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Pharmacology - Midterm #2 > Drugs of Abuse > Flashcards

Drugs of Abuse Flashcards

1
Q

Why do people abuse drugs?

A 
(1) To Feel Good
Novel 
1. Feelings
2. Sensation
3. Experiences 
& share them
(experimenting: mid-late high school/university years)

(2) To Feel Better
Self-medicating to lessen
1. Anxiety
2. Worries
3. Fears
4. Depression
5. Hopelessness
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2
Q

Goal for abuse?

A

Get a “quick fix”

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3
Q

Routes of Administration

A
  1. IV
  2. Inhalation (smoking)
  3. Insufflation (snorting)
  4. Oral - not common b/c takes a long time and high rate of metabolism in gut & liver

Could use topical - but mainly to bust the patch

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4
Q

Which routes of administration are the most intoxicating?

A
  1. IV & smoking

2. Snorting

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5
Q

Placebo Effect

A

30-50%
Feel effect without getting the “high”
Friend vodka story

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6
Q

Origin of Cocaine?

A

Derived from coca plant (South America) in high mountains
Natives -> chewed plant, stimulant
-Inc breathing/O2 intake -> good b/c low O2 in mountains
-Dec appetite -> didn’t need to feed as often

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7
Q

Origin of Coca Cola

A

Cocaine in Coke

  • 9g in 1st version
  • removed by early 1900’s
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8
Q

Cocaine use in the early 1900’s?

A

Local anesthetic (like Lidocaine)

  • Sold over the counter
  • Put on kids teeth (numb the A for toothache)
  • Cops put drugs on gums to see if it was Cocaine (went numb)
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9
Q

Mechanism of action of Cocaine?

A

Blocks dopamine reuptake transporters (blocks pore)
Inc. dopamine in the cleft = inc. signalling (stimulant)

@ high doses = also blocks reuptake of serotonin & NA

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10
Q

Action of Cocaine? (STEAMS)

A
  1. SNS activation (NA response increased)
  2. Inc T (hyperthermia)
  3. Inc. euphoria
  4. Inc. alertness
  5. Inc. mental awareness
  6. Dec sweating
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11
Q

Adverse effects of Cocaine? (Acute - PHATAD, LT - CASR)

A

Acute

  1. Paranoia
  2. Hypertension (Inc. BP)
  3. Anxiety
  4. Tachycardia (Inc. HR)
  5. Agitation
  6. Dyspnea (slowed breathing)

LT

  1. Cardiac arrhymias (fatal)
  2. Seizures
  3. Respiratory failure
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12
Q

Cocaethylene

A

Active metabolite of cocaine in the presence of alcohol

  • Greater potency to dopamine transporters
  • Less potency to serotonin & NA transporters
  • Contributes to cardiotoxicity of cocaine
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13
Q

Cocaine vs. Crack

  • Form
  • Melting Point
  • Solubility
A

Form:

  • Co: white powder (HCl salt), typically smoked or IV
  • Cr: free base form of cocaine, white rocks (makes crackle sound when produced), heat + mix cocaine, NaHCO3 (baking powder) + water

Melting Point

  • Co: unstable at high T, no high if smoked
  • Cr: vaporizes @ 90oC, can be smoked

Solubility - both = IV injected

  • Co: H2O soluble, IV injected easily
  • Cr: not H2O soluble, use lemon juice + vinegar to dissolve
  • *Corrode veins**
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14
Q

Major Side Effects of Opioid Use

A
  1. Nausea
  2. Respiratory depression dangerous
  3. Constipation
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15
Q

How do opioids cause severe constipation?

A

Bind to opioid receptors in the gut, bowel stretches
Intestine responds to stretch
Causes blockage of the intestines -> dec longitudinal motion (propulsive contractions, inc non-propulsive/nonproductive contractions

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16
Q

What is the chain of opioid strength?

A 
Fentanyl (80-100 M)
Hydromorphone (5 M)
Oxycodone (1.5 M)
Morphine (1 M)
Codeine (0.15 M)
Meperidine (0.1 M)
17
Q

How are opioids addictive?

A

All opioids = potential to be addictive
To be addictive, needs to cross the BBB + bind ORs in the brain
Therefore, the more lipophilic a drug is, the more addictive it is

18
Q

How does Methadone work?

