Witches and Wizards: PKPD Flashcards
breakdown of ‘geriatric’ ages
- young old: 65-74
- middle old 75-84
- old old 85+
compared to younger pts, older pts are ____er, ____er, and ____er
fatter, dryer, weaker
cardiac changes
- decrease in contraction and filling capacity -> less cardiac output
- change in conduction -> arrhythmias
- decreased efficiency
- decreased catecholamines
- athersclerosis -> stiffness
- failure i venous valves -> increased risk in vte
collective cardiac changes increase dx of htn, tia, cva
CNS changes
- decreased rate in conductoni
- decresed strength in transmission
- threshold for arousal blurred (some things more sensitive and others less sensitive); chages in electrical charge/signal needed for transmission
- increased recovery time in ANS
respiratory changes
- pretty normal at rest
- compromized under stress (dyspnea on exertion)
- decreased expiration
- decreased elastiicity
- decreased muscle
- decreased ventilation
- decreased O2
genitourinary changes
- nephron degeneratio (loss in functional nephrons)
- reduced glomerular and tubular function
- decreased abilty to concentrate urine
- decreased renal blood flow (independent of decreased cardiac output)
- decreased acid base adaptation when stressed
- incontinence
- bph
- ed
- dyspareunia
situations/cases that can exacerbate the normal physiologic decrease in kidney function
- inadquate fluid intake
- fluid loss from diarrhea/vomiting
- cardiac failure
- sepsis
- bad diuretic use
effect of normal physiologic decrease in kdiney functiton on drugs
reduced clearance of renally eliminated drugs -> supratherapeutic drug levles at normal doses
decrease in testoserone effets
- decreased libido and sexual funciton
- decreased energy
- decreased muscle
- decreased hair
gastrointestinal changes
- dentition and nutrition -> malnutrition
- decreased esophageal motility
- hiatal hernia: (stomach pushes up through lower esophageal sphincter -> pain -> less eating
- stomach is less acidic
- decreased stomach motility
- decreased colon motility
- decreased pancreatic secretions
- smaller liver
- decreased blood flow to liver
- decreased cyp450 in liver
(increased/decreased/same) stomach emptyig with age and consequential effect
decreased -> large insolule produts (asa 325 ec) stay in stomach longer -> decreased rate of absorption
(increased/decreased/same) rate of absorption in stomach with age and consequential effect
decreased -> decreased rate of absorptin of analgesics and hypotics (bad because we want pain meds to work fast)
(increased/decreased/same) intstinal motility with age and consequential effect
EITHER increased or decreased (trick question
- increased motility:
- increased absorptin dt increased dissolution
- decresed absorption (digoxin and phenytoin); less time to be absorbed
- decreased motolity: increased transit time -> increased absopriton of ldopa
(increased/decreased/same) gastric blood flow with age and consequential effect
decreased -> lower absorption of high permeability (water soluble) drugs
HF can also lower gastric blood flow
(increased/decreased/same) first pass effect with age and consequential effect
decreased -> increases F of drugs with high extration (high first pass clearance) -> start iwth lwoer dose
- propranolol
- morphine
- lidocaine
- verapamil
- labetolol
-> decreased F of active metabolite of prodrugs
effect of age on transdermal absorption
dry fat skin with low perufsio -> decreased absorptoin and rate of absorption of hydrophilic compounds (like fentanyl which is bad because we want pain meds to wrk fast)
skin gets even dryer and stuff in cachexia -> fentyl patch super not effectve
(increased/decreased/same) fat with age and consequential effect
increased fat -> increased Vd of lipophilic drugs (benzos)
(increased/decreased/same) water with age and consequential effect
decreased -> low Vd for hydrophilic drugs (Li, theophyline, aminoglycosides, EtOH)
drugmore [in blood]
(increased/decreased/same) muscle mass with age and consequential effect
decreased -> less distribution into muscle -> increased serum level (digoxin)
(increased/decreased/same) albumin with age and consequential effect
same
