Addiction & Toxidromes

Question 1

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Sx:

Answer 1

— cardiovascular effects
- tachycardia
- hypertension
- arrhythmias
- QT prolongation/QRS widening (with cocaine)

— central nervous system (CNS) excitation
- euphoria, agitation, restlessness
- delirium
- seizures

— neuromuscular features
- hyperreflexia
- tremor

— autonomic effects
- hyperthermia
- diaphoresis
- flushing
- pallor
- mydriasis

— gastrointestinal effects
- nausea, vomiting, diarrhoea.

Question 2

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Sedation

Answer 2

1 DIAZEPAM IV

OR

1 MIDAZOLAM IV

OR

1 DIAZEPAM VO

OR

2 HALOPERIDOL IV/IM ((in difficult cases))

The main treatment for overdose with stimulant drugs is sedation with IV BZs for CNS excitation, tachycardia, hypertension, hyperpyrexia and sympathomimetic stimulation (producing complications such as hyperthermia).

VO benzodiazepines may be used in patients with mild to moderate agitation if they are cooperative.

oral antipsychotic is not the preferred option in stimulant-induced agitation, as antipsychotics may lower the seizure threshold and are less effective than benzodiazepines in this context.

Question 3

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Anticonvulsant therapy

Answer 3

1 DIAZEPAM IV

OR

1 MIDAZOLAM IV

If intravenous access is not possible, use:

1 DIAZEPAM rectally

OR

1 MIDAZOLAM IM

Benzodiazepines should be used as the primary anticonvulsant in overdose patients if seizures are not self-limiting within minutes

Higher doses than for sedation are required

NOTE: Phenytoin is ineffective for drug-induced seizures and drug withdrawal, and should not be used because it blocks sodium channels and may increase the risk of arrhythmias.

Question 4

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Hypertension Mx:

If hypertension persists despite CNS sedation

Answer 4

1 glyceryl trinitrate IV infusion,

OR

2 sodium nitroprusside IV infusion

These are short-acting vasodilators

Question 5

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
SVT Mx:

If there is no response to BZs

Answer 5

1 ADENOSINE IV

OR

2 VERAPAMIL IV

Question 6

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Hypertermia Mx:

Answer 6

Hypertermia can present with symptoms of heat stroke:
* BT > 40C
* end-organ dysfunciton (seizures, chest/abdominal pain)

management:
* transfer to hospital for more definitive management BEST INITIAL STEP = Immediate active cooling is the priority (Methods include ice water immersion, evaporative cooling with fans, ice packs to major vessels, cold IV saline)
* Intravenous fluid resuscitationis important for volume depletion, but it is not the immediate priority

Question 7

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
when to treat QRS widening

A normal QRS should be less than 0.12 seconds (120ms)

Answer 7

When QRS widening is associated with:
- any deterioration in mental status
- decompensation in airway, breathing or circulation (eg arrhythmias, hypotension)

Question 8

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
QRS widening Mx

treatment is similar in QRS widening caused by opiod poisoning

Answer 8

sodium bicarbonate

PLUS

hyperventilation therapy
(by intubation and mechanical ventilation)

Question 9

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
Cocaine-related QRS widening Mx

Answer 9

Lidocaine IV

Question 10

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
QT prolongation Mx

treatment is similar in QT prolongation caused by opiod poisoning

Answer 10

• if Hypomagnesaemia
  MAGNESIUM SULFATE
• if Hypokalaemia
  POTASSIUM CHLORIDE
• if Hypocalcaemia
  CALCIUM GLUCONATE/CARBONATE

Question 11

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
INTOXICATION/OVERDOSE
Decontamination

Answer 11

• There is almost no role for decontamination in stimulant drug toxicity and there is significant risk and difficulty inadministering it.
• In rare cases, when patients present early (within 1 hour after ingestion) and their clinical status
  allows them to protect their airway, activated charcoal may be considered

Question 12

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
Withdrawal Sx:

Answer 12

• hypersomnia
• hyperphagia
• irritability and aggression
• depression (low energy, low mood, apathy)
• craving

No medication has been shown to be particularly effective in the treatment of amphetamine withdrawal.
Benzodiazepines may be useful to reduce irritability. Antidepressants may be helpful for treatment of depression
arising from stimulant withdrawal.

Question 13

ADDICTION/SUBSTANCE ABUSE
‘Stimulants’
Dependence Mx:

Answer 13

• little conclusive evidence on the effectiveness of pharmacotherapeutic interventions
• psychological interventions, such as CBT

Question 14

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Intoxication/overdose
Sx:

Answer 14

“ARMED Colonialist”

 A - Analgesia (reduced pain perception)
 R - Respiratory depression
 M - Myosis
 E - Euphoria
 D - Drowsiness (stuporous/comatose)
 C - Constipation

Question 15

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Intoxication/overdose
Decontamination

Answer 15

There is no absolute indication for any form of decontamination in opioid overdose

Activated charcoal is never indicated for short-acting opioids.

