Drugs of abuse

IV Drug use

• Cotton fever
  • Heroin when heated is often filtered through cotton balls before injection
  • Subsequent SIRS response may be immunological with preformed antibodies to antigens in cotton itself, pyrogens in cotton fibres OR more likely, transient bacteraemia/endotoxin from cotton colonisers
  • Options include observation; BC and observation; BC, observation and empirical broad-spectrum antibiotics
  • No clear evidence to guide either way

Amphetamines

• Includes dexamphetamine, MDMA, methamphetamine
• Lethal complications include severe hyperthermia, ACS, aortic dissection, cardiac dysrhythmias and intracranial haemorrhage
• Repeated use leads to long-term neuropsychiatric sequelae
• Risk assessment
  • Small doses can result in significant intoxication
  • Hyperthermia, headache, impaired LOC, focal neurology or chest pain herald significant toxicity
  • Seizures occur in 4% of presentations
  • Children: A single illicit pill can cause life-threatening toxicity

Amphetamines

• Toxic mechanism
  • Structurally related to ephedrine
  • Enhance catecholamine release and inhibit reuptake
  • MAOi
  • CNS and peripheral NA, D and 5-HT agonism all occur
  • Permanent destruction of dopaminergic pathways long-term
  • MDMA can induce SIADH with subsequent hyponatraemia, coma and convulsions
• Toxicokinetics
  • Absorption – Well absorbed
  • Distribution – Lipid-soluble weak bases with large Vd
  • Metabolism – Hepatic
  • Elimination – Metabolites excreted in urine. Half-lives 8-30 hours

Amphetamines

• Clinical features
  • CNS: Euphoria, agitation, paranoid psychosis with visual and tactile hallucinations, hyperthermia, rigidity and myoclonus, seizures
  • CVS: Tachy, hypertension, dysrhythmias, ACS, acute cardiomyopathy, acute pulmonary oedema, haemoptysis
  • Peripheral SNS: Mydriasis, sweating, tremor
  • Complications:
    • Rhabdo, dehydration, renal failure
    • Hyponatraemia and cerebral oedema due to SIADH
    • Aortic or carotid artery dissection
    • SAH and ICH
    • Ischaemic colitis
  • Psychotic paranoid ideation/hallucinations may persist beyond acute intoxication as post-amphetamine psychosis

Amphetamines

• Ix
  • Screening BSL, ECG, paracetamol
  • EUC – Hyponatraemia/renal failure
  • CK
  • Consider troponin if chest pain
  • CXR – Aortic dissection/aspiration
  • CT head if focal neurology/headache/ALOC
  • Serum or urine amphetamine levels not helpful in acute Rx but may rule out as cause if negative

Amphetamines

• Resus as usual
• ACS: Managed as per usual protocols except beta-blockers avoided (subsequent unopposed alpha) and thrombolysis relatively contraindicated as most cases are due to vasospasm or dissection
• Tachycardia and hypertension: Benzos
  • If refractory consider phentolamine 1mg IV q5min or
  • Titrated GTN or sodium nitroprusside
• Seizures managed with IV benzodiazepines
• Agitation managed with titrated IV diazepam 2.5-5mg IV q5-10min up to maximum 60mg
  • Second-line droperidol or olanzapine
• Hyperthermia
  • >38.5 warrants continuous core monitoring
  • >39.5 warrants rapid external cooling +- paralysis/I&V
• Hyponatraemia
  • 3% NaCl 4mL/kg over 30 minutes if Na <120 and ALOC or seizures
  • Target Na >120

Amphetamines

• Decontamination
  • Rapidly absorbed and carry risk of delirium/seizures so not advised to use AC
• Enhanced elimination n/a
• Antidotes n/a
• Disposition
  • Children observed for 4 hours
  • If normal vitals and ECG can manage sympatomatically until well
  • If ongoing chest pain/ALOC/hyperthermia – admit to HDU/ICU
• Handy tips
  • Early benzos
  • Ongoing chest pain or headache require further Ix
• Pitfalls
  • Failure to adequately sedate patient
  • Failure to recognise and treat hyperthermia
  • Failure to detect and treat hyponatraemia

