Week 2: Lifespan Flashcards
How does body composition effect drug response?
With hydrophobic drugs, fact acts as a reservoir similar to protein binding
- ^ fat, dec. potency
2 ways kidney pathology may effect drug response
- Changes along nephron = ^/v excretion = ^/v drugs in systemic circulation
- Changes in kidney function = pH changes due to ^/v Na+
2 ways liver pathology may effect drug response
- First-pass effect
- Enterohepatic cycling
Both result in dec. drugs in systemic circulation
Tolerance
Dec. drug responsiveness due to repeated drug use. Requires higher doses to produce equal effects
3 types of tolerance
Pharmacodynamic, metabolic, and tachyphylaxis
Pharmacodynamic tolerance
Upregulation/downregulation of receptors
Metabolic tolerance
CYP450 induction by some drugs accelerates their own metabolism, creating a faster and faster cycle
Tachyphylaxis
Dec. responsiveness due to multiple doses over a short time period
How malnutrition/poor nutrition impacts drug responses
Dec. albumin = dec. protein binding = inc. “effective” dose
Malnutrition and poor nutrition is especially concerning in regards to what type of drug?
Highly protein-bound drugs
2 ways dietary nutrients effect drug responses
- MAOIs + tyramine (from fermented savory foods) = malignant hypertension
- Grapefruit juice is a CYP450 inhibitor
3 characteristics of drugs most likely to cross into the placenta
- Lipid soluble (Aka unionized and nonpolar)
- Not protein bound
- Affinity for placental pH (ion trapping)
3 physiological changes in pregnant people that effect drug responses
- Faster metabolism
- Faster excretion
- Inc. blood volume
- Dec. protein binding
Compare the effect of drugs on pregnant people against the general population
Drugs that do x in the general population will do it 10x in pregnant people (more potent)
5 characteristics of drugs avoided during pregnancy
- Drugs that can cause spontaneous abortion
- Drugs that cause smooth muscle contractions
- Drugs that have special side effects during pregnancy
- Drugs that can cause physical dependence in the newborn
- Drugs that are teratogenic
3 factors that complicate pediatric pharmacology
- Greater variability in response to drugs
- Immature organ systems
- Lack of reliable dosing information
Most PK parameters are similar to adults by about age ________ EXCEPT that they ___________
~1 year old, metabolize drugs faster
3 clinical implications of PK alterations in pediatric patients
- Challenging dosing information
- Close monitoring is needed to monitor therapeutic effects and dose adjustments
- Close monitoring is needed to monitor for adverse effects, especially since neonates and infants will not be able to express symptoms
What is the most important cause of adverse drug reactions in older adults?
Kidney disease/aging kidney
2 ways PK is altered in older adults
- Naturally dec. albumin, dec. protein binding
- Naturally dec. splanchnic circulation blood flow
Organs of the splanchnic circulation circuit (5)
Stomach, spleen, pancreas, small intestine, and colon
2 ways PD is altered in older adults
- Naturally dec. # of receptors
- Naturally dec. receptor affinity for drug binding
Polypharmacy
Taking multiple medications to treat multiple conditions
5 reasons for inc. adverse drug reactions in older adults
- Drug accumulation due to dec. renal function
- Polypharmacy
- Comorbidities with inc. severity
- Inc. individual variation
- Poor adherence
Pharmacogenomics
Using a patient’s genomic information to tailor the selection of drugs used in their treatment
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
5 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? Why?
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
