Analgesics Flashcards
Discuss the risk assessment of cochicine
Colchicine overdose is uncommon but potentially lethal. Toxicity is characterised by severe gastroenteritis followed by multisystem organ failure.
Aggressive decontamination and supportive care are the cornerstones of management
Any ingestion of colchicine is considered potentially lethal - fatalities are reported with acute ingestion of as little as 0.2mg/kg
- <0.5mg/kg –GIT upset
- 0.5-0.8 mg/kg - systemic toxicity including bone marrow derpession 10% mortality
- > 0.8mg/kg - severe poisoning involving cardiovascular collapse, coaguloapthy, acute renal failure, approaching 100% mortality
Children - ingestion of 1-2 tablets is not problemeatic. Larger ingestion may cause sever GIT upset
Discuss TM and TK of colchicine OD
TM - natually occuring alkaloid, Binds tubulin and prevents microtuble formation, thus inhibiting mitosis as well as other essential intracellular processes. Following overdose tissues with high cellular turnover (GUT, bone marrow) are preferentially affected
TK : - Colchicine is rapidaly absorbed with peak levels occuring from 0.5-2 horus post ingestion.
Bioavailability is only 45% as a result of extensive first pass metabolism
-extensively tissue bound with a VD of 2l?kg
Elimination is by heaptic matabolism with an elimination half life of up to 30 hours
Discuss clinical features of colchicine overdose
2-24 hours: Nausea, vomiting diarrhoea abdominal pain
- Severe GI fluid loss can result in HD instability
- peripehral leucocytosis commonly seen on blood film
2-7 days
- bone marrow suppression and pancytopenia
- rhabdo
- renal failure
- progressive metabolic acidosis
- respiratory insufficiency
- ARDS
- cardiac dysrhythmias and risk of sudden cardiac death
> 7 days \
- Rebound leucocytosis and transient alopecia
- complete recovery is expected in patient who survive to this stage
Discuss management of colchicine overdose
Resus
ABCD
-Patients may present in hypovolaemic shock due to massive GI fluid loss- they will require resus with large volumes of intravenous cyrstalloid
-Meticulous supportive care best supplied by ICU to manage, fluid balance, electrolyte and acidbase mg/kg of balance
-early resp insufficiency and cardiac arrest is anticipated ; airway and ventalory assistance are implelemtned as necessary
D: charcoal as soon as possibole to any patient who has potentially ingested >0.5mg/kg oc colchicine becuase of absorpiton of even a small amount may be life saving
E: Multiple dose activated charcoal may enhance elimiantion but is techically difficult in the vomiting patient.
A: Exist but are not available
D:24 hour observation nil GIT symptoms can be dishcarged
Discuss risk assessment of NSAIDS
Generally benign even following large ingestion
<100mg/kg - asymptomatic
100-300mg/kg - mild GI and CNS
>300mg/kg risk of multisystem organ dysfunction
Discuss risk assessment of opioids
Opioid intoxication causes CNS and respiratory depression frequently occur just above the analgesia dose
-opioid naive or co-ingestion with other CNS depressants compounds risk
Specific risk
- Dextropropoxyphene -10mg/kg likley to cause symptoms , 20mg/kg may cause CNS depression, seizures and cardiac dysrhythmias (fast na channel blocking effects)
- methadone and oxycodone (long QT)
- pethidine - repeated therapeutic dose seizures and impicated in serotonin syndrome
Discuss clinical features of opioid toxicity
The classic opioid toxidrome consist of:
1) CNS depression
2) respiratory depression (rate and depth)
3) miosis
The duration of effects depends on the PK of the individual agent. Heroin intoication is typically short (less than 6 hours) while methadone and oxycodone may last more than 24 hours
Death is due to loss of airway protective reflexes and apnoea
Nausea and vomiting may occur promiting pulmonary aspiration.
Bradycardia is common
Hypothermia, skin necrosis, compartment syndrome, rhabdomyolosis and hypoxic brain injury may complicate prolonged non lethal intoxication.
Discuss management of opioid toxicity
Resus
D: consideation in controlled release but usually not used
E:
A: naloxone
Discuss risk assessment of tramadol
Centrally acting synthetic opioid analgesic. most available formulations are sustained release and in overdose frequently cause delayed onset seizures.
Opioid effects are usually mild and rarely require intervention
The major poetnional risk is seizures and these are usually delayed (>6 hours) . Seizures should be anticipated in patients who ingest >1.5 g tramadol.
Serotonin syndrome may develop if there is co-ingestion of other serotonergically active agents.
CNS depression and seizures can occur with ingestion of >10mg/kg
Describe TM and TK of tramadol
TM: weak partial agnosit at u opioid receptors. It also inhibits serotonin and norad reuptake in the CNS. The toxic effects in OD seem to be primarily a result fo the inhibition of CNS serotonin and norad reuptkae.
TK: well absorbed orally and peak levels occur at 1-3 hours after ingestion of standard preparations and 2-12 hours after ingestion of sustained release prep. The VD is 2-3L/kg. Extensive metabolism in the live and one of the metbaolites is pharm active. Eliianation is in the urine with elimination half lives of 5-7 hours for the parent drug and 6-8 hours for the active metabolite
Discuss clinical features of tramadol OD
Opioid effects are not prominent and consist of mild sedation and mild reps depression
Coma requiring intubation is unusual except in the present of co-ingestion
Serotonin and norad effects are more prominenet and may include tachycardia, agitation, mydriasis and seizures. Seizures are the most serious clinical effect. They are delayed in onset ( usually 6 hours after OD of the sustained release)
Serotonin syndrome may develop
Discuss management of tramadol overdose
RESUS
- the need for I&V is anticipated and performed early in patient with a declining LOC
- Seizures treated with IV benzo
- increased agitation, tachycardia, tremor and myoclonic jerks herald onset of seizures and these symptoms are controlled with titrated IV doses of diaz
- Serotonin syndrome treated
D: Charcoal is considered in patietns who are co-operative present within 2 hours of ingestion of >1.5g of SR
E: nil
A: naloxone may revere CNS and resp depression however this is rarely a clinical concern
