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CNS Pharmacology-
Introduction to Drugs of Abuse
III/Stimulants
Prepared and Presented by:
Marc Imhotep Cray, M.D.
Profess...
2
CNS Stimulants
1. Cocaine, Crack (free base or hydrochloride)
2. Amphetamines
3. Methylxanthines:
caffeine, theophyline,...
3
A. Pharmacology
 Cocaine and amphetamines have very similar effects
on mood, patterns of abuse, the type of dependence
...
4
a. Acute effects
Causes an initial but
temporary euphoria, “rush”
Causes craving within 30
minutes of taking the drug
In...
5
 Given unlimited access to the drugs, animals will
self-administer these drug until they die
B. Acute toxicity/Overdose...
6
Cocaine/Amphetamines
DRUG TAKING CRAVING
The Blues
FATIGUE
DEPRESSION
HYPERPHAGIA
CRASH
sleep
DRUG TAKING
CRAVING
DRUG T...
7
 Acute tolerance may occur in such
people, particularly in those taking the drug
I.V., resulting in the need of increas...
8
 Stimulant overdose results in excessive activation of
the sympathetic nervous system and cardiac toxicity
 tachycardi...
9
Treatment of overdose
- Beta blockers => for autonomic hyperactivity
1 blockade (Atenolol, metoprolol, esmolol and non-
...
10
After the acute toxic effects are handled:
 Antidepressants  for depression
 Haloperidol  for psychosis
 Alprazola...
11
E. Mechanism of Action
 Inhibition of DA reuptake => increase of DA
concentration in N. accumbens
 Everywhere else it...
12
Dopamine reuptake inhibitors
13
GLUCOSE METABOLISM
normalRed: high activity
Blue: low activity
Cocaine
14
15
Amphetamines
1. dextro, levo-Amphetamine,
2. Methylphenidate (Ritalin®, use to treat
attention deficit and hyperactivit...
16
Amphetamines
A. Pharmacology:
 Used as nasal decongestants (benzedrine,
replaced by propylhexedrine)
 Used as antidep...
17
 Present clinical therapeutic use, only in narcolepsy.
 Amphetamine and methamphetamine -HCl (speed),
 Amphetamine o...
18
Psychoactive: Club
Drugs & Inhalants
Amphetamines
19
A. Pharmacology
One of the most widely used licit drugs
Drug found exclusively in the tobacco plant (Nicotiana
tabacu...
20
a. Acute Effects
  Fibrinolytic activity
  Free fatty acids
  Epinephrine and NE release from adrenal gland
  S...
21
Nicotine
22
B. Acute Intoxication
Respiratory arrest due to blockade of respiratory centers
and neuromuscular junctions controlling...
23
E. Withdrawal
Withdrawal symptoms include nervousness,
anxiety, drowsiness, lightheadedness,
insomnia, dizziness, trem...
24
F. Mechanism of action
- Primary site of action is nicotinic ACh
receptors (peripheral and CNS) where it
stimulates at ...
25
26
Drugs causing
hallucinations, delusions or
delusions
1. Psychedelics and hallucinogens
2. Marihuana (Cannabis)
3. Disso...
27
I. Psychedelics and hallucinogens
Indolamines: Lysergic acid diethylamide (LSD), morning
glory seed
(LSM), psilocybin, ...
28
A. Pharmacology
 These four classes of drugs are usually considered
together because of their prominent feature of
int...
29
a. Acute Effects
At low doses:
 Euphoria; Changes in affect (mood): anxiety,
tension, labile mood;
 Thought and feeli...
30
At high doses:
 Dangerous behavior may cause accidents.
For the amphetamines:
 Visual hallucinations => convulsions, ...
31
B. Acute toxicity/Overdose
Depends on the individual drug
1. Tissue toxicity: Some are neurotoxic
2. Psychic toxicity: ...
32
C. Withdrawal
These drugs do not cause physical
dependence, but they have tremendous
abuse potential (psychological dep...
33
D. Mechanism of Action
 LSM (from morning glory seeds), LSD
(synthetic), mescaline (from the peyote
cactus) and psiloc...
34
Systems Affected:
 5-HT: Presynaptic agonists. decrease 5-HT
transmission. “Cocktail party effect" all
sensory informa...
35
Marijuana (Cannabis)
36
A. Pharmacology
 From the Indian hemp plant, or Cannabis sativa
 Medicinal powers => Egyptians
 Probably originated ...
37
 High lipid solubility but does not dissolve well in
water so if taken orally they are absorbed through
the digestive ...
