Class 8-substances Flashcards
1
Q
Which substance is the less susceptible
to cause a toxic psychosis?
A
heroin
2
Q
PATHOPHYSIOLOGY addiction
A
REINFORCING EFFECTS OF SUBSTANCE OF ABUSE
• Posited to be mediated through the mesolimbic reward pathway that involves DA transmission
• Reward pathway originates in the ventral tegmental area and projects to the nucleus accumbens
3
Q
DEPRESSANTS
A
↓ level of alertness and activity of the brain (GABA, mu) - Alcohol - Benzodiazepines - GHB - Morphine and derivates - Methadone - Heroin - Solvents
4
Q
STIMULANTS
A
↑ level of alertness and activity of the brain (DA / NA)
- Cocaine
- Amphetamines
- Methamphetamines
- Methylphenidate and other stimulants
- Nicotine
- Caffeine
5
Q
DISRUPTIVE /
HALLUCINOGENS
A
Modify the brain, alter the senses (5-HT / glutamate)
- Cannabis
- Mushrooms
- PCP / mescaline
- Ketamine
- Ecstasy
6
Q
ALCOHOL PHARMACOKINETIC
A
- Absorption : 80 % (rapid : 5 – 10 minutes)
- Metabolic rate : 20 mg/dL/hour (i.e., one standard drink) and this rate is increased with chronic drinking
- As the alcohol level rises in the body : process saturated and nicotinamide adenine dinucleotide (NAD+) is depleted
7
Q
ALCOHOL DEHYDROGENASE
A
- Located in the liver
- Polymorphism (i.e., asian population)
- Turns ethanol into acetadehyde
8
Q
ALDEHYDE
DEHYDROGENASE
A
Turns acetadehyde into acetate
9
Q
INTOXICATION sx roh
A
- Slurred speed
- Incoordination
- Unsteady gait
- Nystagmus
- Inattention / memory impairment
- Stupor / unconsciousness
10
Q
Pathophysiology ROH
A
GABA / GLUTAMATE:
• Alcohol enhances the effect of GABA and inhibits glutamate receptors
• Chronic use : GABA receptors downregulate and glutamate receptors upregulate
• Abrupt cessation : hyper-excitability because of elevated glutamatergic effects
5-HT
• Chronic consumption
• Disrupt 5-HT transmission
• Obsessive behaviors concerning alcohol intake
11
Q
WITHDRAWAL SYMPTOMS roh
A
LEVEL 1 (6 – 8 hours post abrupt cessation)
Hyperactivity of autonomic nervous system
LEVEL 2 (12 – 24 hours post abrupt cessation)
Hallucinations
LEVEL 3 (12 – 48 hours post abrupt cessation)
Seizure activity
LEVEL 4 (2 – 5 days post abrupt cessation)
Delirium tremens
12
Q
PHARMACOLOGICAL TREATMENT WITHDRAWAL roh
A
- Benzodiazepines ↑ GABA, ↓ withdrawal symptoms and prevent progression to severe symptoms, Anticonvulsant properties, Lorazépam, Diazépam, Chlordiazépoxide
- Other options discussed :
- Anticonvulsants:
- Barbiturics
- Antipsychotics
- Betablockers / clonidine
13
Q
LORAZEPAM +/-
A
- Safer in elderly or hepatic failure
- Predictable IM absorption
- Intermediate onset of action
14
Q
DIAZEPAM +/-
A
- Faster onset of action
- Longer half-life
- Possible accumulation in elderly or hepatic failure
15
Q
CHLORDIAZEPOXIDE +/-
A
- Longer half-life
- Possible accumulation in elderly or hepatic failure
- Intermediate onset of action
16
Q
SYMPTOM-TRIGGERED DOSING benzos
A
- Requires that patients be monitored using the CIWA scale
* Benzodiazepines are administered based on CIWA score (>8)
17
Q
FIXED DOSING benzos
A
- Regularly schedule doses are gradually tapered over several days and include as needed doses
- Risk of overmedicating
18
Q
ANTICONVULSANTS roh withdrawal
A
- Useful to treat seizures
* Do not prevent delirium trements
19
Q
