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Mercy CLS 5: Chemistry > 21) Therapeutic drug monitoring > Flashcards

21) Therapeutic drug monitoring Flashcards

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1
Q

4 parts of pharmacokinetics

A

Absorption
Distribution
Metabolism/Biotransformation
Excretion

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2
Q

Drugs are absorbed from the gastrointestinal tract by either ——– or ———-.

A

passive diffusion
active transport

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3
Q

how does pH affect drug absorption

A

A drug that is uncharged tends to pass through membranes more readily than a charged drug.

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4
Q

Indicates the fractional extent to which a dose of drug reaches its site of action.

A

bioavailability

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5
Q

Metabolism or biliary excretion may occur before it reaches the systemic circulation.

A

first-pass effect

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6
Q

PO disadvantages

A

Limited absorption because of solubility, vomiting, destruction by digestive enzymes, and low gastric pH that may inactivate the drug

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7
Q

counteract disadvantages of PO administration

A

controlled-release drugs

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8
Q

how can first-pass effect work on parenteral meds?

A
  • Partitioning into the lipids located in liver tissue
  • Filtration
  • Elimination as a volatile substance
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9
Q

aqueous solutions or specialized depot preparations in ethylene glycol or peanut oil

A

IM meds

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10
Q

50% of the drug absorbed will bypass the liver; avoids first-pass effect

A

rectal meds

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11
Q

topical anesthetics

A

Tetracaine and lidocaine

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12
Q

applied to eye to induce vomiting

A

atropine

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13
Q

Initially, most of the drug goes to the…

Then, to…

A

liver, kidneys, brain, and other well-perfused organs

muscles, skin, fat, and viscera

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14
Q

tissue distribution of a drug depends on…

A
  • Partitioning of drug between blood and the particular tissue
  • Lipid solubility
  • pH gradients between intracellular and extracellular fluid
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15
Q

2 forms of drug circulating

A

bound and unbound

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16
Q

albumin alpha 1-acid glycoprotein

A

plasma protein that binds drugs

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17
Q

how does hypoalbuminemia affect drug levels?

A

protein binding is reduced, ↑ free drug level

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18
Q

Metabolism of a drug into more hydrophilic metabolites is essential for…

A
  • Elimination of these compounds from the body
  • Cessation of their biological activity
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19
Q

Reactions generate more polar, inactive metabolites that are readily excreted from the body.

A

biotransformation of drugs

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20
Q

2 types of biotransformation

A

Phase I (functionalization)
Phase II (conjugation)

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21
Q

phase I biotransformation reactions

A

Hydrolysis
Reduction
Oxidation

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22
Q

may be rapidly excreted into the urine, or they can react with endogenous compounds to form highly water-soluble conjugates

A

Products of phase I reactions

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23
Q

phase II biotranformation reactions

A

Leads to formation of covalent linkage between a functional group on the parent compound with an endogenously derived:

Glucuronic acid
Sulfate
Glutathione
Amino acid
Or acetate group

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24
Q

concentration of drug < MM constant

A

1st order kinetics
rate of drug metabolism is directly proportional to the concentration of free drug

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25
Q

concentration of drug > MM constant

A

zero-order kinetics
rate of metabolism remains constant over time

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26
Q

drugs that lead to zero order kinetics

A

aspirin
ethanol

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27
Q

Enzymes involved in biotransformation are found mainly in the ——-

A

liver

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28
Q

biotransformation phases location

A

Phase I: Endoplasmic reticulum
Phase II: Cytosol

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29
Q

Major enzyme system that metabolizes drugs

A

cytochrome P450 (CYP) monooxygenase system

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30
Q

most important organs for excretion of drugs and their metabolites

A

kidneys

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31
Q

——- compounds are more efficiently excreted than ——- ones.

