Clinical Chemistry Ii Test 3 - Therapeutic Drug Monitoring

Front 1

What are the requirements for a chemical to be considered a drug?

Back 1

It is selective as to its site of action or target
is reversible in its action
produces a therapeutic or toxic effect

Front 2

What are therapeutic drugs?

Back 2

prescribed drugs that produce a healing or curative effect when an undesirable physiological or psychological condition is present.

Front 3

What is standard dosage?

Back 3

the drug amount that is statistically derived form observations in a healthy population

Front 4

What is TBM?

Back 4

Therapeutic Drug Monitoring. Process of measuring (monitoring) the actual concentration of prescribed (therapeutic) drug that is circulating in plasma or serum.

Front 5

Why do we do TDM?

Back 5

Guard against overdose
Check for compliance

Front 6

What is MEC?

Back 6

Minimum effective concentration. lowest concentration of drug that will produce the desired response.

Front 7

What is MTC?

Back 7

Minimum toxic concentration. lowest concentration of drug that will produce an adverse response.

Front 8

What is TI and how do you calculate it?

Back 8

Therapeutic index
TI = MTC / MEC

Front 9

Why is a high TI good?

Back 9

Because a little bit more than therapeutic amount does not have serious side-effects

Asprin TI = 3
therapeutic level 10 mg/dL
toxicity above 30 mg/dL

Front 10

Why are drugs that have a low TI dangerous?

Back 10

Because a little bit more than therapeutic amount has serious side effects.

Lithium TI = 1.1
Therapeutic level 1.0 mmol/L
Toxicity above 1.1 mmol/L

Front 11

If the TI of a drug is below _____, it should be monitored.

Back 11

2

Front 12

What are the patient variables that effect drug levels?

Back 12

Age/sex
Fat/lean
Metabolic rate
Blood volume
Blood circulation
Conc. of albumin and other carriers in blood
Inheritance
Liver and Kidney function
Concurrent administration of other drugs

Front 13

(TPQ) It is important to monitor drug levels in patients for drugs that have a ________ therapeutic index.

Back 13

Low

Front 14

In most cases, plasma concentration ___________ tissue concentration.

Back 14

reflects

Front 15

Usually, __________ or maximum blood concentration of a drug measured in blood occurs ____ - ____ hours after an oral dose

Back 15

Peak, .5 - 2 hours

Front 16

All drugs and body types take the same amount of time to reach peak. (T/F)

Back 16

False. The time to reach peak is dependent upon drug and individual.

Front 17

What is a peak?

Back 17

maximum blood concentration of a drug measured in blood occurs .5 - 2 hours after oral dose

Front 18

What is a trough?

Back 18

Lowest concentration of drug measured in blood is the most reliable indicator of appropriateness of dosage. Measure blood concentration just before (up to 1/2 hours before) the next dose is given.

Front 19

How is Digoxin an exception to the previously discussed rules?

Back 19

Digoxin takes >8 hours to equilibrate with tissue
Peak concentrations in blood does NOT represent effective conc at tissue level.
Blood conc at least 8 hours after dose reflects whether dose is too high, too low, or OK

Treats congestive heart failure

Front 20

At _________ ___________, Peak concentration of drug (shortly after dose) is just below MTC and through conc of drug (just before next dose) is above MEC within the therapeutic window.

Back 20

steady state

Front 21

If constant dose of drug is given once every half life, steady state concentration is achieved after ____-____ doses.

Back 21

5 - 7

Front 22

A larger or smaller dose will approach steady state in 5-7 doses although the level will be higher or lower. (T/F)

Back 22

True.

Front 23

Larger doses will not reach therapeutic level faster. (T/F)

Back 23

False. Larger doses will reach therapeutic level faster, but higher peak may reach toxic levels

Front 24

What is drug disposition?

Back 24

Drug disposition is the route that the drug follows from its initial exposure to body to production of pharmacologic response.

Front 25

What are the four steps of drug disposition?

Back 25

absorption, distribution, biotransformation, and excretion

Front 26

What are three ways that drugs can be administered to the body?

Back 26

Passive transport, active transport, pinocytosis

Front 27

How does the body "digest" drugs?

Back 27

absorbed through intestine
portal vein
liver - First pass effect, metabolizes drugs

Front 28

What is the first pass effect?

