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PHRM 865: Theraputics V > Lecture 35: Toxicology > Flashcards

Lecture 35: Toxicology Flashcards

1
Q

What is Toxicology?

A
  • Focus on toxic effects in patients by unintentional or intentional overdoses

~77% are unintentional

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2
Q

What are some of the Top Medications Overdose in Adults?

A
  • Analgescis [11.2%]
  • Sedatives/Hypnoyics/Anti-Psychotics [9.8%]
  • Antidepressants [7.2%]
  • Cardio Drugs [6.4%]
  • Alcohols [4.8%]
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3
Q

What are some of the Top Medications Overdoses in Children?

A
  • Analgesics [9.2%]
  • Antihistamines [4.7%]
  • Vitamins [4.3%]
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4
Q

What are some of the first things to consider when helping a potentail overdose patient?

Stabilization? Exposure? Assessment?

A
  • Stabilization: ABC management, Vitals, IV access, Oxygenation
  • Exposure: What drugs, How much, When taken
  • Assessment: Exams/Labs, APAP/Salicylate Tests, Andtidotes?
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5
Q

What is the Anion Gap & Osmolar Gap?

Calculations?

A
  • Anion Gap: difference of Cations and Anions [(Na+K)-(Cl+HCO3)] should be < 14
  • Osmolar Gap: Gap = Measured - Calculated [Calculated = (2xNa)+(BUN/2.8)+(Glu/18)+(EtOH/4.6)] should be < 10
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6
Q

What is the importacne of Activated Charcoal?

A
  • Best used in 2-4 hours [44-95% prevention]
  • Hard to take; bad taste and gritty
  • 1-2g/kg ABW
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7
Q

What are some of the Signs and Symptoms of Opioid Toxicity?

A
  • Respiratory Depression
  • Pinpoint Pupils
  • N/V
  • Drowsiness
  • Bradycardia
  • Hypotension
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8
Q

What is the General Managment of Opioid Toxicity?

Stabilization? Exposure? Assessment?

A
  • Stabilization: ABC Management [NEED TO DO], CNS/Respiratory Management
  • Exposure: What Drug, How much, When?
  • Assessment: Labs/Exams, APAP/Salicylate Test, Naloxone
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9
Q

What is the Treatment of Choice for Opioid Toxicity?

A
  • NALOXONE 0.4 - 2mg IV push, IM, IN
  • Want to give the smallest amount to AVOID withdrawal
  • HIGHER doses for those with illicit drugs use
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10
Q

What are some of the Risk Factors for Acetaminophen Toxicity?

Dose? Conditions?

A
  • Toxic Dose = 7.5-15g
  • Risk Conditions: Those taking 2E1 Inducers & Alcohol
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11
Q

What is the Pharmacology of Acetaminophen?

A
  • 60%: Glucaronidation
  • 30%: Sulfation [more protective in kids]
  • ~10%: 2E1 = necrosis
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12
Q

What is the overall Timeline for Acetaminophen Toxicity?

A
  • 0-24h: no real symtpoms
  • 24-48h: Liver issues begin
  • 48-72h: More liver issues & increased bilirubin
  • 72-96h: Highest liver issues then Hepatic Encephalopathy, Renal Failure, Death
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13
Q

What is the Treatment Options for Aceteminophen Toxicity?

MOA? When to start? Duration?

A
  • N-Acetylcysteine [NAC]
  • MOA: Glutathione Surrogate that pushes more toward Glucoronidation pathway
  • Best to start withinn 8 hours
  • IV = 21h & PO = 72h
  • Rumack-Matthew [above line = GIVE NAC & below line = HOLD NAC]
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14
Q

What is the Dosing Regimen for N-Acetylcystine?

IV? PO?

A
  • IV: Loading Dose [150mg/kg IV over 1h] –> Second Dose [50mg/kg IV over 4h] –> Third Dose [100mg/kg IV over 16h]
  • PO: Loading Dose [140mg/kg] –> Maintenance Dose [70mg/kg PO q4h for 17 doses]
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15
Q

What are some of the Risk Factors for Salicylate Toxicity?

Disorders? Concentraions?

A
  • Disorders: Mixed Acid/Base = Increased Anion Gap [metabolic acidosis] & Hyperventilation [Respiratory Alkalosis]
  • Concentrations: Mild Toxicity = >30 [tinnitus, diszziness] & Severe Toxicity = > 80 [CNS effects]
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16
Q

What are some of the Signs and Symptoms of Salicylate Toxicity?

A
  • Tinnitus & Vertigo
  • Seizure
  • N/V
  • Lethargy/Coma
  • Decreased GI Motility
  • Altered Mental Status
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17
Q

What is the General Managment of Sakicylate Toxicity?

Stabilization? Exposure? Assessment?

