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Pharmacology > 35_Toxicology & Antidotes > Flashcards

35_Toxicology & Antidotes Flashcards

1
Q

What is a toxidrome?

A

It is a toxic syndrome caused by major drug groups

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2
Q

What are the toxidromes for anti-muscarininc (anti-cholinergic) drugs? How do you treat?

A

Delirium, coma, tachycardia, HTN, hyperthermia mydriasis, decreased bowel sounds, urinary retention

Treat with physostigmine not for TCAs tho, treat hyperthermia

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3
Q

What are the toxidromes for cholinomimetic (pro-cholinergic) drugs? How do you treat?

ps these are like organophosphates

A

Anxiety, agitation, seizures, coma, bradycardia, pinpoint pupils salivation, sweating, hyperactive bowels

Treat with atropine and pralidoxome. support respiration

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4
Q

What are the toxidromes for opioids drugs? How do you treat?

A

Lethargy, sedation, coma, brady, hypOtension, pinpoint pupils, cool skin, decreased bowel sounds, flaccid muscles

Treat with naloxone, provide airway and respiratory support

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5
Q

What are the toxidromes for salicylate (aspirin) drugs? How do you treat?

A

Confusion, lethargy, coma, seizures, hyperventilation, hyperthemia, dehydration, hypOkalemia, anion gap metabolic acidosis

Treat: correcta acidosis and fluid e-lyte imbalance. Alkaline diuresis or hemodialysis to aid elimination

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6
Q

What are the toxidromes for sedative hypnotic (barbiturates, benodiazpines, ethanol) drugs? How do you treat?

A

Disinhibition initially, leathargy later. Stupor, coma. Nystagmus, decreased muscle tone, hypothermia. small pupils, hypotension, decreased bowel sounds in severe overdose

Treat: Airway and respiratory support. Avoid fluid overload. Consider FLUMAZENIL for benzodiazapine OD

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7
Q

What are the toxidromes for Stimulants like amphetamines, cocaine, phencyclidine (PCP)? How do you treat?

A

Agitation, anxiety, seizures. HTN, tacky, arrythmias. Mydriasis, nystagmus with PCP. Warm and sweaty skin, hyperthermia, increased muscle tone, possible rhabdomyolysis

Treat: Control HTN, seizures, and hyperthermia

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8
Q

What are the toxidromes for TCA (tricyclic antidepressants) drugs? How do you treat?

A

Anti-muscarinic effects. 3 Cs of coma, convulsions, cardiac toxicity (widened QRS, arrythmias, hypOtension)

Treat: control seizures, correct acidosis and cardio toxicity with ventilation, NaHCO3, and Norepi for the hypotension. control the hyperthermia

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9
Q

What is the general approach to the poisoned patient?

A 
Lab Eval (not always needed, esp if they are awake)
Anion Gap
Osmolol Gap
ECG
Specific Drug Levels
Tox Screens
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10
Q

What is the Anion Gap?

What are the toxins that cause accumulation of unmeasured anions which cause an elevated anion gap metabolic acidosis.

A

AG= Na - (HCO3+Cl)

MUDPILES
Methanol
Uremia (Renal Failure)
Diabetic Ketoacidosis
Paraldehyde
Iron, INH (isoniazid)
Lactate
Ethylene Glycol
Salicylate
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11
Q

What is an Osmolol Gap?

What is an increased osmolol gap assoc with?

A

OG= OsmM-OsmC
- OsmC=2(Na) + BUN/2.8 + Gluc/18

Increased OG seen with uncharged low molecular weight toxins.

Classic board question is Patient has elevated AG and OG has ingested toxic alcohol.
- Its either Methanol or Ethylene Glycol

The possible choices of toxic alcohol are ME DIE

Methanol
Ethanol
DKA Diuretics
Isopropanol
Ethylene Glycol
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12
Q

On the EKG, what does a:
Prolonged QRS due to?
Prolonged QTc?
Other changes?

A

QRS prolonged:
- Due to Na channel blockade

Prolonged QTc:
- Due to K efflux blockade (so no K getting out)

Other changes?
- Digoxin, Li

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13
Q

What are the drugs that you should get a specific drug level for?

A 
Acetaminophen
Salicylate
Ethanol
Commonly monitored drugs
 - if patient taking them or suspected ingestion i.e. Li, Digoxin, anticonvulsants, PT/INR for Coumadin
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14
Q

What are drug screens useful for?

