Flashcards in Yingling- Drugs in Aging- Melissa Deck (38):
Define the following terms:
Perinatal, neonate, infant, child
Perinatal: 26th week gestation--> 1 mos postpartum
Neonate: 0-4 wks
Infant: 5-52 wks
Child: OVER 1 yoa
How are drugs typically administered to neonates and infants?
What are some issues with injections (2) and enteric administration (3)?
Typically administered extravascularly; IV for emergencies
SQ, IM--dependent on perfusion +/- muscle mass
- Gastric pH decreases 6-8--> 3 in first 24 hrs after birth
- Gastric emptying DELAYED for 2 days after birth
- Slow/ irregular peristalsis are typical in little guys
What are some examples of disease states that might alter oral drug absorption? (4)
- congenital heart disease/ CHF
- thyroid disease
- short bowel syndrome
Describe the changes with age in percent body water, fat, and extracellular water: body fat ratio. How do these differ between neonates, premees, and adults?
Percent body water (Most to least)
Premee--> neonate--> adult
- Full term infants will have MORE % body fat than premees (these little guys are all water!)
- Neonates wil have a higher EC water: body weight ratio than adults
How does renal function in neonates differ from that in adults? What does this mean for drug excretion?
GFR is lower at birth and increases 50% within 1st wk life
Adult GFR reached b/w 6-12 mos
This means that drug excretion will occur at SLOWER rate than adults for first 6 mos of life; will increase 50% by 1st sk
How does P450 activity differ between infants and adults?
How does maternal environment influence drug metabolism in infants (2)?
- LESS P450 activity at birth, but increases rapidly
- LESS conjugation reactions EXCEPT glucuronide
- Maternal environment can cause enzyme induction/ inhibit or deliver drugs to babies via breast milk
Describe differences in plasma protein binding between infants and adults--what are two drugs that are displaced by bilirubin?
- Infants have LESS plasma protein binding
- No affinity for acidic/ basic drugs until 10-12 mos
- Phenytoin + Indomethacin displaced by bilirubin
How does Indomethacin affect GFR? Urine flow rate? Electrolytes?
30% decrease GFR--> 60% decrease urine flow rate
How is the half life of digoxin different in neonates than adults?
LONGER in neonates than adults (about double)
What is the most commonly administered diuretic to neonates? How will its effect be changed in the neonate compared to the adult?
Furosemide--immature kidney has decreased perfusion; causes DELAYED response to furosemide
How should we calculate drug dosage for infants and neonates?
USE SURFACE AREA
- Body weight will often underestimate dose
- i.e 3 kg newborn according to weight gets 5% adult dose, according to SA gets 12% adult dose...
What are 3 general principles to hang onto when prescribing to elderly patients?
- generally use lower doses
- increase monitoring
- pay special attention to drug list in hx.-- get all OTCs
What are the 4 most common prescription med classes written for elderly patients?
- CV (HTN, arrhythmia, CHF)
- Psych (TCA, BDZ, Phenothiazines)
- Analgesics (NSAIDS_
What are the MOST COMMON reasons for ADRs that occur in elderly patients on prescription drugs?(2)
- pharmacokinetic changes
- pharmacodynamic changes
What classifies a hypersensitivity reaction to a drug?
unexpected response on behalf of immune system to drug
At what age does CO begin to decline? When does GFR begin to decline?
- CO begins to decline 1%/ year after 30 yoa
- GFR declines 0.5%/year after 20 yoa, up to 1%/year after that
How do total body water, lean body mass, body fat, serum albumin, and hepatic blood flow differ between geriatric (65+ yoa) patients and adults 20-30 yoa?
For geriatric patients:
Body fat: INCREASES
Hepatic blood flow: DECREASES
What are 5 factors that alter drug absorption in GI tract in elderly patients... ?
- Decreased gastric acid secretion--> ^ gastric pH--> DECREASE absorption
- SLOWER gastric emptying
- Decrease splanchnic blood flow
- Decrease mucosal SA in small intestine
- Antacids use
In elderly patients...
What are two drugs with compromised absorption due to decreased gastric acid secretion? What are 4 drugs with compromised absorption due to antacid regimens?
