Download Opioids OD fact sheet

Toxic dose
Toxic
Mechanism
Specific
drugs
Symptoms
Ix
Treatment
Decontamin
ation
Elimination
Antidote
Disposition
Tolerance
OPIOIDS
Single tablet death in children
Tramadol: >10mg/kg or >1.5g
µ1-receptors  analgesia (open K channels)
µ2-receptors  resp depression, physical dependence, miosis, cough supp, euphoria
Peripheral µ-receptors  constipation
K-receptors  meosis, sedation (open Ca channels), decr GI motility, dysphoria, hallucinations
Sigma-receptors  hallucinations, dysphoria
Dopamine receptors  N+V
Histamine release  pruritis
Morphine: 20% BA, 40% protein bound; 90% hepatic metabolism; 10% excreted urine unchanged
Pethidine: stronger kappa; some 5-HT (can cause SS); 50% BA; 60% protein bound; DOA 3hrs; more euphoria and
addiction, seizures
Fentanyl: rapid onset of action; DOA 30-40mins; serotonin syndrome
Remifentanyl: rapid onset; assoc with muscle rigidity; HL 3-10mins; DOA 5-10mins
Codeine: 66% BA
Methadone: 100% BA; DOA 12hrs; QTc prolongation; symptoms >24hrs
Heroin: crosses BBB; very short DOA (peak 3mins; last few hours); can cause NCPO (immediately or delayed 24hrs);
symptoms <6hr; 60% OD deaths occur in company of others; 15% deaths are sudden death after injecting; ambulance called
in only 10% fatal cases; no intervention prior to death in 80%
Oxycodone: less N+V, less sedating; 50-80% BA
Dextropropoxyphene: significant Na channel blocking effect ( long QRS, HB, arrhythmia), seizures if >1g, may require
larger doses of naloxone, can cause death in <1hr
Tramadol: µ-receptor and M1 action; inhibits reuptake of 5-HT and NAD, stimulate 5-HT release; toxic dose > 1.5g
(>10mg/kg); 70-90% BA; HL 5-8hrs; peak level 1-3hrs (3-5hrs if CR); delayed onset Sx >6hrs; mild sedation (coma
unusual), less resp depression, no significant CV effects (incr HR, incr BP), orthostatic decr BP, seizures (may be delayed;
short), agitation, mydriasis, anaphylactoid reactions; interact with SSRI’s and MAOI’s; effects only partially antagonised by
naloxone
Buprenorphine: partial agonist; used as alternative to methadone; may precipitate withdrawal in OD, which may last a few
days
CNS depression (K) / RS depression (µ2) / miosis / hypothermia, skin necrosis, compartment syndrome, rhabdo, hypoxic
brain inj, aspiration, hypotension, decr bowel motility, NCPO (may be delayed)
Miosis absent in: meperidine, morphine, diphenoxylate, propoxyphene
Urine: semi-synthetic and synthetic opioids not detected
Diazepam sedation in tramadol
Charcoal yes, maybe in tramadol
Serum alkalinisation: in dextropropoxyphene
MDAC: in dextropropoxyphene, SR
Naloxone
Indication: GCS <12, RR <6, SaO2 <90%
MOA: pure competitive antagonist of mu (maximal here), kappa and delta receptors  reverses all effects of
opiates
Onset: 1-2mins
DOA: 20-90mins (longer IM); elimination HL 1hr (3hrs in neonates)
Dose: 100mcg IV (400mcg IV if severe, 50mcg if opiate dependent) / 400mcg IM bolus / 800mcg
SC / 2mg IN (2mg Q3minly to max 10mg if apnoea (may be needed in body packers, fentanyl, SR);
10mcg/kg in children)
 rpt IV Q30-60 secs until improvement (to max 2mg)
 infusion at 2/3 initial dose required per hr (dilute 2mg in 100ml N saline)
Observe for at least 2hrs after last dose; give IM if self-discharging
High doses may be needed in tramadol, codeine, methadone, dextroP
CI: opioid dependence, unless RR <8, GCS <12; give the smallest dose possible and don’t aim for full reversal;
withdrawal will last <90mins if induced
SE: ACPO, withdrawal (stop infusion  recommence when asymptomatic at ½ rate)
Observe 4hrs for most PO preps; at least 12hrs if CR / child / tramadol
Must be at least 1hr post-naloxone, SaO2 >92%, RR >10, HR >50, normal T, GCS 15
After 2-3/52; rate with which develops and extent varies between pt and drug (eg. Methadone tolerance develops slower
than morphine); develops better if large doses at short intervals; tolerance disappears after withdrawal syndrome finishes
High: analgesic, sedating (few days to stop), resp depressant (few days to stop), antidiuretic, emetic (several months to
stop), euphoric, cough suppressing and hypotensive effects
Mod: bradycardia; tolerance occurs to mixed agents but to lesser extent as to pure agonists
Low: NOT to miotic, convulsant, constipating; tolerance doesn’t develop to antagonist actions of mixed agonists/antagonists
Dependence
/
withdrawal
or to pure antagonists
Cross tolerance: occurs, esp with μ-agonists; not only to analgesic properties; can be partial/incomplete
Symptoms: Characteristic withdrawal syndrome (not life threatening if natural):
Within hr, peaks at 36-72hrs: anxiety, yawning, craving, lacrimation, rhinorrhoea, diaphoresis, myalgia
In 12hrs, peaks at 72hrs: irritable, tremor, piloerection, mydriasis
In 24-36hrs, peaks at 72hrs: insomnia, spasms, AP+N+V+D
Also: incontinence, sweating, hyperthermia, hyperventilation
Time of onset, intensity and duration depends on drug used and HL; generally 12hrs after last dose  peaks at 2-3/7  stop
at 5-6/7; may get dehydration, aspiration
Morphine/heroin – in 6-10hrs; peak after 36-48hrs; gone by 7-10 days
Meperidine – subsides in 24hrs
Methadone – in >24hrs  peak at 72-96hrs  last for >14/7; less intense
Antagonist-precipitated withdrawal: by giving antagonist (eg. Naloxone); begin at 3mins  peak to 10-20mins 
subside in 1hr; Natural withdrawal less severe than aritifical (delirium only occurs with naltrexone withdrawal)
Mng: supportive; IVF; antiemetics (octreotide is drug of choice), antidiarrhoeal; clonidine / benzos for agitation;
administration of opioids may be helpful
Admit if: severe withdrawal, significant complications / intercurrent illness / psych prob
Opioid replacement: methadone, buprenorphine
Detoxification: using naltrexone, buprenorphine, clonidine; rapid tapering of methadone
Supportive care
Notes from: Dunn, TinTin, ToxBook, Cameron