A

Designed for employment.
Qualititative Results
DO NOT DX INTOXICATION, ONLY EXPOSURE

Use for monitoring, i.e. a psych patient with a drug prob

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15
Q

What are the two other names of acetaminophen (APAP)?

A

acetaminophen, Tylenol, paracetamol

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16
Q

Is acetaminophen toxic?

A

No, its the metabolite thats toxic. Its converted into an active metabolite by the liver.

Phase I: Oxidation; add polar Oxygen functional groups
Phase II: Conjugation; add bulky H2O soluble groups

This allows kidney to excrete

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17
Q

Does Acetaminophen (APAP) require hepatic oxidation? Why or why not?

What other ways does the liver handle APAP?

A

It does not bc its already water soluble. But a small amount (1-1.5%)

Instead of oxidation, it will undergo glucuronidation and sulfation.

However a small amount is oxidized by CYP450

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18
Q

The small amount of APAP thats oxidized is oxidized by what and turned into what?

A

Oxidized by CYP450 into

N-Acetyl-para-benzoquinoneimine (NAPQI)

This metabolite is EXTREMELY REACTIVE with a short half life. It rips e-‘s right off nearby macromolecules

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19
Q

What’s the issue with NAPQI being formed by CYP450 enzymes?

A

Most CYP450 enzymes are in the CENTRILOBULAR portion of the liver lobule. B/c they rip e-‘s right off nearby macromolecules, this can lead to CENTRILOBULAR HEPATIC NECROSIS

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20
Q

Describe the clinical effects of Acute Acetaminophen Overdose?

How many phases are there?

A

There are 4 phases

  1. 0-6 hrs N/V
  2. 4-24 hrs Clinically Silent, LFT and PT elevations
  3. 18-72 hours Toxic Hepatitis. Peaks in 2-3 days for those who will recover, for those who don’t then they get FULMINANT HEPATITIS
  4. Full recovery
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21
Q

What is used to predict who is at risk for liver toxicity?

A

Rumack-Matthew Nomogram

Based on serum APAP level (y axis) v Hours post ingestion.

Derived from acute, single ingestion

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22
Q

When does APAP toxicity occur?

How do you treat an APAP overdose?

A

Toxicity occurs when Glutathione (GSH) stores are depleted. It’s a natural antioxidant

Treat with N-Acetylcysteine. It helps by:
Repleting GSH
Directly reducing NAPQI,
Enhances sulfation of APAP

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23
Q

How is NAC administered?

A

Orally or IV, unclear which is better

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24
Q

Benefits of IV NAC? Risks?

A

Benefits:

Avoids vomiting, patient compliance issues
Shorter therapy (1 day in hosp v 3 days if it were oral)
IV is for 21 hours
Risks:
Higher risk of Anaphylaxis runs
 - Non IgE mediated histamine release
 - Flushing, Rash
 - Wheezing, rare HypoTN

But this could all happen with PO

To treat the risk symptoms, then hold infusion and give DIPHENDHYDRAMINE

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25
Q

What does anti-cholinergic really mean?

Common side effect of many drugs, including:

A

Anti-muscarinic

Common SE of many meds i.e.

Antihistamines
Psych Drugs: Antidepressants, Antipsychotics
Urology: Drugs to control urinary incontinence

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26
Q

What is the Anticholinergic toxidrome?

A

Mydriasis (Large pupils)
Dry Mouth / Skin
Tachy
Slows GI & GU (no peeing or pooping, this is urinary retention)
Altered mental status - staring, mumbling (pts look like zombies, ineffective picking at clothes/sheets

27
Q

How is anticholinergic toxidrome treated?

A

Just supportive til body gets rid of it

IV fluid, sedation

Could use PHYSOSTIGMINE

28
Q

What does physostigmine do?

A

It is used to reverse anticholinergic effects.

It inhibits AchE, therefore raising synaptic Ach levels to overcome blockade

29
Q

What are the two classes of Antidepressants?

A

TCAs (which have a anticholinergic toxidrome, and works via Nav blockade)

SSRIs, SNRIs

30
Q

What are the risks for TCAs?