• the risk of sedation and aspiration, and the availability of an effective and easily administered antidote (naloxone), opioid toxicity can be managed with naloxone or with respiratory supportive care.
• For METHADONE (a long-acting opioid), activated charcoal may be considered if it can be administered within **1 hour **of the estimated time of ingestion to a cooperative, nonsedated patient
• For SLOW-RELEASE preparations overdose, activated charcoal may be considered if it can be administered within 6 hours of the estimated time of ingestion to a cooperative, nonsedated patient

Question 16

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Intoxication/overdose
Antidote

Answer 16

Naloxone IV

long-acting opioid antagonist

• It is recommended that naltrexone is not commenced until 7 to 10 days after the last use of heroin. If heroin or another opioid is taken by a patient who has already been taking naltrexone, all opioid effects are blocked.

Question 17

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Withdrawal
Sx:

Answer 17

– Muscle aches
– Headaches
– seizures (if taking high doses)
– Hyperventilation
– Mydriasis
– Dysphoria
– Insomnia
– Fever
– Sweating
– Nausea and vomiting
– Stomach pains
– Diarrhoea
– Craving

• peak 2-3 days
• resolve within 5-7 days

Question 18

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Withdrawal
Rx:

Answer 18

Buprenorphine VO (Sub-lingual)

Question 19

ADDICTION/SUBSTANCE ABUSE
‘Opioids’
Dependence
Rx:

Answer 19

• psychosocial interventions (such as counselling, cognitive behavioural therapy, social support)

                                \+

• Methadone

                                 OR

• Buprenorphine
  (it is a partial agonist it has a lower risk of overdose and physical dependence compared to methadone; however, the lower agonist activity is not suitable for some patients)

Opioid dependence may present covertly in a general hospital setting when there is intercurrent illness in an opioid-dependent person. These patients may need to be administered an opioid during admission to prevent opioid withdrawal symptoms.
➜ Use buprenorphine as for treatment of withdrawal

In Australia, most detoxification provided to heroin-dependent persons is provided in rehabilitation centres.
Detoxification is often followed by cognitive-behavioural therapy, psychotherapy and counselling for the patient.So
this the best advice.

Naltrexone
Naltrexone is a long-acting, orally effective opioid antagonist. however, even when used as maintenance treatment for carefully selected people who use opioids, only a very small proportion of patients are compliant.
Oral naltrexone is rarely used to treat opioid dependence because
of its limited effectiveness and an observed high death rate from opioid overdose.

Question 20

ADDICTION/SUBSTANCE ABUSE
‘Benzodiazepines’
Overdose/Poisoning
Sx

Answer 20

— CNS effects
* drowsiness
* sedation
* coma
* respiratory depression
* normal pupils (or dilated)

— cardiac effects
* bradycardia and hypotension (with very
large overdoses)

— other effects
* hypothermia (with very large overdoses)

BENZODIAZEPINE HAVE NO SYMPATHOMIMETIC EFFECT (NO PUPIL DILATION/CONTRACTION

Question 21

ADDICTION/SUBSTANCE ABUSE
‘Benzodiazepines’
Overdose/Poisoning
MX

Answer 21

FULL RECOVERY IS EXPECTED

with good supportive care.
Elderly patients and those with significant respiratory disease are more at risk of complications.

Supportive treatment if required
- Airway & breathing = hypoventilation -» monitor alkalosis, oxygen normally not necessary
- Circulation = hypotension -» fluid resuscitation
-

Question 22

ADDICTION/SUBSTANCE ABUSE
‘Benzodiazepines’
Overdose/Poisoning
Decontamination

Answer 22

There is no indication for activated charcoal
in benzodiazepine overdose

due to the rapid onset of sedation and good outcome with supportive care

Question 23

ADDICTION/SUBSTANCE ABUSE
‘Benzodiazepines’
Overdose/Poisoning
Antidote

Answer 23

FLUMAZENIL
(It has little role in managing benzodiazepine overdose)

TIP: Only Clobazam can be individually identify on urine drug testin

(it has a duration of action of approximately 45 to 60 minutes, after which time re-sedation may occur because most benzodiazepines have a much longer duration of action)

Question 24

ADDICTION/SUBSTANCE ABUSE
‘Benzodiazepines’
Overdose/Poisoning
Indications of use of Flumazenil

Answer 24

— ELDERLY or other patients with respiratory disease (eg COPD) where intubation should be avoided, as CNS depression with poor respiratory effort and poor cough may result in atelectasis and respiratory infection

— in the TREATMENT of CNS DEPRESSION due to iatrogenic over-treatment with benzodiazepines (eg in procedural sedation), where short-term use of flumazenil may be beneficial

— unintentional lone paediatric benzodiazepine ingestion with compromised airway and breathing

— benzodiazepine overdose resulting in compromised airway or breathing in settings where resources for
intubation are not available.

