finish lecture 2

what are 5 common toxidrome?

- anticholinergic

- cholinergic

- opioid

- sympathomimetic

- sedative hypnotic

overall, what are 6 drug classes that are considered anticholinergic toxins?

- anticholinergics

- antihistamines

- antipsychotics

- TCAs

- skeletal muscle relaxants

what are 5 anticholinergic drugs?

- atropine

- scopolamine

- glypyrrolate

- benztropine

- trihexyphenidyl

describe the mechanism of tox for anticholinergic toxicity

competitive antagonism of the effects of ACh at muscarinic receptors, both peripheral and central

what key clinical signs are associated with anticholinergic toxicity? (HR/BP, RR, temp, pupils, bowel sounds, diaphoresis)

- HR/BP = increased

- RR = no change

- temp = increased

- pupils = dilated

- bowel sounds = decreased

- diaphoresis = dry skin

what saying can be used to remember the key clinical signs of anticholinergic toxicity?

- hot as a hare (fever)

- red as a beet (flushed skin)

- blind as a bat (mydriasis)

- dry as a bone (dry mouth and skin)

- mad as a hatter (delirium)

- full as a flask (urinary retention)

when are symptoms of anticholinergic toxicity generally seen?

within 6-8 hrs of ingestion

what lab tests are generally ordered with anticholinergic toxicity?

- CK, serum electrolytes and SCr to assess for rhabdomyolysis and AKI

- serum APAP level due to combo products

what diagnostic tests are generally preformed with anticholinergic toxicity to help us understand severity of toxicity?

- ECG and pulse ox

- bladder scan for detection of urinary retention

what specific risk assessments are considered when 1st gen antihistamines contribute to anticholinergic toxicity?

- sedating meds with greater anticholingeric potential than 2nd gens

- exposure less than 7.5 mg/kg of Benadryl are unlikely to cause significant tox

what specific risk assessments are considered when atypical antipsychotics contribute to anticholinergic toxicity?

- toxicity influenced by age, route of admin and home meds

- pediatric pts may experience tox at a much lower threshold

- pts on chronic atypical antipsychotics are unlikely to experience tox with doses less than 5x normal dose

what specific risk assessments are considered when TCAs contribute to anticholinergic toxicity?

- have a very narrow therapeutic index

- in peds one pill can kill

describe the initial management for

anticholinergic toxicity

- supportive therapy = maintain airway, ventilation and establish IV line

- benzos for seizures or agitation

- sodium bicarb for dysrhythmias

- pts condition will drive need for cardiac monitoring

- assess benefits vs risks of gastric decontamination

what is the antidote option for anticholinergic toxicity?

physostigmine

how does physostigmine work?

- carbonate acetylcholinesterase inhibitor = reverses anticholinergic manifesations

- reserved for SEVERE toxicity

describe the doing of physostigmine for anticholinergic toxicity

- 0.5-2 mg IV over at least 5 mins

- repeat every 10-15 mins

what ADEs are associated with physostigmine use?

slow admin reduces risk of ADEs

- bradycardia

- bradudsrhythmia

- seizures

when should physostigmine use be avoided?

known/suspected TCA toxicity

what 4 types of agents are considered to be cholinergic toxins?

- organic phosphorus compounds = pesticides

- nerve agent exposure

- physostigmine

- mushrooms

describe the mechanism of tox for cholinergic toxicity

- inhibition of acetylcholinesterase = causes accumulation of ACh

- overall results in the overstimulation of muscarinic and nicotinic receptors

what key clinical signs are associated with cholinergic toxicity? (HR/BP, RR, temp, pupils, bowel sounds, diaphoresis)

- HR and BP = no change

- RR = no change

- temp = no change

- pupils = pinpoint

- bowel sounds = exist

- diaphoresis = sweating

what 2 sayings can be used to remember the cholinergic symptoms?

- DUMBELLS

- SLUDGE + killer B's

what are the "killer Bs" associated with cholinergic toxicity?

LIFE threatening symptoms

- bradycardia

- bronchospasm

- bronchorrhea

what cholinergic toxicity symptoms does DUMBELLS refer to?

- diarrhea

- urination

- mitosis

- bradycardia, bronchospasm, bronchorrhea

- emesis

- lacrimation

- lethargy

- salivation

what cholinergic toxicity symptoms does SLUDGE + killer Bs refer to?

- salivation

- lacrimation

- urination

- defecation

- GI spasms

- emesis

- bradycardia, bronchospasm, bronchorrhea

describe the general clinical presentation of cholinergic toxicity

- mild symptoms may resolve

- life threatening toxicity can develop within 1-6 hrs of exposure

- insecticides may be absorbed via skin, lungs, eyes or GI tract

what symptoms associated with cholinergic toxicity may be seen within 1-6 hrs

- headache

- confusion

- coma

- seizures

overall, what does death from cholinergic toxicity result from?

death caused by respiratory failure from pulmonary and cardiac effects

what lab tests are seen with cholinergic toxicity?

- serum pseudocholinesterase activity = decreased

- acidosis on ABG, serum electrolytes, BUN and SCr

what diagnostic tests are seen with cholinergic toxicity?

- CXR

- ECG

- pulse ox for complications from toxicity and hypoxia

what 3 things does the severity of cholinergic toxicity depend on?

- route of exposure = IV>inhalation>skin contact

- potency of agent

- total dose received

what triad of cholinergic toxicity symptoms suggests severe poisoning and warrants antidote trial?

- mitosis (pinpoint pupils)

- bronchial secretions

- muscle fasciculations

describe the initial management of cholinergic toxicity

- decontaminants affected body surfaces

- people handling pt should wear gloves and gowns

- discuss risks vs benefits of gastric decontamination

- supportive therapy = maintain airway, ventilation and establish IV line

what 2 antidotal options exist for cholinergic toxicity?