38
B. Mechanism of Action
 In 1990 THC receptor was cloned and in 1992
endogenous cannabimimetic was discovered
They name...
39
 Cannabinoids have effects not related to receptor
function, including activation of PLA2 and intracellular
calcium mo...
40
 A new peripheral cannabinoid receptor, with only 44%
homology to the brain receptor, has been found in
spleen, lymph ...
41
42
eMedicine Articles on Addiction
 Alcohol-Related Psychosis
 Alcoholism
 Amphetamine-Related
Psychiatric Disorders
 ...
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IVMS-CNS Pharmacology Intro to Drugs of Abuse III-Stimulants

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  1. 1. CNS Pharmacology- Introduction to Drugs of Abuse III/Stimulants Prepared and Presented by: Marc Imhotep Cray, M.D. Professor Pharmacology Clinical: E-Medicine Article Cocaine-Related Psychiatric Disorders
  2. 2. 2 CNS Stimulants 1. Cocaine, Crack (free base or hydrochloride) 2. Amphetamines 3. Methylxanthines: caffeine, theophyline, theobromide 4. Nicotine
  3. 3. 3 A. Pharmacology  Cocaine and amphetamines have very similar effects on mood, patterns of abuse, the type of dependence produced, and their toxic effects  Differences are mainly in the pharmacokinetics (t½ of cocaine is shorter (50-90min) vs longer (5-10hrs) t½ for amphetamines)  Cocaine-HCl is injected I.V. => “rush” or “flash => euphoria  Rate of absorption is limited by local vasoconstriction. Cocaine free base (“crack”, “rock”) is smoked => delivered directly to pulmonary circulation, left heart and brain Cocaine
  4. 4. 4 a. Acute effects Causes an initial but temporary euphoria, “rush” Causes craving within 30 minutes of taking the drug Increase alertness, feeling of elation and well being, increased energy, feelings of competence, increased sexuality The user becomes more talkative, restless and often more irritable Consciousness is clear, but delusions may occur as well as visual, tactile (formication) and auditory hallucinations These drugs are sympathomimetic, thus, they cause HR, BP, skeletal muscle tension, but musculature of the bronchi and intestines relax Cocaine
  5. 5. 5  Given unlimited access to the drugs, animals will self-administer these drug until they die B. Acute toxicity/Overdose  “Runs” – Uninterrupted sequences of stimulant abuse to maintain a continuous state of intoxication, to extend pleasurable feeling, and to postpone the postintoxication “crash” than ensues as the drug effects subside Cocaine
  6. 6. 6 Cocaine/Amphetamines DRUG TAKING CRAVING The Blues FATIGUE DEPRESSION HYPERPHAGIA CRASH sleep DRUG TAKING CRAVING DRUG TAKING DRUG TAKING CRAVING “The Run”
  7. 7. 7  Acute tolerance may occur in such people, particularly in those taking the drug I.V., resulting in the need of increasingly larger doses  This spiral of tolerance and dose increases continues until the drug is depleted or the person collapses from exhaustion  Drug taking and drug seeking take a compulsive character Cocaine
  8. 8. 8  Stimulant overdose results in excessive activation of the sympathetic nervous system and cardiac toxicity  tachycardia and hypertension  myocardial infarction  cerebrovascular hemorrhage  Cocaine can cause coronary vasospasms and cardiac dysrhythmias  CNS symptoms include anxiety feelings of paranoia and impending doom, and restlessness  Users exhibit unpredictable behavior and may become violent Cocaine
  9. 9. 9 Treatment of overdose - Beta blockers => for autonomic hyperactivity 1 blockade (Atenolol, metoprolol, esmolol and non- selective : labetolol).  This treatment is controversial: Problems with using non- selective blockers may lead to unopposed effects => BP - Nitroglycerine or other nitrites/nitrates  for angina - Calcium channel blockers (verapamil, diltiazem)  for hypertension - Ice baths  for high fever. - Acidify urine  to hasten excretion Cocaine
  10. 10. 10 After the acute toxic effects are handled:  Antidepressants  for depression  Haloperidol  for psychosis  Alprazolam  for panic attacks Cocaine
  11. 11. 11 E. Mechanism of Action  Inhibition of DA reuptake => increase of DA concentration in N. accumbens  Everywhere else it also causes: 1. Increase activation of DA receptors 2. Negative feedback inhibition 3. May also produce dopamine release from nerve endings 4. Inhibition of NE and 5-HT reuptake also occurs Cocaine