BARBITURICS roh withdrawal
A
- For resistant withdrawals
- Narrow therapeutic indexi
- Risk of dependence, respiratory distress
20
Q
ANTIPSYCHOTICS roh withdrawal
A
- Useful to treat psychiatric symptoms associated with delirium tremens
- ↓ convulsion threshold
21
Q
BETA BLOCKERS / CLONIDINE roh withdrawal
A
- Useful to treat a few symptoms (tachycardia, hypertension, tremors)
- Do not prevent delirium tremens and convulsions
22
Q
THIAMINE
A
Commonly depleted in people with alcohol use disorders
because of altered GI absorption or a diet lacking sufficient thiamine
v Prevention and treatment of Wernicke’s encephalopathy
v Dosing : 100 mg PO, IM, IV daily for at least 1 – 4 weeks
23
Q
ALCOHOL USE DISORDER
PHARMACOLOGICAL TREATMENT
A
- Naltrexone
- Disulfiram
- Acamprosate
24
Q
NALTREXONE
A
mu opioid receptor antagonist
Blocks the pleasurable effects of alcohol
CONTRAINDICATIONS : opioid use within the last 7 days, acute hepatitis, severe hepatic impairment
SIDE EFFECTS : nausea, headache, insomnia, nervousness
25
DISULFIRAM
Irreversible inhibitor of ALDH
Resulting in accumulation of acetaldehyde after alcohol
consumption
SYMPTOMS OF THE INTENDED DISULFIRAM-ALCOHOL REACTION:
warmness and flushing of skin, ↑heart rate, palpitations, ↓blood pressure, nausea, vomiting, shortness of breath, sweating, anxiety, dizziness, blurred vision, confusion
(goal is to increase motivation to avoid alcohol consumption)
CONTRAINDICATIONS : psychosis, use of ethanol/metronidazole, severe
myocardial disease
SIDE EFFECTS : fatigue, drowsiness, metallic taste, hepatotoxicity (rare)
26
ACAMPROSATE
```
NMDA receptor antagonist
Enhances GABA receptor activation and restores the
GABA/glutamate balance
CONTRAINDICATIONS : renal failure
SIDE EFFECTS : diarrhea, insomnia
```
27
GHB
DESIRED EFFECTS : euphoria, sedation, relaxation, sexual disinhibition
ONSET OF ACTION : 15 minutes
DURATION OF ACTION : approximately 3 hours
COMMENTS : use in gyms, use in replacement of alcohol (less caloric)
28
OPIOIDS types
NATURALS
• Morphine (StatexMD, M-EslonMD, KadianMD)
• Codeine
SEMI-SYNTHETICS
• Hydromorphone (DilaudidMD, Hydromorph ContinMD)
• Oxycodone (SupeudolMD, OxycontinMD, OxyneeoMD)
• Buprenorphine
• Heroin
SYNTHETICS
• Methadone
• Mepiridine (DemerolMD)
• Fentanyl (DuragesicMD)
• Tramadol (UltramMD, ZytramMD, RaliviaMD, TriduralMD)
29
MECHANISM OF ACTION OPIOIDS
```
mu receptor:
AGONISTS
• Methadone
• Heroin
• Morphine, oxycodone, hudromorhone, etc.
PARTIAL AGONIST
• Buprenorphine
ANTAGONISTS
• Naloxone (only absorbed IM/IN) Naltrexone: only PO
```
30
mu receptor:
* Analgesia
* Euphoria
* Reward system
* Sedation
* Respiratory distress
* Myosis
* ↓ gastrointestinal motility
31
INTOXICATION OPIOIDS
* Myosis
* Slurred speech
* Impaired attention / memory
* Drowsiness / coma
* Death
32
WITHDRAWAL OPIOIDS
* Dysphoria
* Nausea / vomiting
* Myalgias
* Lacrimation / rhinorrhea
* Mydriasis / piloerection / sweating
* Diarrhea
* Fever
* Insomnia
33
PHARMACOLOGICAL TREATMENT INTOXICATION OPIOIDS
NALOXONE
mu opioid receptor antagonist
Reversal of opioid activity
Onset of action : very rapid (< 5 min)
Duration of action : depending on the route of administration (often need to be repeated)
Side effects : abrupt reversal of opioid intoxication (tachycardia, hypertension, etc.)
