Introduction To Principals Of Toxicology Flashcards Preview

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Flashcards in Introduction To Principals Of Toxicology Deck (23)
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1

What is the primary determinant of drug/substance toxicity?

The dose of the substance.
- almost everything can be toxic at the right dose

2

Toxic dose vs Lethal dose

Toxic dose (TD50) = the minimal dose of a product that produces toxic effects in 50% of subjects

Lethal dose (LD50) = the minimal dose of a product that kills 50% of subjects

**legally a poison must have an LD50 of less than 50mg/kg**

3

Therapeutic index

LD50/ED50

ED50 = effective dose = the minimal dose required for 50% of subjects to experience therapeutic effects

**the larger the number, the safer the drug**

***is a measure of relative safety as well***

**botulinum toxin has the lowest LD50 of any drug on the market currently**

4

What are extra toxicological terms and definitions that are used?

TLV = threshold limit value
- concentration below which there is no expected adverse effects over a 40hr week

ALD = average lethal dose
- estimated number from accidental deaths in humans

STEL = short term exposure level
- 4x a day which the average being equal to the TLV

5

What are the safeguards for poisoning?

Airway = get an ET tube and monitor for vomit aspiration

Breathing = supplemental O2 via canal or bags as needed

Circulation = ECG and pulses and BP

Get antidotes if present and able
- glucose/insulin = diabetic shock or hypoglycemia
- naloxone = narcotic overdose

Consider dialysis, N-Acetylcistine and activated charcoal, apomorphine/ipecac as needed to remove/reduce drug exposure

6

What are the common substances used to induce emesis in toxicity cases?

Apomorphine

Ipecac (methylcephaeline/ cephaeline)

Contraindications to emesis
- ingestion of petroleum hydrocarbons (will induce chemical pneumonitis)
- caustic acid/alkali agents
- seizing or comatose patients

7

What is gastric lavage?

Tubs is inserted through nose or stomach and irrigate substances out of the stomach

8

Activated charcoal

Oral administrative agent that binds/chelates numerous toxins and prevents absorption
- almost always induces emesis
- **contraindicated in caustic agents and petroleum hydrocarbons again (induces emesis and causes pneumonitis)

Extra info:
- is known to inactivate ipecac so dont use together
- **in order to achieve maximum effect, must administer within 30 min-2 hrs of ingested poison

9

Cathartics

Liquid substances that promote very rapid movement and elimination of poison through the GI tract while chelating the poison substances
- induces watery diarrhea very quickly

**includes sorbitol, magnesium citrate/sulfate**

10

Pralidoxime

chelating agent that is used for organophosphate poisoning (cholinergic toxidrome such as insecticides, sarin, tabun, etc.)

***administered w/ atropine to block muscarinic effects of parasympathetic nervous system.

11

Cyanide

Binds to cytochrome c oxidase and mitochondrial membranes of all cells and prevents ETC and cellular respiration
- really hits CNS and cardiac tissues the hardest and causes toxicity to these systems

LD50 = 2 mg/kg and produces death in 1-15 minutes

***antidote = give amyl nitrate/sodium nitrite and sodium thiosulfate with oxygen and whole blood. This causes methemoglobin to be produces and combines with cyanide to chelate it and allow it to be eliminated***

12

Botulinum toxin

**most potent poison known and very rapidly absorbed**

Prevents ACh release form nerve terminals by cleaving SNARE proteins.
- induces respiratory depression to kill

Treatment = lavage/emesis/charcoal or anti-toxin (type A/B/E) if time frame doesnt allow for the previous
- **also always remember your ABCs to seat up safety net

13

Heavy metals

All pharmacological heavy metals are chelators
- BAL/EDTA/DMSA/DMPS/EDTA
- **most commonly used are BAL (British anti-lewisite (dimercaprol)) and DMSA (dimercaptosuccinic acid (succimer))

14

DMSA (succimer)

Used to treat arsenic/mercury or lead poisoning

ADRs
- chills/fever/diarrhea/nausea/vomiting

Dosage
- children 1-11 yrs = 10mg/kg every 8 hrs for 5 days. Then every 12 hrs for 14 days (total 19 days)
- adults and children > 12 yrs = 10 mg/kg every 8 hrs for 5 days

15

Trivalent antitoxin (A/B/C)

Used for botulinum toxicity
- contains neutralizing antibodies against the most common human botulinum forms

