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Clinical Pharmacology > Introduction > Flashcards

Introduction Flashcards

1
Q

Do drugs modify or confer new functions?

A

Modify

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2
Q

What are pharmacodynamics?

A

what the drug does to the body

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3
Q

What are pharmacokinetics?

A

What the body does to the drug

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4
Q

What is a specialized target that binds a drug or endogenous ligand and mediates the pharmacologic action?

A

drug receptor

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5
Q

What is it called when a drug is bound to the receptor and as a result has binding that leads to the biological response?

A

drug-receptor complex

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6
Q

Why are there a large variety of receptors and channels at the membrane?

A

Because most drugs are lipid soluble

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7
Q

What is the compound that binds to the receptor and mimics the response of the endogenous ligand?

A

agonist

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8
Q

What is the compound that blocks or reverses the affect of agonists and have no effect on their own?

A

antagonist

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9
Q

The ____ _____ is not as effective because it occupies all receptors but doesn’t activate the ligand binding site, opens ion channels differently or incompletely, and can act as antagonist if given with full antagonist

A

partial agonist

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10
Q

What is a competitive antagonist?

A

Compete for the same site on the receptor that the agonist wants (increasing dose can overcome this)

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11
Q

What are noncompetitive antagonists?

A

Bind to different site to reduce maximal response that an agonist can produce, not overcome by increased potency

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12
Q

What is an inverse agonist?

A

Opposite effect than agonist :)

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13
Q

What is the maximal response a drug can produce?

A

Efficacy

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14
Q

What is the measure of dose required to produce a response?

A

Potency

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15
Q

Lethal dose 50 / effective dose 50

A

Therapeutic index

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16
Q

What is it called when two drugs with opposite effects are given together?

A

Functional antagonism

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17
Q

What is it called when an antagonist is administered with an agonist?

A

Competitive antagonism

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18
Q

What is a diminished response to the same drug over time?

A

Tolerance

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19
Q

What are different ways of tolerance?

A

receptor desensitization, down-regulation (less receptor synthesis)

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20
Q

What is tachyphylaxis?

A

body quickly develops reduced response to drug, requiring higher doses

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21
Q

What is an enhanced response to a drug?

A

Hyperactivity

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22
Q

What is the enhancement of one drug by another which has no effect on its own?

A

Potentiation

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23
Q

What is the production of a greater response by two drugs when given together than each individually?

A

synergism

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24
Q

What are some adverse effects of drugs?

A

Overextension, organ-directed toxicities, fetal toxicities

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25
Q

What is the amount of the drug absorbed after oral administration compared with after IV?

A

bioavailability

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26
Q

AUCoral/AUCiv=f

A

bioavailability

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27
Q

Does a smaller or bigger molecule absorb faster?

A

smaller

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28
Q

Does a smaller or bigger particle absorb faster?

A

smaller particle

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29
Q

Does a drug dissolve faster in aqueous or oily solutions?

A

aqueous

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30
Q

Can ionized or unionized drugs cross membrane?

A

unionized

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31
Q

Does lower or larger surface area absorb faster?

A

larger

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32
Q

Less or more blood flow for absorption?

A

More

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33
Q

What is it called when oral drugs are metabolized by the liver before reaching systemic circulation?

A

first pass effect

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34
Q

What are the inactive drugs metabolized by the liver to make an active form?

A

prodrugs

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35
Q

What is albumin’s role in drug distribution?

A

Binds to drug like other plasma proteins, sequesters drugs in blood, slows transfer, prolongs their duration of action

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36
Q

What happens when drugs bind to tissue proteins?

A

accumulate in certain tissues which makes it stay in the body for weeks after stopped

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37
Q

What is the process of converting a drug into another chemical called a metabolite?

A

drug metabolism, mostly by the liver!

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38
Q

What are the minor metabolizing organs?

A

GI tract, lungs, kidneys, skin

39
Q

How does drug metabolism work?

A

by making the molecule more water soluble to enhance removal

40
Q

What phase involves introducing a polar functional group to up renal elimination?

A

Phase I with the cytochrome P-450 enzymes

41
Q

What enzyme metabolizes over 50% of the medications?

A

CYP3A4

42
Q

What phase involves conjugating to make it more polar to up renal elimination?

A

phase II

43
Q

What’s the most common form of drug deactivation?

A

active drug to inactive metabolite

44
Q

What is the kidney’s role in drug elimination?

A

excrete most drugs and metabolites into urine, depends on renal function involving: glomerular filtration, proximal tubular secretion, distal tubular reabsorption

45
Q

What is enterohepatic recycling?

A

drugs secreted into the bile –> reabsorption in small intestine –> systemic circulation or back to bile (prolonged amount of time the drug is in the body)

46
Q

dose (mg)/plasma concentration (mg/mL)

A

volume of distribution (assuming it is evenly distributed throughout the body with no metabolism or elimination)

47
Q

what is the rate at which a drug is cleared from the body?

A

Clearance

48
Q

Rate of drug (mg/min)/plasma concentration (mg/mL)

A

clearance

49
Q

What order kinetics is the elimination rate of the drug is concentration dependent?

A

PERCENTAGE – first order (exponential)

50
Q

What is the fraction of a substance that is removed per unit time measured?

A

elimination rate constant

51
Q

What is the time it takes for half blood level concentration of a drug?

A

half life

52
Q

What is the steady state concentration?

