Drug classifications psychomotor_stim_history_pk

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Drug classifications psychomotor_stim_history_pk

  1. 1. Drugs & Behavior 65.2 Bases for Classification of Drugs
  2. 2. Molecular Structure-Activity Relationships• Grouping drugs according to molecular structure • Drugs may have similar behavioral effects• Optical isomers or enantiomers can have different effects on the body • Leva (l-dopa) rotates to the left in solution • Dextro (d-amphetamine) rotates to the right in solution • Stereospecific: when the two isomers display differential receptor-binding properties• Minor changes in molecular structure can change its basic activity in the body • Examples: change in position of chain attached to nitrogen atom to down or up position OR added OH group
  3. 3. Molecular Structure-Activity Relationships
  4. 4. Depressant vs. Stimulant Classification• Grouping drugs according to their effects on the CNS• What do the words imply: • Depressants: decrease mood, motor activity, metabolic and physiological activities, reduce alertness and induce sleep, decrease brain activity and neurotransmitter turnover • Stimulants: do the exact opposite• Why is this misleading? • Simultaneous occurrence of effects? • Dosage? • Activation of receptor causes influx of cations or anions? • Increase and decrease of firing rates of different neural populations that have inhibitory or excitatory effects? • Emotion?
  5. 5. Drug Use Classification• Drugs grouped according to what they are predominantly used for• Antidepressant, anxiolytic, antipsychotic, neuroleptic, sedative, hypnotics, blood-pressure control, etc…• What issues arise with this classification? • A drug may be used for several widely disparate symptoms • Phenobarbital • Some drugs that seem to have the ideal properties for alleviating certain symptoms do not work in the long run • Amphetamine • The qualitative effects of a drug are often dependent upon dosage or on how long the drug has been taken, leading to different classification schemes
  6. 6. Schedule-Controlled Drugs• Drug Enforcement Administration• Five Classes of Controlled Substances • Schedule I: • no currently accepted medical use in treatment in the U.S. • High potential for abuse • Schedule II: • Some currently accepted medical uses in U.S. • High abuse potential • Schedules III, IV, & V: • Current medical uses • Lower abuse potential than I and II• Penalties rise accordingly; Schedule I holds the highest, etc…• Underground Chemists & Designer Drugs
  7. 7. Schedule-Controlled Drugs
  8. 8. Drugs & Behavior 65.2 Psychomotor Stimulants History
  9. 9. Psychomotor Stimulants• What do they all have in common: • MAs: E, NE, DA, 5-HT • Sympathomimetics• Which occur naturally and which are synthetic? • Amphetamines • Optical isomers: d-amphetamine and l-amphetamine • Dl-amphetamine is a mixture of the two • Methamphetamine: cold medication, iodine, hydrocloric acid, ether, ammonia; sold as crystal-meth • Methylphenidate (Ritalin) slight chemical alteration of amphetamine • Ephedrine: ma huang • Cocaine: coca bush extract • Cathinone: cocaine-like drug from Catha-edulis shrub; also known as khat in Yemen • Methcathinone: a.k.a. ephedrone, jee-cocktail, cosmos
  10. 10. Psychomotor Stimulants• History – Cocaine: coca leaves chewed by Indian tribes of South America • Coca leaves were delivered to Columbian Indians by people of the Milky Way in a canoe drawn by an anaconda
  11. 11. Psychomotor Stimulants• History – Cocaine: • Incas held coca as sacred, to be used only by priests and nobility for ceremonial purposes • Not used by common folk – Spanish conquered Incas and banned coca use • later learned of its value and used it as payment for labor in gold and silver mined in Andes
  12. 12. Psychomotor Stimulants• History – Cocaine – Albert Niemann in 1860 • Credited for isolating and naming the drug • Still did not have medical use – Sigmund Freud • Addictions & Depression – Karl Koller • Anesthetic Properties; real medical use
  13. 13. Psychomotor Stimulants• History – Cocaine • Isolation of the drug stimulated search for medical uses • People of upper class would inject it with morphine – 20th century writers and intellectuals • Robert Louis Stevenson – The Strange Case of Dr. Jekyll and Mr. Hyde • Sir Arthur Conan Doyle – Sherlock Holmes was a prototypical cocaine user – Dr. Watson argued against it, but Holmes inject the drug to keep his “keen mind” stimulated
  14. 14. Psychomotor Stimulants• History – Cocaine • 1863, Angelo Mariana, Chemist – Produced Wine • John S. Pemberton, Pharmacist – French Wine of Cola, Ideal Tonic – Later removed replaced alcohol with kola nut – 1906 Pure Food and Drug Act Outlawed Cocaine
