Therapeutics Flashcards
most important period of organ and fetal development (most sensitive to drugs)
first trimester
most common prescription drugs prescribed to pregnant women
oral contraceptives, amoxicillin, progesterone, albuterol, promethazine, and estrogenic compound
most common OTC drugs prescribed to pregnant women
acetaminophen, ibuprofen, decussate, pseudo ephedrine, aspirin, naproxen
factors that affect drug transfer across the placenta
- molecular weight of drug
- pKa of drug and degree of ionization
- protein binding of drug
- placental drug transporters
most drugs have a mol. Wt of… and therefore …
<500D; most drugs cross over to fetal circulation
how does pKa of the drug and degree of ionization affect drug transfer across placenta?
ionized drug transfers incompletely across; they become trapped (not always true for drugs like ampicillin and methicillin which are strong acids and are ionized but have lipophilic groups that allow transfer)
drug transporters
like P-glycoprotein, breast cancer resistance protein(BCRP), and multidrug resistance protein (MRP) protect the fetus by efflux of drug from fetal to maternal circulation
FDA Classification - Category A
safe
FDA Classification - Category B
likely safe, animals OK
FDA Classification - Category C
uncertain, risks vs benefits
FDA Classification - Category D
likely unsafe risk vs benefit
FDA Classification - Category X
unsafe, do not use
Why is there more data on drug use in the age groups young and middle aged adults?
clinical trials are normally performed on them and patients at the two extremes (children and elderly) range markedly in their response to drugs
why do children and elders respond differently to drugs?
difference in physiology makes dose adjustments necessary
Variability in pharmacokinetics can be expected to be greatest when…
body physiology is changing (in newborns or premature baby or during puberty)
In premature and newborn babies, what is necessary for sake and effective treatment?
dose adjustment and therapeutic drug monitoring for drugs with narrow therapeutic indices to prevent toxicity
T/F: Drug clearance values vary linearly with either body weight or body surface area.
FALSE- a one year old infant will not necessarily have lower clearance compared to a ten year old for all drugs
Hepatic drug metabolizing enzymes are …. in infants, especially in premature infants
not fully developed
Clearance values of most drugs are … in children and adults
different
Most drug-metabolizing enzymes are expressed….
at low levels at birth
CYP3A4 is expressed… in infants
1 week: administering a drug metabolized by it before it is expressed is likely to produce toxicity
newborns and glucoronic acid
they are unable to conjugate glucoronic acid during phase 2 metabolism
Renal elimination of drugs is reduced in neonates, therefore..
dosing for drugs should be reduced to account for reduced renal clearance to avoid toxicity (e.g. amino glycoside antibiotics)
GFR is only… in neonates and …. in adults.
2-4mL/min/1/73m^2; 100-130ml/min/1.73m^2
GFR increases to adult levels by… of age
8 to 12 months
Antihistamines and barbiturates in adults and children
- sedation in adults
- hyperactivity in children
Children have increased sensitivity to sedating effects of propofol, resulting in…
cases of overdoses with myocardial failure, metabolic acidosis, and multiorgan failure
glucocorticoids
can attenuate linear growth of bones
Elderly take … of drugs prescribed to all age groups
1/3
Elderly take an average of..
5 drugs
Elderly report … of drug adverse reactions of all age groups.
25%
Common physiological changes that affect pharmacokinetic and pharmacodynamic responses to drugs in elderly:
- reduction in lean body mass
- reduction in serum albumin
- reduction in total body water
- increases % of body fat (increase volume of distribution of lipid soluble drugs)
- kidney/liver function
GFR declines at an average of … after the age of 30 years
0.8 ml/min/1.73m^2
decline in GFR is an indicator of…
renal function
When does the decline of GFT accelerate?
after age of 65-70
an average 85 year olds GFR
55-60… approximately 50% decrease from age 30
Elderly people over the age of 75 can be expected to have…. (renal clearance)
significantly reduced renal clearance of drugs and therefore carefully calculated dose reduction of drugs
Elderly people can be expected to have…. (hepatic)
- reduced hepatic blood flow and drug metabolism with great variability between individuals
- reduced hepatic CYP activity(conjugating enzymes not affected)
- more susceptible to CNS depressants and psychotropic drugs to produce more hypotension