Question 25

**ADDICTION/SUBSTANCE ABUSE** '*Benzodiazepines*' Withdrawal/discontinuation Sx

Answer 25

**manifestations of sympathetic hyperactivity:** - anxiety - insomnia - irritability - myoclonic jerks - palpitations - hypertension - sensory disturbances such as hyperacusis and photophobia - Abrupt discontinuation in patients taking high doses (eg greater than 50 mg diazepam daily or equivalent) may be accompanied by seizures - Hallucinations | MX: Diazepam ## Footnote Benzodiazepines, like alcohol, exert their inhibitory effects via GABA receptors, and their sudden withdrawal leads to an excitatory state. Sudden discontinuation can lead to withdrawal symptoms within 24-48 hours; withdrawal symptoms from long-acting benzodiazepines may develop over a more protracted period.

Question 26

**ADDICTION/SUBSTANCE ABUSE** '*Benzodiazepines*' stable individuals motivated to withdraw from Long-term use

Answer 26

**Gradual dose reduction** of diazepam is the most appropriate initial management for a person with long-term benzodiazepine use who is not acutely intoxicated or in withdrawal. ## Footnote - Tapering the dose slowly minimises the risk of withdrawal symptoms, including anxiety, insomnia, agitation, and potentially life-threatening seizures. - **Long-acting benzodiazepines such as diazepam are preferred for withdrawal management due to their smoother pharmacokinetic profile**.

Question 27

**ADDICTION/SUBSTANCE ABUSE** '*Benzodiazepines*' DEPENDENCE Mx: (If failure to withdraw)

Answer 27

Patient may be allowed to continue Hypnotic if: 1-Patient is aware of dependence 2-There is no history of any adverse event or adverse side effect from that medication. 3-Reduction program has been unsuccessful Refer for inpatient withdrawal immediately may be necessary for people at high risk of severe withdrawal (such as those with a history of seizures, polysubstance use, or significant comorbidities)

Question 28

**ADDICTION/SUBSTANCE ABUSE** '*Cannabis*' Intoxication/Overdose Sx

Answer 28

- **sedation** - euphoria - **increased appetite** - **elevated heart rate** - **reddening of the eyes** - cognitive (including memory loss) and psychomotor impairment - altered time perception.

Question 29

**ADDICTION/SUBSTANCE ABUSE** '*Cannabis*' Harmful side effects of chronic use

Answer 29

– Chronic cough (not COPD) – Increased risk of stroke and heart disease – Poorer academic achievement – Increased risk of suicide attempts – Drug-induced Psychosis – Increased risk of development of psychotic illness (schizophrenia, most common)

Question 30

**ADDICTION/SUBSTANCE ABUSE** '*Cannabis*' Dependence Mx

Answer 30

- CBT ## Footnote There is no evidence for pharmacological treatment of cannabis withdrawal or relapse prevention

Question 31

**ADDICTION/SUBSTANCE ABUSE** '*Alcohol*' Dependence Mx - Naltrexone

Answer 31

- Naltrexone blocks the effect of endogenous opioids released following alcohol intake. As a result, the person who drinks alcohol reports less pleasurable effects, even though alcohol-induced impairment remains unaffected. - Some studies report fewer cravings for alcohol. - Because naltrexone reduces rate of relapse to heavy drinking and increases the number of abstinence days it may be most effective in patients with a history of binge drinking and those who have been drinking heavily. It is also suitable for those who have a stable social support and living situation. - Naltrexone does not precipitate a withdrawal syndrome in alcohol-dependent people who do not use opioids. - There are no adverse effects from combining alcohol and naltrexone. ## Footnote - Naltrexone is contraindicated in: 1. Patients receiving opioid analgesics. 2. Patients currently dependent on opioids since an acute withdrawal syndrome may ensue. 3. Patients in acute opioid withdrawal. 4. Any individual with acute hepatitis or liver 5. It is not used in the management of marijuana ddiction

Question 32

**TOXINDROMES** '*TCA's*' overdose/intoxication Sx

Answer 32

* deteriorating level of consciousness * broad QRS complex (more than 120 ms). * Anticholinergic symptoms (e.g., Mydriasis, warm dry skin, tachycardia, dry mouth and occasionally urinary retention and decreased bowel sounds)

Question 33

**TOXINDROMES** '*TCA's*' overdose/intoxication Mx

Answer 33

Sodium Bicarbonate +/- intubation (if severe respiratory depression) ## Footnote Class IA (eg, procainamide) and Class IC agents (eg, flecainide) are contraindicated given their inhibition of rapid sodium channels, an effect similar to that induced by TCAs. Class III agents (eg, amiodarone) are poorly studied in this setting and the QTc prolongation associated with these drugs makes them potentially dangerous. Despite prominent anticholinergic toxicity in some patients with TCA poisoning, physostigmine is contraindicated as it is associated with cardiac arrest in the setting of TCA toxicity