A

5 half lives (3-4 to start to feel the effect)

53
Q

What is a loading dose?

A

large dose used to raise plasma concentration to a therapeutic level more quickly

54
Q

What is the kinetics of a constant AMOUNT of drug is lost per unit time?

A

zero-order kinetics (LINEAR)

55
Q

What is a maintenance dose?

A

alternations should be made in either the dose or dosing interval according to renal or hepatic diseases

56
Q

When is maintenance dose adjustment necessary?

A

Only when hepatic disease alters clearance

57
Q

What is the hepatic extraction ratio?

A

fraction of drug removed during one pass through the liver

58
Q

Are high extraction ratio drugs or low extraction ratio drugs more affected by liver disease?

A

high extraction ratio drugs

59
Q

What is a series of alleles found in a linked locus on the chromosome?

A

haplotype

60
Q

What is the inherited variation in the DNA sequence?

A

polymorphism

61
Q

What enzyme metabolizes up to 1/4 of all drugs including beta blockers, opioids, antipsychotics?

A

CYP2D6

62
Q

What enzyme has a preference for acidic drugs, like PPI, antidepressants, antiplatelets, with polymorphism more prevalent in Asian populations?

A

CYP2C19

63
Q

What enzyme metabolizes polymorphism of east asian and oceania populations disproportionally?

A

CYP2B6

64
Q

What are the two Phase II enzymes?

A

UGT1A1 and TMPT, with clinical significance in cancer and immuno treatments

65
Q

What is the enzyme that is in the PPP, most prevalent in African/Mediterranean populations in deficiency?

A

G6PD

66
Q

What genetic component determines if sustained virologic response of anti-viral medication is likely (european populations)?

A

IFNL3

67
Q

What polymorphisms have increased sensitivity to Warfarin and are higher incidence in Asian populations?

A

CYP2C9 reduces clearance and VKORC1 decreased expression

68
Q

What drug can HIV patients with HLA-B*5701 + not take or else risk of serious/fatal hypersensitivity reactions?

A

Abacavir (ziagen)

69
Q

What drug can patients of Asian descent and + HLA-B*1502 allele not take or risk serious/fatal dermatologic reactions to use for bipolar disorder including Stevens-Johnson syndrome?

A

carbamazepine (tegretol)

70
Q

What drug for HIV patients do they need to test + for CCR5 to use it?

A

Maraviroc (selzentry)

71
Q

What drug for gout and patients of Chinese or Thai or Korean with renal impairment need to test + of HLA-B*5801 to avoid serious dermatologic reactions and DRESS syndrome?

A

allopurinol (aloprim)

72
Q

What drug needs the CYP2C19 genotype tested due to allele differences?

A

clopidogrel (plavix) 2 or 3 alleles are mostly non functional and have cardiovascular issues

73
Q

What drug needs to be tested of the CYP2D6 allele due to exaggerated responses from fast metabolization?

A

codeine

74
Q

What drug needs to have tested both CYP2C9 and VKORC1 genotypes?

A

Warfarin
2nd or 3rd alleles need lower starting dose due to increased risk of bleeding (decreased metabolism)

75
Q

What are compounds likely to be therapeutically useful?

A

lead compounds

76
Q

What is a chemical modification of a known active molecule?

A

analogue

77
Q

What did the Pure Food and Drug Act (1906) do?

A

protected from mislabeled or adulterated drugs

78
Q

What is important to know about the FDA?

A

made in 1906, pre-market safety approval in 1938, increased in 1962

79
Q

What phase is animal studies, undergoing pre-clinical safety and toxicity?

A

pre-clinical

80
Q

What is the phase of first testing in humans (healthy volunteers)?

A

phase 1

81
Q

What is the phase of drug studied in patients with target disease?

A

phase 2

82
Q

What is the phase that lasts 2-10 years and is a much bigger group?

A

phase 3

83
Q

What is the phase that is when it’s approved?

A

phase 4

84
Q

What is bioequivalence?

A

A way to fast track approval for a drug with an absence of significant difference

85
Q

What drug should not be prescribed if a Chinese or Thai or Korean ancestry patient tests positive for HLA-B*5801?

A

allopurinol

86
Q

What gene should you test Chinese or Thai or Korean patients with renal impairment/prescription of allopurinol?

A

*5801 + is a no

87
Q

What enzyme do you need to test for clopidogrel?

A

CYP2C19…1st allele is fully functional, the others have > cardio events

88
Q

What gene should you test for codiene?

A

CYP2D6… 2nd allele has exagerrated response (scary!)

89
Q

What genes do you need to test for Warfarin (coumadin)?

A

CYP2C9 and VKORC1

2nd or 3rd allele or G>A variant in VKORC1 need to use LOWER STARTING DOSE or increased risk of bleeding

90
Q

What is the gene you need to test whether there is sustained virologic response of anti-viral medication (hypersensitivity…prevalent in European populations)

A

IFNL3

91
Q

What gene do you need to test to prescribe Abacavir (Ziagen)?

A

HLA-B*5701 … cannot be prescribed if positive, could be fatal

92
Q

What gene do you need to test in order to prescribe carbamazepine (tegretol) in patients of Asian descent and make sure they are NOT POSITIVE?

A

HLA-B*1502, if positive do not prescribe, could be fatal

93
Q

What gene do you need to test for before prescribing Maraviroc (Selzentry)?

A

CCR5, must be positive to take it

Clinical Pharmacology (14 decks)

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