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)
2
Q
How long does it take to develop a drug
A
between 7.25 and 19.5 years
3
Q
Naturally occuring stimulant sources
A
- Cocaine- erythroxylum coca
- Ephedrine (ephedra)- shrub
- Cathinon(khat)-shrub… methcathinone
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)
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”
6
Q
When was cocaine isolated?
A
- in the 1850s
- concentrated
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
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)
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)
10
Q
Coca cola
A
contained 60 mg cocaine per 8 ounce
11
Q
1914
A
- Harrison act limited cocaine from products
- Although not a narcotic, included cocaine due to increased misuse
12
Q
1920s-1930s
A
- cocaine declined in use (flipped w amphetamines)
13
Q
late 1960s-1980s
A
cocaine use increased which peaked in the 1980s
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
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
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
freebasing
* mixing w/ ether (flammable)
* Crack (mix w baking soda and H2O)
26
Pharmacokinetics route of administration
* PK depends on route of administration
* intra-nasally/oral- 10-15m before drug action
* iv and smoking/inhaling (fastest)
27
PK duration of action
* difference between cocaine and amphetamines
* cocaine: 20-80 mins; amphetamines: 4-12 hrs
28
PK Similar elimination
* -5 days for metabolites
* The major metabolite is benzoylecgonine
* A small amount is metabolized to an avtive compound norocaine
* Used for drug testing
29
PD- PNS
* potent local anesthetic (surgical use)
* purity tested by tasting (causes numbing)
* powerful constrictor of vessels (surgical use)
30
PD-CNS
* powerful psychostimulant with strong reinforcing qualities (behavioral)
* Potentiates (increases) the synaptic action of dopamine, norepinephrine, and serotonin (physiologically)
31
Neurotransmission Ending
* 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
Cocaine NT ad PD
* acutely blocks transported re-uptake of dopamine, norepinephrine, and serotonin
