Clinical Pharmacology in Old Age

Question 1

2 simple principles in absorption of drugs?

Answer 1

1. Acidic drugs require an acidic environment (pH <7.35) for absorption, e.g: phenytoin, aspirin, penicillins
2. Basic drugs require a basic environment (pH >7.35) for absorption, e.g: diazepam, morphine, pethidine

Question 2

How do PPIs affect absorption of drugs?

Answer 2

Reduce acidity of the stomach environment and so affect absorption of acidic drugs

Question 3

When is increased gastric pH and decreased small bowel surface area an issue?

Answer 3

If a patient has had a previous GI surgery

If they have an NG tube or PEG feed

Transdermal patches and oedema

Question 4

Changes in the elderly that affect distribution of drugs?

Answer 4

Protein binding

Increased fat

Decreased body water

Question 5

Protein binding in the distribution of most drugs?

Answer 5

Albumin, a basic protein, binds to acidic drugs

Alpha-1 acid glycoprotein (A-1 AG), an acidic protein, binds to basic drugs

Question 6

How does protein binding of drugs change in older individuals?

Answer 6

Older individuals often have lower albumin but higher A-1 AG; thus, they distribute more basic drugs, contributing to the increased effect of basic drugs, like morphine, compared to younger individuals

Question 7

Lipid binding in older people as involved with distribution of drugs?

Answer 7

Increased fat (proportional mass) increases the Vd of lipophylic drugs, e.g: diazepams and anaesthetics

This contributes to a longer 1/2-life

Question 8

Define the half-life?

Answer 8

Duration of time taken for the drug to reach half its initial conc.

Question 9

Define the volume of distribution (Vd)?

Answer 9

A hypothetical volume used to understand how lipophilic a drug is

Question 10

Implications of increased fat present in elderly patients in the distribution of drugs?

Answer 10

As this increases the Vd of lipophylic drugs, if the patient enters a starvation state, fat will break down and release the sequestered drug

Patient may suddenly become toxic

Question 11

How does decreased body water in the elderly change the distribution of drugs?

Answer 11

The most important change is a decrease in the Vd of hydrophilic drugs, e.g: lithium and digoxin

Question 12

If there are so many changes in the elderly affecting distribution of the drug, why is it that the 1/2-life of most drugs remains unchanged?q

Answer 12

Both the Vd and CrCL are decreased

However, accompanying disease states can change this, e.g: renal disease

Question 13

Routes by which drugs are metabolised and excreted?

Answer 13

Hepatic metabolism

Renal metabolism

Question 14

Elderly changes in hepatic metabolism?

Answer 14

Reduced liver function due to decreased liver size, blood flow and disease, e.g: CHF

1st pass metabolism is reduced, e.g: due to drugs like propranolol

In general, bio-transforming enzymes, like CYP 450, are reduced in the elderly

Question 15

Elderly changes in renal metabolsim?

Answer 15

Lower GFR due to decreased size, tubular secretion and renal blood flow

Question 16

Measuring renal function in older patients?

Answer 16

Serum creatinine is not a reliable measure

CrCl is the creatinine clearance rate

Question 17

Formula for calculation of the CrCl?

Answer 17

(140 - age) x body weight (kg)

Divided by

Serum creatinine (micromol/L)

This fraction is multiplied by 1.23 in women and by 1.04 in men

Question 18

General changes in drug doses in older patient?

Answer 18

Lower doses achieve the same effect, e.g: alcohol

BUT some effects are decreased, e.g: β-blockers and heart rate

In general, older patients require much lower doses

Question 19

What is the therapeutic index?

Answer 19

The gap between the lethal dose and the dose required to achieve some therapeutic effect

i.e: it is equal to the LD50 / ED50
OR
MTC / MEC

Question 20

10 main drugs that have a narrow therapeutic index, i.e: <2?

Answer 20

All of these are rigorously monitored;
• Theophylline 
• Warfarin
• Lithium
• Digoxin 
• Gentamicin 
• Vancomycin
• Phenytoin
• Cyclosporin
• Carbamezapine
• Levothyroxine

Question 21

How does the therapeutic index change as a patient grows older?

Answer 21

Therapeutic window narrows as the therapeutic response to the drug decreases and the toxic response increases

Question 22

How do ADRs occur?

