Drug overdose

Pharmacology

define drug overdose.

the ingestion or application of a drug or other substances in quantities greater than are recommended or generally practiced

what are the 2 ways of possible drug overdose?

-accidentally
-deliberately

what are the common drugs which are intentionally used to self-poison?

-benzodiazepines
-analgesics
-antidepressants
this drugs are usually taken with alcohol

what are the risks of drug overdose caused by drugs?

-narrow therapeutic window
-steep dose-response curse (high dose+ high effect)
-enzyme inhibitors (P450)
-enzyme inducers
-high toxic potential (kidney failure from antibiotics)

what are the risk of drug overdose caused by patients?

-polymorbidity
polypharmacy
-treatment lasting longer
-chronic diseases
-abuse
-non-compliance
-self-treatment
-ordering different drugs from different dr.

what is the formula for therapeutic index?

dose causing toxicity/ dose providing efficacy

give an example of drugs which have a narrow therapeutic window?

-aspirin
-digoxin
-lithium
-aminoglycoside antibiotics
- quinidine
-valproic acid

How is overdose treated?

-immediate measures evaluation (ABC, history etc)
-supportive measures (cardiac/respiratory arrest)
-prevent absorption (activated charcoal, gastric lavage)
-elimination (alkaline diuresis)
-antidotes (using interaction in advantage)
-psychiatric assessment

what is included in the evaluation after an overdose?

-recognise the poisoning
-identify which agents are involved
-assessment of how severe it was
-prediction of toxicity

what is included in the supporting care after an overdose

-A: airways B:breating C: circulation
-protect the airway
-vital signs, mental status, pupil size
-pulse oxymetry, cardiac monitoring, ECG
-IV access
-cervical immobilization (if trauma suspected)
-rule out hypoglycaemia (similar symptoms)

what is included in the prevention of absorption?

-gastric lavage
-induce vomiting
-activated charcoal

how is activated charcoal used?

-it absorbs toxic substances or irritants + inhibits GI absorption
-oral 25-100g
-cannot absorb petroleum distillantes +inorganic acid and alkali + alcohol + metal ions + cyanide +lithium

what is a gastric lavage?

-flushing of stomach contents via a tube from the nose into the stomach
-saline is injected into the tube
-patients are usually unconscious unless intubated

what steps are included in the elimination of poisons?

-renal elimination
-forced alkaline diuresis
-haemodialysis or hemoperfusion

haemodialysis or hemoperfusion

-for severe poisoning
-drug needs to be protein bound with low Vd
-can be used long or short term if the kidney are damaged

Forced alkaline diuresis

infusion of NS+NAHCO3
eliminates acidic drug that mainly excreted by the kidney
fluid and electrolytes disturbance may occur

renal elimination

-meds to stimulate urination or defecation to get rid of excess drug faster

antidotes and mechanism for methanol opiate poisoning

mechanism: pharmacological antagonists
ethanol and naloxone

mechanism and antidote for belladona alkaloid poisoning)

enhance physiological function to compensate
physostigmine

mechanism and antidote for organophosphate poisoning

restore active site of drug target
pralidoxime

mechanism and antidote for beta-blocker poisoning

bypass block
glucagon

mechanism and antidote for digoxin poisoning

Sequester poison
digibind

mechanism and antidote for bromide/iodine overdose

speed up excretion
chlorine

stage I of paracetamol overdose (0.5 to 24hr)

no symptoms
-->nausea & vomiting, malaise

stage II of paracetamol overdose (24 to 72hr)

-subclinical elevation of hepatic aminotransferases
-increase of prothrombin time and total bilirubin
-right upper quadrant pain, liver enlargement and tenderness
-oliguria and renal function abnormalities

stage III of paracetamol overdose (72 to 96hr)

jaundice, confusion, elevation in hepatic enzyme, hyperammonaemia, bleeding diathesis hypoglycaemia, lactic acidosis, renal failure, death.

stage IV paracetamol overdose (4 days to 2 weeks)

recovery phase

paracetamol overdose management

ADR of aspirin

-GI bleeding and prolonged bleeding
-activation of respiratory centre
-interference with metabolism --> ATP isn't formed + a.a. isn't metabolised

intoxication levels of aspirin overdose

40-50 mg/dL

fatal dose of aspirin in children and adults

3g (children)
30g (adults)

aspirn overdose effects

-metabolic acidosis --> acidic pH movement of salicylate into tissue
-respiratory alkalosis --> more breathing = more CO2
-electrolyte imbalance --> vomiting + more renal excretion of bicarbonate

symptoms of aspirin overdose

burning throat pain
decrease urination
double vision
fever
ringing in the ears or inability to here
seizures
stomach pain
vomiting

aspirin overdose management

-activated charcoal
-fluid replacement --> to combat salicylate toxicity
-urine alkalinization --> excretion of ionised acid form of salicylate

indication of hemodialysis

-renal failure
-acute lung injury
-persistent CNS disturbances
-severe acid-base or electrolyte imbalance (after treatment)
-hepatic compromise with coagulopathy

opioid overdose symptoms

-respiratory depression
-pinpoint pupil
-decrease level of consciousness
-hypotension and bradycardia

opioids binding site

specific opioid receptor in CNS

opiate (morphine) overdose management

antidote - naloxone
- I.V, I.M 04-2mg every 2-3 mins

checks done during opiates overdone management

BP changes
arrhythmias
seizures
withdrawal

pesticide

-organophosphate
-irreversible anticholinesterases (AChE)

nicotinic signs for increase in Ach

twitching
fasciculations
muscle weakness
cyanosis
elevated BP

muscarinic signs for increase in Ach

-bronchoconstriction
-increase secretion (blocked in airway)
-sweating
-GI
-miosis (extensive dilation of pupil)

CNS signs of increase of Ach

-anxiety
-restlessness
-confusion
-headache

pesticides management

-clear airways
-AChE regenerator
Pralidoxime (antidote) i.v. 1-2g 15-30 min
-treatment needs to start early
-doesnt enter CNS because +ve charge
-use atropine to control muscarinic excess

what is the pretreatment for pesticides poisoning

-reversible inhibitors
-protect against excessive AChE inhibition --> when deatly poison is anticipated