Therapeutic Drug Monitoring

Front 1

A chemical is considered a drug if:
1.
2.
3.

Back 1

1.It is selective as to its site of action or target.
2. Is reversible as to its site of action or target.
3. It produces a therapeutic or toxic effect.

Front 2

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

Back 2

therapeutic drug

Front 3

is statistically derived from observations in a healthy population (phamacokinetics)

Back 3

standard dosage (amount administered)

Front 4

process of measuring (monitoring) the actual concentration of prescribed (therapeutic) drug that is circulating in plasma or serum.

Back 4

TDM: Therapeutic drug monitoring

Front 5

why TDM?
-
-

Back 5

-guard against overdose or underdose
-check for compliance

Front 6

lowest concentration of drug that will produce the desired response.

Back 6

Minimum effective concentration (MEC)

Front 7

lowest concentration of drug that will produce an adverse response.

Back 7

Minimum toxic concentration (MTC)

Front 8

Therapeutic index TI =

Back 8

MTC/MEC

Front 9

Patient variables that effect drug levels

Back 9

-age/sex
-fat/lean
-metabolic rate
-blood volume
-blood circulation
-concentration of albumin & other carriers in blood
-inheritance
-liver and kidney function
-concurrent administration of other drugs

Front 10

in most cases _______ reflects tissue concentration.

Back 10

plasma concentration

Front 11

usually, ___ or maximum blood concentration of a drug measure in blood occurs 1/2 -2 hrs after an oral dose. bur each drug and each individual has different length of time to reach ____. measured ____ concentration is an approximation.

Back 11

Peak

Front 12

_____ or 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 hour before) the next dose is given.

Back 12

Trough

Front 13

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

Back 13

drug disposition

Front 14

at _______, peak concentration of drug (shortly after dose) is below MTC and trough conc. of drug (just before next dose) is above MEC within the therapeutic window.

Back 14

steady rate

Front 15

If constant dose of drug is given once every half life (t1/2), steady state concentration is achieved after _____ doses. A larger or smaller dose will still approach steady state in ___ doses although the level will be higher or lower. larger dose will reach therapeutic level faster, but higher peak may reach toxic levels.

Back 15

5-7

Front 16

drug disposition can be divided into 4 steps:
1.
2.
3.
4.

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Absorption
Distribution
Biotransformation
Excretion

Front 17

factors that affect absorption

Back 17

1. blood flow to absorption
2. drug formulation - unstable at pH of GI tract
3. polarity- drug interacts with substances in GI to form insoluble product
4. Molecular weight of the drug
5..nature of the membrane to be crossed- contact with membrane is shortened due to diarrhea

Front 18

factors that effect degree of distribution are:
-
-

Back 18

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

Front 19

depending on the pH of the environment, drugs exist in both ____ and ___ forms.

Back 19

ionized and nonionized

Front 20

only _____ drugs are lipid soluble.

Back 20

nonionized

Front 21

describes proportion of drug in the absorbable nonionized form.

Back 21

HH equation

Front 22

are transported easily in circulation, insoluble drugs combine with carrier proteins.

Back 22

water-soluble

Front 23

acidic drugs attach to ____.

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albumin

Front 24

basic drugs attach to ______.

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alpha-1-glycoprotein

Front 25

change in protein concentration will _____ effect the total drug concentration.

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not effect

Front 26

only _____ drug attaches to target organ receptors and causes the pharmacological effect. measurement of free vs. total drug concentrations.

Back 26

free (non-protein-bound)

Front 27

major site of drug biotransformation is _____. Minor site include kidneys, brain, lungs, skin and GI tract.

Back 27

liver

Front 28

There are two major metabolic pathways:
-
-

Back 28

-phase 1
-phase 2

Front 29

metabolism may effect the drug in one of three ways:
-
-
-

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-increase activity (activation)
-decrease activity (Inactivation or detoxification)
-no effect on activity

Front 30

Most drugs are metabolized according to ________.

Back 30

first order kinetics

Front 31

rate of metabolism is dependent on concentration of the substrate (drug).

