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Medsci303 Lecture 16&17 > Lecture 16 Drugs In The Elderly > Flashcards

Lecture 16 Drugs In The Elderly Flashcards

0
Q

What makes the elderly a high risk population from ADRs?

A

Drug treatment increases almost exponentially with age.
Increased prevalence of sub clinical and clinical disease
Increased poly pharmacy resulting in drug drug interactions and compliance problems
Decreased function of physiological systems
Altered pharmacokinetics and pharmacodynamics

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1
Q

What is the issue with drugs in the elderly?

A

A huge proportion (90%) of elderly receive at least 1 prescription drug along with many OTC medications.
A significant proportion (30%) of these suffer from ADRs (more than 2-3x frequently than the general population)

Drug effects such as those caused by benzodiazepines, and antidepressants account for a significant number of falls and fractures.
The elderly are a rapidly increasing part of the general population

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2
Q

What is the relationship between the prevalence of chronic diseases with age

A

The prevalence of 3 illnesses increases the most with age

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3
Q

What are the age related changes in physiological systems with relevance to PKs?

A

Decreased:

  • total body mass
  • stomach emptying and gut motility
  • plasma albumin concentration
  • cardiac output
  • renal function
  • hepatic blood flow, size and certain functions

As well as a change in body composition (decreased body water, but increased body fat)

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4
Q

What are the main changes in absorption in the elderly?

A

Decreased (gastric) motility may delay absorption but passive diffusion is unchanged

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5
Q

What are the main changes in bioavailability in the elderly?

A

Bioavailability is Increased by a reduction in FPM in the gut/liver

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6
Q

What are the main changes of distribution in the elderly?

A

Volume of distribution can be increased or decreased depending on the lipophilicity of the drug (as elderly have increased body fat).

There is a decrease in plasma protein binding (due to decreased plasma albumin which binds most drugs.)

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7
Q

What are the main changes of metabolism on the elderly?

A

Phase I reactions are variable decreased however phase II reactions are relatively unaffected.

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8
Q

What is the main changes of renal excretion in the elderly?

A

This is decreased due to reduce GLomerular filtration and tubular secretion

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9
Q

What is the effect of propranolol bioavailability in the elderly?

A

Propranolol is a high hepatic extraction drug known to undergo FPM. The reduced FPM in the elderly resulted in a 4x higher plasma AUC requiring a 25% reduction in the dose in order to avoid toxicity and still achieve therapeutic benefit

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10
Q

What is the result of body weight changes in the elderly?

A

Need to consider actual body weight for dosing

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11
Q

What is the effect of fat content increase in the elderly

A

This will increase the Vd and T1/2 of lipophilic drugs (taking longer to get to steady state)

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12
Q

What is the effect of decreased body water in the elderly?

A

A decreased Vd for hydrophilic drugs

A danger of acute toxicity

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13
Q

What is the effect of the on the pharmacokinetics of diazepam?

A

Because there is no correlation between clearance and age,

We can conclude that a change in the half life must be due to a change in the volume of distribution

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14
Q

What is the effect of age on the hepatic CYP450 content and activity?

A

After 40 there is some decline in the content of CYP450 in the liver
After 60 there is some decline in the activity of CYP450

This is shown by a decreased Antipyrine clearance which is metabolised by a lot of CYP450

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15
Q

What is the effect of age on the clearance of theophylline (which has a low hepatic extraction?

A

Although there is some slight decline with age, it is still very variable.

16
Q

What the effect of CrCl with age?

A

In both males and females, creatinine clearance decreases with age,
This is more significant than a decrease in metabolism, therefore we should take into account the drugs mainly excreted by the kidney.

17
Q

What sorts of drugs are predominantly eliminated renally and therefore should consider a dose reduction?

A 
Aminoglycoside antibiotics (gentamicin)
Antimycotocs (fluconazole)
Antivrals (acyclovir, gancyclovir)
Beta blockers (atenolol)
Betalactam antibiotics (penicillins, cephalosporins)
Digoxin
H2 blockers
Lithium
18
Q

What is the effect of age on the PD and PKs of IV midazolam?

A

Although this was a small study, the lower EC50 indicates a lower sensitivity to this drug.
The difference in EC50 of the young and elderly suggests possibility of pharmacodynamic differences

Turns out, this is dependent on the concentration entering the brain.
In the elderly the efflux pumps decline resulting in a decreased amount of drug reaching the target site.

19
Q

What are the PD changes of diazepam in the elderly?

A

Increased sedation and postural sway

20
Q

What are the PD changes of morphine in the elderly?

A

Increased analgesic effect

Pretty much the same effect of respiratory depression

21
Q

What is the PD effect of propranolol in the elderly?

A

Decreased beta blocking effect

22
Q

What is the PD effect of scopolamine in the elderly ?

A

Decreased cognitive function

23
Q

What is the PD result of temazepam in the elderly?

A

Increased postural sway

24
Q

What is the PD effect of verapamil in the elderly?

A

Increased acute antihypertensive effect

25
Q

What is the PD effect of warfarin in the elderly?

A

Increased anticoagulant effect.

26
Q

What are the characteristics of drugs that should be used with caution in the elderly?

A

CNS active drugs
Drugs with high FPM
Drugs primarily eliminated by kidneys
Drugs with narrow TI
Drugs with anticholinergic properties such as phenothiazines, TCAs, neuroleptics
Drugs causing orthostatic hypotension (postural hypotension) e.g. Antipsychotic phenothiazines due to alpha blocking activity

27
Q

What are specific drug categories causing problems in the elderly?

A

Narcotics/opiods
Antipsychotics
Long acting benzodiazepines

28
Q

What are the problems associated with narcotics and opioids in the elderly?

A

Urinary retention
Constipation
Sedation
Confusion

29
Q

What are the problems associated with antipsychotics (anticholinergics) in the elderly?

A 
Sedation
Confusion
Dry mouth
Urinary retention 
Movement disorders
Other toxicities
30
Q

What are the problems associated with long acting benzodiazepines in the elderly?

A

Over sedation
Confusion
Falls
Fractures

Medsci303 Lecture 16&17 (2 decks)

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