MDMA specifics

• Pharmacological similarities to mescaline and amphetamines
• Sympathomimetic that causes release of endogenous catecholamines (NA and dopamine) and blocks their reuptake presynaptically
• Similar structure to serotonin with increased release of serotonin and reuptake inhibition
• Sympathomimetic + Serotonin syndrome
• Minor effects – Euphoria, alertness, agitation, nausea, bruxism (grinding teeth), ataxia, tachycardia, HTN

MDMA specifics

• Hyperthermia
  • Due to combination sympathomimetic, serotonergic, exertion and environmental (dancing in hot room)
• Hyponatraemia
  • Marked increase in fluid intake with persistent secretion of ADH that slows rate of water excretion
  • Often free water intake to attempt to prevent hyperthermia and treat dehydration from dancing
• Seizures and status epilepticus can occur
• Hepatotoxicity
  • Well recognized syndrome with hepatitis, centrilobular necrosis and hepatic fibrosis even in absence of severe hyperthermia or DIC

Barbiturates

• Phenobarbitone, primidone, thiopentone
• Uncommon but can mimic brain death
• Risk assessment
  • >8mg/kg of phenobarbitone is expected to cause toxic neuro symptoms
  • Self-administration is likely to be lethal unless coma ensues before entire dose delivered
• Toxic mechanism
  • Enhanced GABA inhibitory neurotransmission
  • Bind to GABA-A to increase duration of Cl- channel opening (benzos increase frequency of opening)
  • Antagonise glutamate receptors

MDMA

• Onset within 1 hour and lasts 4-6 hours typically
• Cardiac
  • Acute increases in NA can cause prolonged hypertension and tachycardia with subsequent hyperdynamic heart failure

Barbiturates

• Supportive cares while in coma
• Enhanced elimination techniques reserved for long-acting primidone and phenobarbitone
• Multiple-dose AC increases rate of elimination by interrupting enterohepatic circulation and enteroenteric circulation
  • Has not been shown to reduce duration of coma or ICU LOS
• Haemodialysis effectively removes phenobarbitone and is indicated with markedly elevated levels or severe poisoning clinically
• Must consider in cases of coma and hypotonia of unclear cause (esp. if vet, doctor or epilepsy)

Benzodiazepines and sedative-hypnotics

• Involved in up to 1/3 of deliberate self-poisonings
• Excellent prognosis with supportive care
• Risk assessment
  • Isolated benzos – mild self-limiting CNS depression
  • Alprazolam has a greater degree of CNS depression
  • Zolpidem and zopiclone rarely cause CNS or resp depression if used alone
  • Co-ingestion greatly increases risk of complications, LOS and death
  • Elderly and those with cardiorespiratory comorbidities suffer greater complications
  • Children: 1-2 tabs manifests as mild sedation and ataxia within 2 hours

Sedative-hypnotics

• Toxic mechanism
  • Increase GABA-A receptor frequency of opening
• Toxicokinetics
  • Absorption – Well absorbed orally
  • Distribution – Highly protein bound. Vd 0.5-4L/kg
  • Metabolism – Hepatic with active metabolites (except oxazepam)
  • Duration of effect depends on CNS tolerance and redistribution rather than rate of elimination
  • Clinical features poorly correlated to levels

Sedative-hypnotics

• Clinical
  • Within 1-2 hours ataxia, lethargy, slurred speech drowsiness and reduced responsiveness
  • Hypothermia, bradycardia and hypotension in very large overdoses
  • Resolution usual within 12 hours (more prolonged in elderly)
• Ix – Screening BSL, para, ECG
• Management
  • Resus + supportive cares
  • Activated charcoal not indicated due to onset of sedation within first hours
  • Enhanced elimination not useful
  • Flumazenil
    • High risk and rarely utilised

Sedative-hypnotics

• Disposition
  • Children: Observe at home and if any symptoms – present to ED
  • Mild sedation: Ward until clinically well and d/c in daytime
• Handy tips
  • Profound coma, ECG changes, tachycardia suggest co-ingestant

