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Year 3 - Geriatrics and Genetics > Drugs and Polypharmacy > Flashcards

Drugs and Polypharmacy Flashcards

1
Q

Why learn about adverse drug reactions (ADRs)?

A

> Over 2 MILLION serious ADRs yearly (USA)

> 100,000 DEATHS yearly

> ADRs 4th leading cause of death ahead of pulmonary disease, diabetes, AIDS, pneumonia, accidents, and automobile deaths

> Ambulatory patients ADR rate – unknown

> Nursing home patients ADR rate – 350,000 yearly

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2
Q

Note

A

As the number of drugs is increased the percentage of patients with adverse effects increases

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3
Q

What percentage of individuals suffering from ADRs in an ambulatory setting are preventable?

A

Nearly one third (30%)

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4
Q

What percentage of individuals suffering from ADRs in an nursing facilities are preventable?

A

Half of adverse drug events in nursing facilities are preventable

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5
Q

Common iatrogenic drug problems?

A

> Confusion, dry mouth, constipation, blurred vision, urinary retention and orthostatic hypotension with anticholinergics

> Confusion and unsteady gait with tricyclics

> Digoxin toxicity with normal serum concentrations

> CNS toxicity with long-acting benzodiazepines

> Confusion with narcotics

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6
Q

Common iatrogenic drug problems - anticholinergics?

A

Confusion, dry mouth, constipation, blurred vision, urinary retention and orthostatic hypotension

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7
Q

Common iatrogenic drug problems - benzodiazepines

A

CNS toxicity with long-acting benzodiazepines

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8
Q

Common iatrogenic drug problems - tricyclics

A

Confusion and unsteady gait with tricyclics

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9
Q

Common iatrogenic drug problems - Digoxin

A

Digoxin toxicity with normal serum concentrations

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10
Q

Common iatrogenic drug problems - Narcotics?

A

Confusion with narcotics

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11
Q

Costly medication-related problems/ADRs in older patients

A 
> Falls
> Cognitive Loss /delirium
> Dehydration
> Incontinence
> Depression
> End result can be
> Loss of functional capacity
> Poor quality of life 
> Nursing home placement
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12
Q

Note

A

Adverse drug reactions look like “growing old”

Unsteadiness
Dizziness
Confusion
Nervousness
Fatigue
Insomnia
Drowsiness
Falls
Depression
Incontinence
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13
Q

Medical conditions might have different presenting signs and symptoms in elderly patients - Hyperthyroidism?

A 
> Depression
> Cognitive impairment
> Muscle weakness
> Atrial fibrillation
> Heart failure
> Angina
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14
Q

What are the worst drugs within polypharmacy?

A 
NSAIDs   29.6% 
Diuretics  27.3% 
Warfarin   10.5% 
ACE-I  7.7% 
Antidepressants  7.1% 
Beta blockers 6.8% 
Opiates  6.0% 
Digoxin   2.9% 
Prednisolone  2.5% 
Clopidogrel  2.4%
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15
Q

Which drugs cause the most adverse events in polypharmacy?

A

Anticholinergics

Sedatives

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16
Q

Gastrointestinal antispasmodics?

A
  • Dicycloverine hydrochloride

- Hyoscine butylbromide

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17
Q

Drugs for overactive bladder - Antimuscarinics?

A
  • Oxybutynin hydrochloride

- Tolterodine tartrate

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18
Q

Tricyclic antidepressants?

A
  • Amitriptyline hydrochloride

- Dosulepin hydrochloride

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19
Q

Sedating antihistamines?

A
  • Chlorpheniramine maleate

- Hydroxyzine hydrochloride

20
Q

Antiemetics?

A
  • Prochlorperazine

- Hyoscine hydrobromide

21
Q

Antopsychotics?

A
  • Chloropromazine hydrochloride

- Haloperidol

22
Q

Changes in absorption with age, what is the exception to the rule?

A

Physiological changes occur that effect the rate but generally not the extent of absorption from the GI tract
- May lead to a delay in onset of action

Exception is levodopa– used for Parkinsons disease. Substantial mucosal metabolism of this drug occurs by the enzyme dopa-decarboxylase, there is a reduced amount of dopa decarboxylase in the elderly- leading to a substantial increase in the absorption of levodopa in the elderly. Elderly patients show a slightly higher peak plasma level and a shorter time to peak than healthy young subjects.

23
Q

Distribution changes in elderly?

A

> Body composition changes

  • Reduced muscle mass
  • Increased adipose tissue = Fat soluble drugs: ↑ Vd, ↑ T1/2, ↑ duration of action e.g. diazepam
  • Reduced body water = Water soluble drugs: ↓Vd, ↑ serum levels e.g. digoxin

> Protein binding changes
- Decreased albumin = ↓ binding, ↑ serum levels acidic drugs e.g. furosemide

> Increased permeability across the blood-brain barrier

24
Q

How are fat soluble drugs effected in the elderly?

A

For fat soluble drugs, in the elderly the Vd is increased owing to the increase in body fat. E.g. Diazepam, haloperidol, The adipose tissue acts as a reservoir for these drugs and an enhanced t1/2 is also seen, resulting in a prolonged duration of action.

25
Q

How are water soluble drugs effected in the elderly?