A

Seizures
Cardiac Dysrhythmias

With the dysrhythmia, if there is a wide QRS, then threat with NaHCO3

31
Q

Are SSRIs / SNRIs safe or unsafe in overdose? How does serotonin syndrome happen?

A

Generally safe in overdose

Serotonin syndrome more common as a drug-drug interaction, but can occur from single drug overdose

32
Q

What is serotonin syndrome?

A

Neuromusc effects: Myoclonus, rigidity, hyperreflexia, tremor, all of these more in lower limb

Autonomic Effects (Tachy, Hyperthermia, HTN or hypotn, diaphoresis)

Altered Mental Status
- Typically agitation, Seizure, Coma

Agitation, Mydriasis, Increased Bowel Sounds, may have diarrhea

33
Q

How is Serotonin syndrome treated?

A

Stop drugs, treat with Benzodiazepines (BZD) and maybe cyproheptadine

34
Q

What is neuroleptic Malignant Syndrome?

How do you treat?

A

It is a rare but life threatening complication of neuroleptic / antipsychotic drugs

  • Muscle rigidity
  • Hyperthermia
  • Autonomic Instability
  • Altered Mental Status / Delirium
  • Rhabdomyolysis

Treatment: mostly supportive
- might give DANTROLENE, BROMOCRIPTINE, AMANTADINE

35
Q

What does aspirin irreversibly inhibit?

A

COX; by acetylating the active site

36
Q

With Aspirin overdose, how is it eliminated?
How is half-life affected?
Primary route of excretion?

A

It goes from 1st order to zero order elimination
Half life increases from 2-4 hrs to 20 hrs
Renal

37
Q

What are Aspirin toxic effects?

A

PRIMARY RESPIRATORY ALKALOSIS!! (hyperventilation)
- This stimulates brainstem respiratory center which causes hyperventilation

PRIMARY METABOLIC ACIDOSIS

TINNITUS
- ringing, roaring/rushing sound, decreased hearing

38
Q

How is ASA overdose treated?

A

GI decontamination

  • activated charcoal
  • risk for drug BEZOAR

Maintain urine output

  • IV fluid bolus
  • Ion trapping with NaHCO3

Hemodialysis for severe cases

39
Q

What are some toxicities seen in beta blockers?

How do you treat?

A

Bradycardia and hypotension

Treat by giving supportive care

  • ie IV fluids
  • Atropine
  • Vasopressors
  • Antidote which is glucagon bc it bypasses blocked B receptors
40
Q

What are some toxicities seen with CCBs? How do you treat?

A

Bradycardia, HypoTN, Hyperglycemia (bc w/o Ca, L type Ca2+ channels in pancreas cant open, so no Insulin released)

Treat with
IV Fluids
Atropine
Vasopressors
Ca2+ Salts
High Dose Insulin
41
Q

For both B Blocker and CCB toxicity, what should be given?

A

High dose insulin for the hyperglycemia, mechanical adjuncts i.e. IABP (intra aortic balloon pump) to increase myocardial O2 perfusion, or even bypass bc the heart may stop beating all together bc of the brady.

42
Q

What is the toxidrome for cholinesterase inhibitors?

A

Induce cholinergic toxidrome which is SLUDGE / DUMBBELSS where basically fluid is produced wherever possible.

Diarrhea
Urination
Miosis
Bradycardia
Bronchospasm
Excitation of Sk. Muscle
Lacrimation
Sweating
Salivation

Salivation
Lacrimation
Urination (relax internal sphincter, contract detrusor)
Defecation (relax internal sphincter)
GI upset (excitation of s. muscle, also get diarrhea, abd pain)
Emesis
(M) for Miosis (stimulation of pupillary constrictor muscle)

43
Q

How to treat cholinergic toxidrome?

A

Atropine

  • or other anticholinergic agent, but this fixes the muscarinic effects only
  • Titrate to effect
  • Fixes Muscarinic Only

Pralidoxime (2-PAM)

  • Regenerates AchE but give before aging
  • Treats Nm & Nn (both muscarinic and nicotinic)
44
Q

What molecule does Cyanide avidly bind? What does this binding cause?

A

Avidly binds Fe3+ in iron-sulfur complexes in mitochondria.

This turns off aerobic metabolism which results in:

Elevated anion gap metabolic acidosis
Elevated Serum Lactate Levels
Coma: Bc brain not getting ATP bc mitoch is messed up
Hypotn

45
Q

What are the antidotes for CN poisoning?

