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.Pharmacology > Lecture 5: Variations in Drug Responses in Special Populations > Flashcards

Lecture 5: Variations in Drug Responses in Special Populations Flashcards

1
Q

what are the characteristics of the typical subject in a phase 1 clinical trial?

A

young (usually male) adult with no underlying disease conditions

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2
Q

changes in doses populations of different ages, weight, and organ function are typically made by ___

A

estimates

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3
Q

what is pharmacogenetics?

A

alteration of a single gene results in modified drug response

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4
Q

what is pharmacogenomics?

A

combination of multiple genetic differences across the genome resulting in varied responses to drugs

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5
Q

the largest source of variation in response to drugs in the adult population is due to ____ differences

A

genetic

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6
Q

there are genetic variations in many of the drug ___ enzymes

A

metabolizing

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7
Q

CYP2d^ is an example of an enzyme with ____ that result in cliniycallysignificant variations in response. This enzyme is responsible for the conversion of ___ to ___

A

genetic polymorphisms; codeine to morphine

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8
Q

t/f many genetic polymorphisms have beeb identified, but most don’t have clinically relevant results

A

true

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9
Q

____ metabolizers are most people and get the predicted effects of the drug

A

extensive (EM)

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10
Q

___metabolizers have less than the predicted effects in the case of a pro-drug such as codeine

A

poor (pm)

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11
Q

____ metabolizers have a greater than predicted effect in the case of pro-drugs such as codeine

A

ultra rapid (URM)

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12
Q

how can the issue of ultra-rapid metabolizers be corrected for mother’s breastfeeding?

A

choosing a different drug that does not have active metabolites

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13
Q

what is the function the OATP1B1 hepatic transporter?

A

facilitates entry on organic anions into hepatocytes for metabolism

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14
Q

what 2 genetic variations have been found in the OATP1b1 hepatic transporters?

A
  1. single amino acid changes that alter the function

2. reduced function phenotypes

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15
Q

how might a reduced OATP1B1 result in adverse reaction to simvastatin?

A

simvastatin has potential to cause muscle toxicity, and if the OATP1B1 has reduced function, there will be higher simvastatin concentration and more risk

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16
Q

the normal function of the OATP1B1 transporters are required for drug ___

A

metabolism and clearance

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17
Q

if a patient has reduced OATP1B1 function, should they be prescribed a lower or higher dose of statin?

A

lower

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18
Q

alteractions in the protein structure of the B2–AR influence ____ responses to regular ___ treatment

A

airway; bronchodilator

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19
Q

what is the single genetic change on the B2–AR receptor that influences the response to bronchodilators?

A

switch of Arg vs Glycolysis on codon 16

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20
Q

patients with the homozygous arginine on codon 16 of the B2–AR receptors experience what change in responsiveness to bronchodilators?

A

greater receptor desensitization and diminished responsiveness

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21
Q

patients with the homozygous glycine codon 16 of the B2–AR receptor experience what change in responsiveness to brocnhodilators?

A

less receptor desensitization and no change in responsiveness

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22
Q

neonates and infants have have ___ body water %

A

higher

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23
Q

premature babies have ___ body fat %

A

lower

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24
Q

elderly have ___ body water %

A

lower

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25
Q

elderly have ___ body fat %

A

higher

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26
Q

bioavailability of drugs ___ in class 3 obesity

A

increases

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27
Q

obesity

A

multifactorial disease that impacts many body systems, not simply a higher percentage of body fat

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28
Q

highly lipophilic drugs are expected to ___ Vd with higher adipose tissue in the body

A

increase

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29
Q

Obese patients often have ___ metabolism

A

unpredictable

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30
Q

many obese patients also suffer from hypertension, causing a ___ in renal excretion of drugs

A

decrease

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31
Q

it is important to consider drugs that cross the ___ in pregnant women

A

placenta

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32
Q

drugs that cause birth defects are called

A

teratogen

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33
Q

systems in what phase are most susceptible to teratogens?

A

developing

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34
Q

early in embryo development, teratogen exposure poses the highest overall risk to the development of ______ that may result in ___

A

anatomic abnormalities ; miscarriage

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35
Q

what is an example of early embryo anatomic abnormality that results in miscarriage

A

neural tube detects in the CNS

36
Q

in later phases of fetal development, most of the major organs are formed, but teratogen exposure may impact ____ or ___

A

physiological function or final development of structures

37
Q

what are the 5 FDA pregnancy categories for teratogens?