Back 28

the drug on its first pass through the liver immediately after absorption is substantially metabolized and eliminated

Front 29

What role does the liver play in drug absorption?

Back 29

drug metabolism, parent drug levels in serum drop - trough happening. Most metabolites are biologically inactive.

Front 30

Sometimes, metabolites have new or enhanced activity. What is an example of a drug who's metabolite is just as active as the parent drug?

Back 30

procainamide metabolite is NAPA (N-acetyl-procain-amide) which is also active. NEED TO MONITOR BOTH

Primidone is metabolite of phenobarbital which is also active. anti epileptic drug. primidone breaks down faster

*KNOW THIS

Front 31

What are five factors that affect absorption?

Back 31

Blood flow to absorption site
Drug formulation
polarity
Molecular weight of the drug
Nature of the membranes to be crossed

Front 32

What are the factors that effect the degree of drug distribution?

Back 32

pH of the physiological environment
degree to which drug binds to plasma proteins

Front 33

Drug ionization is independent of pH environment. (T/F)

Back 33

False, dependent.

Front 34

Which form of the drug is lipid soluble?

Back 34

nonionized

Front 35

What is the HH equation for weakly basic drugs?

Back 35

pH = pK + log (nonionized form / ionized form)

Front 36

What is the HH equation for weakly acidic drugs?

Back 36

pH = pK + log (ionized form / nonionized form)

Front 37

What is true when pH = pK?

Back 37

ionized and nonionized drug is present in equal amounts

Front 38

What is the form of an acidic drug if pH is greater than pK?

Back 38

ionizable

Front 39

What is the form of an acid drug if pH is less than pK?

Back 39

nonionizable

Front 40

What is the form of a basic drug if pH is greater than pK?

Back 40

nonionizable

Front 41

What is the form of a basic drug if pH is less than pK?

Back 41

ionizable

Front 42

Basic drugs are absorbed easier than acidic drugs. (T/F)

Back 42

False. Acidic drugs are absorbed easier.

Front 43

Water soluble drugs are transported easily in circulation, insoluble (lipid soluble) drugs combine with which carrier proteins?

Back 43

Acidic drugs attach to albumin
Basic drugs attach to alpha-1-glycoprotein

Front 44

A change in protein concentration will effect the total drug concentration. (T/F)

Back 44

False. protein concentration and drug concentration is independent.

Front 45

Only free (non-protein-bound) drug attaches to target organ receptors and causes the pharmacological effect. (T/F)

Back 45

True.

Front 46

What disorder would cause problems with free vs. total drug concentrations?

Back 46

liver disorders would cause a decrease in carrier proteins.

Front 47

What is biotransformation?

Back 47

Metabolism of a drug. liver is major site.

Front 48

In what three ways may metabolism effect the drug?

Back 48

increased activity (activation)
Decreased activity (inactivation or detoxification)
No effect on activity (most common)

Front 49

What is phase 1 of biotransformation?

Back 49

When reactions metabolize lipophilic drugs to more polar forms to facilitate renal excretion. accoplished by redox reactions such as hydroxylation, deamination, sulfoxidation, etc.

Front 50

Is the product that comes out of phase 1 active or inactive?

Back 50

Active

Front 51

What is phase 2 of biotransformation?

Back 51

Polar drugs, or drugs rendered polar by phase 1 proceed to go through reactions involving conjugation of drugs with compounds such as glutathione, glucuronic acid, sulfate and phosphate. conjugates produced are water soluble and can be excreted by the kidneys.

Front 52

Which drugs go though phase 1 and 2?

Back 52

lipid drugs. Polar drugs start at phase 2.

Front 53

Most drugs are metabolized according to zero or first order kinetics

Back 53

First order. The rate of metabolism is dependent on concentration of the substrate (drug).As long as the conc of drug is within the capacity of the detox/conjugation reactions, then removal rate is 1st order (as compared to drug conc)

Front 54

If drug conc exceeds these capacities then removal rate becomes zero order (independent of conc) with respect. (T/F)

Back 54

True

Front 55

How are most water-soluble drugs and their metabolites excreted?

Back 55

Through the Kidney

Front 56

How are lipid soluble drugs excreted?

