Geriatric Pharmacology

Question 1

geriatric pharmacology

Answer 1

• Geriatrics Gr. geras, old age, iatrike, medical treatment.
• Usually refers to patients over 75 years old.
• Altered pharmacokinetics in the geriatric patient makes adjusted dosing of drugs a requirement.
• Changes in life style, polydrug therapy, increased use of “alternative therapies”, multiple disease conditions and psychiatric changes makes dose adjustment even more important.

Question 2

geriatric pharmacokinetic changes

Answer 2

• Absorption: (all contribute to lowered blood levels of many drugs).
• reduced stomach acidicity
• reduced gastric motility
• reduced first pass biotransformation
• reduced dermal absorption
• Geriatrics are much different than the people that the drugs were tested on!!

Question 3

pharmacokinetic changes

Answer 3

• Drug Absorption:
• Decreased absorption of the drug from the GI often due to (altered nutritional habits, increased use of OTCs, antacids, TUMS, laxatives etc (block drug absorption), slower gastric emptying in the elderly)

Question 4

distribution (Vd)

Answer 4

• lowered body water and higher body fat
• lipophilic drugs remain in fat longer
• altered albumin levels (increased free drug levels)

Question 5

drug distribution altered due to:

Answer 5

• reduced lean body mass
• reduced percentage of body water
• increase in body fat (relative to body mass)
• decreased serum albumin (main protein for binding drugs in serum)
• decreased Vd requires a decrease in dose

Question 6

biotransformation

Answer 6

• Phase I reactions (MFOs) changes can lead to problems (less efficient biotransformation)
• Phase II reactions mostly unaffected
• WE HAVE TO MAKE THINGS WATER SOLUBLE IN ORDER TO GET THEM OUT OF THE BODY
• If a drug leaves the body primarily or exclusively through phase 2 reaction, it is still safe in the elderly

Question 7

decreased rate of metabolism often due to:

Answer 7

• decreased capacity of Phase I (MFO) enzymes
• decreased blood flow to the liver (cardiac related)
• nutritional deficiency alters liver function
• effects on drug biotransformation seen with drugs that require Phase I steps for clearance

Question 8

pharmacokinetic changes

Answer 8

• CYP Inhibitor Drugs Cleared By This CYP
• 2C9 fluconazole ibuprofen, celecoxib
• 3A4 grapefruit juice, itraconazole alprazolam, clarithromycin

Question 9

elimination of drugs

Answer 9

• reduced glomerular filtration rate (CC)
• drug doses need to be calculated based on CC
• “Start Low and Go Slow.” (often ~50% of the standard dose).

Question 10

drug elimination

Answer 10

• Decreased renal clearance of drugs due to
• decreased renal function, 2/3 of all geriatric patients have a decrease in Creatinine Clearance (CC).
• increased t1/2 results with the possibility of drug accumulation and toxicity

Question 11

creatinine clearance (CC)

Answer 11

• Drugs that are eliminated by the kidney (the vast majority) must have dose adjustment for lowered CC.
• For example, CC of 50 mL/min is 50% reduced. If the standard dose of a drug is 250 mg/day, then lower the dose by 50%, or 125 mg/day.
• Most product inserts provide a chart with CC values and the required dose to match the patient’s CC.
• Cockcroft-Gault Equation
• Use to calculate CC (CC mL/min = [(140-Age) (Pt weight kg)] / [71 (Cp creatinine mg/dL)]
• RI for Cp creatinine = 0.7 - 1.3 mg/dL
• CC values decrease ~ 6.5 mL/min per decade
• Think 100 mL/min as reference interval (RI)
• IMPAIRMENT mL/min
• Borderline 62 - 80
• Slight 52- 63
• Mild 42 - 52
• Moderate 28 - 42
• Marked < 28

Question 12

glomerular filtration rate

Answer 12

• GFR = 180 L/day (125 mL/min) of blood plasma is filtered out into the tubules.
• Total body plasma = ~ 3 L, then the entire plasma in the body passes through the glomerulus about 60 times per day.
• GFR is most often measured by the Creatinine Clearance (CC) because creatinine is: (a) formed at a constant rate, (b) present in blood in a constant amount, (c) secreted with no (almost) reabsorption in the tubules.

Question 13

pharmacodynamic changes

Answer 13

• Receptor affinity and/or receptor numbers can change
• Post-receptor factors can change
• Homeostatic mechanisms may be altered. (These changes can lead to increased, (adverse) response to CNS drugs.)