A

Tx. for opioid addiction (OR agonist)
Activates the receptor + keeps in the safe zone, prevents the individual from entering too low of the drug that they go into withdrawal

19
Q

Narcan

A

OR antagonist
Kicks off all the opioid from OR, blocks receptor
Inhibits respiratory depression, brings the individual back to life

20
Q

Trends in opioid ODs (2016-2018)

A 
3023->4588
Appears to be levelling off
Top provinces of opioid use:
1. BC
2. ON
3. AB
21
Q

Fentanyl ODs

A

2012->2018

13->1500 (115x increase)

22
Q

Percocet

A

2.5 or 5 mg of oxycodone with some acetaminophen

Pain relief lasts for 4-5 hours

23
Q

Oxycontin

  • Contents
  • Pain relief
  • Advertising
  • Nickname
  • Time of abuse
A

Contents:
10, 20, 40 or 80 mg of oxycodone

Pain relief:
slow release -> 12-14 hours of relief

Advertising:
advertised as non-addictive
people could crush & take via insufflation, IV, or oral
get intense euphoric high

Nickname:
Hillbilly Heroin

Time of abuse:
2011

24
Q

Oxyneo

  • Time of Introduction
  • Unique formulation
  • Tamper resistance/Solubility
  • Effect on Street Price of Oxy
A

Time of Introduction:
Early 2012

Unique formulation:
add polyethylene formulation

Tamper resistance/Solubility
can’t crush into fine powder/harder
when tablet broken retains some slow release properties
when add H2O = forms a viscous gel, “can’t” be injected

Effect on Street Price of Oxy
Inc. b/c can’t get proper high

25
Targin - Unique formulation - Tamper resistance - Effect on Street Price of Oxy
Unique formulation combo of naloxone + oxycodone indications = severe pain requiring daily treatment & relief of opioid induced constipation give oral dose -> Naloxone = high first pass effect in gut & liver metabolite = naloxone 3-glucuronide (very low affinity to mu opioid receptor), 0 antagonistic activity Tamper resistance if abusers crush up tablet & dissolve in H2O, get both agonist & antagonist activity in systemic circulation only able to get agonist alone if take the oral dose Effect on Street Price of Oxy inc. price of Hydromorph Codone (hydromorphone)-more potent opioid didn't dec the amount of people on drugs- they just switched to other opioid drugs
26
Carfentanil
Used to sedate elephants 10,000 - 100,000M Need multiple vials of Narcan to treat an overdose
27
Typical Dosing of Narcan
0.4 mg/IV admin | 2 mg/Nasal spray
28
Loperamide
Imodium - common name Anti-diarrheal medication Binds to mu OR in the gut, causes constipation Not addictive - b/c can't cross the BBB (need to cross in order to be addictive)
29
P-glycoprotein (MDRI)
Efflux transporter @ the BBB - restricts opioid entry into the brain (14x fold difference in opioid concentration when working vs. not) - High affinity to loperamide Abusers - try to get high off loperamide - Either inhibit p-glycoprotein (using other meds) - Or take a lot of loperamide (saturate the transporter) - gives them a lot of constipation
30
Amphetamines - Normal Treatments - Drugs of Abuse
``` Stimulant Inc. levels of NT in the brain Similar symptoms of cocaine -Inc alertness -Dec fatigue -Insomnia -Dec appetite suppression ``` Normal Treatments - ADHD - Narcolepsy Drugs of Abuse -Methylphenidate (Ritalin) -Methamphetamines Methylenedioxmethamphetamine -Ephedrine = basis of all drugs, sim to endogenous NTs
31
Methylphenidate
Ritalin | -Treatment for ADHD
32
Methamphetamines - Mechanism - Action - Side Effects (Acute & LT) - Production
Crystal Meth/Speed Mechanism - Reverses transport of VMAT-2 @ PM - Normally brings dopamine into presynaptic neuron + vesicles - Now, pumps out all dopamine into cytosol + cleft (MASSIVE RUSH) - Properties of MDMA may cause the change in transport (basic-H+ gradient for tx) Action - Intense euphoria - Taken IV, snorting, smoking, rarely orally - Cocaine = 1 hr - Meth = 10-12 hrs (lasts much longer) Side Effects (Acute & LT) - Acute (DASHIH) - diarrhea - agitation - sweating - hypertension - insomnia - heart palpitations, constant fight or flight response (has to do with tweaking) - LT - paranoia - psychosis - CV disease - meth mouth (lose/grind teeth, poor saliva, recessed jaw) - Crank bugs - dec BF - Dec dopamine transporters (like PD) Production - make-shift labs in homes, trailers, or cars - high risk of explosion d/t volatile solvents + by-products - paint thinner - gum scrubbers - toluene - acetone - rock salts
33
Methylenedioxmethamphetamine - Mechanism - Action - Side Effects (Acute & LT)
MDMA/Ectasy - club drug (stimulant + hallucination) - age group = 16-26 yrs (uni) - typically taken orally (4-8 hrs) Mechanism - Serotonergic neurons - Stimulates serotonin release, inhibits metabolism + blocks reuptake (5HT2) - hallucinations = d/t 5HT2 Action - euphoria - social interactivity - empathy - visual + tactile hallucinations Side Effects (Acute & LT) - insomnia - appetite suppression - thirst - hyperthermia - teeth grinding/jaw clenching Blue/Suicide Tuesday - week following use - depression, agitation, & suicidal tendencies - too low serotonin in brain - still see dec serotonin (2 wks + 7 yrs later) - impacts LT depression + alters BF to brain

Pharmacology - Midterm #2 (9 decks)

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