A

polar
nonpolar

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32
Q

Measure of the body’s efficiency in eliminating drugs

A

Clearance (CL)

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33
Q

clearance (CL)

A

amount of renal plasma flow multiplied by the extraction ratio

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34
Q

extraction ratio

A

C2/C1

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35
Q

a function of clearance (mL/ min) times plasma drug concentration (mg/mL)

A

Excretion rate (mg/min)

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36
Q

Sum of the clearances from the various body organs that metabolize and eliminate drugs

A

total body clearance

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37
Q

CLtotal =

A

CL hepatic + CL renal + CL pulmonary + CL other

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38
Q

Clearance of a drug indicates…

A

the volume of biological fluid from which a drug would have to be completely removed to account for elimination

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39
Q

Measure of the apparent space the body has available to contain the drug

A

volume of distribution

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40
Q

volume of distribution (Vd) =

A

D/C

units: L

C = plasma conc; D = total drug in body

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41
Q

Takes —— half-lives to achieve steady state

A

5-7

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42
Q

A parameter that changes as a function of both clearance and volume of distribution

A

elimination half-life

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43
Q

elimination half-life =

A

0.693(Vd/CL)

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44
Q

conditions that alter half-life of drug

A
  • Decreased renal blood flow
  • Addition of a second drug that may displace the first drug from its carrier protein
  • Decrease in metabolism because of hepatic insufficiency
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45
Q

Point when the total amount of drug in a human does not change over multiple loading dose intervals.

A

steady state

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46
Q

dosing rate (mg/min) =

A

CL(mL/min) x Css (mg/mL)

Css = the concentration at steady state

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47
Q

MEC
MTC

A

minimum effective conc.
minimim toxic conc.

between them –> therapeutic range

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48
Q

C maxss

A

minimum steady-state conc

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49
Q

Fraction of drug dose reaching the systemic circulation following administration by any route.

A

bioavailability

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50
Q

used to maintain the steady-state concentration of the drug associated within the therapeutic window

A

maintenance dose

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51
Q

Usually results in the attainment of target drug concentration in a shorter period of time

A

loading dose

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52
Q

Occurs more frequently in long-term treatments of diseases antihypertensive, antiretroviral, and anticonvulsant drugs

A

pt non-compliance

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53
Q

Fundamental action(s) of drugs

A

pharmacodynamics

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54
Q

The formation of a ——– leads to a biologic response or effect.

A

drug-receptor complex

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55
Q

The probability that a drug molecule will interact with its receptor to form the drug-receptor complex

A

drug affinity

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56
Q

The measurement of biological effectiveness of a drug-receptor complex

A

intrinsic affinity

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57
Q

Least amount of drug required to produce the maximum effect

A

potency

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58
Q

Measure of a drug’s ability to produce the desired therapeutic effect

A

efficacy

59
Q

drug-induced complications

A

Drug allergies, blood dyscrasias, hepatotoxicity and nephrotoxicity, teratogenic effects, behavioral toxicity, drug dependence, and drug addictions

60
Q

specimen of choice for the majority of therapeutic drugs measured in the clinical laboratory

A

serum
plasma is also OK
gel tubes are not preferred

61
Q

WB can be used to measure…

A

Cyclosporine & Tacrolimus

62
Q

Amikacin, Gentamicin, and Tobramycin

A

aminoglycosides antibiotics

63
Q

Tissue concentrations are low, although high concentrations are found in the renal cortex and in the endolymph and perilymph of the inner ear

A

aminoglycosides

64
Q

Broad spectrum against GN including most strains of Serratia, Proteus, and Pseudomonas aeruginosa

A

Amikacin

65
Q

Active against nearly all strains of Klebsiella, Enterobacter, and Escherichia coli that are usually resistant to gentamicin and tobramycin

A

Amikacin

66
Q

Often administered in combination with penicillin to treat serious gram-negative microbial infections

A

Gentamicin

67
Q

Superior for treatment of P. aeruginosa

A

tobramycin

68
Q

Shows poor activity in combination with penicillin against many strains of Enterococci

A

tobramycin

69
Q

Most strains of Enterococcus faecium are highly resistant to…

A

tobramycin

70
Q

Treatment of severe infections caused by gram-positive bacteria in patients who cannot receive or who have failed to respond to penicillin and cephalosporins

A

vancomycin

71
Q

Minimally removed by hemodialysis or peritoneal dialysis, but substantially removed by hemofiltration

A

vancomycin

72
Q

Ototoxicity and nephrotoxicity are the most serious adverse effects of parenteral ———– therapy.