Cannabinoids

• Delta-9-tetrahydrocannabinol (THC), delta-8-THC, cannabinol and cannabidiol
• Most widely used recreational illicit drug in Australia
• Risk assessment
  • No reports of death
  • Unpleasant symptoms in dose-dependent manner
    • Low-dose: Mild sedation, disinhibition, disorientation, euphoria
    • High-dose: Tachycardia, postural hypotension, CNS depression, anxiety, perceptual disturbances and psychotic symptoms
  • Co-ingestion carries greater risk
  • Chronic use leads to long-term neuropsychiatric sequelae and a withdrawal syndrome
  • Children: Ingestion may lead to life-threatening CNS depression

Cannabinoids

• Toxic mechanism
  • Central sympathomimetic and antiemetic properties
  • Acts on cannabinoid receptors in central and peripheral NS (CB1) and immune cells (CB2)
  • Augments dopamine release
  • Delta-9-THC is the most potent component
• Toxicokinetics
  • Inactive and active hepatic metabolites excreted in urine for several days

Cannabinoids

• Clinical features
  • 4 hours duration after inhalation and 8 hours after ingestion in adults
  • Coma in children can last up to 36 hours
• Cannabinoid hyperemesis syndrome
  • Cyclic vomiting, abdominal pain and compulsive bathing behaviours in chronic cannabis users
  • Can lead to acid-base disturbance and renal failure
  • Metabolic alkalosis, hypokalaemia
  • Repeated therapeutic hot showers is seen
  • Poorly understood
  • Need to exclude alternative causes
  • Vomiting resolves with abstinence
  • Urine drug screen may confirm cannabis use and allow a more forthright discussion

Cannabinoids

• Disposition
  • Children – Observe for 4 hours and if no symptoms can be d/c
• Handy tips
  • Profound coma or ECG changes suggest co-ingestant
• Pitfall
  • Failure to anticipate potential CNS depression in paediatric ingestions
• CHS management
  • Fluid rehydration
  • Marijuana cessation
  • Droperidol 10mg IM/IV up to 30mg daily

Cocaine

• Risk assessment
  • >1g is potentially lethal
  • Small doses in non-tolerant individuals can produce significant toxicity
  • Pregnancy: Teratogenic with increased risk of miscarriage and fetal demise
  • Lactation: Excreted in breast milk and may give rise to infant intoxication
  • Children: Ingestion is potentially lethal
  • Usual dose in one line is 20-30mg
• Toxic mechanism
  • Sympathomimetic, vasospastic and sodium channel blocking (LA)
  • Blocks presynaptic reuptake of NA
  • Sodium channel blockade can lead to ventricular dysrhythmias as in TCA
  • CNS excitation can lead to acceleration, seizures and hyperthermia

Cocaine

• Toxicokinetics
  • Well absorbed
  • BA 25-80% intranasal, 60-70% if smoked
  • Metabolism – Rapid by liver and plasma cholinesterases to water-soluble metabolites
  • 1% of drug unchanged in urine and the rest metabolites
  • Clinical duration of effect 60 minutes

Cocaine

• Clinical features
  • CNS: Euphoria, agitation, paranoid psychosis (tactile/visual hallucinations), hyperthermia, rigidity, myoclonus, seizures
  • CVS: Tachycardia, hyperthermia, dysrhythmias, ACS, QT prolongation, APO
  • Peripheral sympathomimetic: Tremor, sweating, mydriasis, hyperthermia, muscle fasciculations
  • Complications
    • Rhabdo, AKI, cerebral oedema
    • Aortic and carotid dissection
    • ACS
    • SAH/ICH
    • Ischaemic colitis
    • Pneumothorax
    • Pneumomediastinum
    • Miscarriage

Cocaine

• Ix as for amphetamines
• ECG may show ischaemia, infarction, QT prolongation, Brugada-type pattern (sensitivity of ECG to detect MI is low in cocaine)
• Management
  • VT treated with sodium bicarb as for TCA
  • Lignocaine 1.5mg/kg IV for refractory cases (as for TCA)
  • ACS standard therapy but beta-blockers CI
    • Thrombolytics CI if severe HTN, seizures, ICH or aortic dissection
  • Urgent coronary angiography if ST elevation persists despite GTN
  • Sinus tachy and hypertension managed with benzos
  • SVT refractory to benzos treated with verapamil 5mg IV or adenosine +- cardioversion
  • Hypertension refractory to benzos
    • Phentolamine 1mg IV q5min or GTN/SNP infusion
  • Seizures/agitated delirium treated with IV diazepam
  • Treat hyperthermia aggressively

