lecture 13- Stimulants pt. 1 Flashcards

Exam 2

1
Q

Stages of drug development

A
  • Synthesis/isolation of compound (1-2 years)
  • Preclinical studies (2-4 years)
  • Scrutiny and grant permission for clinical trials (.25-.5 years)
  • Pharmaceutical formulation, standardization of the compound (.5-1 year)
  • Clinical studies (3-10 years)
  • Review and grant of marketing permission (.5-2 years)
  • Post-marketing surveillance (no fixed duration)
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2
Q

How long does it take to develop a drug

A

between 7.25 and 19.5 years

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3
Q

Naturally occuring stimulant sources

A
  • Cocaine- erythroxylum coca
  • Ephedrine (ephedra)- shrub
  • Cathinon(khat)-shrub… methcathinone
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4
Q

Synthetic stimulant sources

A
  • Amphetamines (Adderall, Dexedrine)
  • Methamphetamines (crystal, ice, crystal meth)
  • Methylphenidate (ritalin)
  • Pipradrol (1950 to treat obesity, banned from US in 1970)
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5
Q

Erythroxylum coca history

A
  • Used (chewed) by Incas during the 16th century for religious medicinal, and work-related uses as it provided energy
  • Spanish conquistadors (catholic influence) in 15th and 16th centuries, used it as a payment but didn’t use the leaves, did not encourage other Europeans)
  • In the 1800s, Europeans began to experiment with coca. This led to exaggereated positive and negative tales from “naturalists”
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6
Q

When was cocaine isolated?

A
  • in the 1850s
  • concentrated
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7
Q

How are cocaine and coca different?

A
  • the concentration is higher for cocaine
  • method of administration: coca is chewed (slow PK), cocaine can be snorted, injected, inhaled, rubbed on gums giving it a fast PK
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8
Q

Sigmund Freud’s “On Coca”

A
  • Used as treatment for: asthma, depression, indigestion, syphilis, addiction (to morphine and alcohol)
  • Local anesthetic which revolutionized surgery (procaine/novocaine)
  • In 1902, 92% of all cocaine sold in tonics available from drug stores, without prescriptino (patent medicines)
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9
Q

Notable cocaine users

A
  • Robert Louis Stevenson (author of Dr. Jekyll and Mr. Hyde)
  • Thomas Edison (invented the light bulb)
  • Ulysses Grant (18th US president)
  • Sherlock Holmes (fictional character)
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10
Q

Coca cola

A

contained 60 mg cocaine per 8 ounce

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11
Q

1914

A
  • Harrison act limited cocaine from products
  • Although not a narcotic, included cocaine due to increased misuse
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12
Q

1920s-1930s

A
  • cocaine declined in use (flipped w amphetamines)
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13
Q

late 1960s-1980s

A

cocaine use increased which peaked in the 1980s

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14
Q

Amphetamines: synthetic stimulants

A
  • Prescribed for cold/sinus symptoms, obesity, narcolepsy, and ADHD (paradoxical effects)
  • Use rose during WWII (1939-45)- Japan, Sweden, other European countries recognized problems
  • Us became more educated about potential hazards/misuse in 60s… amphetamine addiction rates rose due to prescribing for heroin misuse (users called speed freaks)
  • In 1970s cocaine believed to be natural, less harmful alternative… increased trafficking of more potent cocaine also available
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15
Q

Anti-Drug Abuse Acts of ‘86 and ‘88

A
  • Specified penalties for sale and possession
  • Set limits on amount
  • Higher penalty for crack than cociaine posession
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16
Q

Fair Sentencing Act

A
  • 2010
  • Obama Administration
  • Eliminated minimum-sentence requirement for small amount of crack
17
Q

Comprehensive methamphetamine Control Act 1996

A
  • Increased penalties for meth manufacture/trafficking
  • downside is that then cocaine use increases
18
Q

Combat Meth Epidemic Act 2006

A
  • Regulate sale of products containing pseudoephedrine and ephedrine (ex. sudafed)
19
Q

Where has stimulant production returned to

A

mexico

20
Q

Cocaine from plant to street

A
  • After harvest, plant is processed by mashing and soaking (kerosene, sulfuric acid, etc)
  • Resulting paste allowed to dry and can be placed at end of cigarette or mixed with tobacco for smoking
  • Converted into cocaine hydrochloride (street cocaine) by adding various chemicals, then allowed to dry
  • can be snorted or dissolved to inject
21
Q

How is freebase cocaine made

A
  • mixed with ether (highly flammable) because ccaine hydrochloride can break down at high temperatures
  • Heated to vaporize; vapor is inhaled
22
Q

Crack cocaine

A
  • mixed with baking soda and water which forms crystals
  • heated to vaporize; vapor is inhaled
  • heat makes cracking sound (baking soda)
23
Q

Cocaine sulfate

A

smokeable

24
Q

How is Cocaine-HCl/street cocaine (powder) used

A
  • nasally
  • injected (sometimes oral or topical)
25
Q

freebasing

A
  • mixing w/ ether (flammable)
  • Crack (mix w baking soda and H2O)
26
Q

Pharmacokinetics route of administration

A
  • PK depends on route of administration
  • intra-nasally/oral- 10-15m before drug action
  • iv and smoking/inhaling (fastest)
27
Q

PK duration of action

A
  • difference between cocaine and amphetamines
  • cocaine: 20-80 mins; amphetamines: 4-12 hrs
28
Q

PK Similar elimination

A
  • -5 days for metabolites
  • The major metabolite is benzoylecgonine
  • A small amount is metabolized to an avtive compound norocaine
  • Used for drug testing
29
Q

PD- PNS

A
  • potent local anesthetic (surgical use)
  • purity tested by tasting (causes numbing)
  • powerful constrictor of vessels (surgical use)
30
Q

PD-CNS

A
  • powerful psychostimulant with strong reinforcing qualities (behavioral)
  • Potentiates (increases) the synaptic action of dopamine, norepinephrine, and serotonin (physiologically)
31
Q

Neurotransmission Ending

A
  • To terminate cell activity, deactivation of neurotransmitters by:
  • destruction or metabolism of NT (enzymes: ase)
  • Reuptake- back into the vesicles by transportes found on presynptic terminals and glial cells
32
Q

Cocaine NT ad PD

A
  • acutely blocks transported re-uptake of dopamine, norepinephrine, and serotonin