A

vancomycin

73
Q

Hyaline or granular casts in urine

A

vancomycin toxicity

74
Q

combination of drugs often used to treat seizure

A

Phenobarbital and phenytoin

75
Q

May be used to assist patients who are in the process of drug withdrawal from persistent use of barbiturate or non-barbiturate hypnotics

A

phenobarbital

76
Q

Severe tiredness/dizziness
Inability to wake up
Very slow breathing rate

A

phenobarbital toxicity

77
Q

Not recommended for the solo treatment of pure absence (petit mal) seizures because it may increase the frequency

A

phenytoin

78
Q

5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH)

A

metabolite of phenytoin

79
Q

valproic acid

A

antiepileptic

80
Q

used for migraine headaches, with or without aura

A

Divalproex sodium
(valproic acid)

81
Q

Effects of the drug may be related in part to increased brain concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)

A

valproic acid

82
Q

Drowsiness
Coma
Irregular/slow heartbeat

A

valproic acid toxicity

83
Q

carbamazepine

A

antiepileptic

84
Q

Used both as an anticonvulsant and for the relief of pain associated with trigeminal neuralgia (tic douloureux)

A

carbamazepine

85
Q

other uses of carbamazepine

A
  • Used in the symptomatic management of the acute phase of schizophrenia
  • Used for management of aggression or uncontrolled rage outbursts or loss of control (dyscontrol)
  • Used for alcohol withdrawal syndrome
  • Used to relieve neurogenic pain
  • Used for antidiuretic effects in the management of neurohypophyseal diabetes insipidus
86
Q

Slowed breathing, loss of consciousness, muscle twitching, uncontrolled movements, and very fast heartbeat

A

carbamazepine toxicity

87
Q

Generally considered the drug of choice in the management of absence seizures

A

ethosuximide

88
Q

ethosuxamide

A

antiepileptic

89
Q

primidone

A

antiepileptic

90
Q

Structural analog of phenobarbital

A

primidone

91
Q

Used mainly in the prophylactic management of partial seizures with complex symptomatology (psychomotor seizures)

A

primidone

92
Q

Slowly excreted in urine as phenylethylmalonamide (PEMA), phenobarbital, and p-hydroxy phenobarbital

A

primidone

93
Q

false positive phenobarbital result

A

pt also on primidone

94
Q

topiramate

A

antiepileptic

95
Q

Enhances postsynaptic gamma-aminobutyric acid (GABA-receptor) currents and also limits activation of the AMPA-kainite-subtypes(s) of glutamate receptor

A

topiramate

96
Q

dizziness, headache, diplopia, nausea, somnolence, and skin rash

A

topiramate toxicity

97
Q

Lamotrigine

A

antiepileptic

98
Q
  • Partial seizures in adults and children
  • Primary generalized tonic-clonic seizures
  • Myoclonic seizures of juvenile myoclonic epilepsy
A

Levetiracetam (Keppra)

99
Q

Levetiracetam (Keppra)

A

antiepileptic

100
Q

decreased hematocrit and RBC count, decreased neutrophil count, somnolence, asthenia, and dizziness

A

Levetiracetam (Keppra) toxicity

101
Q

———– contains a sugar or monosaccharide moiety within its structure. This is not true of most anti-epileptic drugs.