Question 14

ADRs in geriatric patients

Answer 14

1. They take more drugs compared to younger population.
2. Prescription errors due to lack of consideration of pharmacokinetic changes in the elderly.
3. Multiple physicians treat same patient and are not aware of all the drugs patient is on resulting in incompatible drug combinations.
4. Increased usage of OTCs among the elderly which increases the risk for ADRs.
5. Patient drug compliance decreases in direct proportion to the number of different drugs being taken.
6. Increased dosing requirements (more drugs more often administered by staff) among elderly patients in nursing facilities increases the possibilities for a dosing error.
   - Among the elderly the avg number of different prescription drugs being taken is between 6 and 8.
   - Rates of ADRs vary from 10% with one drug to 100% when 10 different drugs being taken.
   - Up to 50% of patients in long-term care facilities are estimated to have ADRs.

Question 15

CNS drugs: sedative hypnotics

Answer 15

• The t1/2 of most benzodiazepines and barbiturates increase from 50 - 150% between the ages of 60 - 70.
• Benzodiazepines often biotransformed into active metabolites which adds to potential of toxicity
• Increased half-life often due to decreased renal function (CC) and altered liver function.
• Increased Cp levels of benzodiazepines often results in toxic signs of ataxia….increased falls and bone fractures. Lorazapam and oxazepam less effected.

Question 16

CNS drugs: analgesics

Answer 16

• Elderly are more sensitive to the respiratory depression induced by opioid drugs.
• Low dose to start with adjustments upward based on response is required.

Question 17

CNS drugs: antidepressants

Answer 17

• Lithium used in bipolar disorders is cleared by kidney exclusively and CC adjustment required due to high potential for toxicity (TI for lithium 0.6 - 1.2 mmol/L)
• Concurrent use of thiazide diuretics reduces renal clearance of lithium.
• Antidepressant drugs widely used in the elderly due to high rate of depression (twice the national average in those over 65 years).
• Major depression in the elderly resulting in apathy, flat affect, social withdrawal is often mistaken for senile dementia.
• Reduced renal clearance and other factors increase risk of toxicity of the TCA antidepressants.

Question 18

CNS drugs: Alzheimer’s

Answer 18

• Disease progresses from memory loss and reduced cognitive function to a complete vegetative state and death.
• Disease associated with decreased neuronal function of acetylcholine (Ach).
• Tacrine is a long acting AchE inhibitor. Liver toxicity in up to 50% of patients (elevated AST, ALT) with dose reduction or drug elimination required.
• Donepezil, rivastigmine and galantamine are newer less toxic CNS AchE inhibitors.
• Co-administered drugs that inhibit CYP450 enzymes required for AchE inhibitor drug biotransformation should be avoided (ketoconazole antifungal).

Question 19

antihypertensive drugs

Answer 19

• Systolic pressure increases with age especially in Western countries with high dietary salt intake.
• “late-onset systolic hypertension” treated with diet, salt reduction, weight reduction encouraged.
• Diuretics in low doses to avoid hypokalemia, hyperglycemia, increased Cp uric acid levels.
• All the general cautions about altered pharmacokinetics in the elderly apply when treating systolic hypertension.

Question 20

positive inotropic drugs

Answer 20

• High incidence of heart failure in the elderly often treated with digoxin.
• Digoxin has a narrow TI of 1-2 ng/mL
• Impaired CC requires dose adjustment.
• Narrow TI increases risk of toxicity (forget dose, take double dose etc)
• Digitalis toxicities occur more frequently in the elderly (arrhythmias, delirium, visual changes and endocrine abnormalities).

Question 21

antimicrobial drugs

Answer 21

• Decreased host defense mechanisms in the elderly increases the incidence of infections.
• Most commonly used antibiotics are cleared through renal mechanisms. CC dose adjustment required for the beta lactams and the aminoglycosides.
• Aminoglycosides cause cranial nerve damage with loss of hearing and renal failure. Constant use of Cp levels and dose adjustment required.

Question 22

aminoglycosides

Answer 22

• A class of antibiotics widely used for the treatment of Gram neg bacterial infections.
• Nephrotoxicity incidence between 5-25%.
• Drugs administered iv and often required because of bacterial resistance to less toxic antibiotics that can be given by mouth.