A
  • Stabilization: ABC, IV, Vitals, Oxygen
  • Exposure: When, How Much, What Drug
  • Assessment: Exams/Labs, Sodium Bicarb
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18
Q

What is the Treatment of Choice for Salicylates Toxicity?

MOA? Monitoring?

A
  • Sodium Bicarb 1-2mEq/kg IV push over 1-2mins
  • MOA: Urine Alkalinization
  • For Salicylate Conc. > 30, Anion Gap Acidosis, Altered Mental
  • Monitor pH & Electrolytes
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19
Q

What are some of the Signs and Symptoms of Sedative Toxicity?

A
  • CNS Depression
  • Respiratory Depression
  • Bradycardia
  • Hypotension
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20
Q

What is the General Managment of Sedative Toxicity?

A
  • Stabilization: ABC, IV, Vitals, Oxygen
  • Exposure: When, How Much, What Drug
  • Assessment: Exams/Labs, Flumazenil?
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21
Q

What is the Treatment of Choice for Sedative Toxicity?

MOA? Side Effects? Is it really used?

A
  • Flumazenil 0.2mg IV push
  • MOA: competing with BZDs at the GABA site [complete inhibitor]
  • Can cause withdrawal symtpoms [causes seizures]
  • NOT RECOMMENDED because of its FULL INHIBITION of GABA
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22
Q

What are some of the Indications and ** Examples** of TCAs?

A
  • Indications: Bed wetting, Depression, Insomnia, Mirgraines, Neruopathy
  • Examples: Amitriptyline, Nortiptyline, Doxepin…
23
Q

What are some of the signs and symptoms for TCA Toxicity?

A
  • Prolonged QRS
  • Anticholinergic Symptoms
  • Seizures
  • Altered Mental Status
  • Hypotension
  • Tachycardia

Antichoinergic: Blind as a Bat, Hot as Hades, Red as a Beat, Dry as a Desert, Mad as a Hatter

24
Q

What are some of the effects of the QRS Prolongations within TCA use?

A
  • > 100 msec = increase seizure risk
  • > 150 msec = increased cardiac arrhythmias
25
Q

What is the treatment for TCA Toxicity?

MOA? Indications? Monitoring?

A
  • Sodium Bicarb 1-2 mEq/kg IV push over 1-2 mins
  • MOA: Increase sodium gradient
  • Indications: QRS > 100, Arrhythmias, Acidosis
  • Monitoring: pH 7.45-7.55; QRS < 100, Stable
26
Q

What are some of the Examples of some of the Antipsychotics?

Pharmacology?

A
  • Typical: Haloperidol, Fluphenazine, Chlorpromazine, Thioridazine, Perphanazine
  • Atypical: Aripiprazole, Clozapine, Olanzapine, Paliperidone, Ziprasidone

1st gen: D2 antagonism
2nd gn: Serotonin/D2 antagonis

27
Q

What are some of the Signs and Symptoms of Antipsychotic Toxicity?

A
  • Hypotension
  • Tachycardia
  • QT/QRS Prolongation
  • EPS
  • NMS
  • Sedation
28
Q

What is important to know about Atypical Antipsychotics Toxicity?

A
  • NOT defined
  • Symptoms within 1-2h
  • Peak symptoms within 4-6h
  • Duration is 12-48h
29
Q

What are some of the important things to note about NMS Complications?

Treatment?

A
  • High Fever [108] with very stiff muscles; happens in 3-9d –> Death can happen
  • Mainly caused by Haloperidol, Depot Fluphenazine or Chlorpromazine
  • DC agent; cooling; Benzos;
30
Q

What is the differences between Serotonin Syndrome and NMS?

A
  • Serotonin Syndrome: Lower Fever; Lasts < 24h; Lower Limbs; Cyproheptadine
  • NMS: Higher Fever; Lasts > 24h; Stiff Muscles; Bromocriptine
31
Q

What is the cause for Digoxin Toxicity?

A
  • Dig blocks Na/K ATPase causing more K to be outside = toxicity
32
Q

What are some of the Signs and Symptoms of Digoxin Toxicity?

Non-Cardiac? Cardiac?

A
  • Cardiac: Bradycardia, Heart Blocks, Arrhythmias, Hyperkalemia
  • Non-cardiac: N/V, Ab Pain, Norexia, Confusion, Vision Changes
33
Q

What is the General Management for Digoxin Toxicity?

A
  • DC Digoxin
  • ABC, Vitals, ECG
  • Activated Charcaol: within 2 hours
  • Digibind
  • Hemodialysis NOT Effective
34
Q

What is the Treatment that is used for Digoxin Toxicity?

MOA? Indications?

A
  • Digibind
  • MOA: Binds to free dig in the body
  • Indications: NOT Responsive to Atropine, Hyperkalemia, Ingested > 10mg in adults & > 4mg in kids
35
Q

What is important to know about the Dosing for Digibind in Digoxin Toxicity?