34
OPIOID WITHDRAWAL AND
| DETOXIFICATION PHARMACOLOGICAL TREATMENT
- Methadone
| - Buprenorphine (+/- naloxone)
35
METHADONE
mu opioid receptor agonist
• less « peaks » vs heroin
• ↓ or cancel effect of other opioids if consumed (because has better affinity)
• No euphoria if taken by oral route of administration
DURATION OF TREATMENT :
- Detoxification : few days to 6 months
- Maintenance treatment : can be continued indefinitely
PHARMACOKINETICS
- Good bioavailability
- Long half-life (die)
- Metabolism via numerous CYP : interactions ++
ORAL SOLUTION
- Mixed with orange juice to avoid injection (high risk of addiction if injected)
- Patient must take it in front of the pharmacist
Pharmacodynamics:
- CNS depressants
- Rx causing QTc prolongation
SIDE EFFECTS:
- Similar to other opioids
- Sedation
- Transpiration
- Weight gain
- QTc prolongation
Useful for severe withdrawal (patients on a high dose of opioids)
36
BUPRENORPHINE
mu opioid receptor partial agonist
• Reduces craving and withdrawal symptoms
• Administering buprenorphine to patient who are currently taking full
agonists can precipitate withdrawal à induction after patient presents
withdrawal symptoms
DURATION OF TREATMENT :
- 7 – 10 days for acute withdrawal phase
- Maintenance treatment : years or lifelong
37
BUPRENORPHINE + NALOXONE
- Decreases abuse potential of buprenorphine if crushed and injected
- There is no effect from oral or sublingual naloxone secondary to poor absorption
PHARMACOKINETICS
- Long half-life (die)
- Metabolism via CYP3A4 (less interactions than methadone)
SCHEDULE
- Many possible schedules when patient is stabilized (die, q2 days)
SIDE EFFECTS
- Better tolerated than methadone (less sedation)
- Headache
- Constipation
- Nausea / vomiting
- Sweating
INTERACTIONS
- Few pharmacokinetics interactions
- Pharmacodynamics
- CNS depressants
• Useful for less severe withdrawal (higher risk of withdrawal symptoms if patients on a high dose of opioids)
38
GUIDELINES opioid use disorder
* Buprenorphine + naloxone if possible, for a safer use
* Methadone if buprenorphine + naloxone not effective enough
* Methadone if treatment with buprenorphine is not the best choice
39
NICOTINE
Binds to nicotinic acetylcholine receptors (nAchRs)
ABSORPTION : Readily absorbed throughout the pulmonary alveoli
and passes directly into the blood avoiding first-pass metabolism
DISTRIBUTION : < 10 seconds to reach the brain
METABOLISM : primarily hepatic
ELIMINATION : half-life 1 – 2 hours
40
SYMPTOMS INTOXICATION NICOTINE
* Nausea, vomiting
* Diarrhea
* Dry mouth
* Palpitations
* Headache
* Insomnia
41
SYMPTOMS WITHDRAWAL NICOTINE
* Depressed mood
* Insomnia
* Anger, irritability
* Anxiety
* Trouble concentrating
* Restlessness
* ↑appetite
42
NICOTINE AND SCHIZOPHRENIA
- Patient more vulnerable to effects of nicotine (dependence +)
- Effect of nicotine can modulate symptoms / response to treatment
- Mesolimbic pathway : DA cells receive direct nicotine cholinergic input that is stimulated by cigarette smoking, which likely mediates the reward experience
- Long-term disrupt of these neurotransmitters
43
PHARMACOLOGICAL TREATMENT nicotine
To reduce motivation to smoke / withdrawal symptoms
- Nicotine replacement therapy (NRT)
- Bupropion
- Varenicline
- Others : tricyclic antidepressants, clonidine
44
NRT
Nicotine substitution that alleviates withdrawal,
including long-term cravings
NICOTINE PATCH 1 cig= 1 mg
- Slow liberation (16 – 24 hours)
NICOTINE GUM, LOZENGE, ORAL INHALER, SPRAY
- Fast acting
- Often used in combination with the patch to reduce cravings
SIDE EFFECTS
- Insomnia / nightmares (take off the patch before bedtime)
- Nausea
- Cutaneous irritation with the patch (fluticasone before application)
Contraindications : pregnancy, cardiac arrhythmias (RELATIVE!!)