Cocaine

• Decontamination – AC not indicated
• Enhanced elimination n/a
• Antidotes n/a
• Disposition
  • Children observed for 4 hours
• Handy tips
  • Early benzos
  • Ongoing chest pain or headache requires further Ix
  • CT brain prior to any anticoagulation or angiography if headache is a feature

GHB

• Slang: Cherry meth, easy lay, fantasy, G, Liquid E
• Rapid onset CNS and respiratory depression, myoclonic jerking and bradycardia
• Duration of effect is short with complete recovery within 4-8hrs
• Standard recreational doses 30mg/kg
• >50mg/kg can cause above
• Overdose is life-threatening without support
• Maximal toxicity usually evident at time of arrival to ED
• Co-ingestion of other sedatives increases complications
• Children: Any ingestion potentially fatal

GHB

• Toxic mechanism
  • Precursor and metabolite of GABA
  • Unclear MOA
• Toxicokinetics
  • Rapidly absorbed, peak plasma concentrations 25-60min. Food reduces BA
  • Distribution: Variable
  • Metabolism: Rapidly oxidised to CO2 and water with saturable kinetics
  • Elimination half-life <1 hour

GHB

• Clinical features
  • Onset within 20 minutes and peaks at 30-60min
  • Rapid euphoria, drowsiness, enhanced sexual desire, performance and orgasm
  • In overdose, brief euphoria followed by coma
  • Often rousable then deeply somnolent again
  • Sudden recovery around 2-3 hours
  • Recovery has short period of agitation, delirium and vomiting
  • Complete recovery expected within 8 hours
• Supportive management
• If clinically well at 2 hours, discharge

GHB

• Handy tips
  • Resolution of coma can be abrupt with sudden self-extubation
  • Suspect in any young person found collapsed in nightclub
• Pitfalls
  • Coma >8 hours suggests an alternative diagnosis
  • GBL (GHB precursor) can cause metabolic acidosis
  • GHB withdrawal (daily use, waking up at night to use)
  • Can be severe and presents like alcohol withdrawal
  • Requires blockade of GABA-A and GABA-B e.g. baclofen and oral diazepam

Opioids

• Dextropropxyphene
  • 10mg/kg likely to cause symptoms
  • 20mg/kg CNS depression, seizures and dysrhythmias (fast Na channel blocker)
• Methadone and oxycodone
  • QT prolongation
• Pethidine
  • Seizures in repeat dosing (active metabolite)
  • Implicated in serotonin syndrome

Opioids

• Buprenorphine (Norspan/Subutex/Buvidal)
  • Half-life 24-60 hours
• Suboxone (Buprenorphine + Naloxone)
  • Naloxone half-life 2-12 hours
• Naltrexone (long-acting opioid antagonist ‘Revia’)
  • Half-life 3-10 hours

Opioids

• Children: Leading cause of death in poisoned children
  • Single tab or sip of methadone liquid can be fatal
  • >2mg/kg of codeine can cause symptoms and >5mg/kg can cause respiratory arrest
• Toxic mechanism
  • Mu agonist – Euphoria, analgesia, physical dependence, sedation and respiratory depression
  • Dopamine agonist – Nausea and vomiting
  • Peripheral mu agonism – Constipation
  • Histamine release – Pruritis
• Toxicokinetics
  • Variable oral absorption but all rapidly (unless XR)
  • Large Vd
  • Most hepatic metabolism with active metabolites for most

Opioids

• Clinical features
  • CNS depression, respiratory depression (rate and depth) and miosis
  • Bradycardia is common but tachycardia can occur in response to hypoxia/hypercarbia
  • Methadone and oxycodone QT prolong
  • Can get neuro-excitatory symptoms e.g. myoclonus
• Management
  • Supportive care
  • Seizures in dextropropxyphene overdose are managed with IV sodium bicarbonate as per TCA (100mmol (1mmol/kg) q2-3min to pH 7.5-7.55)

