1. Pearl Isaac & Anne Kalvik
Stimulants
Pearl Isaac & Anne Kalvik

2. LEARNING OBJECTIVES
1. Develop an understanding of the effects and toxicity of stimulant drugs.
2. Become familiar with the issues surrounding stimulant (especially cocaine) abuse including dependence and current treatment approaches.

3. CNS STIMULANTS
Nicotine
Caffeine
Cathinone (Khat)

4. CNS STIMULANTS “STREET STIMULANTS” OTC STIMULANTS caffeine ephedrine
PPA (phenylpropanolamine)
OTC STIMULANTS
Caffeine
Pseudoephedrine (Sudafed)
Ephedrine
Herbals (e.g. mahuang, guarna)

5. CNS STIMULANTS AMPHETAMINES AMPHETAMINE-LIKE DRUGS
dextroamphetamine (Dexedrine)
methamphetamine
AMPHETAMINE-LIKE DRUGS
methylphenidate (Ritalin)
diethylpropion (Tenuate)
phentermine (Ionamin)
(“Phen-Fen”)
“Ecstasy” (MDMA)

6. STIMULANTS COCAINE Powder Crack (freebase) Some Street Names:
C, coke, flake snow, rock

7. MEDICAL USES OF STIMULANTS
COCAINE
local anesthetic in ENT surgery
AMPHETAMINES
ADHD
narcolepsy
depression
AMPHETAMINE-LIKE DRUGS
appetite suppressant

8. MEDICAL USES OF STIMULANTS
CAFFEINE
Augmentation of analgesia
Mild stimulant to stay awake
By injection for apnea in newborns
OTC STIMULANTS
Nasal decongestion
Symptomatic relief of asthma
Appetite suppression (U.S.)

9. WHY ARE THEY ABUSED? WHO ABUSES?
CNS STIMULANTS
WHY ARE THEY ABUSED?
WHO ABUSES?

10. STIMULANT ABUSE SIGNS OF USE irritability restlessness insomnia
panic, confusion
weight loss
paranoia

11. STIMULANT ABUSE SIGNS OF OVERDOSE hypertension cardiac arrhythmia
chest pain, myocardial infarction
convulsions
cerebral hemorrhage
coma
death

12. PHARMACOKINETICS OF COCAINE
ABSORPTION
snorted (limited by vasoconstriction)
injected
smoked (volatile, stable)

13. PHARMACOKINETICS OF COCAINE
DISTRIBUTION, METABOLISM, ELIMINATION
penetrates brain rapidly
euphoria in approx 35 minutes (nasal); within 1 minute for IV and inhaled use
half-life 3090 minutes
> 95% metabolized
inactive metabolites excreted in urine

14. COCAINE: PHARMACOLOGICAL EFFECTS
SHORT-TERM USE: LOW DOSE
euphoria
increased energy
increased alertness
decreased appetite
increased heart rate and blood pressure

15. COCAINE: PATTERNS OF USE
Intermittent
Compulsive
“Binge” use: “coke run”  until supplies run out, then “crash”

16. COCAINE: PHARMACOLOGICAL EFFECTS
SHORT-TERM USE: HIGH DOSE
intensified high
increased BP & heart rate
increased temperature
anxiety, muscle twitching, insomnia
bizarre/erratic behaviour, psychosis
seizures
arrhythmias, MI

17. COCAINE: PHARMACOLOGY
Blocks dopamine reuptake
Also NE and serotonin

18. Effects of Cocaine on Dopaminergic Activity
Chronic cocaine use
Normal (no cocaine)
Presynaptic neuron
Presynaptic neuron
Dopamine release
Dopamine release
Reuptake carrier
Normal amount of dopamine in synapse
Dopamine in
synapse
Reuptake
carrier
Cocaine blockade
Postsynaptic neuron
Postsynaptic neuron
Decreased postsynaptic receptors
Postsynaptic receptors
Cocaine withdrawal
Acute cocaine use
Presynaptic neuron
Presynaptic neuron
Dopamine release
Dopamine release
Reuptake carrier
Increased dopamine in synapse
Decreased dopamine in synapse
Reuptake carrier
Cocaine blockade
Postsynaptic neuron
Postsynaptic neuron
Decreased postsynaptic receptors
Postsynaptic receptors