Dosage = 10 mL vial diluted 1:10 with isotonic saline and administered via IV drip infusion
- usually does not require additional doses since the dose antibodies far exceed the serum levels

16

More details about Cyanide antidote

Requires a “kit” that includes amyl nitrate, sodium thiosulfate and sodium nitrate

1) sodium nitrate MOA: oxidizes hemoglobin iron intro the ferric state and converts it to methemoglobin. Cyanide has highest affinity to bind to methemoglobin
** must be careful with dosage though because too much methemoglobin causes hypotension and hypoxia

2) sodium thiosulfate MOA: reacts with cyanmethemoglobin (methemoglobin + cyanide) to produce thiocyanate + hemoglobin
- essentially takes the cyanide from hemoglobin
- thiocyanate is very easily excreted via urine

17

Alcohol (ethanol) as an antidote

Used for ethylene glycol/methanol and isopropyl alcohol poisoning

Ethanol competitively inhibits the above substances from being converted into toxic metabolites
- also often need to give hemodialysis in conjunction to ensure safety

Normal conversion
1) any alcohol -> acetaldehyde/formaldehyde
- uses alcohol dehydrogenase (slowly)
- ** this is where ethanol can be used to inhibit

18

Ethylene glycol specifics

Gets metabolized by alcohol dehydrogenase into 4 toxic metabolites
- glycoaldehyde
- glycolate
- glycolic acid
- glyoxylate

**produces high anion gap metabolic acidosis with hypocalcemia and lactic acidosis**

***in addition, metabolites will bind with calcium to form calcium crystals and induces nephrotic syndrome and renal failure***

Antidote therapy
1) IV ethanol (maintain around 100/150 mg/dL)

2) fomepizole (blocks alcohol dehydrogenase)
- **drug of choice for both ethylene glycol and methanol toxicity
- 15 mg/kg initially IV then 10-15 mg/kg every 12 hrs until normal levels are achieved

3) hemodialysis is a must for symptomatic patients

4) can consider giving any of the following as well as adjuvants (#1-3 are required though)
- sodium bicarbonate = corrects acidosis
- pyridoxine = inhibits metabolism of glycolic acid -> oxalic acid
- thiamine = inhibts metabolism as well

19

Carbon monoxide poisoning

Common means of suicide attempts
- auto exhaust or industrial emissions

*carbon monoxide has 210x greater affinity for Hb than does O2 = produces carboxyhemoglobin which cant bind oxygen*

Symptoms: (based off of levels of carboxyhemoglobin)
- 20-30% = headache and exertional dyspnea
- 40-60% = severe neurological symptoms and cherry red apperance
- > 60% = coma and convulsions

Treatment
- artificial respiration with pure O2 to promote displacement of CO
- hyperbaric oxygen chamber, if symptomatic

20

Warfarin review

Blocks all vitamin K- dependent cofactors
- 2/7/9/10/protein C and S

ADRs
- hemoptysis
- excessive bruising
- spontaneous bleeding
- bloody stools/urine
- if toxic levels = severe hemorrhages and very elevated INR

**reversal of toxic dosing of warfarin = injection of vitamin K and FFP with prothrombin complex as needed**

21

Naloxone vs naltrexone review

Naloxone
- acts on mu/Kappa/delta receptors to block effects of opiods
- duration of action though = 45 minutes
- usually given in emergency situations
- always induces withdrawal

Naltrexone
- same MOA but has longer duration of action
- 24-72 hrs
- usually given after emergency

22

Methemoglobinemia antidote

*methemoglobinemia is high levels of methemoglobin (which present with Fe3+ ferric iron instead of Fe2+ ferrous iron.*
- cant bind oxygen

Causes = nitrates, sulfa drugs, genetic causes (G6PD, PK deficiency, methemoglobin reductase deficiency, etc.)

**becomes cyanotic skin at 10-15%, lethal is 70%**

Antidote = methylene blue!!
- MOA = causes direct chemical reactions to reverse the iron state back to ferrous which can bind oxygen
- does = 1-2 mg/kg via IV
- **toxic effects = serotonin syndrome (be careful in patients using serotonin medications)**

23

What is the one weird opioid that presents abnormal to the common opioid toxidrome

Meperidine

Presents with dilated pupils (miosis) and increased HR
- this is due to anti muscarinic effects (only one to have this)