Opioids

• Decontamination
  • Activated charcoal not routinely indicated as antidote and supportive therapy usually good outcome
  • AC may reduce LOS if presenting early after controlled release morphine overdose
• Enhanced elimination n/a
• Antidotes
  • Naloxone

Opioids

• Naloxone
  • Reverses CNS and respiratory depression
  • Avoid in opioid-dependent individual unless RR <8/hypoxia/GCS <12
  • Pure competetive opioid antagonist at mu, kappa and delta receptors
  • Elimination half-life of 60-90 minutes and duration of effect usually 20-90 minutes
  • Initial bolus 100mcg IV or 400mcg IM/SC (can go higher if not opioid dependent)
  • Repeat 100mcg IV every 30-60 seconds until adequate spontaneous respiratory drive
  • Doses >400mcg are rarely required after heroin overdose may larger doses often required in the setting of partial opioid antagonists
  • Clinically significant re-sedation is very unusual following heroin overdose, however, is expected after morphine XR, oxycodone or methadone OD
  • Commence naloxone infusion at 2/3 initial dose required per hour
  • Monitor closely
  • Endpoints
    • Opioid-naïve: Dose sufficient to maintain full alertness
    • Opioid-dependent: Dose sufficient to maintain  airway reflexes, RR >8 and rousable but not full reversal
  • Observe all patients for 2 hours after deliver

• Disposition
  • 4 hours observation for standard-release preparations usually adequate
  • CR should be observed 12 hours
  • All children monitored for 12 hours
• Handy tips
  • Respiratory depression can be delayed up to 12 hours following CR morphine or oxycodone dosing
• Pitfalls
  • Failure to appreciate lethal nature of paediatric ingestion
  • Failure to observe closely for respiratory depression (in-hospital deaths have occurred)

Tramadol

• Centrally-acting synthetic opioid analgesic
• Mostly sustained release
• Delayed-onset seizures are common in overdose
• Risk assessment
  • Opioid effects are usually mild (Tapentadol > Tramadol)
  • Seizures often occur >6 hours. Anticipate in all ingestions >1.5g
  • Serotonin syndrome may develop if other serotonergic agents co-administered
  • Children: CNS depression and seizures if >10mg/kg

• Toxic mechanism
  • Weak partial mu agonist
  • SNARI
• Toxicokinetics
  • Good oral absorption. Peak levels at 1-3 hours after IR and 2-12 hours after SR
  • Peak levels may be delayed in overdose
  • Vd 2-3L/kg
  • Metabolism
    • Hepatic to O-desmethyltramadol (active)
  • Elimination
    • Urine with half-life 5-7 hours and 6-8 hours for active metabolit

• Clinical features
  • Serotonergic and noradrenergic symptoms are most common with sweating, tachycardia, agitation, mydriasis and seizures
  • Seizures are often delayed >6 hours of SR preparations, short-lasting and usually easily controlled with benzodiazepines
  • Monitor for serotonin syndrome (with tramadol in presence of other serotonergic agents)
  • Tramadol can cause hypoglycaemia
• Management
  • Support + Benzos for seizures/agitation/tachycardia/tremor/myoclonic jerks
  • Manage serotonin syndrome with above + consideration of cyproheptadine 8mg PO q8h

• Decontamination
  • Oral AC if alert and cooperative within 2 hours of ingestion of >1.5g SR tramadol
  • Consider seizure likelihood when making decision
  • All patients who are intubated
• Enhanced elimination n/a
• Naloxone may reverse opioid-type effects (rarely required)
• Disposition
  • Children >10mg/kg or adults following IR overdose observe for 12 hours
  • Children >10mg/kg and adults >1.5g SR observed with IV in place for 24 hours
  • Observe all patients until asymptomatic
• Handy tip
  • Prophylactic liberal benzo use with any signs of agitation/tachy/tremor/myoclonus will prevent most seizures
• Pitfalls
  • Failure to anticipate delayed seizures
  • Administration of AC shortly before seizure activity