19. COCAINE: VIDEO PRESENTATION

20. COCAINE: LONG-TERM USE
psychological dependence
craving
paranoid psychosis
weight loss, malnutrition
impotence
sleep disturbances
nasal congestion, septal perforation

21. COCAINE TOXICITY SUDDEN DEATH OTHER MEDICAL COMPLICATIONS
arrhythmias, hypertension
seizures
brain hemorrhage, stroke
OTHER MEDICAL COMPLICATIONS
heart disease
respiratory complications
acute renal failure
psychiatric

22. COCAINE: WITHDRAWAL PHASE 1 : “THE CRASH” lasts up to 4 days
profound decrease in mood and energy
craving, agitation, anxiety, paranoia
followed by hunger, fatigue, sleepiness
“cocaine blues”

23. COCAINE: WITHDRAWAL PHASE 2 : “WITHDRAWAL DYSPHORIA”
prolonged dysphoria, anhedonia, lack of motivation/energy
increased craving
lasts 1 to 10 weeks
high risk of relapse

24. COCAINE: WITHDRAWAL PHASE 3: “EXTINCTION” episodic craving
triggers to use
craving extinguishes over time
duration indefinite

25. COCAINE: TREATMENTS bromocriptine antidepressants anticonvulsants
neuroleptics
vaccine
vigabatrin ????
NO EFFECTIVE PHARMACOLOGICAL TREATMENT YET
treat co-morbid disorders

26. COCAINE POLYSUBSTANCE ABUSE:
e.g., “speedball”, benzodiazepines, alcohol, methadone clients

27. STREET STIMULANTS & OTCs
Like cocaine and amphetamines but much weaker
High doses
Toxicity: alone and in combination
“STREET STIMULANTS”
availability
restrictions
OTC’S

28. METHAMPHETAMINE “crystal”, “ice”, “speed”, “meth” increasing trend
precursors (e.g., OTCs)
internet: recipes and supplies
manufacture: “home-made” labs
smoked, injected, snorted, swallowed
effects on presynaptic release of dopamine
some effects on serotonin & norepinephrine

29. METHAMPHETAMINE rapid onset (similar to cocaine) LASTS 10 -12 HOURS
intense high (“rush”)
alertness, well-being
decreased appetite
“like buzz of 1000 cups of coffee”

30. METHAMPHETAMINE Toxic Effects
irritability, insomnia, high BP, palpitations
chest pain,MI, death possible
hyperthermia, seizures
Paranoia, hallucinations, formication
violent behaviour

31. METHAMPHETAMINE WITHDRAWAL: NEUROTOXIN peak in 23 days
abdominal distress, increased appetite, headaches, lethargy, depression, suicidal ideation
NEUROTOXIN

32. METHYLPHENIDATE Well studied treatment for ADHD
Abuse potential similar to cocaine and amphetamines
Diversion: classmates, parents, etc.
Crushed and snorted
Injection possible (e.g.,“T’s & R’s”)
Rapid onset (like cocaine) when snorted or injected
Lasts about 6 hours

33. METHYLPHENIDATE UNDESIRABLE EFFECTS:
loss of appetite, anxiety insomnia, hypertension, headache, psychosis
chest pain, tremors, seizures, paranoia, formication (“coke bugs”)
stroke, MI, death

34. METHYLPHENIDATE Tolerance Withdrawal: user vs. “abuser”
exhaustion, lethargy, depression

35. METHYLPHENIDATE
How to treat those with a history of substance and ADHD?

36. DEXTROAMPHETAMINE Also prescribed for ADHD
Abuse similar to methylphenidate

37. What can a pharmacist do?
STIMULANT ABUSE
What can a pharmacist do?

38. STIMULANT ABUSE Refer for treatment
Monitor prescriptions for methylphenidate and other stimulants
Monitor OTC sales
Remember polysubstance abuse