A

Water soluble drugs tend to experience a reduction in Vd, resulting in higher serum levels. This can be found in the case of theophylline, atenolol, propranolol and hydrochlorthiazide.

26
Q

Acidic drugs in the elderly?

A

Acidic drugs such as cimetidine, furosemide, NSAIDs and sulphonylureas, diazepam, salicyic acid are bound by serum albumin and will be affected.

Higher protein bound drugs such as warfarin and phenytoin chlorpropamide, propranolol and quinidine are also likely to be affected.

Theoretically, a reduction in albumin would mean there is a greater concentration of unbound acidic drugs in the plasma. Predisposing patients to risk of adrs

27
Q

Changes within the CNS and drugs in the elderly?

A

An increase in permeability across the blood brain barrier allows drugs to be more readily distributed in the CNS.

28
Q

Thoughts around digoxin use in the elderly?

A

Digoxin, although water-soluble has a high Vd. This is due to widespread distrubution into the muscle. The reduction in muscle mass in older people means there is a significant reduction digoxins Vd. The clinical consequence of this is that the loading dose has to be substantially reduced in the elderly.

Drugs with a low Vd such as warfarin is not widely distributed. Those with large Vd e.g. digoxin, amiodarone are extensively distributed.

29
Q

Changes in hepatic metabolism in the elderly?

A

Hepatic metabolism is affected by:

- Decreased liver mass
- Decreased liver blood flow
30
Q

Consequences of changes in hepatic metabolism in the elderly and drugs?

A

Consequences
> Toxicity due to reduced metabolism/excretion
> Reduced first pass metabolism
- ↑ in bioavailability with some drugs e.g. propranolol
- Can cause ↓ bioavailability of pro-drugs e.g. enalapril

31
Q

How is excretion of drugs effected in the elderly?

A

Renal function decreases with age

Reduces clearance and increases half-life of many drugs leading to toxicity

32
Q

Pharmocodynamic changes in the elderly?

A

> Increased sensitivity to particular medicines

> Due to:

  • Change in receptor binding
  • Decrease in receptor number
    - Altered translation of a receptor initiated cellular response into a biochemical reaction.

> Examples: diazepam (↑ sedation), warfarin (↑ anti-coagulation)

33
Q

Principles of prescribing for older people?

A

Where possible, be clear about the diagnosis to avoid prescribing a drug to manage an adverse effect

Consider whether drug therapy is the best therapeutic action

Lower doses (or reduced frequency of administration) are generally needed

Think about whether the drug causes particular problems in elderly patients

Check whether a lower dose is recommended in the elderly: start at the lowest dose and titrate up slowly (‘start low, go slow’)

Review the new drug and check whether it is achieving its aim

Review all prescriptions regularly and stop any medicines that are not beneficial

Try to keep regimens as simple as possible

Consider compliance issues which elderly patients in particular may experience

Elderly patients should not be denied proven beneficial medicines on the basis of age

But bear in mind that clinical trials are often performed in a younger population which may mean that benefits do not translate to an older age group

34
Q

Where to get drug information?

A

The BNF

35
Q

Prescribing tools and guides?

A

> Beers’ criteria

  • List of ‘inappropriate’ drugs for older people
  • Updated occasionally but many weaknesses

> START-STOPP criteria (O’Mahony et al)

  • Advice on medical optimisation
  • A lot to remember, so mostly research tool

> NHS Scotland Polypharmacy Guidance

36
Q

What should be done with statins towards end of life?

A

Discontinued

37
Q

Note

A

Some evidence that it is safe and/or beneficial to stop antihypertensives, benzodiazepines, antipsychotics

38
Q

Sedatives in the elderly?

A

Sedatives problematic - Increased effects of benzodiazepines = Falls, confusion

39
Q

Anti-psychotics in the elderly?

A

Increased adverse effects = Postural hypotension, stroke, confusion, movement disorders

40
Q

Anti-depressants in the elderly?

A

Less effective, more dangerous?

41
Q

Opiods in the elderly?

A

> More sensitive to effects, lower doses needed

> Pethidine and tramadol may be less useful

42
Q

NSAIDs in the elderly?

A

Increased adverse effects
> Renal impairment
> GI bleeding

43
Q

Digoxin in the elderly?

A

Increased toxicity

Lower doses needed

44
Q

Diuretics in the elderly?

A

> Decreased peak effect, but reduced clearance
- Abnormal urea and electrolytes

> Other issues around continence and mobility

> Often inappropriate indication (swollen legs)

45
Q

Anti-hypertensives in the elderly?

A

> May have exaggerated effects on BP and HR

> More likely to be issues with postural hypotension

> ACE inhibitors often pro-drugs which may not be metabolised to the active form

> Renal adverse effects

46
Q

Anti-coagulants in the elderly?

A

> More sensitive to warfarin

> Greater risk from warfarin i.e. GI bleeding, falls

47
Q

Antibiotics in the elderly?

A 
Increased adverse effects
> Diarrhoea and c. diff infection
> Blood dyscrasias (trimethoprim, co-trimoxazole)
Delirium (quinolones)
> Seizures
> Renal impairment (aminoglycosides)

Year 3 - Geriatrics and Genetics (10 decks)

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