Decreased secretion gastric acid = decreased absorption ferrous sulfate + ketoconazole
Antacid regimines = decreased absorption cemitidine, digitalis, tetracycline, phenytoin
How does Vd change for lipid soluble, water soluble drugs in elderly patients?
What are some examples of these drugs?
How about Vd for drugs that bind muscle?
How will this affect t 1/2 for all of the above?
- Vd ^ for fat soluble drugs (BDZs, amioderone)
- Vd DECREASES for water soluble drugs (ETOH, procainamide, atendol)
- Vd DECREASES for drugs that bind muscle (digoxin)
Thus, t 1/2 will DECREASE for water soluble drugs and increase for everything else!
How does phase I metabolism change with age?
Phase I metabolism DECERASES--> this will INCREASE t 1/2 for drugs like diazepam
Describe changes in plasma protein binding that occur with age:
How does plasma albumin change?
What are two factors that can decrease protein binding?
What is one factor that can cause binding displacement?
- Plasma albumin DECREASES--> ^ Free fraction of acidic drugs (WARFARIN! PHENYTOIN); amplified by illness
- Renal disease and low protein diet can cause changes in protein binding
- Concomitant use of drugs can cause binding displacement (i.e warfarin + ASA)
How does liver blood flow anodize change with age?
How are phase I and II metabolism changed with age?
How do we determine clearance?
- Hepatic blood flow and liver size both DECREASE
- phase I metabolism DECREASES
- phase II metabolism DOES NOT CHANGE***
***IT IS DIFFICULT TO PREDICT WHETHER OR NOT CLEARANCE WILL CHANGE!!!***
7 drugs whose hepatic clearance is DECREASED with age?
- Diaz, Fluraz-epam
What are 6 drugs whose clearance is NOT affected by age?
- Lor, Nit, Ox-azepam
How does renal clearance change with age?
What are 4 disease states/ conditions that might amplify such changes?
- GFR decreases up to 50% w/ decrease in # functional nephrons
- Made worse by heart disease, dehydration, hypoTN, DM
7 Drugs/ drug classes whose renal elimination is diminished in the elderly?
- gentamicin, tobramycin
- 1st gen cephalosporins
What is the equation for Cr Clearance!?
How is it changed for women and the elderly?
(140-age) x (weight in Kg)/ 6365 x (serum Cr umol/L)
(140-age) x (weight in Kg)/ 72 x (serum Cr mg/L)
Multiply by 0.85 for women; note that elderly have less muscle mass and lower Cr production...
***I DID THIS WITH Dr. MAYS!!!! IT IS REALLY IMPORTANT AND SHE DOES IT ALL THE TIME! COOL!***
How are adrenergic receptor response and opioid receptor response changed in the elderly?
- DECREASE in adrenergic receptor response (lessens effect of B agonist/ antagonist; LESS brady with propranolol)
- INCREASE response to opiates and BDZs (MORE sedation with less dose)
Describe the details of how digoxin elimination is changed in the elderly?
Increase or decrease? What is the change in Vd?
When should we exercise caution when prescribing this drug?
- DECREASE renal elimination
- LOWER muscle mass = LOWER Vd
- may have toxicity within therapeutic range
- careful use in combo with diuretics
Describe complications of diuretic use in elderly patients.
- ^ incidence of complications
- Thiazide + furosemide --> careful for K+ depletion
- Thiazides only--> careful for Mg++ depletion
Depression in elderly may be confused with...
How does response to phenothiazines change in elderly patients?
How does chlorpromazine affect orthostatic HTN in elderly adults?
makes it worse!
Which psychotropic drugs have BB warning for use in the elderly?
atypical and typical dopamine antagonists
What is important to remember when prescribing lithium to elderly patients?
Why do we prescribe NSAIDS to elderly patients?
What are some ADRs associated with use?
How do they alter renal function (4)?
Tx inflammation, arthritis, pain, etc.
Cause GI ulceration + Alter renal function:
- ^ Na/ H2O/ K+ retention
- DECREASE RBF + GFR
- Impair function of certain diuretic
- can cause PAPILLARY NECROSIS