18 PK/PD Changes in Elderly Kim

Question 1

What drug would benefit from the larger Vd and longer t1/2 for lipophilic drugs in the elderly?

Answer 1

Diazepam (lipophilic)

Question 2

What changes are there in plasma protein in the elderly?

Answer 2

Decrease in albumin. Higher free drug concentration for highly bound drugs

Question 3

What are some highly protein bound drugs?

Answer 3

Phenytoin, Amiodarone, Warfarin, Valproate, NSAIDs, Benzos (Diazepam, Lorazepam, Temazepam)

Question 4

How does the liver change in the elderly?

Answer 4

Decreased hepatic blood flow. Content of CYP450 enzymes diminishes with age and lower dosage required for highly metabolized drugs

Question 5

What are some common renally eliminated drugs that should have lower dosages?

Answer 5

Many antibiotics (Vanco, Levo, Most beta-lactams (except Oxacillin or Ceftriaxone)), Allopurinol, Sotalol, MTX, Cisplatin

Question 6

What gastrointestinal changes occur in the elderly?

Answer 6

Increased gastric pH (iron and calcium both need acidic environments for absorption). Decreased iron and vitamin B12 absorption

Question 7

What sort of drugs are effected d/t the decrease in Vd of hydrophilic drugs?

Answer 7

Aminoglycosides with higher initial plasma concentration. Less effective distribution of other water-soluble drugs: Sotalol, Atenolol, many antibiotics

Question 8

What sort of drugs are effected d/t the increase in Vd of lipophilic drugs?

Answer 8

Amiodarone, Diazepam, Haloperidol (which can increase the risk of QT prolongation)

Question 9

Which drugs are affected by Phase II (conjugation) metabolism, not having to worry about them as much?

Answer 9

Lorazepam, Temazepam

Question 10

What happens with the autonomic nervous system in the elderly?

Answer 10

Reduction in Beta-Adrenergic receptors in cardiovascular system and respiratory tract

Question 11

Which types of drugs increase the risk of falls in elderly d/t increased risk of orthostatic hypotension?

Answer 11

Anti-Hypertensive. Antiepileptics (Keppra is a big issue). Benzos

Question 12

Which drug classes do the elderly have an increased response to?

Answer 12

Opioid analgesics. Benzos. Warfarin. ACE-Is. CCBs

Question 13

Which drug classes do the elderly have a decreased response to?

Answer 13

Beta agonists and antagonists (e.g. Albuterol; may not have the effects but can still have the ADRs). Diuretics

Question 14

Which Sulfonylurea is preferred in the elderly?

Answer 14

Glipizide > Glyburide (has active metabolites that are renally eliminated, higher risk of hypoglycemia in elderly patients)

Question 15

Which medication classes cause the most ADRs leading to hospitalization?

Answer 15

Digoxin. Warfarin. ASA. NSAIDs. Psychoactive. Antihypertensive

Question 16

Which Benzos are preferred in the elderly?

Answer 16

Short-Acting Preferred (LOT): Lorazepam, Oxazepam, Temazepam

Question 17

Which GI medication needs to be avoided in elderly?

Answer 17

Cimetidine d/t its potential CNS side effects and high DDIs

Question 18

When must anticholinergics be avoided?

Answer 18

In patients with closed-angle glaucoma

Question 19

Which TCAs have greater anticholinergic activity?

Answer 19

Tertiary amines: Amitriptyline, Imipramine, Doxepin

Question 20

What is the most common potentially serious ADR from TCAs?

Answer 20

Orthostatic hypotension is most common. Less risk with Nortriptyline (second gen)