Pharmacology and Older People

Question 1

Describe the concept of bioavailability
What are 2 examples of drugs whose bioavailability is affected?

Answer 1

Bioavailability= the fraction of a drug dose reaching the systemic circulation (combination of A, M & distribution)

Eg iron binds with levothyroxine to form an insoluble complex that cannot be absorbed, reducing levothyroxine’s bioavailabilty
Alendronic acid alr has low bioavailability (approx 2%)- w a meal it reduces to nothing - consider the practicalities of this

Question 2

Pharmacokinetics and pharmacodynamics can be affected in old age by affecting absorption, distribution and metabolism

How is absorption imapaired with old age?

Answer 2

Absorption is impaired by:

• swallowing issues
• slower gastric emptying
• increased gastric pH.

Despite these, if meds are taken correctly then these changes are small.

Question 3

Pharmacokinetics and pharmacodynamics can be affected in old age by affecting absorption, distribution and metabolism

Distribution refers to how much of the drug goes to the target tissue.
In elderly, what alters distribution?

Answer 3

Decreased body water increases distribution vol for hydrophilic drugs (eg alcohol)
Decreased plasma protein (esp albumin) affect transport of drugs that bind to proteins, increasing distribution vol (e.g. warfarin)
Decreased lean body mass (sarcopenia) decreases distribution vol for for drugs that bind to muscles (e.g. digoxin)
Increased body fat reduces distribution vol for lipophilic drugs (e.g. benzodiazepines)

(larger Vd means that a higher dose of the drug may be needed to achieve therapeutic concs in the body bc more of the drug is in tissues instead of the plasma)

Question 4

Metabolism= conversion of active drug–> inactive metabolites, mostly done by liver CYP450
What happens to metabolism as you age?

?: impaired by ?
Drugs stay ? in circulation and ?-> ?
Drugs w ? most likely to be affected

? reactions more significantly affected than ? reactions
Significantly affected if ?

1st pass drugs: ?

Answer 4

Hepatic metabolism: impaired by decreased Liver size and blood flow.
Drugs stay longer in circulation and at higher levels–> accumulation and toxicity
Drugs w extensive 1st-pass metabolism most likely to be affected

Phase 1 reactions (oxidation, reduction, hydrolysis) more significantly affected than Phase 2 reactions (conjugation & glucuronidation)
Significantly affected if pt smokes, has HF, portal hypertension etc)

(1st pass drugs: nitrates, propranolol, nifedipine, barbituates)

Question 5

What are the age-related changes in pharmacodynamics?

Increased sensitivity to ? and ?, due to increased ?
Sensitivity to ?
Increased ? of ? effects
Increased ? to ?

Due to these changes, ? should be used carefully – start w ?

Answer 5

Increased sensitivity to sedation (esp benzos) and neuroleptic medication/psychomotor impairment, due to increased BBB permeability
Sensitivity to anti-cholinergic effects
Increased intensity and duration of opioid effects
Increased cardiac sensitivity to digoxin

Due to these changes, opioids should be used carefully – start w lowest possible dose and titrate up

Question 6

What happens to excretion with age?

• Decreased ?
• ? reduces by ?. Measurement of ? may not always reflect this
• Changes ? if patient is ? or?
• Less drug or metabolite is ?, so ? is slower–> increased ?

? ? ? are drugs that can accumulate due to this

Answer 6

• Decreased renal BF, kidney size & functioning nephrons
• GFR reduces by ~8 mL/min. Measurement of eGFR may not always reflect this (use CrCl)
• Changes amplified if patient is hypertensive or diabetic
• Less drug or metabolite is filtered, so elimination is slower–> increased half-life and reduced clearance

digoxin, gentamicin, lithium are drugs that can accumulate due to this

Question 7

For each of these drugs, outline the pharmacodynamic affect and if there is an age related change

Answer 7

Do we need to know this??

Question 8

Polypharmacy: Typically defined as a taking 5 or more medications

How can we prevent or better control polypharmacy?

Answer 8

Right drug, right dose, right person
Consider non-pharmacological management
Review risk / benefits
Involve the patient in decision making

STOPP/START: Screening Tool= basically long drug lists pts should be reviewed for/maybe should be stopped. Eg beta blockers can mask hypoglycaemia, so we should consider alt in diabetic elderly patients
BNF
Polypharmacy: Manage Medicines app
The MDT

Question 9

What are the risk factors for poor adherence in the elderly?

Answer 9

• Complex regimens
• Multiple prescribers
• Medication storage / formulation issues
• Multimorbidity
• Cognitive impairment (don’t understand why they need it or how to take it)
• Physical limitations- eg issues in manual dexterity or visual problems mean you cant retrive the meds/ read dose instructions

Question 10

How can you ensure safe prescribing in older adults?

Answer 10

• Pt centred- involve them in decision making
• Discuss all options inc non-pharmacological
• Review current meds before starting new ones, consider ADRs
• Start low and go slow
• Review the response and change if needed
• Consider the formulation of the medication
• Consider the overall regime and adherence

Question 11

ADRs contribute to 6.5% of admissions and 4% of bed capacity
Present in 10% of inpatients
More than 50% of ADR-related admissions are preventable

compare type A vs B vs C vs D vs E ADR reactions?

Answer 11

Type A= exaggeration of a drug’s expected actions. E.g. bleeding from Warfarin. OR expected side-effects e.g. dry mouth from TCAs

Type B – Novel responses, not immediately expected by drug action. E.g. Anaphylaxis from penicillin.

Type C – Continuing reactions (long-term use) eg osteonecrosis of jaw from bisphosphonates

D – Delayed reactions (leucopaenia 6 weeks after lomustine, delayed cholestasis from co-amoxiclav)

E – End of use reactions e.g. withdrawal of benzos )