A
  1. A
  2. B
  3. C
  4. D
  5. X
38
Q

category A of drugs in pregnancy

A

shown to be safe for use in pregnancy

39
Q

categories B/C of drugs in pregnancy

A

may cause harm or pose risk to fetus

40
Q

category D of drugs in pregnancy

A

drug likely to cause harm, use caution

41
Q

category X of drugs in pregnancy

A

will cause harm DO NOT USE

42
Q

category X drugs are typically those that interfere with pathways involved in fetal ___

A

developemtb

43
Q

give 4 examples of category X drugs for pregnancy

A

ACE inhibitors, warfarin, anti seizure drugs, valproic acid

44
Q

ACE inhibitors in pregnancy can result in ___ and ___

A

fetal renal and cardiovascular damage

45
Q

warfarin in pregnancy can result in ___, ____, and ___

A

anatomical malformations, CNS and CV damage, high rate of miscarriages

46
Q

antiseizure drugs in pregnancy can result in ___ and ___

A

neural tube defects and cardiovascular damage

47
Q

valproic acid in pregnancy can result in ___ , ____ and ___

A

neural tube defects, anatomical malformations and CNS & CV damage

48
Q

neural tube defects result in malformations of the ___ and ___

A

spinal cord and CNS

49
Q

list 5 examples of drugs safe for use in pregnancy (category A)

A
  1. penicillin
  2. heparin
  3. diphenhydramine
  4. short acting benzodiazepines such as lorazepam in the 3rd trimester
  5. topically applied drugs like inhaled corticosteroids for asthma
50
Q

t/f it is impossible to know if a drug will be 100% safe for use in pregnancy

A

true

51
Q

the new FDA requirements for drug use in pregnancy are more ____ and provide much more information regarding ___ and ___

A

descriptive; risks and evidence

52
Q

the teratogenic risk of ibuprofen depends on the

A

trimester

53
Q

ibuprofen can be listed as what class teratogen?

A

B, C, D

54
Q

what is the preferred analgesic for mild pain relief during pregnancy

A

acetaminophen

55
Q

there are major birth defects in ___% of the population and of this population, ___% are thought to be caused by drug use

A

1-3; 2-3

56
Q

t/f it is possible that a mother’s uncontrolled medical condition may cause more harm to the fetus than the medication used to control the condition

A

treu

57
Q

even if a drug doesn’t have teratogenic effects, a neonate constantly exposed to a drug, such as opioids, can develop ___ and suffer from ___ after birth

A

dependence; withdrawal

58
Q

drugs that interfere with development of healthy bones and teeth should not be used in ___ unless absolutely necessary

A

children

59
Q

why are tetracycline antibiotics not recommended for children?

A

tetracycline binds to calcium in teeth and becomes permanently embedded, resulting in yellow/drown discolouration that cannot be removed

60
Q

what is something to consider when thinking of adverse effects in children?

A

many drugs are net studied in children, so they may have unexpected effects and may not be able to articulate the exact effects as well as an adult may be able to

61
Q

how are absorption and distribution different in children?

A

children have constant body composition and organ function as they develop and grow

62
Q

___, ___ and ___ can significantly impact the bioavailability of drugs in very young children

A

blood flow, muscle mass, GI function

63
Q

drug metabolizing enzymes are expressed at varying levels throughout development, which results in variations in ___ compared to adults

A

drug clearance

64
Q

neonates have ____ clearance compared to adults

A

slower

65
Q

clearance may be much ___ in children than adults

A

faster

66
Q

t/f phenobarbital, a barbiturate has a shorter half life in toddlers than adults

A

true

67
Q

when paediatric dosing hasnt been determined by the drug manufacturer, dosing is typically considered to be more accurately determined based on ___ rather than weight

A

body surface area

68
Q

why is body surface area a more accurate measurement for dosing in children than weight?

A

due to variations in body compositions of children compared to adults

69
Q

absorption processes are not known to change in healthy aging, however there are some effects of ____ that are more common in older adults

A

lifestyle modification

70
Q

t/f inconsistent diet and irregular eating patterns can have significant impact on drug absorption

A

true

71
Q

what are 2 ways in which metabolism changes with old age?

A
  1. decreased hepatic metabolsim

2, reduced capacity of some CYP enzymes

72
Q

how is excretion of drugs impacted by aging?

A

reduced renal function, therefore decreased clearance

73
Q

what is the greatest effect on altered pharmacokinetics in older adults?

A

the decrease in glomerular function to excrete drugs

74
Q

what is glomerular filtration?

A

process in which molecules are removed from the blood in the nephrons and transferred to the urine

75
Q

a decrease in glomerular filtration results in

A

drugs circulating for longer period of time

76
Q

how does the cardiac index in old age affect renal and hepatic function?

A

decreased blood flow, which slows filtration

77
Q

rate of removal of drug may be reduced if renal function is __

A

impaired

78
Q

if there is renal impairment, active or toxic metabolites may accumulate to ___

A

unsafe levels

79
Q

what is creatinine?

A

metabolic waste product removed by the kidneys

80
Q

serum levels of creatinine in a healthy adult should be very ___, which makes this protein a good surrogate measure for ___ and ___

A

low; glomerular filtration rate and kidney function

81
Q

in old age there is greater sensitivity to respiratory ___

A

depression

82
Q

in old age there is a ___ in delivery of inhaled drug, why is that?

A

decrease; because it is more common to experience respiratory drepression, preventing the optimal delivery

83
Q

patient with diabetes have an increased risk of ___ diseases and may have other organ system impairments such as ____, ___ and ___

A

retinopathies; neuropathies and nephropathies

84
Q

polypharmacy increases the risk for ___ and ____

A

drug interactions and serious adverse effects

85
Q

it has been estimated that there is a nearly 100% chance of an adverse reaction when a patient is taking ___ or more medications

A

10

.Pharmacology (55 decks)

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