  12. 12. 12 Dopamine reuptake inhibitors
  13. 13. 13 GLUCOSE METABOLISM normalRed: high activity Blue: low activity Cocaine
  14. 14. 14
  15. 15. 15 Amphetamines 1. dextro, levo-Amphetamine, 2. Methylphenidate (Ritalin®, use to treat attention deficit and hyperactivity disorders in children), 3. Phenmetrazine (used to treat obesity), 4. Methamphetamine (“crystal”, “speed”, “ICE”) 5. methylendioxyamphetamine, (MDA). 6. methylenedioxymetamphetamine, (MDMA, ecstasy, XTC)
  16. 16. 16 Amphetamines A. Pharmacology:  Used as nasal decongestants (benzedrine, replaced by propylhexedrine)  Used as antidepressants and to treat obesity (anorectic) => can cause dependence  Used to stay awake
  17. 17. 17  Present clinical therapeutic use, only in narcolepsy.  Amphetamine and methamphetamine -HCl (speed),  Amphetamine or methamphetamine => I.V.  D-methamphetamine (“ice”) => smoked like cocaine but has a much longer duration of action Psychological Dependence - Similar to Cocaine - May cause hallucinations  MDA, DOM, MDMA Amphetamines
  18. 18. 18 Psychoactive: Club Drugs & Inhalants Amphetamines
  19. 19. 19 A. Pharmacology One of the most widely used licit drugs Drug found exclusively in the tobacco plant (Nicotiana tabacum, serves as a natural insecticide), which is harvested, cured, and manufactured into snuff, chewing tobacco, pipe tobacco, cigars and cigarettes  Nicotine is absorbed best by the lungs and it is distributed rapidly throughout the body It has a half-life of about 30 min. Highly lipophylic: Crosses BBB and placenta Nicotine
  20. 20. 20 a. Acute Effects   Fibrinolytic activity   Free fatty acids   Epinephrine and NE release from adrenal gland   Sympathetic and Parasympathetic activity   ACTH release from pituitary  depolarization of thermo, mechano, and nociceptors  depolarization of carotid body and other ganglia  depolarization of baroreceptors  depolarization of chemoreceptors in area posterma => Stimulation of emetic centers Nicotine
  21. 21. 21 Nicotine
  22. 22. 22 B. Acute Intoxication Respiratory arrest due to blockade of respiratory centers and neuromuscular junctions controlling breathing C. Chronic effects Associated diseases: Heart disease, lung disease, cancer, babies with small birth weight, asthma in children, others D. Detoxification treatment Smoking therapy => substitution, tapering off: nicotine gum (Nicorette), nicotine patches, nicotine nasal spray Nicotine
  23. 23. 23 E. Withdrawal Withdrawal symptoms include nervousness, anxiety, drowsiness, lightheadedness, insomnia, dizziness, tremor, sleep disturbances, decrease inability to concentrate, irritability and an intense craving for tobacco  Other physical symptoms include nausea, headache, constipation and an increase in appetite and increase body weight Nicotine
  24. 24. 24 F. Mechanism of action - Primary site of action is nicotinic ACh receptors (peripheral and CNS) where it stimulates at low doses and blocks at high doses - Stimulates release of DA from VTA terminals onto N. accumbens - Presynaptic receptors regulate release of neuro- transmitters: NE, EPI, DA, ACh, GABA Nicotine
  25. 25. 25
  26. 26. 26 Drugs causing hallucinations, delusions or delusions 1. Psychedelics and hallucinogens 2. Marihuana (Cannabis) 3. Dissociative anesthetics (PCP) 4. Anticholinergics
  27. 27. 27 I. Psychedelics and hallucinogens Indolamines: Lysergic acid diethylamide (LSD), morning glory seed (LSM), psilocybin, psilocin, ibogaine, dimethyltryptamine (DMT). Phenyethylamines: mescaline, bufotenin, dimethoxymethyl-amphetamine (DOM). II. Cannabis/ Marihuana: delta-9-THC III. Dissociative anesthetics: Ketamine, Phencyclidine (PCP) IV. Anticholinergics: Mandrake root, jimson weed, atropine, scopolamine Drugs causing hallucinations, delusions or delusions
  28. 28. 28 A. Pharmacology  These four classes of drugs are usually considered together because of their prominent feature of intoxication (hallucinations, delusions, illusions),  But they differ in almost every aspect: chemical structure, mechanism of action, CNS receptor involved, picture of intoxication, type and seriousness of their toxic effects  They occur naturally in plants, mushrooms and in some frogs Hallucinogens