Answer 22

As a result of:

1. Drug-drug interactions
2. Drug-disease interactions
3. Drug-food interactions
4. Drug side effects
5. Drug toxicity

Question 23

Common examples of drug-drug interactions?

Answer 23

Theophylline and macrolide antibiotics

Statins and macrolides / statins and fibrates (40x increased risk of rhabdomyolysis)

TCAs (tricyclic anti-depressants) and type 1 anti-arrhythmic drugs

Warfarin and multiple drugs

ACEIs increase the hypoglycaemic effects of sulfonylureas

Clopidogrel and PPIs

Question 24

Common drug - OTC/herbal interactions?

Answer 24

Grapefruit juice inhibits the CYP450 system and

Gingko biloba used for dementia has an anti-coagulant effect

Saw palmetto used for BPH has an anti-coagulant effect

Glucosamine used for OA can cause hyperglycaemia and has an anti-coagulant effect

St. John’s wort used for depression can induce the CYP 3A4- CoC)

Question 25

Examples of drug-disease interactions?

Answer 25

Patients with Parkinson's disease have an increased risk of drug-induced confusion NSAIDs / COX-2 / TZDs can exacerbate CHF Urinary retention in BPH patients on decongestants or anti-cholinergics Constipation worsened by calcium, anti-cholinergics, CCBs Neuroleptics, tramadol and quinolones result in lower seizure thresholds (not advised in epileptic β-blockers and asthma

Question 26

Examples of drug-food interactions?

Answer 26

Bananas, oranges and green leafy veg (potassium rich) interact with ACEIs, ARBs and K+ - sparing diuretics Apples, chickpeas, spinach, nuts, spinach, kiwi and brocolli (vit E and K) interact with warfarin Chicken, turkey, milk, cheese, soy, yoghurt (alter pH) interact with antibiotics, thyroid medications, digoxin and diuretics Grapefruit, apple, oranges and cranberry (affect CYP450) interact with statins and anti-histamines

Question 27

Types of adverse drug reactiona?

Answer 27

A - augmented pharmacologic effect (extension of the drug's normal pharmacology) B - bizarre effects (occur unpredictably and often have high morbidiy/mortality) C - chronic effects (occur during prolonged treatment and not with single doses) D - delayed effects (occur remote from treatment, e.g: in children of treated patients or in patients years after treatment) E - end-of-treatment effects (occur when a drug is stopped, esp. if this is done abruptly)

Question 28

Example of an augmented pharmacologic effect?

Answer 28

Hypoglycaemia due to insulin injection

Question 29

Example of a bizarre effect?

Answer 29

Anaphylaxis due to penicillin

Question 30

Example of a chronic effect?

Answer 30

Iatrogenic Cushing's with long-term prednisolone use

Question 31

Example of a delayed effect?

Answer 31

2nd cancers in those treated with alkylating agents for Hodgkin's disease Clear-cell carcinoma of the vagina in the daughters of women who took diethylstilbestrol during pregnancy

Question 32

Example of end-of-treatment effects?

Answer 32

Unstable angina after β-adrenoceptor antagonists are abruptly stopped

Question 33

Drugs that are most commonly assoc. with ADRs in older patients?

Answer 33

Warfarin, digoxin, insulin, benzodiazepines Diuretics, NSAIDs, corticosteroids, anti-hypertensive, opiods, theophylline

Question 34

Anticipatory prophylaxis commonly used when prescribing drugs?

Answer 34

Optiods - begin lactulose or senna Steroids - if long term, osteoporosis prevention is required

Question 35

Side effects of NSAIDs?

Answer 35

GI haemorrhage (decreased risk with COX-2 inhibitors) Decline in GFR (COX-2 inhibitors also do this) Decreased effectiveness of diuretics and anti-hypertensive agents

Question 36

Alternative to NSAIDs for mild OA?

Answer 36

Paracetamol is as effective as NSAIDs in mild OA

Question 37

Side effects of opioids and benzodiazepines?

Answer 37

Impair psychomotor function (GABA-A mediated) Falls and confusion

Question 38

Side effects of antibiotics?

Answer 38

Resistance C. diff diarrhoea