Back 56

in bile

Front 57

Acid urine facilitates elimination of basic drugs and alkaline urine facilitates elimination of acidic drugs.
(T/F)

Back 57

True.

Front 58

Decreased kidney function may lead to decreased excretion and increased blood levels of drug. (T/F)

Back 58

True.

Front 59

What two factors determine the clearance rate of a drug?

Back 59

volume of distribution and half-life

Front 60

What is volume of distribution?

Back 60

Vd = (dose administered) / immediate plasma conc

Front 61

How do you calculate K elimination?

Back 61

t(1/2) = (0.693) / K elimination

Front 62

How do you calculate clearance?

Back 62

Clearance = Vd x K elim

Front 63

(TPQ) Given that a drug has a half life of 10 hours and is administered once every half life, how long will it take to reach steady state?

Back 63

50 hours

Front 64

(TPQ) ___________ is a situation where the amount of drug administered is equal to the amount of drug excreted from the body between two doses.

Back 64

Steady state

Front 65

(TPQ) Kinetic process where rate of change of drug concentration is dependant upon the drug concentration is know as:

Back 65

First order kinetics

Front 66

Which of the following statements regarding drug half life is true?

Back 66

Half life is equal to time required to reduce drug level by 50%

Front 67

How is therapeutic drug monitoring performed?

Back 67

Measured using EIA, FPIA, gas chromatography or HPLC. Calorimetric methods are also being used.

Front 68

What is the specimen of choice for TDM?

Back 68

Serum

Front 69

Which is the only acceptable anticoagulant to use in TDM and why?

Back 69

Heparin because of its neutral pH

Front 70

What is Digoxin?

Back 70

CARDIOACTIVE DRUG
Major cardiac glycoside derived from the digitalis plant.
It improves cardiac contractility by altering force of contraction through its effect on Na+ - K+ - ATPase pump in heart muscle, affecting sodium, potassium and calcium transport in the heart.
Treats CHF patients
Rate of distribution is slow – peaks in 6 to 10 hours
Toxicity affects many organ and cell types and produces symptoms of nausea, rapid heart rate and visual impairment.
Lipophilic - goes through phase 1 and 2

Front 71

What is Lidocaine?

Back 71

CARDIOACTIVE DRUG
Antiarrythmic drug – treats irregular heartbeat that produces inappropriate ventricular contraction or tachycardia
Treats AMI patients
Binds to alpha1-acid glycoprotein and is almost completely metabolized in liver producing two active metabolites that can be measured in blood
Toxicity produces depression, disorientation, seizures, severe decrease in blood pressure and possible respiratory arrest

Front 72

What is Procainamide?

Back 72

CARDIOACTIVE DRUG
Antiarryhthmic drug
Metabolized in liver to form an active metabolite, NAPA, that produces the same effect as the parent drug
Serum levels for both drugs must be analyzed for TDM
Toxicity results in bradycardia (slow heartbeat), nausea and arrhythmia

Front 73

What is Quinidine?

Back 73

CARDIOACTIVE DRUG
Antiarrythmic myocardial depressant that lowers the heart’s ability to conduct current.
Metabolized in liver to produce several active metabolites, including 3-hydroxyquinidine.
Toxic effects are nausea, vomiting and abdominal discomfort

Front 74

What is Aminoglycosides?

Back 74

ANTIBIOTIC
A group of chemically related antibiotics that treat gram negative bacterial infections –for bacteria that are resistant to less toxic drugs
Examples are gentamicin, tobramycin, amikacin and kanamycin

Front 75

What is Vancomycin?

Back 75

ANTIBIOTIC
Glycopeptide antibiotic, effective against gram-positive cocci and bacilli

Front 76

What are some examples of Antiepileptic drugs?

Back 76

ANTIEPILEPTIC
Phenobarbital
Phenytoin (Dilantin)
Valproic acid
Carbamazepine (Tegretol)
Ethosuximide

Front 77

What are some examples of psychoactive drugs?

Back 77

PSYCHOACTIVE
Lithium
Tricyclic antidepressants (TCA)
Ex: doxepin, imipramine

Front 78

What is an example of a bronchodilator?

Back 78

BRONCHODILATOR
Theophylline

Front 79

What are some examples of immunosuppressive drugs?

Back 79

IMMUNOSUPPRESSIVE
Cyclosporine
Tacrolimus