  29. 29. 29 a. Acute Effects At low doses:  Euphoria; Changes in affect (mood): anxiety, tension, labile mood;  Thought and feeling disorders: perceptual changes (distortion), depersonalization, illusions visual hallucinations, time and visual distortions, synesthesias; nausea, pupils are dilated, HR, BP, temperature, reflexes, tremors  Panic, paranoia Hallucinogens
  30. 30. 30 At high doses:  Dangerous behavior may cause accidents. For the amphetamines:  Visual hallucinations => convulsions, coma Subjective reason for taking these drugs: Allows insight into oneself and new ways of looking at the world  Cross-tolerance between LSD and mescaline  Usually polydrug users Hallucinogens
  31. 31. 31 B. Acute toxicity/Overdose Depends on the individual drug 1. Tissue toxicity: Some are neurotoxic 2. Psychic toxicity: Acute transient psychosis, Flash backs 3. Behavioral toxicity: Distorted behavior, aggressive, violent Hallucinogens
  32. 32. 32 C. Withdrawal These drugs do not cause physical dependence, but they have tremendous abuse potential (psychological dependence) - Use is more frequently occasional Hallucinogens
  33. 33. 33 D. Mechanism of Action  LSM (from morning glory seeds), LSD (synthetic), mescaline (from the peyote cactus) and psilocybin (from mushrooms) have chemical resemblances to 5-HT, NE and DA  Scopolamine is a cholinergic antagonist  They all cause hyperarousal of the CNS Hallucinogens
  34. 34. 34 Systems Affected:  5-HT: Presynaptic agonists. decrease 5-HT transmission. “Cocktail party effect" all sensory information goes in. temporal lobe. Postsynaptic agonists to 5-HT1A and 5-HT1C receptors.  NE: Postsynaptic agonists. increase NE activity in temporal lobe. Produce a lot of “bad trips”. Anxiety and hyperactivity.  Ach: Produce delirium. Anticholinergic effects. Not addictive. Hallucinogens
  35. 35. 35 Marijuana (Cannabis)
  36. 36. 36 A. Pharmacology  From the Indian hemp plant, or Cannabis sativa  Medicinal powers => Egyptians  Probably originated in Central Asia  Delta-9-tetrahydrocannabinol (THC) is the active ingredient  Marihuana, marijuana, bhang, ganja, hashish or charas, sinsemilla, red oil, weed, bush Marijuana (Cannabis)
  37. 37. 37  High lipid solubility but does not dissolve well in water so if taken orally they are absorbed through the digestive system rather slowly  Smoking causes 50% of cannabinoids to enter the lungs  Holding the smoke in the lungs maximizes absorption Marijuana (Cannabis)
  38. 38. 38 B. Mechanism of Action  In 1990 THC receptor was cloned and in 1992 endogenous cannabimimetic was discovered They named it anandamide (ànanda, in Sanskrit = bliss)  Anandamide is the ethanolamine of arachidonic acid  Cannabinoids as well as anandamide inhibit Adenylate Cyclase (which produces cAMP) both in brain and periphery, via G protein-coupled cannabinoid receptors  They also inhibit the N-type calcium channel current, which may affect regulation of neurotransmitter release Marijuana (Cannabis)
  39. 39. 39  Cannabinoids have effects not related to receptor function, including activation of PLA2 and intracellular calcium mobilization  THC causes the release of serotonin, causes an elevation of ACh and inhibits the synthesis of prostaglandins  They have also been known to influence levels of NE, DA and GABA  THC concentrates in the limbic system, particularly in hippocampus and amygdala and sensory centers for hearing Marijuana (Cannabis)
  40. 40. 40  A new peripheral cannabinoid receptor, with only 44% homology to the brain receptor, has been found in spleen, lymph nodes and leukocytes Thus, they appear confined to the immune system  Cannabinol, a compound also found in marihuana but with less psychotropic effects seems to have preference for this receptor Dronabinol. Medicinal grade cannabinol. Approved as an antiemetic Marijuana (Cannabis)
  41. 41. 41
  42. 42. 42 eMedicine Articles on Addiction  Alcohol-Related Psychosis  Alcoholism  Amphetamine-Related Psychiatric Disorders  Caffeine-Related Psychiatric Disorders  Cannabis Compound Abuse  Cocaine-Related Psychiatric Disorders  Hallucinogens  Inhalant-Related Psychiatric Disorders  Injecting Drug Use  Nicotine Addiction  Opioid Abuse  Phencyclidine (PCP)-Related Psychiatric Disorders  Sedative, Hypnotic, Anxiolytic Use Disorders  Stimulants  Substance-Induced Mood Disorders: Depression and Mania

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