toxicology tests

Question 1

What are the most common toxic exposures in adults and children?

Answer 1

adults: analgesics; sedatives/hypnotics/antipsychotics, antidepressants; alcohols; cardiovascular drugs; street drugs
children: cosmetics; cleaners; pesticides; analgesics;

Question 2

What is the labs role in toxicology?

Answer 2

Assessment of toxicity
ID the drug
Management and therapy

Question 3

Which drugs cause the anion gap?

Answer 3

A lcohol
T oluene
M ethanol
U remia
D iabetic ketoacidosis
P araldehyde, phenformin
I ron, isoniazid
L actic acidosis (cyanide, CO)
E thylene glycol
S alicylates

anion gap = [Na] - ([Cl] + HCO3])
(normally < 14 mEq/L)

Question 4

Which drugs cause the osmotic gap?

Answer 4

M ethanol
E thanol
D iuretics
I sopropanol
E thylene glycol

osmolality (calculated) =
2*[[[[Na nM]]]] + [[[[gllllucose mg/dL]]]]/18 + [[[[urea mg/dL]]]]/2….8
(normally 280 - 295 mOsm/kg)

Question 5

Which drugs cause a combined anion and osmotic gap?

Answer 5

Alcohol
Methanol
Uremia
Ethylene glycol

Question 6

When is identification of the drug most useful?

Answer 6

antidote available or specific treatment is indicated

delay in presentation of symptoms

Question 7

antidote for acetaminophen

Answer 7

Nacetylcysteine (NAC, Mucomyst)

Question 8

antidote for B blockers

Answer 8

glucagon

Question 9

antidote for digoxin

Answer 9

digibind

Question 10

antidote for ethylene glycol/methanol

Answer 10

Antizole (fomepizole, 4- methylpyrazole), ethanol

Question 11

antidote for heavy metals (lead, mercury, arsenic)

Answer 11

dimercaprol, BAL, EDTA, D-penicillamine

Question 12

antidote for iron

Answer 12

deferoxamine (DFO)

Question 13

antidote for isoniazide

Answer 13

pyradoxine

Question 14

antidote for nitrites, analins, local anesthetics

Answer 14

methylene blue

Question 15

antidote for opiates

Answer 15

naloxone (Narcan)

Question 16

antidote for organophosphates

Answer 16

atropine, 2-PAM

Question 17

antidote for warfarin

Answer 17

phytonadione (vitamin K1)

Question 18

What is treated with charcoal hemoperfusion?

Answer 18

theophylline, carbamazepine

Question 19

What is treated with hemodialysis and antidote?

Answer 19

ethylene glycol, methanol

Question 20

What is treated with hyperbaric oxygen?

Answer 20

CO

Question 21

What is treated with hemodialysis?

Answer 21

◦ salicylate

◦ lithium

Question 22

Which drugs have a delayed toxicity ?

Answer 22

acetaminophen
iron
hypoglycemic
agents
propoxyphene
tricyclic
antidepressants

Question 23

What is the most commonly used toxicity screening test?

Answer 23

urine test

Question 24

What is the mechanism of acetaminophen toxicity?

Answer 24

Mechanism
◦ reactive intermediate metabolite accumulates
when enzymatic pathways are saturated

Toxicity profile
•stage 1 (0 - 24 h) none to anorexia, nausea
•stage 2 (24 - 48 h) none to mild GI distress
•stage 3 (3 - 4 d) hepatic necrosis, jaundice,
bleeding, vomiting, neurological changes,
hepatic encephalopathy, death

Question 25

What is the management of acetaminophen toxicity?

Answer 25

Antidote/ treatment ◦ decontamination ◦ N-acetylcysteine
Lab management ◦ first serum level at 4 h, then repeat ~2-4 h
use normogram or calculate t1/2 ◦ monitor LFTs

Question 26

What is the mechanism of acetyl salicyclic acid toxicity (ASA)?

Answer 26

Mechanism ◦ direct CNS respiratory stimulant
hyperventilation and respiratory alkalosis ◦ direct uncoupling of oxidative phosphorylation
hyperthermia, inc’d O2 consumption and metabolic rate ◦ indirect metabolic acidosis (Krebs cycle impairment)

Question 27

What is the management of ASA toxicity?

Answer 27

```
Lab management ◦ serum concentrations ◦ ABG’s ◦ electrolytes ◦ LFT’s ```

Question 28

What is the mechanism of heavy metal toxicity?

Answer 28

Arsenic, lead, mercury, copper, iron
Mechanisms and Symptoms ◦ protein/ enzyme inhibition, free radicals generation, etc ◦ neurological, GI, renal, cardiovascular
Samples (use metal free containers) ◦ blood: lead ◦ serum: iron ◦ urine: arsenic, mercury, copper, lead, etc

Question 29

What are the goals of therapeutic drug monitoring? (TDM)

Answer 29

To increase eficacy of treatment
To increase safety of treatment
To decrease global costs of treatment

Question 30

What are some commonly monitored drugs?

Answer 30

Cardioactive drugs: Digoxin, Digitoxin, Amiodarone, Mexiletine
Antiepileptic drugs: Carbamazepine, Phenytoin, Phenobarbital, Valproic acid, Theophylline
Antibiotics: Amikacin, Netilmycin, Vancomycin
Immunosupressants: Cyclosporine A, Tacrolimus
Antineoplastic drugs: Metotrexate

Question 31

What are some clinical indications for TDM?

Answer 31

no therapeutic effect
toxic effect suspected
noncompliance suspected
impaired liver or renal function resultin in altered elimination of the drug
drug-drug interactions in the pharmacokinetic phase
no information about earlier drug administration

Question 32

What is TDM sampling time?

Answer 32

at steady state; 4 – 5 x T0.5
after absorption and distribution of the last dose
usually – just before administration of the next dose (trough concentration)

Question 33

What are 3 important things about the steady state of TDM?

Answer 33

1. Constant tissue drug concentration. 2. The rate of input of the drug equals the rate of elimination. 3. Serum drug concentrations measured at the same time points of dosing interval should remain constant.

Question 34

What are TDM laboratory methods?

Answer 34

CHROMATOGRAPHY
gas-liquid chromatography (GLC),
high preasure liquid chromatography (HPLC, RP-HPLC) ``` IMMUNOASSAYS
enzyme immunoassays,
fluorescence immunoassays,
chemiluminescence immunoassays
immunoturbidometry ```

Question 35

How are TDM results interpreted?

Answer 35

```
Comparison with therapeutic concentration ranges
Estimation of individual values of pharmacokinetic parameters in the patient  compartmental modelling  bayesian forecasting ```

Question 36

What is the required data for Bayesian forecasting?

Answer 36

``` 1. Patient – age, height, body weight, diseases, liver and kidneys status, symptoms of toxicity 2. Drug – preparation, mode of administration, dosage schedule, start of traetment, other administered drugs 3. Assay – serum drug levels, date and time of last dose and sample collection ```