LSD

• Direct serotonin agonists producing vivid visual hallucinations
• May result in acute psychosis
• Sympathomimetic effects
• Hyperthermia indicates severe toxicity and is usually due to psychomotor agitation
  • DDx – Serotonin syndrome
• Management
  • Supportive care
  • Benzos

Solvents

• Aliphatic hydrocarbons
  • Acetylene
  • Butane
  • Cyclopropane
  • Isobutane
  • Hexane
  • Propane
• Aromatic hydrocarbons
  • Toluene
  • Xylene
• Mixed hydrocarbons
  • Petrol
  • Kerosene

Solvents

• Halogenated hydrocarbons
  • Carbon tetrachloride
  • Chloroform
  • Enflurane
  • Halothane
  • Isoflurane
  • Methoxyflurane
• Nitrites
  • Amyl nitrite
  • Butyl nitrite

Solvents

• Oxygenated compounds
  • Acetone
  • Butanone
  • Diethyl ether
  • Ethyl acetate
  • Methyl acetate
  • Nitrous oxide

Solvents

• Toluene has highest potential for abuse. Found in glue, spray paint and laquer
• Peak blood concentrations within 20-30 minutes of inhalation
• Preferentially distributed to lipid-rich organs e.g. brain/liver
• Metabolised by the liver with elimination half-lives of 15-72 hours
• Toxicity
  • Potent CNS depressants
  • High risk of micro-aspiration and pneumonitis
  • Myelin toxicitity can cause neuropsychiatric with long-term use
  • Myocardial sensitization to catecholamines can induce arrhythmia/sudden cardiac death

Solvents

• Modes of abuse
  • Huffing – Liquid solvent poured into bag or cloth and held up to face
  • Baggin – Poured into bag and bag held over head
  • Sniffing
• Acute intoxication
  • Altered cognition resembling ethanol intoxication
  • Can be severe confusion, obtundation, seizures and coma
  • Intense irritation to eyes/nose/airways
  • Risk of chemical pneumonitis
  • Sudden death may be due to asphyxiation or arrhythmia

Solvents

• Chronic abuse
  • Toluene
    • Long-term use causes structural and functional brain abnormalities as well as neuropsychiatric complications
    • White matter demyelination with impaired cognition, poor working memory and executive function
    • Unclear whether long-term abstinence can reverse these effects
    • Chronic toluene use also causes NAGMA due to RTA
      • Hypokalaemia may be profound

Solvents

• Management
  • Benzos titrated to response
  • Acid-base and electrolyte normalization (NAGMA/RTA/HypoK)
• Disposition
  • Observe until effects resolved
  • May be hours to days
  • Address chronic issues – mostly social deprivation
  • Foetal solvent syndrome is a risk

Nangs

• Nitrous oxide (N2O)
• Abuse can result in myeloneuropathy, subacute combined degeneration, peripheral neuropathy, bladder/bowel issues, sexual dysfunction, altered mentation, Lhermitte’s sign (electric sensation with neck flexion), delirium and pulmonary complications (PTX, PE)
• Oxidises cobalt moiety on B12 to render it inactive
• Methionine synthase (which requires active B12) is irreversibly blocked
• Leads to depletion of methionine and tetrahydrofolate required for DNA synthesis and myelin production
• Results in pernicious anaemia (bone marrow suppression and polyneuropathy -> subacute combined degeneration
  • Loss of vibriosense and proprioception most marked
• Most commonly presents with peripheral neuropathy with combined posterior (proprio- and vibrio-sense) and lateral column signs (motor weakness) +- macrocytic anaemia
• Neuropsychiatric features are also common
• B12 levels may be normal but MMA levels (intermediate that requires functional B12 for further metabolism) are raised
• Potentially reversible with B12 supplementation

Nangs

• Ix
  • Total and active B12 can be normal
  • MRI may demonstrate demyelination in typical V-pattern through cervicothoracic cord
• Management
  • B12 supplementation only
    • IM dosing initially – 1000micrograms 2nd daily for 2 weeks, then weekly for four weeks, then monthly until maximal recovery
  • Methionine
    • 1g TDS orally for 2 weeks
  • Folinic acid
    • 30mg IV if evidence of bone marrow suppression

Last Updated on August 28, 2023 by Andrew Crofton