IC2 (PKPD changes)

Question 1

If an elderly patient is on gastric acid suppression, what deficiencies are they predisposed to?

What can it possibly lead to?

Answer 1

vitamin B12
calcium
iron

anemia and fragile bones

Question 2

What 2 antifungals and 2 anticancer drugs do acid suppression therapy drugs interact with?

Answer 2

antifungals: itraconazole, ketoconazole
TKIs: dasatinib, nilotinib

Question 3

What two reasons can prolong gastrointestinal transit time?

Answer 3

diseases (e.g. gastroparesis from diabetes)
drugs (e.g. antispasmodics, anticholinergics)

Question 4

What drug is of concern in elderly with prolonged transit time?

Answer 4

bisphosphonates (alendronate and risendronate)

risk that 30 minutes may not be long enough, risk of esophageal ulceration

Question 5

What effect does phenytoin have on PGP (efflux transporter)?
What drug is implicated?

Answer 5

induces it
dexamethasone - decreases bioavailability

Question 6

What effect does clarithromycin have on PGP (efflux transporter)?
What drug is implicated?

Answer 6

inhibits it
digoxin - increases Cmax significantly, hence increasing risk of SE and toxicity

Question 7

What are the two main causes of concern for absorption via transdermal routes in elderly that increases absorption?

Answer 7

epidermis and dermis thinning
more likely to experience high fevers

Question 8

What is the main causes of concern for absorption via transdermal routes in elderly that decreases absorption?

Answer 8

lower cutaneous blood supply

Question 9

How does ageing affect serum albumin?

Answer 9

Decreases (about 10-15%)

Question 10

How does ageing affect the BBB?
How does this affect elderly patient’s response to certain drugs?

Answer 10

More porous (more significant w dementia)
More susceptible to CNS SE like sedation from anticholinergics

Question 11

Briefly describe the double whammy experienced by alcoholic elderly patients taking paracetamol

Answer 11

Alcohol induces CYP2E1 and produces more NAPQI (toxic metabolite)
Glutathione is depleted in malnourished patients (eg. alcoholics), cannot quench the toxic metabolite

-> further liver damage

Question 12

How is phase I metabolism different in the elderly?

Answer 12

Decreases mainly due to reduced liver mass, hepatic blood flow and sinusoidal endothelium

Question 13

Name 3 well-known “dirty” inhibitors

Answer 13

azole antifungals
clarithromycin
cimetidine

Question 14

Name 3 well-known “dirty” inducers

Answer 14

phenytoin
carbamazepine
rifampicin

Question 15

What is important to take note of for TB pts on rifampicin?

Answer 15

Rifampicin is a strong 3A4 inducer, so other drugs are likely to have their concentrations increased
After TB treatment has finished, remember to bring down and doses that were increased

Question 16

How is phase II metabolism different in the elderly?

Answer 16

not much change

Question 17

How does excretion change in elderly?

Answer 17

General poorer kidney function, less able to eliminate drugs

Question 18

How do baroreflex receptors change in elderly?

Answer 18

baroreflex receptors are less sensitive, body cannot regulate BP well, more likely to experience postural hypotension

Question 19

What two diseases are affected by neuroleptic sensitivity reaction?

Answer 19

lewy body dementia
parkinson’s disease dementia

Question 20

How does neuroleptic sensitivity reaction manifest? (4)

Answer 20

increased sedation and confusion
increased parkinsonism
cognitive decline
higher death rate

Question 21

What medications should DLB/PDD patients NOT be on? (4)

What pathway do these drugs affect?

Answer 21

metoclopramide
promethazine
prochlorperazine
antipsychotics (except low dose quetiapine)

these drugs act via the dopaminergic pathway and DLB/PDD patients are very sensitive to dopaminergic changes

Question 22

What 2 drugs are recommended for DLB/PDD patients experiencing psychosis?

Answer 22

clozapine
pimavanserin

effective in treating psychosis without worsening motor symptoms (low D2 receptor activity)