur in users who routinely consume caffeine and then suddenly stop

5. Nicotine Mechanism- in low doses causes ganglionic depolarization and blockade at high doses. Nicotine receptors exist in CNS (same actions) Actions-( CNS ) low doses cause degree of euphoria, arousal, relaxation, and improves attention, learning, problem solving and reaction time and high doses cause central respiratory paralysis & severe hypotension due to medullary paralysis - Peripheral : stimulation of sympathetic ganglia & adrenal medulla increases blood pressure and heart rate; stimulation of parasympathetic ganglia causes increased motor activity of the bowel; at high doses BP falls and activity ceases in GIT and Bladder due to nicotine induced block of parasympathetic ganglia

6. Nicotine cont. PK - Highly lipid soluble hence absorption via oral mucosa, lungs, GI mucosa and skin readily occurs; crosses placental membrane and is secreted in milk; readily crosses the BBB; clearance involves metabolism in the lung and liver and urinary excretion Adverse effects - irritability and tremors, intestinal cramps, diarrhea, increased heart rate and BP; increases the rate of metabolism of a number of drugs; Withdrawal syndrome due to its addictive nature

7. Cocaine Mechanism- blockade of norepinephrine, serotonin and dopamine reuptake into the presynaptic terminals Actions- ( CNS ) stimulation of cortex and brainstem increases mental awareness; feeling of well being and euphoria; also produces hallucinations, delusions and paranoia. Cocaine increases motor activity and high doses produce tremors and convulsions followed by respiratory and vasomotor depression Peripherally (SNS) potentiates the action of norepinephrine to produce the “fight or flight syndrome” Uses- local anesthetic during eye, ear and nose surgery- due to a block of voltage activated sodium channels

8. Cocaine cont. PK- self administered by chewing, intranasal snorting, smoking and IV; peak effect occurs 15 -20 min and high disappears after 1.5hrs. Adverse effects- Anxiety that induces hypertension, tachycardia, sweating and paranoia Mental depression on withdrawal Can induce seizures and fatal cardiac arrthymias

9. Amphetamine Neurologic and clinical effects are similar to those of cocaine Mechanism- indirect and achieved by release of intracellular stores of catecholamines; also blocks MAO Actions- (CNS) due to release of dopamine, amphetamine stimulates the entire cerebrospinal axis, cortex, brainstem, and medulla- leads to increased alertness, decreased fatigue, depressed appetite, & insomnia; high doses induce convulsions (SNS) stimulates the adrenergic system indirectly through norepinephrine release Use- limited due to psychological and physical dependence & development of tolerance to the euphoric and anorectic effects with chronic use - Attention deficient syndrome(hyperactive) in young children particularly its derivative methylphenidate; narcolepsy (uncontrollable desire for sleep)

10. Amphetamine cont. PK- completely absorbed from GIT, metabolized by liver, and excreted in urine. Abusers often administer via IV or smoking; euphoria lasts 4-8 times longer than cocaine Adverse effects- (central) insomnia, irritability, weakness, dizziness, tremor, hyperactive reflexes, confusion, delirium, panic states and suicidal tendencies in mentally ill patients (CVS) palpitations, arrhythmias, hypertension, angina pain, & circulatory collapse (GIT) anorexia, nausea, vomiting, abdominal cramps & diahhrea

11. Hallucinogens/psychotomimetic drugs Lysergic acid diethylamide (LSD)- shows serotonin (5-HT) agonist activity at presynaptic receptors in the mid-brain; Activates SNS. Effects are psychological-altered awareness of surrounding, perceptions & feelings hence mainly used as a recreational drug Taken orally or sublingually Tolerance and dependence may occur; adverse effects include anxiety, paranoia and delusions; nausea and muscular weakness may occur

12. Tetrahydrocannabinol Tetrahydrocannabinol (dronabinol)- marijuana alkaloid; produces euphoria followed by drowsiness and relaxation; impairs short term memory & mental activity; decreases muscle strength; increases appetite, xerostomia , visual hallucinations, delusions Mechanism unknown Adverse effects: increased heart rate, fall in BP, red conjunctiva, tolerance and physical dependence Sometimes used for the severe emesis due to some cancer chemotherapeutic agents

13. Phencyclidine (PCP) Inhibits reuptake of dopamine, 5-HT and norepinephrine Also has anticholinergic effect but produces hyper salivation Analog of ketamine- causes dissociative anesthesia & analgesia Also produces numbness of extremities, staggered gait, slurred speech, & muscle rigidity Hostile and bizarre behavior In high doses, anesthesia, stupor or coma result but eyes remain open Tolerance develops with continued use