Lifespan COPY Flashcards
Renal disease usually leads to drug _______.
Accumulation
What is the most important cause of adverse drug reactions in older adults?
Kidney disease/aging kidney
Liver disease usually leads to drug ______.
Accumulation
Definition: Tolerance
Decreased drug responsiveness due to repeated drug administration
pharmacodynamic tolerance
upregulation/downregulation of receptors (cell adjusts based on continuous agonist/antagonist activity)
metabolic tolerance
CYP450 induction (some drugs increase activity of this enzyme system resulting in more rapid metabolism)
tachyphylaxis
decreased responsiveness to a drug due to multiple doses over a short period of time.
Low albumin (low protein concentration) results in _______ (higher or lower) drug concentration
higher
Does decreased protein binding decrease drug toxicity?
No - the opposite. It increases drug toxicity
Drugs can get trapped in the fetal circulation due to:
ion trapping
teratogenesis
production of congenital anomalies
list the pregnancy drug categories
A: safe, no demonstrated fetal harm
B: animal research suggests safety (inadequate human studies)
C: animal research suggests risk (inadequate human studies)
D: fetal risks are shown, but benefits may outweigh risks in certain situations
X: never an indication to use during pregnancy
Does a higher or lower concentration of drug pass through the blood brain barrier in neonates/infants?
Higher due to immature BBB development
Is the CYP450 system faster or slower in neonates/infants? What are the implications?
Slower. Drug accumulation
Is renal drug excretion faster or slower in neonates/infants? What are the implications?
Slower. Drug accumulation
At what age do pediatric pharmacokinetics approach adult values?
1year
List some causes of adverse drug reactions in the older adult
*decrease renal function
other pharmacokinetic abnormalities
comorbidities
polypharmacy
poor adherence
wider variation in response
multiple healthcare prescribers
pharmacogenomics
how genes affect a person’s response to drugs
Why is a drug that is excreted in the urine a bad choice for an elderly patient?
Elderly patient’s have decreased GFR, higher effective dose, drug is excreted slower —> toxicity
How should you treat someone who has an adverse reaction to a drug that acts as a positive allosteric modulator?
Target the receptor system in an opposite way, give antagonist to receptor
What is a more suitable drug for a patient with low GFR?
Drug with a shorter 1/2 life, drug that is not dependent on the kidney to be excreted
General variances in drug responses
- body weight, body composition
- pathologies
- tolerance
- variances in absorption (gastroparesis, food intake, diarrhea/constipation)
- diet and malnutrition
- non adherence
- age
- placebo effect
How does body fat affect drug response?
- more fat = store more drug / larger reservoir
- less fat = more side effects (smaller reservoir / overflow bucket —> more drug is in the blood)
- people w/ lower body fat have higher potency and need lower dose
First pass metabolism & pathologies
- drug travels from lumen of GI to liver via portal vein
- issues w/ portal vein (HTN) = poor metabolism of drug due to less blood flow to liver
- cirrhosis = poor metabolism
Tolerance requires
Higher dose to produce equal effects
Example of a drug that is susceptible to tachyphylaxis
Nitroglycerin - taken for heart pain, works well 1st time but works less and less well after subsequent doses
Risks is increased with ____ protein bound drugs
Highly
Drugs affected by specific nutrients
- MAOIs + tyramine (cheese, deli meat, pickles) —> malignant HTN
- Many drugs (statins) + grapefruit juice (strong CYP450 inhibitor)
Guidance from 1977 to 1993 related to testing drugs on pregnant women
Females of childbearing age should be excluded from clinical trials
Basic considerations for drugs and pregnancy / breastfeeding
Do not give drugs that:
- can transfer through the placenta
- are secreted in breast milk
Only want maternal system to be exposed to drug
Physiological changes in pregnant women
Increased GFR and effective renal plasma flow (drugs are excreted and metabolized faster)
What types of drugs pass through the placenta?
- lipid soluble
- unionized
- not protein bound (lower concentration of albumin in pregnant women due to large blood volume)
Drugs to avoid in pregnancy
- adverse drug reactions affecting the pregnant individual —> systemic effects that can have secondary effect on fetus
- drugs that can complicate pregnancy / cause spontaneous abortion (avoid drugs that cause smooth muscle contraction)
-drugs that have special side effects during pregnancy (heparin = osteoporosis) - drugs that can cause physical dependence in newborn (withdrawal symptoms and/or physiologic alterations)
- drugs that are teratogenic
Pregnancy drug categories
Pregnancy, lactation, females & males of reproductive potential
Basic considerations for pediatrics
- greater variability in response to drugs (every child develops differently)
- immature organ systems in very young —> altered PK & PD
- many drugs have not been tested in children specifically, lack of reliable dosing info
Splanchnic circulation
Aorta —> coeliac, superior mesenteric & inferior mesenteric artery —> GI organs —> portal vein —> liver —> inferior vena cava
What organs are fed by the coeliac artery?
Stomach, spleen, pancreas
What organs are fed by the superior mesenteric artery?
Pancreas, small & large intestine
What organs are fed by the inferior mesenteric artery?
Large intestine
Splanchnic circulation in older adults
Decreased, blood takes longer to reach liver
Neonate metabolism & excretion
CYPs & UGTs decreased
Albumin decreased
Renal function decreased
Infant (4 weeks - 1year) metabolism & excretion
CYPs = very increased
UGTs same as adults
Albumin & renal function same as adult
Child metabolism and excretion
CYPs increased
UGTs, albumin & renal function = same as adults
Elderly metabolism and excretion
Decreased CYPs & UGTs
Decreased albumin & renal function
PD changes in older adults
- changes in # of receptors
- alterations in receptor affinity for drug binding
- beta blockers = less effective (decreased receptors and receptor affinity)
Ultra rapid metabolizers
- use CYP2D6 to convert codeine (doesn’t go to CNS) into morphine (does go to CNS)