Back 31

first order kinetics

Front 32

as long as the conc. of drug is withing the capacity of the detox/conjugation reactions, then removal rate is _____.

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1st order (proportional to drug conc.)

Front 33

if drug conc. exceeds these capacities then removal rate becomes ______ with respect to drug.

Back 33

zero order (independent of conc.)

Front 34

water soluable drugs and their metabolites are mainly excreted though the ____ (some drugs especially lipid-soluble ones are excreted in bile).

Back 34

kidney

Front 35

facilitates elimination of basic drugs and alkaline urine facilitates elimination of acidic drugs.

Back 35

acid urine

Front 36

may lead to decreased excretion and increased blood levels of drug.

Back 36

decreased kidney

Front 37

clearance rate of a drug depends on _____ and _____.

Back 37

-volume of distribution (Vd)
-half-life (t1/2)

Front 38

Vd=

Back 38

(dose administered)/immediate plasma concentration

Front 39

t1/2=

Back 39

(0.693)/K^elimination

Front 40

clearance rate of drugs =

Back 40

Vd X K^elimination

Front 41

Calculate Vd from _______ and _____.

Back 41

-size of dose (known)
-plasma conc. (measured)

Front 42

calculate K^elimination by determining _____.

Back 42

t(1/2)

Front 43

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

Back 43

TDM

Front 44

specimen of choice for TDM. certain drugs have a tendency to be absorbed in gel of serum separator tubes.

Back 44

serum

Front 45

is the only acceptable anticoagulant for plasma. urine metabolites are meausred in some cases.determinations should be made after steady rate has been achieved.

Back 45

heparin

Front 46

major cardiac derived from the digitalis plant.

Back 46

digoxin

Front 47

it improves cardiac contractility by altering force of contaction to its effect on Na+- K+ - ATPase pump in heart muscle, affecting sodium, potassium, and calcium transport in the heart.

Back 47

digoxin

Front 48

treats CHF patients.

Back 48

digoxin

Front 49

rate of distribution is slow- peaks in 6 to 10 hrs.

Back 49

digoxin

Front 50

toxicity affects many organ and cell types and produces symptoms of nausea, rapid heart rate and visual impairment.

Back 50

digoxin

Front 51

antiarrythmic drug- treats irregular heartbeat that produces inappropriate ventricular contraction or tachycardia. Treats AMI patients.

Back 51

lidocaine

Front 52

binds to alpha-1-acid glycoprotein and is almost completely metabolized in liver producing two active metabolites that can be measured in blood.

Back 52

lidocaine

Front 53

toxicity produces depression, disorientation, seizures, severe decrease in blood pressure and possible respiratory arrest.

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lidocaine

Front 54

antiarryhthmic drug. matabolized in the 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.

Back 54

procainamide

Front 55

antiarrythmic myocardial depressant that lowers the heart's ability to conduct current.

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quinidine

Front 56

metabolized in the liver to produce several active metabolites, including 3-hydroxyquinidine.

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quinidine

Front 57

toxic effects are nausea, vomiting, and abdominal discomfort.

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quinidine

Front 58

a group of chemically related antibiotics that treat gram negative bacterial infections- for bacteria that are resistant to less toxic drugs.

Back 58

aminoglycosides

Front 59

Examples are gentamicin, tobramycin, amikacin, and kanamycin,

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aminoglycosides

Front 60

glycopeptide antibiotic, effective against gram-positive cocci and bacilli.

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vancomycin

Front 61

antiepileptic drugs
-
-
-
-

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-phenonbarbital
-phenytoin (dilantin)
-valproic acid
-carbamazepine (tegretol)
-ethosuximide

Front 62

examples of psychoactive drugs:
-
-

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-lithium
-tricyclic antidepressants (TCA)

Front 63

example of brochodilators:
-

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theophyline

Front 64

-cyclosporine
-tacrolimus

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examples of immunosuppresive drugs:

Front 65

-doxepin
-imipramine

Back 65

examples of TCA (tricycyclic depressants)

Front 66

antiarryhthmic drug. matabolized in the 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.