  15. 15. Psychomotor Stimulants• History – Cocaine • Early 20th Century there was backlash from FDA – Professionals were still injecting it – Drug started to become associated with corruption and crime in popular thinking • Harrison Narcotic Act of 1914 – Banned use of cocaine as well as opium and morphine – Cocaine became an underground drug until WWII, 1939 when interest in stimulants were reinvigorated
  16. 16. Psychomotor Stimulants• History – Amphetamines • China: ephedrine (ma huang) used in tea for > 5,000 yrs – 1924 Ko Kuei Chen & C.F. Schmidt pointed out similarities of ephedrine to epinephrine, used to treat asthma – Epinephrine was unstable; injection method – Ephedrine could be taken in pill form; less toxic – Supply was dwindling
  17. 17. Psychomotor Stimulants• History – Amphetamines • 1887, L. Edealeno synthesized amphetamine – Didn’t explore its uses • 1910, G. Barger & Sir H.H. Dale – First published paper about effects amphetamines and other sympathomimetic drugs on body • 1927, Gordon Alles, American Chemist/Pharmacologist – Suggested amphetamine be used as a cheap substitute for ephedrine
  18. 18. Psychomotor Stimulants• History – Amphetamines • 1927; AMA – Amphetamine as a “pick-me-up” for sleep disorder, Narcolepsy – Stimulant for Depression • 1943; ½ of drug Sales – Weight loss and diet control – Antidepressant and stimulant effects – Extend periods of alertness – Inhaler treatment for asthma sold over the counter
  19. 19. Psychomotor Stimulants• History – Amphetamines • 1940s; Smith, Kline, and French Co. – Held Patent • Ciba – Methylphenidate (now known as Ritalin) marketed as the “nonamphetamine” stimulant • Current prescribing of amphetamines is limited to a number of conditions – Narcolepsy, hyperactivity in children – NOT for weight control
  20. 20. Psychomotor Stimulants• History – Amphetamines • What do you think happened when medicinal sources of amphetamines dried up? • Current: Western countries mainly abuse cocaine
  21. 21. Psychomotor Stimulants• History – Amphetamines
  22. 22. Psychomotor Stimulants• History – Cathinone or Khat • Alexander the Great to General Harrar – Cure for Melancholia • Arab physicians recommend for variety of disorders • Amda Sion – 14th Century ruler of Ethiopia – 1st recorded Khat Addict • 1982; 1st Case of Khat Psychosis – UK & Europe Followed
  23. 23. Psychomotor Stimulants• Pharmacokinetics – Administration & Absorption, Distribution, Metabolism, Excretion
  24. 24. Psychomotor Stimulants• Routes of Administration and Absorption – Amphetamines • Weak bases – pKa of between 9 & 10 – What does that mean when drug is taken orally for medicinal purposes? – Slow rate of absorption, constant blood level, increased dosage compared to abused methods • Abusers use injection, inhalation, and snorting
  25. 25. Psychomotor Stimulants• Routes of Administration and Absorption – Cocaine • pKa of 8.7 • Coca leaves in mouth mixed with lime to raise pH of saliva – Reduction of ionization and increased rate of absorption • Abusers smoke, snort, inject cocaine HCL – Smoking method termed “tooting” • Freebasing separates cocaine from HCL – highly combustible chemicals; vapor has increased lipid solubility • Method replaced by “crack” cocaine – Cocaine HCL mixed with baking soda; water is evaporated and chunks or rocks are left behind – Same effect as freebasing but cheaper and faster
  26. 26. Psychomotor Stimulants• PK: Routes of Administration and Absorption – Amphetamine • Oral administration affected by – Food present? Physical Activity – Peak blood levels reached between 30 min to 4 hrs – Cocaine • Intranasal Snorting – Peak blood levels 10-20 minutes – Rate of Absorption for vaporized freebase or crack unknown, but very rapid » Cocaine molecule is in unionized form; lipid solubility – Methcathinone • Injected in Russia, in US sniffing
  27. 27. Psychomotor Stimulants• PK: Distribution – Amphetamines, Coaine and other drugs in this class cross the blood-brain barrier – Concentrated in the spleen, kidney, and brain
  28. 28. Psychomotor Stimulants• PK: Metabolism & Excretion – Amphetamines • Mainly liver metabolism – Active and inactive metabolites result – Active metabolites extend effects; long half-lives • Excretion dependent upon pH of urine – Ionized at acidic pH, so will not be reabsorbed from nephron – Sweat, saliva • Half-life 7-14 hours when urine is acidic • Half-life 16-34 hours when urine is basic
  29. 29. Psychomotor Stimulants• PK: Metabolism & Excretion – Cocaine & Cathinone • Cocaine mainly liver metabolism – Active (narcocaine) and inactive metabolites • Excretion dependent upon pH of urine – Ionized at acidic pH, so will not be reabsorbed from nephron – Unchanged- sweat, saliva, stool, urine • Cocaine half-life of about 40 minutes • Cathinone half-life of about 90 minutes – Intermediate between cocaine and amphetamine

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