Special Populations Flashcards
4 types of special populations
Comorbidity
Pregnancy
Age
Sex
Most of understanding of special populations are from _____________
Less is known about ____________
pharmacokinetics
pharmacodynamics
Two impairments that are the primary affect on pharmacokinetics in diseas?
hepatic and renal impairment
GFR over 90mL/min : represents what in chronic kidney disease? 60-89? 30-59? 15-29? less than 15?
- kidney damage w/ normal GFR
- kidney damage with mild decrease in GFR
- moderate decrease in GFR
- severe decrease in GFR
- Kidney failure
Renal impairment can slow ______________________
drug excretion
Example of drug that is poorly excreted renally in kidney disease?
ganciclovir
used to treat cytomegalovirus
What is used as a proxy for GFR measurements?
creatinine clearance
ACE I renoprotection in diabetes?
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
ACE I and renal failure?
If you already have chronic kidney disease (reduced afferent flow), taking ACE I can decrease GFR even more and cause renal failure
Classification of liver disease:
5 clinical/biochemical indicators? what are their ranges?
serum bilirubin (2-3) serum albumin (3.5-2.8) prothrombin (4-6) encephalopathy (0-4) ascites (absent, slight, moderate)
Classification of liver disease:
How many points is mild? moderate? severe?
mild = 5-6 moderate = 7-9 severe = 10-15
The amount of drug removed by liver is dependent on what?
hepatic blood flow
In the case of hepatic impairment, this decreases ____________ and ____________
blood flow
metabolism
True of False : Hepatic impairment affect all CYP450 genes the same way.
Why?
False
Because CYP450 genes metabolize drugs differently
When hepatic function decreases, which of these is most affected? (put in order) CYP2E1 CYP1A2 CYP2C19 CYP2D6
CYP2E1 (least affected)
CYP2D6
CYP1A2
CYP2C19 (most affected)
Cirrhosis is caused by what?
alcohol abuse
viral hepatitis B and C
Liver impairment affects what?
This depends on the extent of ____________
Oral drug bioavailability
Hepatic extraction
Highly extracted drugs from the liver : difference in plasma concentration in healthy and cirrhosis patients?
What about low extraction drugs?
Healthy : low conc.
Cirrhosis : high conc.
Low extraction : no difference
Which drug has a high hepatic extraction ratio?
It is used to treat what?
Chlormethiazole
Treats acute alcohol withdrawal
What are some physiological changes that happen in pregnancy? (5)
- increased GFR
- altered hepatic metabolism
- GI motility slows
- Changes in drug distribution
- Others (BP, HR, etc…)
What is an example of a drug that changes during pregnancy? Explain
Amoxicillin
Concentrations lower during pregnancy
Due to increased GFR during pregnancy (drug has higher clearance)`
Can drugs pass through the placental barrier?
Yes
What is a teratogenic drug?
Disturbs the development of embryo or fetus
5 FDA categories of safety in pregnancy? Explain
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
2 examples of drugs that are dangerous to pregnant women? Why?
Tetracycline : discoloration of teeth in infant and children
Thalidomide: 40% survival with major deformities
Male/Female differences? (4)
Male weigh more
Females have higher body fat
GFR higher in men
Diff. in drug metabolizing enzyme activities
Effect of renal excretion male vs. female? Pregnancy?
M>F
Increased
What is midazolam used for? It is cleared by what? Higher clearance by what administration? Higher clearance in males or females?
Used for sedation or trouble sleeping
Cleared by CYP3A4
Higher clearance orally
Higher clearance in women
Example of a sex-dependent difference in pharmacodynamics?
Why is this thought to be? (2)
Females have higher risk of drug-induced Long QT syndrome
- Women have longer baseline QT intervals
- Differences in abundance of potassium cardiac channels
Difference in distribution children vs. adults? (3)
- More extracellular body water in children
- Difference in body fat
- Lower proportion of proteins in children
How does renal elimination change in children?
Decreased in newborns
Increased in children
(decreases again with age)
Hepatic elimination in children : What two things take time to develop?
CYP and glucuronidation activity
What is gray baby syndrome? Thought to be caused by what? (2)
Why are newborns more susceptible to toxic levels? (2)
Adverse event in newborns due to toxic levels of chloramphenicol
- Reduced glucuronidation of chlor.
- Reduced renal elimination of chlor.
- Toxic levels could be the result of direct administration or passing through breast milk
What is reye’s syndrome? Causes what?
Rare adverse event associated with giving aspirin to children with viral infections
-Causes swelling in the liver and brain
What are 3 factors/risks associated with elderly people and drugs?
- Increased health issues
- Frailty
- Adverse drug interactions
4 changes in body composition in the elderly?
- Increase body fat
- Decrease in plasma volume
- Decrease in total body water
- Decrease in extracellular body fluid
3 changes in metabolism in the elderly?
- Drugs metabolized more slowly
- Decrease in ability for the liver to recover from injury
- Cardiac disease and malnutrition decreases hepatic function
What are three measurements of drug elimination that decrease with age?
GFR
Cardiac index
Maximal breathing capacity