A

Two of them:

Traditional:

  • Amyl Nitrite Perles & Na Nitrite IV
    • Induce Methemoglobinemia
  • Na Thiosulfate
    • Enhances normal detox

2nd is Hydroxycobalamin
- Vit B12a + CN- = Vit B12

46
Q

What are the side effects of hydroxycobalamin?

A

Red Skin, urine, plasma, etc

47
Q

How is digoxin toxicity treated?

A

Supportive Care, atropine may correct the bradycardia.

Digoxin Immune Fab
- Ovine Fab Ab Fragments, called DigiFab

48
Q

What is the antidote for Benzodiazepines?

What channel does this antidote compete with?

What is the primary indication for this antidote?

A

Flumazenil

Has a BZD like structure so it competes for the GABA Cl- channel

Not used for drug overdose, bc it may cause seizure/w/drawal

Primary Function: Iatrogenic Toxicity, esp during procedural sedation

49
Q

What are the antidotes for Ethylene Glycol and Methanol?

What does it compete for?

A

Ethanol & Fomepizole

Competes for ADH

50
Q

What is the toxidrome for Opioids?

Whats the antidote?

A

Toxidrome:

Miosis
CNS depression
Respiratoy Depression

Antidotes:
Naloxone givine IV, IM, ETT, nebulized BUT SHORT ACTING

51
Q

If someone gets a rattlesnake bite, what shouldn’t someone do for them?

A

DO NOT

Cut & Suck bc could damage structures even more

Compound the Local Injury by:

  • Putting on a tourniquet
  • Apply or Immerse in Ice
  • Use electrical shock

No need to bring the snake to the hospital bc even dead ones can still bite for up to an hour post mortem

52
Q

How many types of anti-venom are there? What snakes is it effective against?

What is it called?

A
  1. All north american pit viper species

Called Cro-Fab

53
Q

How many types of toxic effects are there from rattlesnake venom?

A

3.

Local tissue injury
- progressive pain and swelling that extends proximally up the limb

Hematologic Effects

  • Platelets & Fibrinogen decreased, Coagulopathy Increased (Increased PT/INR)
    • IN SEVERE CASES, CAN LOOK LIKE DIC

Neurologic Effects
-Parasthesias, metallic taste, muscle twitching which is MINOR ISSUE w/rattlesnake venom

54
Q

When is anti-venom warranted?

A

Anything other than mild pain, minimal swelling or trivial lab abnormalities. so if there are any of these, no need for anti-venom

55
Q

How is Cro-Fab made?

A

Sheep injected with snake venom, become hyperimmune. Get IgG from them.

IgG treated with PAPAIN to form Fab fragments.

These fragments are less immunogenic than a whole IgG Ab

BTW, this Cro-Fab is hella expensive

56
Q

What are the typical findings of a venomous snake bite

A

Hemorrhagic Blebs which are most common on bitten fingers

Hemorrhagic Lymphangitis
- This is due to the venom; its not infectious and Abx NOT indicated

57
Q

There are other anti-venoms. What is another snake where one is made against? Hint: This snake’s venom is paralyzing

A

CORAL SNAKE

not found in Cali

Antivenom is not being made anymore, so what little is around, ppl always trying to extend its shelf life.

58
Q

What anti-venom is given if a black widow spider bites you?

A

Whole IgG. Its infrequently used.

30 diff species of black widow worldwide, but L hesperus in CA

59
Q

If a scorpion bites you, what kind of anti-venom?

A

Fab fragment

60
Q

What is theophylline and what is it used for?

A

Nearly obsolete therapy for Asthma / COPD.

- still used occasionally for neonatal apnea

61
Q

What is theophylline closely related to?

A

Caffeine

62
Q

Describe theophylline toxicity?

A

Common: tachy, tremor, vomiting
Severe: Seizures (difficult to treat)

63
Q

How do you treat theophylline toxicity?

A 
Supportive Care
Activated Charcoal
Aggressive Seizure Mgmt: Barbs>>BZDs
B Blockers (ESMOLOL DRIP...KNOW THIS)
 - May work for B2 mediated hypotn
Hemodialysis
 - for levels >90 mg/l in acute overdose

Pharmacology (17 decks)

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