DLA5- Toxicology (common drugs) Flashcards
describe the typical presentation of salicylate (ASA) overdose (hint- 2 main features, include brief mechanism)
Mixed respiratory alkalosis and metabolic acidosis:
-Hyperventilation via stimulation of respiratory center
- ASA is weak acid:
- -> too much causes impaired renal function => sulfuric / phosphoric acid accumulation
- uncouples oxidative phosphorylation + inhibits Krebs cycle => inc anaerobic metabolism –> inc ketones and lactic acid
ASA overdose:
- (1) typical progression if untreated
- (2) Tx
1:
- eventual depressant effects of ASA on respiratory center => death via respiratory depression / paralysis (respiratory acidosis)
- circulatory collapse via vasomotor depression
2- IV fluids, IV NaHCO3 (for acidosis and promote ASA excretion) —– severe cases require hemodialysis
Acetaminophen toxicity:
- (1) is the main effect
- (2) is the main mediator, describe formation and mechanism
Hepatic Necrosis:
- 5% acetaminophen metabolized into NAPQI (N-acetyl-p-benzoquinoneimine)
- in small amounts detoxified via glutathione detoxification
- if glutathione stores become depleted (high doses) => NAPQI damages cellular proteins –> heptocyte death
describe the progression of acute acetaminophen toxicity
1) initially asymptomatic or mild GI upset
2) (24-36hrs) liver injury: elevated aminotransferases, hypoprothrobinemia
3) (severe cases) fulminant liver failure –> hepatic encephalopathy –> death
[possible renal failure also]
describe acetaminophen toxicity Tx
1) supportive therapy + gastric lavage
2) N-acetylcysteine (acetadote) –> AEs: rash, n/v/d, anaphylaxis
3) possible liver tranplant (if fulminant liver failure)
list the many possible effects of Amphetamine / stimulant overdose
- restlessness, agitation
- acute psychosis
- HTN, tachycardia
- prolonged muscular hyperactivity –> dehydration, hypotension
- seizures + muscular hyperactivity –> hyperthermia, rhabodomylosis –> brain damage, hypotension, coagulopathy, renal failure
describe Tx of stimulant (amephetamine) overdose
(no specific antidote)
supportive therapy:
-ammonium chloride to acidify urine to enhance elimination
- phentolamine / nitroprusside for HTN
- propanolol / esmolol for tachycardia
- IV benzodiazepines for seizures
-cool down measures for hyperthermia OR neuromuscular paralysis if very severe
describe the effects of Anticholinergic overdose (note- can be due to drugs with anticholinergic activity as additional action)
- skin flushed (red as a beet)
- hyperthermia (hot as a hare)
- dry mucous membranes (dry as a bone)
- blurry vision (blind as a bat)
- confusion, delirium (mad as a hatter)
describe Tx for anticholinergic overdose
Physostigme (AChE inhibitor):
-peripheral and central
-small IV doses, slow infusion (or causes bradycardia, seizures)
[not in TCA overdose]
benzodiazepine, antipsychotic for seizures if necessary
describe presentation of β-blocker overdose (include most toxic agent)
(propanolol is most toxic, non-selective)
-QRS widening via Na+ channel blockade in heart => ventricular arrhythmia
- seizures, coma (propanolol is lipophilic –> crosses BBB)
- bradycardia, hypotension
______ is the Tx for β-blocker overdose, describe brief mechanism
IV glucagon- inc intracellular [cAMP] that β-blockers dec
describe presentation of Ca channel blocker overdose
- depresses sinus node automaticity + slows AV conduction
- dec CO and BP => serious hypotension
______ is the main Tx for Ca channel blocker overdose
______ may be useful is treating some Sxs
IV Ca++ –> inc cardiac contractility (not as usefule for nodal block, circulatory collapse)
-glucagon, epinephrine to inc BP and HR
describe the main effects of TCA overdose, include of actions that TCAs may have
blockade of Na+ fast channels –> slows conduction –> wide QRS, depressed contractility => arrhythmia, hypotension, AV block
-anticholinergic, antiadrenergic, antihistamine
- (1) is drug of choice for TCA overdose in general
- (2) is specific for TCA cardiac effects
-(3) has been deemed ineffective, and (4) is avoided as seen in anticholinergic overdose Tx
1- norepinephrine
2- sodium carbonate (bolus)
3- dopamine
4- physostigme
list the two main serious adverse effects seen with MAOI use and describe Tx
Tyramine Reaction:
- α-adrenergic blockade, phentolamine
- combined α-/β-adrenergic blockade (labetalol)
Serotonin Syndrome:
- cyproheptadine (5-HT2 antagonist)
- benzodiazepines for seizures, rigidity, agitation
______ is used for opioid overdose
Naloxone or nalmefene (opioid antagonists)
to prevent respiratory depression
Overdose with sulfonylureas, meglitinides causes (1). It can be treated with (2), and if that fails then (3)- (4) is an alternative to (3).
1- hypoglycemia
2- glucose bolus infusion
3- octreotide (somatostatin analog)
4- diazoxide (inhibits insulin release)
Neuroleptic Malignant syndrome is a common severe side-effect of using (1); (2) describes the management of this syndrome
Antipsychotics
- discontinue antipsychotic
- dantrolene or bromocriptine are drugs of choice
