Special Populations

Question 1

4 types of special populations

Answer 1

Comorbidity
Pregnancy
Age
Sex

Question 2

Most of understanding of special populations are from _____________
Less is known about ____________

Answer 2

pharmacokinetics

pharmacodynamics

Question 3

Two impairments that are the primary affect on pharmacokinetics in diseas?

Answer 3

hepatic and renal impairment

Question 4

GFR over 90mL/min : represents what in chronic kidney disease?
60-89?
30-59?
15-29?
less than 15?

Answer 4

• kidney damage w/ normal GFR
• kidney damage with mild decrease in GFR
• moderate decrease in GFR
• severe decrease in GFR
• Kidney failure

Question 5

Renal impairment can slow ______________________

Answer 5

drug excretion

Question 6

Example of drug that is poorly excreted renally in kidney disease?

Answer 6

ganciclovir

used to treat cytomegalovirus

Question 7

What is used as a proxy for GFR measurements?

Answer 7

creatinine clearance

Question 8

ACE I renoprotection in diabetes?

Answer 8

Diabetes has a high afferent flow so it increases pressure in glomerulus and increases GFR.
ACE I inhibits angiotensin II which decreases the pressure and therefor GFR

Question 9

ACE I and renal failure?

Answer 9

If you already have chronic kidney disease (reduced afferent flow), taking ACE I can decrease GFR even more and cause renal failure

Question 10

Classification of liver disease:

5 clinical/biochemical indicators? what are their ranges?

Answer 10

serum bilirubin (2-3)
serum albumin (3.5-2.8)
prothrombin (4-6)
encephalopathy (0-4)
ascites (absent, slight, moderate)

Question 11

Classification of liver disease:

How many points is mild? moderate? severe?

Answer 11

mild = 5-6
moderate = 7-9
severe = 10-15

Question 12

The amount of drug removed by liver is dependent on what?

Answer 12

hepatic blood flow

Question 13

In the case of hepatic impairment, this decreases ____________ and ____________

Answer 13

blood flow

metabolism

Question 14

True of False : Hepatic impairment affect all CYP450 genes the same way.
Why?

Answer 14

False

Because CYP450 genes metabolize drugs differently

Question 15

When hepatic function decreases, which of these is most affected? (put in order)
CYP2E1
CYP1A2
CYP2C19
CYP2D6

Answer 15

CYP2E1 (least affected)
CYP2D6
CYP1A2
CYP2C19 (most affected)

Question 16

Cirrhosis is caused by what?

Answer 16

alcohol abuse

viral hepatitis B and C

Question 17

Liver impairment affects what?

This depends on the extent of ____________

Answer 17

Oral drug bioavailability

Hepatic extraction

Question 18

Highly extracted drugs from the liver : difference in plasma concentration in healthy and cirrhosis patients?
What about low extraction drugs?

Answer 18

Healthy : low conc.
Cirrhosis : high conc.

Low extraction : no difference

Question 19

Which drug has a high hepatic extraction ratio?

It is used to treat what?

Answer 19

Chlormethiazole

Treats acute alcohol withdrawal

Question 20

What are some physiological changes that happen in pregnancy? (5)

Answer 20

1. increased GFR
2. altered hepatic metabolism
3. GI motility slows
4. Changes in drug distribution
5. Others (BP, HR, etc…)

Question 21

What is an example of a drug that changes during pregnancy? Explain

Answer 21

Amoxicillin
Concentrations lower during pregnancy
Due to increased GFR during pregnancy (drug has higher clearance)`

Question 22

Can drugs pass through the placental barrier?

Answer 22

Yes

Question 23

What is a teratogenic drug?

Answer 23

Disturbs the development of embryo or fetus

Question 24

5 FDA categories of safety in pregnancy? Explain

Answer 24

A - Lowest risk : no risk to woman or fetus
B : Animals studies do NOT show a risk, not proven in women
C : Animal studies show risk, no studies on women
D - Shows a risk to fetus, but could save woman in life-threatening situation
X - High Risk : Significant risk to woman and fetus

Question 25

2 examples of drugs that are dangerous to pregnant women? Why?

Answer 25

Tetracycline : discoloration of teeth in infant and children | Thalidomide: 40% survival with major deformities

Question 26

Male/Female differences? (4)

Answer 26

Male weigh more Females have higher body fat GFR higher in men Diff. in drug metabolizing enzyme activities

Question 27

Effect of renal excretion male vs. female? Pregnancy?

Answer 27

M>F | Increased

Question 28

What is midazolam used for? It is cleared by what? Higher clearance by what administration? Higher clearance in males or females?

Answer 28

Used for sedation or trouble sleeping Cleared by CYP3A4 Higher clearance orally Higher clearance in women

Question 29

Example of a sex-dependent difference in pharmacodynamics? | Why is this thought to be? (2)

Answer 29

Females have higher risk of drug-induced Long QT syndrome 1. Women have longer baseline QT intervals 2. Differences in abundance of potassium cardiac channels

Question 30

Difference in distribution children vs. adults? (3)

Answer 30

1. More extracellular body water in children 2. Difference in body fat 3. Lower proportion of proteins in children

Question 31

How does renal elimination change in children?

Answer 31

Decreased in newborns Increased in children (decreases again with age)

Question 32

Hepatic elimination in children : What two things take time to develop?

Answer 32

CYP and glucuronidation activity

Question 33

What is gray baby syndrome? Thought to be caused by what? (2) Why are newborns more susceptible to toxic levels? (2)

Answer 33

Adverse event in newborns due to toxic levels of chloramphenicol 1. Reduced glucuronidation of chlor. 2. Reduced renal elimination of chlor. - Toxic levels could be the result of direct administration or passing through breast milk

Question 34

What is reye's syndrome? Causes what?

Answer 34

Rare adverse event associated with giving aspirin to children with viral infections -Causes swelling in the liver and brain

Question 35

What are 3 factors/risks associated with elderly people and drugs?

Answer 35

1. Increased health issues 2. Frailty 3. Adverse drug interactions

Question 36

4 changes in body composition in the elderly?

Answer 36

1. Increase body fat 2. Decrease in plasma volume 3. Decrease in total body water 4. Decrease in extracellular body fluid

Question 37

3 changes in metabolism in the elderly?

Answer 37

1. Drugs metabolized more slowly 2. Decrease in ability for the liver to recover from injury 3. Cardiac disease and malnutrition decreases hepatic function

Question 38

What are three measurements of drug elimination that decrease with age?

Answer 38

GFR Cardiac index Maximal breathing capacity