- however albumin decreases in certain disease states (like frailty) -> incresed free fraction of acidic drugs (asa, phenytin ,vpa) -> increased effect of those drugs
(increased/decreased/same) AAG with age and consequential effect
same no change lol
- however AAG may be elevated in certain conditions (acute illness, cancer, infection, inflammation) -> decreased unbound drug -> decrease effect
there is a (increased/decreased/same) incidence of slow metabolziers in elderly compared to general population
same, but those slow metabolizers are realllll slow -> more susceptible to ADR
drugs that the elderly may not metabolize well
- benzos
- nsaids
- ccbs
- psych meds (VPA, trazodone, haloperidol)
- SSRI: sertraline, paroxetine)
- fentanyl
- warfarin
- phenytoin
drugs that have a significant renal component to elimination
- hydrophilic beta blockers (atenolol
- some ACEi
- gabapenti
- ABX: AGs, vanco, cipro,
- heart: clonidine, digoxin
- H2RAs
- Li
- metforomin
- nicotinc acid
- ripseridone
relavent for old people because their kidneys suck; think about drugs that we dose adjust based on kidneys
(increased/decreased/same) CYP3A4 hepatic activity with age and consequential effect
decreased
(increased/decreased/same) hydroxylation with age and affected drugs
decreased; affected drugs
- alprazolam
- triazolam
- midazolam
- quinidine
- propranolol
- R-warfarin
(increased/decreased/same) demethylation with age and affected drugs
decreased; affected drugs
- imipramine
- sertraline
- verapamil
- theophylline
(increased/decreased/same) glucoronidation with age and affected drugs
same; affected drugs
- lorazepam, oxazepam, temazepam
If VERY old >80 ; reduced a little (oxazepam)
(increased/decreased/same) acetylation with age and consequential effect
same; affects isoniazid
(increased/decreased/same) liver mass with age and consequential effect
decreased -> reducd hepatic metabolism
(increased/decreased/same) liver volume with age and consequential effect
decreased -> redued hepatic metabolism
(increased/decreased/same) liver blood flow with age and consequential effect
decreased (potentially ipacted by cardiac ouput) -> affects high extractio drugs
clearance of asa and metoclopramide in frail patients
reduced
(increased/decreased/same) GI active transport with age and consequential effect
decreased -> reduced F for some drgus
if reduced clearance (increased/decreased/same) t1/2
increased t 1/2
PD changes in elderly: change in baseline
at same [ ], an older person will experience more drug effect → lower [ ] achieve same effect, but adverse even threshold is also at lwoer [ ]
Same slope, higher x intercept
PD changes in elderly: change in sensitivity
greater change in drug effect in older people per unit increase in drug [ ]
Same x intercept, steeper slope
there is more research and literature in the eldrly on PK or PD
PK
(increased/decreased/same) response to agonists and antags at beta adrenergic receptors 1 and 2with age and consequential effect
reduced ->
- diminshed reponse for isproterenol and propranlol
- hydralazine induced reflex cardiostimulation blunted
- hypotension
- beta adreneric response to hypoglycemia blunted
(increased/decreased/same) cardiovagal tone with age and consequential effect
decreased -> vagolyti effects of atropine diminished
unclear but could affect vagolytic effects of TCA and antipsych
CNS PD changes
- altered neurotransmitters and/or receptors
- hormonal changes
- impaired glucose metabolism or decreased availability of glucose and oxygen as cerebrovascular function declines
- extrapyramidal reactions
- parknsonism reaction dominates dt already compromised nigrostriatial pathway
- tardive dyskinesia
- muscarinic deficit
- role of anticholinergics in cog decline
(increased/decreased/same) functional pgp activity in brain and consequential effect
decreased -> increased CNS drug [ ] and increased time in CNS
(increased/decreased/same) benzo cns depression and consequential effect
increased -> lower blood [ ] needed for desired effects
warfarin pd changes
decreased clearance and increased intrinsic sensitivity -> decreased dose needed
uncharacteristic behaviors of drugs (both exagerated and blunted) are ofen due to (PD/PK) changes
PD
