Geriatric Pharmacology Lecture PDF

Question 1

Alzheimer’s disease

Answer 1

A type of dementia which is degenerative or progressive in nature that occurs in half of all patients with dementia

Question 2

Dementia basic definition

Answer 2

Condition characterized by a decline in cognitive function

Question 3

Mild cognitive impairment (MCI)

Answer 3

Cognitive decline greater than expected for an individuals age and educational level but not interfering with activities of daily living, may represent transition between normal aging and earliest stages of dementia

Question 4

Pathophysiology of dementia (4)

Answer 4

Unknown but few contributing factors

• degeneration of neurons (hippocampus for memory particularly short term, cerebral cortex for functioning and speech)
• Reduced cholinergic transmission (low acetycholine in the hippocampus, very low in advanced stage)
• Neuritic plaques and beta amyloids (form outside of neurons and all hallmark found upon autopsy)
• neurofibrillary tangles and tau (hallmark feature of Alzheimer disease where tangles form inside neurons result from disruption of orderly arrangement of microtubules)
• homocysteine (formed from dietary methionine, increased risk of alzheimar’s disease occurs in those with elevated plasma levels - believed to promote atherosclerosis or direct injury to nerve cells, risk reduced by eating foods or taking vitamin supplements

Question 5

Amyloid hypothesis

Answer 5

Amyloid protein deposition in the brain is associated with alzheimers dissease pathology and a decline in cognitive function, toxic to hippocampus and when injected directly into brain produce condition identical to alzheimer’s disease but only in old age not young so aging must make brain more susceptible

Question 6

4 cholinesterase inhibitors approved by FDA for treatment of mild to moderate alzheimer’s disease, effectiveness

Answer 6

• tacrine (cognex)
• donezepil (aricept)
• rivastigmine (exelon)
• galantamine (reminyl)

Treatment can produce clinically significant improvement but modest effects at best so guidelines do not recommend drugs for all patients, use of anticholinergics can blunt their effect

Question 7

Tacrine (cognex) mech of action

Answer 7

centrally acting noncompetitive reversible cholinesterase inhibitor, can also block reuptake of dopamine, seratonin and norepi

Question 8

Tacrine (cognex) ADR’s

Answer 8

-increase in serum alanine aminotransferase in almost 50% of patients, requiring LFTs as it can cause focal necrosis and hepatitis while being used

Question 9

Donezepil (aricept) function

Answer 9

Acetycholinesterase inhibitor used for treatment of severe alzheimar’s disease, high degree of selectivity in CNS with little peripheral activity, has long half life and can be dosed once daily and has no major interactions with minimal ADR’s (no hepatotoxicity, only really weight loss and nausea) unlike tacrine making it a preferred agent

Question 10

Rivastigmine (exelon) function

Answer 10

Acetycholinesterase inhibitor used for treatment of severe alzheimer’s disease similar to donezepil in that it has no major ADR’s but is unique in that it can be applied as a patch opposed to oral

Question 11

Memantine (namenda) drug class, mech of action, function, ADR (1)

Answer 11

• NMDA receptor antagonist
• modulates action of glutamate (excitatory CNS neurotransmitter) by blocking NMDA receptor and therefore blocks calcium influx when extracellular glutamate is low but allows influx when extracellular glutamate is high (improves memory by allowing signaling when it is necessary and not small constant releases of glutamate causing continued entry of calcium which negatively impacts memory)
• approved for treatment of moderate to severe alzheimer’s disease, causes modeset effects that can slow decline in function and may cause symptoms to improve
• well tolerated, can cause confusion and hallucinations

Question 12

Antipsychotics use in dementia patients (2) and ADR (1)

Answer 12

Used to treat agitation, although not FDA approved, atypical 2nd gen (risperdone and olanzapipne) generally prescribed because of decreased risk of extrapyramidal effects

-increased risk of death for unknown reasons in elderly

Question 13

Supplements for alzheimer’s disease (2)

Answer 13

• ginko bilopa
• axona

effectiveness is not well known

Question 14

Estimates suggest that persons greater than 65 take __ medications daily on average

Answer 14

7!!!

Question 15

Impact of polypharmacy (3)

Answer 15

• potentially preventable hospital admission and treatment complications due to medication use
• hospitalized patient has 1/3 chance of iatrogenic complications developing secondary to medication use during hospital stay
• lack of general understanding of impact of multiple medication use in the body

Question 16

How does age alter oral absorption?

Answer 16

It generally doesn’t in absence of malabsorption syndromes

Question 17

Volume of distribution and its impact in the elderly drug distribution

Answer 17

Theoretical space in a given patient that a drug occupies, significantly affected by relative proportions of lean body mass vs fat, as we age see fat increase relative to lean mass, as a result lipid soluble drugs will have a greater Vd than water soluble drugs which have smaller, medications that are water soluble tend to see higher conc per dose resulting in more intense effects, while fat soluble tend to sequester into fat prolonging half life and decreasing intensity of effects

Question 18

Metabolism of drugs in the liver and its impact on the elderly

Answer 18

Hepatic blood flow decreases steadily by age, can decrease significantly first pass effect and can see increased activity per unit dose in older patient

Question 19

Protein binding of drugs and its impact on the elderly

Answer 19

Not clinically significant changes in healthy elderly but those with severe chronic disease or malnutrition - hypoalbuminemia becomes relevant when considering drugs that are highly bound to protein, because fewer binding proteins increases plasma conc. and increases intensity of effects to potentially toxic levels

Question 20

Excretion of drugs and its impact on the elderly

Answer 20

Renal drug excretion undergoes progressive decline from adulthood onward, coexistence of renal pathology can further compromise function, renal functioning should be assessed in nephrotoxic drugs (creatinine clearance huge for this)

Question 21

Adverse drug reactions in geriatrics (the prescribing cascade)

Answer 21

More common accounting for greater than 10% of hospital admissions among older individuals, misinterpretation of an adverse effect as a new medical condition requiring treatment may lead to prescription of additional medications with their own potential for side effects

Question 22

Rule of thumb to prevent polypharmacy and adverse reactions

Answer 22

Try to alleviate symptoms by stopping medications before starting new ones

Question 23

Most common form of noncompliance in drug taking of a patient

Answer 23

Underuse of drug as prescribed

Question 24

Unintentional (3) and intentional (2) noncompliance reasons when a patient is prescribed a drug

Answer 24

• forgetfulness
• failure to comprehend instructions
• inability to pay
• conviction that drug was not needed in dose prescribed
• unpleasant side effects

Question 25

Pharmacodynamic changes in the elderly

Answer 25

Alteration in receptor properties may underlie altered sensitivities to drugs, for example B blocker being less effective at the same dose in elderly compared to younger patients, thought to be due to either decreased receptor number or reduced affinity