A

Topiramate

102
Q

methotrexate

A

antineoplastic

103
Q

Antifolate, or folic acid analog, that inhibits dihydrofolate reductase

A

methotrexate

104
Q

management of lymphoblastic leukemia in children

leukemic meningitis in children & adults

A

methotrexate

105
Q

Intrathecal(spinal cord) administration is used for treatment or prophylaxis

A

methotrexate

106
Q

Resistant if used alone for uterine choriocarcinoma and testicular choriocarcinomas

A

methotrexate

107
Q

High affinity for dihydrofolate reductase and prevents the formation of tetrahydrofolate

A

methotrexate

108
Q

main methotrexate toxicity

A

renal failure

109
Q

Leucovorin

A

used to counteract methotrexate

110
Q

Alopecia, dermatitis, interstitial pneumonitis, nephrotoxicity, defective oogenesis or spermatogenesis, and teratogenesis

A

methotrexate toxicity

111
Q

lithium

A

antipsychotic

112
Q

very narrow therapeutic window

A

lithium

113
Q

important tube consideration for drug level

A

lithium – no lithium heparin tube

114
Q
  • Inhaled glucocorticoids
  • ß-adrenergic receptor agonists
  • Leukotriene-modifying drugs
A

used to tx asthma

115
Q

Theophylline

A

bronchodilator

116
Q

cardiac glycoside

A

digoxin

117
Q

Indirect actions on the cardiovascular system through the influence on the autonomic nervous system

A

digoxin

118
Q

Spironolactone (synthetic steroid- diuretic)

A

causes false positive digoxin

119
Q

hyper/hypokalemia

A

digoxin toxicity

120
Q

lidocaine

A

cardioactive drug
anesthetic

121
Q
  • For acute treatment of ventricular arrhythmias that occur following myocardial infarction
  • During cardiac manipulative procedures such as cardiac surgery or cardiac catheterization
A

lidocaine

122
Q

Class I (membrane-stabilizing) antiarrhythmic agent

A

lidocaine

123
Q

procainamide

A

cardioactive drug
anesthetic

124
Q

major metabolite is N-acetyl procainamide (NAPA)

A

procainamide

125
Q

Major hepatic metabolism pathway is conjugation by N-acetyl transferase to form N-acetylprocainamide (NAPA)

A

procainamide

126
Q

——- is 70% as effective as Procainamide but stays in the circulation longer

A

NAPA

127
Q

quinidine

A

cardioactive drug
antimalarial

128
Q

Alkaloid obtained from the bark of the cinchona tree

A

quinidine

129
Q

quinidine contraindications

A
  • Long QT syndrome
  • glucose-6-phosphate dehydrogenase deficiency
  • Myasthenia gravis
  • Optic neuritis
  • If you have taken quinine in the past and it caused a blood cell disorder or severe bleeding
130
Q

As of April 2019, ———– is the new CDC recommended treatment for malaria

A

artesunate

131
Q

Prevents arrhythmias, atrial flutter, atrial fibrillation, and paroxysmal supraventricular tachycardia

A

quinidine

132
Q
  • Calcineurin inhibitors
  • Glucocorticoids
  • Antiproliferative and antimetabolic compounds
A

immunosuppressants used after transplants

133
Q

cyclosporine

A

immunosuppressive

134
Q

It is lipophilic and strongly hydrophobic, it must be made soluble for clinical administration

A

cyclosporine

135
Q

Trough whole blood levels are usually used to measure in lab (EDTA or Heparin)

A

cyclosporine

136
Q

blood level alone should not be deciding factor for changes in treatment

A

cyclosporine

137
Q

Used to prevent the rejection of liver and renal allografts

A

tacrolimus

138
Q

tacrolimus

A

immunosuppressive
Macrolide of fungal origin

139
Q

Shown to be 10-100 times more potent than cyclosporine

A

tacrolimus

140
Q

In the T-cell cytoplasm, binds to a specific binding protein called immunophilin

A

tacrolimus

141
Q

Used as prophylaxis and a therapy for steroid refractory acute and chronic graft-versus-host disease in hematopoietic stem cell transplant recipients

A

sirolimus

142
Q

sirolimus

A

immunosuppressive

143
Q

used for select dermatological disorders and management of uveoretinitis (inflammation of the uvea and retina of the eye)

A

sirolimus

144
Q

Pulmonary toxicity, lower effectiveness of the immune system, decreased glucose tolerance, and insensitivity to insulin

A

sirolimus toxicity

Mercy CLS 5: Chemistry (24 decks)

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