IC2 PKPD changes in older persons Flashcards
how does gastric acid secretion change in older adults
not all older adults experience change in gastric secretions
even if mucosal atrophy occurs, other factors like concomitants meds are more likely to affect gastric acid production
ie proton pump inhibitors, H2RA
what drugs are affected by gastric acid suppression
1) vit b12, calcium, iron absorption reduced
2) AZOLES
itraconazole (tolsura brand has higher BA, sporanox brand has reduced BA) ; ketconazole (reduced BA)
3) CANCER therapy esp ~tinib drugs
= lower BA
how is gi transit time affected
longer in older persons BUT ORAL BA is unaffected.
- affects timing but not the extent of gastric emptying
what drug MAY be affected by longer GI transit time + counsel
biphosphonates may require longer time upright (usual is 30min)
counsel to avoid breakfast for a longer period of time
what drugs may affect gastric emptying
opioids
anticholinergics
effects of drug absorption in GI from a metabolism pOV?
first pass metabolism
- drugs are metabolised via first pass before it reaches systemic circulation (liver and intestines)
- ? effect of age
efflux
- pgp transporters will reduce absorption BUT effect of age is not obvious
effect mainly still drugs
- phenytoin reduce dexamethasone BA
- clarithromycin increase digoxin Cmax
effects of absorption in older persons (transdermal)
skin atrophy = epidermis and dermis thinning with age
- increases absorption
cutaneous blood supply drops
- decreases absorption
OVERALL: hard to say?
MAINLY external factors/
external factors that affect drug absorption in transdermal (eldely)
HEAT
1) heat packs
2) fever
WILL increase drug delivery
= opioid patches = increase sedation/death
= GTN patch = severe hypotension = MI or stroke
COUNSELLING IS IMPORTANT!
how is distribution affected in elderly patients (what are the physiological changes in elderly) (NON BRAIN)
1) total body water and lean muscle mass drop … fat increases
2) albumin decreases (10-15% decrease, more if sick EG infection/inflammation)
3) a1 glycoprotein increases (mainly due to illness)
ALL ARE NOT CLINICALLY IMPORTANT
what drugs would be affected by elderly changes to distribution
drugs that are highly albumin bound may be affected by decreases in albumin
eg sodium valproate AND phenytoin (serum albumin drop = more free phenytoin = free phenytoin decreases faster = same free concentration, lower total concentration)
- physicians may misinterpret and increase the dose (seeing that total conc is lower = need to use phenytoin albumin correction).
how is distribution affected in elderly patients (what are the physiological changes in elderly)
(INTO THE BRAIN)
BBB and PGP
- BBB more leaky in old age (and DEMENTIA) = may increase sensitivity to psychoactive drugs (e.g., anticholinergic) = MORE ADR
- PGP also more leaky?
types of metabolism in humans
metabolism mainly in liver
- inactivate drug
- activate drug
- facilitate elimination
- remove toxic metabolite (e.g., paracetamol toxic metabolite NAPQI converted to non toxic with glutathione)
two types
- phase 1: cyp p450
- phase 2: conjugation (glucuronidation, acetylation, sulfation)
how is metabolism affected in elderly patients
phase 1 LOWER with age
- reduced liver mass, hepatic blood flow, thickening of sinusoidal endothelium
- cyp affected by frailty (increased inflammation)
- drug cyp interactions
phase 2 NOT AFFECTED
- cyp may not be affected by age (enzymatic ACTIVITY may decrease with small liver AND frailty)
OVERALL: frailty causes a decrease in enzymatic activity for both phase 1 and 2
how is excretion affected in elderly patients
kidney function declines = decrease in drug/metabolite elimination
- due to old age diseases / drugs
insults (e.g., AKI) may cause even healthy (kidney) function to recover less quickly in older patients
what are some key (external) factors that may affect excretion
once again related to kidney function (angiotensin and prostaglandins help to maintain GFR)
- NSAIDs, ACEI and diuretics
- chronic dehydration (common in elderly)
increases the risk of AKI
signs of dehydration? (lab values also
tongue dryness?
increased BUN/SCr
(>20 suggests dehydration, >10 suggests
changes in PD in elderly patients? (OVERALL)
Altered PD may be the result of
changes in receptor affinity for medication,
postreceptor events such as signals from the cell membrane receptor to the cell nucleus,
altered homeostatic control mechanisms
= INCREASED SIDE EFFECTS
changes in PD in elderly patients? in terms of CNS)
more sensitivity to CNS suppressant
eg benzodiazepines
changes in PD in elderly patients? in terms of HR)
- reduced sensitivity to baroreflex
drugs that affect HR or vasodilation = may have less HR increase or more BP lowering
(more sensitive to orthostatic hypotension when dehydrated or given antihypertensives)
- e.g., diuretics
how does dementia affect PD of drugs
reduce cholinergic reserves = increased CNS side effects of anticholinergics
neuroleptic sensitivity = drugs to look out for
neuroleptic (antipsychotic) sensitivity reaction in patients with DLB OR PDD
- increased sedation, confusion, parkinsonism, cognitive decline
DO NOT GIVE METO, PROMETHAZINE, PROCHLOPERAZINE, ANTIPSYCH (EXCEPT quetiapine)
- Pimavanserin may be suitable
overall conclusion for PKPD changes in elderly patients
start low
go slow
consider concomitant diseases AND medications (drugs) = affect cyp interactions and enzymatic activity/binding.