45
BUPROPION (ZYBAN)
Inhibits the recapture of NA/DA
- Can be combined with NRT
- Start approximately a week before smoking cessation
46
VARENICLINE (CHAMPIX)
```
Nicotinic receptors partial agonist
- Partial stimulation prevent withdrawal symptoms /prevents nicotine to bind and reduce pleasure (or reward effect) associated with smoking
- Can be combined with NRT
SIDE EFFECTS
- Nausea
- Insomnia
- Neuropsychiatric effects? not really
```
47
SMOKING CESSATION AND
| SCHIZOPHRENIA
• More complex
• Auto-medication ?
• Cardiovascular and metabolic side effects of tobacco
• Risk of relapse
NICOTINE REPLACEMENT DURING HOSPITALIZATION
- Be aware of interactions : no more induction of CYP1A2
48
E-CIGARETTE
* Less nicotine than a traditional cigarette
* Important variability between the products
* Few clinical studies on effectiveness and long-term safety
* Not recommended except if failure to other treatments
49
MECHANISM OF ACTION cocaine
↑ monoamines (DA, NE)
50
Clinical differences between amphetamine and cocaine
- Speed of onset of effects is generally quicker with injected or smoke cocaine
- Duration of effect longer with amphetamine
- Cocaine = DA transporter blocker, whereas amphetamines also increase release of DA
51
METHAMPHETAMINES
* More powerful than amphetamines
* Often found in synthetic drugs
* Dependence ++ (if inhaled or injected)
* Risk of psychosis
* Consequences : cardiac, pulmonary, psychiatric, neurologic
52
INTOXICATION stimulants
```
• Nausea, vomiting, weight loss
• Tachycardia or bradycardia ↑ or ↓ BP
• Mydriasis
• Chills or diaphoresis
• Myalgia, hyperventilation, chest pain,
or arrhythmias
• Seizures, confusion, coma
• Psychomotor agitation/retardation
```
53
WITHDRAWAL stimulants
* Fatigue
* Vivid, unpleasant dreams
* Insomnia or hypersomnia
* ↑ desire to eat
* Psychomotor agitation/retardation
54
PHARMACOLOGIC TREATMENT intoxication stimulants/
* Symptomatic management (VS, hydration, calm environment)
* Benzodiazepines : for agitation, anxiety, seizures, hypertension
* Antipsychotics : if psychosis do not recover spontaneously
55
INTOXICATION sx cannabis
* Impaired motor coordination
* Euphoria
* Anxiety / social withdrawal
* Sensation of slowed time
* Impaired judgment
* Xerostomia
* Tachycardia
* ↑ appetite
56
sx cannabis withdrawal
```
• Irritability, anger, aggression
• Nervousness
• Insomnia
• Anorexia or weight loss
• Restlessness
• Depressed mood
• Physical symptoms : fever, chills, headache,
tremors, diaphoresis, abdominal pain
```
57
PHARMACOLOGIC TREATMENT INTOXICATION cannabis
* Supportive care
* Benzodiazepines : for anxiety
* Antipsychotics : for psychosis
58
PHARMACOLOGIC TREATMENT cannabis withdrawal
* Topiramate ?
| * Pregabaline ?
59
Ecstasy MECHANISM OF ACTION
↑ 5-HT
Part of the disruptive drugs even if it has a stimulant effect
- Also stimulates the reward center : ↑ DA
A few hours after :
- ↓ 5-HT : withdrawal and depressive symptoms
Less addictive than other drugs
60
SYNTHETIC DRUGS
* Modification of the chemical formula of a drug to obtain a new molecule
* Danger :
* Attractive tablets / low price
* We don’t know which substance is contained in the tablet
* Variability between tablets
* Consequence : unpredictable effects
61
SYNTHETIC CANNABIS
* Sold as incense « Not for human consumption »
* Variety of spices, herbs or vegetal material
* Unpredictable and powerful effect
62
QUETIAPINE
MIXED WITH COCAINE : Q-Ball
To replace heroin in the combination Speedball
Maximise effect of cocaine and prevent dysphoria at the end of the dose
** More accessible than benzodiazepines, often prescribed as PRN, no legal control
63
OVER-THE-COUNTER
* Codein (cocktails : Purple Drank)
* 1st generation antihistamines
* Dextrometorphan
* Decongestives (e.g. pseudoephedrine)
* Laxatives
* Ipeca
* Caffeine
