(8) TDM & Toxicology Flashcards by Kyle Snyder

What is therapeutic drug monitoring?

A process of determining the quantity of a therapeutic drug required to produce a predetermined desirable effect.

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Define the following term:

Half-life.

Time required for the concentration of a drug to be decreased by half.

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Define the following term:

Steady State.

Reached when the amount of drug in the dose given is sufficient only to replace the amount of drug eliminated since the last dose.

Can be measured after 5 drug half-lives because then the blood will have reached 97% of the steady state.

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Define the following term:

Compartment

Specific place in the body where a drug is present (e.g. plasma, tissue).

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Define the following term:

First Order Kinetics

Rate of metabolism is dependent on the concentration of the substrate.

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Define the following term:

Peak Concentration

Highest concentration of drug is measured in the blood.
Collection time varies based on the absorption of the drug.

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Define the following term:

Therapeutic Range

Concentrations between the minimum effective concentration and the minimum toxic concentration.

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Define the following term:

Trough Concentration

Lowest concentration of a drug measured in the blood.
Collection is usually immediately prior to the administration of the next dose.

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Name the five-step process that takes place when a therapeutic agent is administered to a patient.

Liberation - release of the drug
Absorption - drug taken into the body enters the blood
Distribution - drug must be translocated to its site of action
Metabolism (biotransformation) - occurs mainly in the liver. Unmetabolized drug is a parent compound, products of metabolism are metabolites
Excretion - if drug is water-soluble or can be rendered water soluble through metabolism, it is eliminated through the urine

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What is the normal therapeutic range and the classification of the following drug:

Theophylline

10 - 20 ug/mL
Bronchodilator

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What is the normal therapeutic range and the classification of the following drug:

Quinidine

2 - 5 ug/mL
Anti-arrhythmic

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What is the normal therapeutic range and the classification of the following drug:

Acetaminophen

10 - 30 ug/mL
Analgesic

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What is the normal therapeutic range and the classification of the following drug:

Phenytoin

10 - 20 ug/mL
Anticonvulsants

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What is the normal therapeutic range and the classification of the following drug:

Lithium

0.5 - 1.5 mEq/L
Psychotropic

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What is the normal therapeutic range and the classification of the following drug:

Gentamicin

Peak: 5.8 - ug/mL
Trough: 1 - 2 ug/mL

Aminoglycosides

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What is the normal therapeutic range and the classification of the following drug:

Digoxin

0.8 - 2.0 ng/mL
Anti-arrhythmics

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What is the normal therapeutic range and the classification of the following drug:

Phenobarbital

15 - 40 ug/mL
Anticonvulsants

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What is the normal therapeutic range and the classification of the following drug:

Primidone

5 - 12 ug/mL
Anticonvulsants

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What is the normal therapeutic range and the classification of the following drug:

Tobramycin

Peak: 5 - 8 ug/mL
Trough: 1 - 12 ug/mL

Aminoglycosides

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What is the normal therapeutic range and the classification of the following drug:

Procainamide

4 - 10 ug/mL
Anti-arrhythmics

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What is the normal therapeutic range and the classification of the following drug:

Carbamazepine

4 - 12 ug/mL
Anticonvulsants

What is the normal therapeutic range and the classification of the following drug:

Valproic Acid

50 - 100 ug/mL
Anticonvulsants

What plant is digoxin derived from?

The foxglove plant (Digitalis lanata or purpurea)

What are the toxic effects of digoxin?

It effects cellular potassium transport, resulting in bradycardia, followed by arrhythmia, coma, and death.

Why do we test Procainamide/NAPA drug levels on a patient?

NAPA has anti-arrhythmic activity similar to procainamide; often measured together.

# Define the following term: Acute Toxicity

Single short-term exposure to the toxic effects of a substance in a dose sufficient to cause a toxic effect. An example would be an overdose of sleeping pills taken in bulk.

# Define the following term: Chronic Toxicity

Involves repeated exposure to a substance causing toxic effects over an extended period of time. A single dose does not have a toxic effect but an accumulation of substance has effect. An example would be slow poisoning.

Contrast TD₅₀ and LD₅₀ of a toxic substance.

**TD** is the dose predicted to produce a toxic response in 50% of the population, causing a pathogenic response but not death. **LD** is the dose predicted to produce death in 50% of the population.

**Describe the toxic effect of the following:** Acetaminophen

* Severe hepatoxicity due to minimal renal filtration * Free radical formation leading to cell death * Toxic effects seen 3 - 5 days following overdose * Cleared rapidly from serum, so overdose may be hard to detect * Initial symptoms are vague

**Describe the toxic effect of the following:** Salicylate

* Metabolic acidosis due to acid ingestion * Respiratory alkalosis due to hyperventilation

What is the principle of the salicylate testing procedure?

Salicylate acid + Fe²⁺ ⇢ Violet color complex | (not very specific, but low false negatives)

What is the trough level of salicylates?

\<100 mg/mL

What is the toxic levels of salicylates?

\>100 ug/mL

Discuss the “spot test” for carbon monoxide poisoning.

Carboxyhemoglobin is bright cherry read, giving the EDTA specimen a characteristic color. A 1:20 dilution of whole blood is created. 5 mL of the diluted specimen is added to 5 mL of 40% NaOH. Persistence of a pink solution is indicative of a carboxyhemoglobin level of 20% or greater.

**What is the pharmacological classification of the following drugs:** Cocaine

Stimulant

**What is the pharmacological classification of the following drugs:** Heroin

Narcotic

**What is the pharmacological classification of the following drugs:** Methadone

Narcotic

**What is the pharmacological classification of the following drugs:** Diazepam

Depressant

**What is the pharmacological classification of the following drugs:** Amphetamine

Stimulant

**What is the pharmacological classification of the following drugs:** Codeine

Narcotic

**What is the pharmacological classification of the following drugs:** Meperidine

Narcotic

**What is the pharmacological classification of the following drugs:** Methamphetamine

Stimulant

**What is the pharmacological classification of the following drugs:** Morphine

Narcotic

**What is the pharmacological classification of the following drugs:** Ethanol

Depressant

**List the principle urinary metabolites of the following drug:** Cocaine

Ergoninemethyl ester, benzoylecgonine, ecgomine

**List the principle urinary metabolites of the following drug:** Heroin

6-acetylmorphine, morphine, morphine glucoronide

**List the principle urinary metabolites of the following drug:** Methadone

2-ethlidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine, 2-ethyl, 5-methyl-3, 3-diphenylpyrroline, methadol, normethadol, conjugates

**List the principle urinary metabolites of the following drug:** Diazepam

Nordiazepam, oxazepam, 3-hydroxydiazepam, glucuronide conjugates.

**List the principle urinary metabolites of the following drug:** Amphetamine

Benzoic acid, p-hydroxyamphetamine, p-hydroxynorephedrine, phenylacetone.

**List the principle urinary metabolites of the following drug:** Codeine

Morphine, norcodeine, conjugates

**List the principle urinary metabolites of the following drug:** Meperidine

Normeperidine, meperidin (Demerol)