- atropine = antidotal in nature (not true antidote)

- pralidoxime (2-PAM) = antidote

describe the dosing of atropine used for cholinergic toxicity

- younger than 12 = 0.05-0.1 mg/kg IV

- older than 12 = 2-6 mg IV

- can repeat every 5-10 mins until secretions or rales resolved

how does atropine work for cholinergic toxicity?

- competitively blocks ACh action on receptors

- no effect on inhibited enzyme = little effect on muscle paralysis or respiratory failure

- clinical effects = alleviates bronchospasm and reduces bronchial secretions

what are 3 ADEs associated with atropine use for cholinergic toxicity?

- coma

- hallucinations

- tachycardia

when is pralidoxime (2-PAM) used for cholinergic toxicity?

- revered for SEVERE organophosphate poisonings

- needs to be admin within 36-72 hrs of exposure

- should be given WITH atropine

- dose = 2 grams

how does pralidoxime (2-PAM) work for cholinergic toxicity?

- regenerates enzyme activity

- breaks covalent bond between cholinesterase and organophosphate

what are 4 ADEs associated with pralidoxime use?

- dizziness

- diplopia

- tachycardia

- headache

what monitoring is used for cholinergic toxicity?

- vital signs, blood gases, pulse ox

- leukocyte count with differential to assess for infection development

- CXR to evaluate for pulmonary edema of pneumonia

describe the mechanism of tox associated with opioid toxicity

opioid analgesics bind to mu opioid receptors in the central and peripheral nervous system in an agonist manner

what additional mechanisms are seen with nor-meperidine (in addition to opioid mechanism)

- CNS excitation

- leading to delirium, tremor, seizure

what additional mechanisms are seen with meperidine (in addition to opioid mechanism)

blocks serotonin reuptake = serotonin syndrome

what additional mechanisms are seen with methadone (in addition to opioid mechanism)

- blocks potassium efflux on myocardium

- leading to TdP, syncope and sudden death

what additional mechanisms are seen with tapentadol and tramadol (in addition to opioid mechanism)

- blocks reuptake of NE and 5HT

- associated with seizure

what key clinical signs are associated with opioid toxicity? (HR/BP, RR, temp, pupils, bowel sounds, diaphoresis)

- HR/BP = decrease

- RR = decrease

- temp = decrease

- pupils = pinpoint

- bowel sounds = absent

- diaphoresis = dry

describe the general clinical presentation seen with opioid toxicity

- life threatening respiratory depression, less than 12 bpm

- mins-hrs after use

what lab tests should be ordered with opioid toxicity?

- acidosis on ABG

- serum electroluytes in response to hypoxia

- serum BG

- determine serum APAP due to combo products

what diagnostic tests are used with opioid toxicity?

- pulse ox. continuous ECG monitoring

- CXR and physical symptoms to monitor pulmonary complications

- monitor for complications of rhabdomyolysis and AKI if immobile for several hrs

what is the severity of opioid toxicity dependent on?

- route of exposure = IV>inhalation of fumes>inhalation of particles

- formulation of product

- potency

- concurrent drugs

- coexisting conditions

- pharmacogentic chartacteristics

describe the risk assessment used during opioid toxicity

- symptoms and presence of drugs/devices at scene can help indicate risk

- clonidine and certain atypical antipsychotics may present similarly

- antidote should NOT be delayed pending labs = GIVE IT

what triad of symptoms associated with opioid toxicity suggest poisoning and warrant antidote therapy?

- depressed respirations = less than 12

- coma

- pinpoint pupils

describe the initial management for opioid toxicity

- adequate respiratory support and admin naloxone

- naloxone = primary treatment

- risk vs benefit of gastric decontamination

- goal of therapy = restore adequate spontaneous respirations

how does naloxone work?

- competitive opioid receptor antagonists that reverses toxic effects of opioids

- adim rapidly and IV acts within 2 mins

- short duration = 20-90 mins may require repeat dose

describe the typical IV naloxone dose for an overdose

- initial dose = 0.04-2 mg

- repeat with escalating doses (increasing) every 2-3 mins, can repeat from 2-4-10 mg

- if no response at 10 mg = consider other causes

- after reversal, may need to readmin doses in 20-60 min intervals depending on exposure

- continuous infusion IV may be required for long acting opioids

what are 9 examples of sympathomimetic toxins?

- caffeine

- cocaine

- amphetamines

- methamphetamines

- ritalin

- LSD

- theophylline

- MDMA

- pseudoephedrine

describe the mechanism of tox for sympathomimetic toxicity

- increased in sympathetic tone through the release of catecholamine

- inhibition of reuptake

- by direct receptor stimulation and alterations in neurotransmitter metabolism

what key clinical signs are associated with sympathomimetic toxicity? (HR/BP, RR, temp, pupils, bowel sounds, diaphoresis)

- HR and BP = increased

- RR = increased

- temp = increased

- pupils = dilated

- bowel sounds = increased

- diaphoresis = sweating

what are 7 examples of sedative-hypnotic toxins?

- anti anxiety meds

- muscle relaxants

- anti epileptics

- pre anestehtic agents

- barbs

- benzos

- alcohol

describe the mechanism of tox for sedative-hypnotic toxicity

- all facilitate inhibitory neurotransmission via the GABA receptor chloride channel

- modifies the frequency or duration of channel opening

- may decrease glutamate transmission and/or interact with NMDA receptors

what key clinical signs are associated with sedative-hypnotic toxicity? (HR/BP, RR, temp, pupils, bowel sounds, diaphoresis)

- HR/BP = decreased

- RR = decreased

- temperature = decreased

- pupils = no change

- bowel sounds = decreased

- diaphoresis = dry