A
  • Based on the 0.5mg vials
  • Acute Ingestion: (mg of dig x 0.8) / 0.5mg
  • Serum Dig: (Dig Conc. x Weight [kg]) / 100

Tells how many Digibind vials we have to give

36
Q

What are some of the Signs and Symptoms for CCB and BB Toxicity?

What do they have in common?

A
  • CCBs: HYPERglycemia, Metabolic Acidosis, Ileus…
  • BBs: HYPOglycemia, Bronchospams
  • BOTH: Hypotension, Bradycardia, Arrhythmias, Cardiogenic Shock, CNS Depression
37
Q

What is the General Management for CCB and BB Toxicity?

Potential Antidotes?

A
  • ABC, Vitals, ECG
  • Activated Charcoal [depends on time and amount]
  • Potential Antidotes: Atropine, Calcium, Vasopressors, Glucagon, High Dose Insulin, Lipid Emulsion
38
Q

What is the MOA for Atropine in CCB and BB Toxicity?

Effective?

A
  • MOA: Blocks Parasympathetic activity to increase the heart rate
  • 0.5-1mg IV push
  • NOT ALWAYS EFFECTIVE
39
Q

What is the MOA of Calcium in CCB and BB Toxicity?

Effective? Dosing?

A
  • MOA: Promotes Ca release = contractility
  • Dosing: Ca Cloride is 3x more better than Ca Gluconate
  • MORE effective in CCB than BB overdose
40
Q

What is important about Vasopressor Therpay in CCB and BB Toxicity?

A
  • Higher doses are used
  • Vasodilatory Shock = Norepinephrine
  • Cardiogenic Shock = Epinephrine
41
Q

What is the MOA of Glucagon in CCB and BB Toxicity?

Dosing?

A
  • MOA: Causes contractility by hitting Gs to activate ATP to cAMP
  • Dosing: HIGHER than in diabetes [3-10mg IV in adults]
  • Pre-medicate with Ondasetron to decrease N/V
42
Q

What is the MOA for High Dose Insulin in CCB and BB Toxicity?

Monitoring? Dosing?

A
  • MOA: Increases inotropy
  • Dosing: titrate to systolic BP > 90-100
  • Monitoring: Improved Contractility within 15-60mins, Glu = 100-250, Check Electrolytes
43
Q

When can Iron Toxicity occur within someone?

A
  • 10 - 60 mg/kg of elemental iron
44
Q

What are the phases of Iron Toxicity?

A
  • 0.5 - 2h: GI upset, ab pain
  • 6 - 24h: Recovery? should monitor
  • 2 - 24h: shock stage [acidosis, hypotension, poor CO]
  • 48 - 96h: Hepatoxicity
  • Days - Weeks: GI Scarring, Obstructions…
45
Q

What is the General Managment of Iron Toxicity?

A
  • ABC, Vital, Fluids
  • Activated Charcoal NOT good
  • Whole Bowel Irrigation
  • Deferoxamine?
46
Q

What is the Treatment for Whole Bowel Irrigation in Iron Toxicity?

A
  • Polyethylene Glycol
  • Takes 4 - 6h to work; should be by a toilet
47
Q

What is the Antidote Treatment for Iron Toxicity?

MOA? Indications?

A
  • Deferoxamine
  • MOA: Chelates iron and enhances renal elimination
  • Indicated: Metabolic Acidosis, Iron Tabs in KUB, Conc. > 500

15mg/kg/hour

48
Q

What are some of the Toxic Alcohols that are can cause Toxicity?

A
  • Ethylene glycol [antifreeze], Methanol [washer fluid, paint remover], Isopropyl Alcohol [rubbing alcohol, paint remover]
49
Q

What are some of the Clinical Presentations assoicated with Toxic Alcohols and what are the results?

A
  • Anion Gap & Osmolar gap
  • Anion gap + Osmolar gap = Methanol; Ethylene
  • Osmolar Gap NO Anion Gap = Isopropyl
50
Q

What are the Phases of Toxicity for Alcohol Toxicity?

A
  • 30 min - 12 h: CNS, N/V, Inebriation, Lethargy
  • 12 - 24h: Metabolic Effects, Cardio issues, Anion Gap
  • 2 - 3d: Renal issues, Crystals
51
Q

What is the General Managment of Ethylene Gylcol and Methanol Toxicity?

Treatment?

A
  • Non-Pharm: Gastric Lavage or Aspirations when < 1h; Charcoal NOT good
  • Pharm: Ethanol & Fomepizole –> inhibits alcohol dehydrogenase limiting toxic Metabolites
52
Q

What is Fomepizole?

A
  • Helps with Ethylene and Methanol toxicity
  • NO CNS depression & ICU not required
53
Q

What is the Treatment of Isopropyl Toxicity?

A
  • Hydration
  • Hemodialysis

PHRM 865: Theraputics V (42 decks)

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