Back 66

procainamide

Front 67

antiarrythmic myocardial depressant that lowers the heart's ability to conduct current.

Back 67

quinidine

Front 68

metabolized in the liver to produce several active metabolites, including 3-hydroxyquinidine.

Back 68

quinidine

Front 69

toxic effects are nausea, vomiting, and abdominal discomfort.

Back 69

quinidine

Front 70

a group of chemically related antibiotics that treat gram negative bacterial infections- for bacteria that are resistant to less toxic drugs.

Back 70

aminoglycosides

Front 71

Examples are gentamicin, tobramycin, amikacin, and kanamycin,

Back 71

aminoglycosides

Front 72

glycopeptide antibiotic, effective against gram-positive cocci and bacilli.

Back 72

vancomycin

Front 73

-phenonbarbital
-phenytoin (dilantin)
-valproic acid
-carbamazepine (tegretol)
-ethosuximide

Back 73

antiepileptic drugs

Front 74

-lithium
-tricyclic antidepressants (TCA)

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examples of psychoactive drugs:

Front 75

theophyline

Back 75

example of brochodilators:

Front 76

therapeutic level is 10mg/dL
toxicity level is 30mg/dL
ex. asprin TI=3

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high TI

Front 77

therapeutic level is 1.0 mmol/L
toxicity above 1.1 mmol/L
ex. lithium TI=1.1

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low TI

Front 78

is good: a little bit more than therapeutic amount does not have serious side effects.

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high TI

Front 79

is dangerous: a little bit more than therapeutic amount has serious side effects.

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low TI

Front 80

used to treat congestive heart failure. takes > 8hrs to equilibrate with tissues. peak concentration in blood does NOT represent effective conc. at tissue level. blood conc at least 8hrs after dose reflects whether dose is too high, too low or OK.

Back 80

Digoxin

Front 81

Absorption of oral drug.
-Must pass through _____ into blood stream.
-Intestinal blood goes through _____ to liver which is in charge of removing xenobiotics.
-in liver, some drugs undergo _____- the drug on its first pass through liver immediately after absorption is substantially metabolized and eliminated.

Back 81

-intestinal lining
-portal vein
-first pass effect

Front 82

Absorption of oral drug.
Blood concentration of parent drug is decreased due to the production of _____ that are not biologically active.

Back 82

-metabolites

Front 83

Absorption of oral drug.
Sometimes the metabolites have new or _____ activity. ex. procainamide metabolite is NAPA (N-acetyl-procain-amide) which is also active and primidone is metabolite or phenobarbital which is also active.

Back 83

enhanced

Front 84

when pH=pK, both ionized and nonionized drug is present in ____ amounts.

Back 84

equal

Front 85

basic drugs are ____ absorbed as easily as acidic drugs.

Back 85

NOT

Front 86

for acidic drugs:
-if pH>pK, drug mainly exists in ____ form.
-if pH<pK drug exists in _____ form.

Back 86

-ionizable
-nonionizable

Front 87

for basic drugs:
-if pH>pK drug exists in ____ form.
-if pH<pK drug mainly exists in ____ form.

Back 87

-nonionizable
-ionizable

Front 88

Reactions metabolize to lipophilic drugs to more polar forms to facilitate renal excretion.

Back 88

phase 1

Front 89

Accomplished by oxidative or reductive processes such as hydroxylation, deamination, sulfoxidation etc.

Back 89

phase 1

Front 90

cytochrome P-450 enzymes on microsomal membranes (smooth ER) undergo redox reactions that inactivate(detoxify) drugs. metabolic products are active.

Back 90

phase 1

Front 91

polar drugs or drugs rendered polar by phase 1 undergo phase 2 reactions.

Back 91

phase 2

Front 92

reactions involve conjugation of drugs with compounds such as gluthathione, glucuronic acid, sulfate, and phosphate. conjugates produced are water soluable and can be excreted by the kidneys.

Back 92

phase 2