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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
What does anti-cholinergic really mean? | Common side effect of many drugs, including:
Anti-muscarinic Common SE of many meds i.e. Antihistamines Psych Drugs: Antidepressants, Antipsychotics Urology: Drugs to control urinary incontinence
26
What is the Anticholinergic toxidrome?
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
How is anticholinergic toxidrome treated?
Just supportive til body gets rid of it IV fluid, sedation Could use PHYSOSTIGMINE
28
What does physostigmine do?
It is used to reverse anticholinergic effects. It inhibits AchE, therefore raising synaptic Ach levels to overcome blockade
29
What are the two classes of Antidepressants?
TCAs (which have a anticholinergic toxidrome, and works via Nav blockade) SSRIs, SNRIs
30
What are the risks for TCAs?
Seizures Cardiac Dysrhythmias With the dysrhythmia, if there is a wide QRS, then threat with NaHCO3
31
Are SSRIs / SNRIs safe or unsafe in overdose? How does serotonin syndrome happen?
Generally safe in overdose Serotonin syndrome more common as a drug-drug interaction, but can occur from single drug overdose
32
What is serotonin syndrome?
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
How is Serotonin syndrome treated?
Stop drugs, treat with Benzodiazepines (BZD) and maybe cyproheptadine
34
What is neuroleptic Malignant Syndrome? | How do you treat?
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
What does aspirin irreversibly inhibit?
COX; by acetylating the active site
36
With Aspirin overdose, how is it eliminated? How is half-life affected? Primary route of excretion?
It goes from 1st order to zero order elimination Half life increases from 2-4 hrs to 20 hrs Renal
37
What are Aspirin toxic effects?
PRIMARY RESPIRATORY ALKALOSIS!! (hyperventilation) - This stimulates brainstem respiratory center which causes hyperventilation PRIMARY METABOLIC ACIDOSIS TINNITUS - ringing, roaring/rushing sound, decreased hearing
38
How is ASA overdose treated?
GI decontamination - activated charcoal - risk for drug BEZOAR Maintain urine output - IV fluid bolus - Ion trapping with NaHCO3 Hemodialysis for severe cases
39
What are some toxicities seen in beta blockers? How do you treat?
Bradycardia and hypotension Treat by giving supportive care - ie IV fluids - Atropine - Vasopressors - Antidote which is glucagon bc it bypasses blocked B receptors
40
What are some toxicities seen with CCBs? How do you treat?
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
For both B Blocker and CCB toxicity, what should be given?
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
What is the toxidrome for cholinesterase inhibitors?
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
How to treat cholinergic toxidrome?
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
What molecule does Cyanide avidly bind? What does this binding cause?
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
What are the antidotes for CN poisoning?
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
What are the side effects of hydroxycobalamin?
Red Skin, urine, plasma, etc
47
How is digoxin toxicity treated?
Supportive Care, atropine may correct the bradycardia. Digoxin Immune Fab - Ovine Fab Ab Fragments, called DigiFab
48
What is the antidote for Benzodiazepines? What channel does this antidote compete with? What is the primary indication for this antidote?
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
What are the antidotes for Ethylene Glycol and Methanol? What does it compete for?
Ethanol & Fomepizole Competes for ADH
50
What is the toxidrome for Opioids? Whats the antidote?
Toxidrome: Miosis CNS depression Respiratoy Depression Antidotes: Naloxone givine IV, IM, ETT, nebulized BUT SHORT ACTING
51
If someone gets a rattlesnake bite, what shouldn't someone do for them?
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
How many types of anti-venom are there? What snakes is it effective against? What is it called?
1. All north american pit viper species Called Cro-Fab
53
How many types of toxic effects are there from rattlesnake venom?
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
When is anti-venom warranted?
Anything other than mild pain, minimal swelling or trivial lab abnormalities. so if there are any of these, no need for anti-venom
55
How is Cro-Fab made?
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
What are the typical findings of a venomous snake bite
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
There are other anti-venoms. What is another snake where one is made against? Hint: This snake's venom is paralyzing
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
What anti-venom is given if a black widow spider bites you?
Whole IgG. Its infrequently used. 30 diff species of black widow worldwide, but L hesperus in CA
59
If a scorpion bites you, what kind of anti-venom?
Fab fragment
60
What is theophylline and what is it used for?
Nearly obsolete therapy for Asthma / COPD. | - still used occasionally for neonatal apnea
61
What is theophylline closely related to?
Caffeine
62
Describe theophylline toxicity?
Common: tachy, tremor, vomiting Severe: Seizures (difficult to treat)
63
How do you treat theophylline toxicity?
``` 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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