Lecture 7- Special populations Flashcards
1
Q
Special populations
A
Drugs don’t work the same in every person
People respond in different ways
- disease
- pregnancy
- age
- sex
2
Q
Most of our understanding of special populations comes from
A
Pharmacokinetics
- how the body changes the drug
- changes in ADME
We know very little about changes due to pharmacodynamics
- drug response caused by drug-receptor interactions
3
Q
Disease: special populations
A
- Many diseases alter drug exposure and response
- Most disease is the result of Hepatic (liver) and renal (kidney) impairment
- Effect of hepatic and renal impairments on pharmacokinetics are multifactorial
- Organ size
- Tissue composition
- Blood flow
- Enzyme activities
- Transport activities
- Protein binding
4
Q
Chronic kidney disease
A
- Kidney effectiveness= GFR
- how well they are filtering per min
- Using GFR as a metric -> putting people into different classes of kidney failure
5
Q
A
6
Q
Ganciclovir
A
- anti-viral used to treat cytomegalovirus (CMV)
- eliminated primarily through kidney excretion
- creatine clearance is used as a proxy for GFR
- *renal impairment can slow drug elimination*
7
Q
Example of ACE inhibitors being renoprotective
A
- ACE inhibitors is renoprotective in diabetes
- ACE inhibitors lower bp
- in diabetes, there is higher afferent flow
- leads to higher pressure in glomerulus
- ACE inhibitors block Ang 2, leads to dilation of efferent
- balances out the pressure
8
Q
Example of ACE inhibitors in renal failure
A
- Renal failure: have reduce afferent flow
- opening it up even more, having no pressure coming through capillaries
- kidneys lose ability to filter
9
Q
Relationship between Hepatic impairment and metabolism
A
- the amount of drug removed by the liver is dependent on hepatic blood flow
- Hepatic impairment -> decreased blood flow -> decreased metabolism
- As hepatic function decreases, all the different CYP enzymes decrease at different rates
- some drugs metabolized by diff CYPs,
- Do get decreased drug metabolism with impairment of the liver
10
Q
Liver impairement and oral drug bio-availability
A
- The magnitude of change in drug exposure due to the effect of hepatic impairment on oral bioavailability depends on the extent of hepatic extraction
- Some drugs are metabolized more by the liver by first pass than others
11
Q
Cirrhosis
A
- complication of liver disease
- commonly caused by:
- long term alcohol abuse
- viral hepatitis B and C
- loss of liver cells and permanent scarring
- liver function greatly decreased
12
Q
Chlormethiazole
A
- has a high hepatic extraction ratio
- used to treat and prevent symptoms of acute alcohol withdrawal
- alcohol use can lead to overdose
13
Q
Pregnancy
A
profound physiological change
- increased GFR
- altered hepatic metabolism
- GI motility slows
- changes in drug volume of distribution
- many other changes: respiratory rate, bp, plasma albumin, heat rate, etc
All of these changes affect pharmacokinetics
ex: amocillin concentrations are lower during pregnancy than post-partum
* due to increased GFR
Many drugs can pass through the placental barrier
14
Q
teratogenic
A
- agent that can disturb the development of an embryo or fetus
15
Q
FDA safety categories
A
16
Q
Tetracycline
A
- teratogenic antibiotic
- causes permanent discoloration of teeth in infants and children when used during pregnancy
17
Q
Thalidomide
A
- sedative used for morning sickness in the 50’s
- caused severe birth defects
18
Q
Male and female differences
A
- males weigh more, yet many drugs dosing is not corrected for body weight
- body fat: females > males
- GFR: females < males
- differences in drug metabolizing enzyme activities: some CYPs are more active in males/females
19
Q
Midazolam
A
- AKA Versed
- used for procedural sedation or trouble sleeping
- cleared primarily by CYP3A4
- given orally -> first pass metabolism-> do see a mean difference between women and men of serum concentrations , higher clear in women
20
Q
Sex dependent differences in pharmacodynamics
A
Long QT syndrome
- no signs or symptoms
- can lead to fainting, seizures, and sudden death
- women have a higher risk of drug-induced Long QT syndrome
- are thought to be due to females having longer baseline QT interval and a difference in the abundance of potassium cardiac channels
21
Q
Drug differences with children (distribution)
A
- children have a higher distribution of extracellular body water than adults
- results in hydrophilic drugs distributing more
- differences in body fat affect hydrophobic drug distribution
- children have a lower proportion of proteins –> decreased protein binding –> changes distribution
22
Q
Drug differences with children (renal elimination)
A
- renal elimination changes during development
- decreased in newborns
- increased in children
- Kidney function in infants: GFR decreased compared to an adult
- Kids can clear drugs faster than adults, may receive a higher dose
23
Q
Drug differences with children (hepatic elimination)
A
- CYP and glucuronidation activity take time to develop
- slower elimination rates and increased half-life in newborns
- toddlers tend to have a higher metabolic activity than adults
- Decreased hepatic elimination early in life
- Don’t see normal CYP3A4 activity until later on
24
Q
Gray baby syndrome
A
- an adverse event occurring in newborn infants following I.V administration of the antimicrobial, chloramphenicol
- drug not usually used in newborns or premature babies
Caused by:
- reduced glucuronidation of chloramphenicol
- reduced renal elimination of chloramphenicol
25
Q
Reye’s syndrome
A
- rare adverse event occurring associated with giving aspirin to children who have viral infections (flu, chickenpox, respiratory infections)
- causes swelling in the liver and brain
- cause = unknown
- DON’T USE ASPIRIN IN BABIES
26
Q
Considerations for geriatrics
A
- reduction in hepatic mass and blood flow
- changes in plasma protein composition
- reduction in renal mass and GFR
- Increased body fat -> hydrophobic drugs better distributed