Question 23

mechanism of action

Answer 23

1. Block peptide formation at initiation step.
2. Cause misreading of mRNA, wrong amino acid inserted, non-functional protein.
3. Cause breakup of polysomes into non-functional monosomes.

Question 24

pharmacokinetics

Answer 24

• Most given im or iv only (except neomycin and kanamycin, po and mostly topical)
• Once daily dosing iv is usual
• Toxicity correlates with Cp levels, > 2 ug/mL trough level (just before next iv dose) is considered toxic.
• Dosage adjustments must be made for impaired renal function (CC) to avoid toxicity.

Question 25

adverse effects and ADRs

Answer 25

• Ototoxicity, nephrotoxicity and neuromuscular toxicity.
• Small margin of safety (tobramycin trough 2-4 ug/mL, toxic > 4 ug/mL)
• Ototoxicity: auditory damage (tinnitus, high frequency hearing loss) vestibular damage (vertigo, ataxia, loss of balance)
• Nephrotoxicity: rise in CC, rise serum Creatinine, rise in trough level.
• Curare-like effect at neuromuscular junction, respiratory paralysis. Reverse with neostigmine.

Question 26

anti-inflammatory drugs

Answer 26

• Osteoarthritis is common disease in the elderly.
• Corticosteroids induce osteoporosis which results in fractures.
• NSAIDs both COX-1 and COX-2 selective and nonselective (aspirin, ibuprofen, naproxin) can cause renal damage after prolonged high dose use.
• Loss of good prostaglandins lead to kidney failure
• Loss of bad prostaglandins leads to prolongation of life

Question 27

NSAIDs

Answer 27

• Incidence varies from 1-18% of all patients with end-stage renal disease requiring dialysis.
• Cell necrosis in tubules may result from decreased production of prostaglandins (PGs).
• PGs are potent vasodilators, lack of PGs in nephron may result in vasoconstriction which results in ischemia and cell death.
• Drugs such as aspirin, ibuprofen, naproxin, and indomethacin etc.
• All NSAIDs act through inhibition of cyclooxygenase 1 and 2 (COX 1 &2) to block synthesis of inflammatory prostaglandins.
• Analgesic nephropathy can result from chronic use of NASIDs (> 3 years).

Question 28

aspects to prescription writing for the elderly

Answer 28

1. Consider lower cost alternative drugs (new NSAIDs can cost $100/month, aspirin, $5/month)
2. Caution against stopping an antibiotic by the patient due to relief from symptoms.
3. Integrate prescription drug choices with what other care-givers are prescribing to help avoid ADRs.
4. Most patients regard herbal medicines as not being “drugs” and are safe. Work to find out about drugs being taken by the patient. Up to 70% of patients will not disclose taking herbal medicines for various reasons.
5. “Child proof” containers are often “patient proof” in patients with arthritis.
6. Patients with tremor, arthritis, visual problems can not self-administer correctly (take one-teaspoon, printing on bottle label too small, drugs that require measuring out the dose etc).
7. When possible reduce the number of drugs being taken, co-ordinate their dosing requirements to reduce number of different times required.

Question 29

prescribing for the elderly

Answer 29

-24% of all patients over 65 receive at least one “inappropriate” prescription medication.

Question 30

7 steps to writing safe prescriptions

Answer 30

1. “Start low and go slow” Begin at 1/2 the usual adult dose and titrate to the desired effect.
2. Prescribe the fewest drugs possible and use the simplest dosing regimen.
3. Patient instruction and education about dose and dosing schedule require more time than expected.
4. Keep cost in mind. Work with patient’s on fixed income and limited or no insurance.
5. Review patient’s drug list periodically. Have patient bring all drugs. OTC and herbal medicines to office once a year.
6. Provide patient with a portable prescription record to take to other physicians. This helps avoid drug-drug ADRs and duplication.
7. Make home health nurses and aides aware of your need to know about any ADRs observed in your patient.

Question 31

adherence vs compliance vs persistence

Answer 31

• Adherence = follow what PA ordered
• Compliance = patient is dealing with their disease
• Persistence = duration patient will take their meds
• DECREASE THE COMPLEXITY OF THE PRESCRIPTION

Question 32

the role of the pharmacist

Answer 32

• Pharmacist plays a major role in out patient/in patient drug management
• Ultimate responsibility however (in my opinion) is with the PA or MD who wrote the prescription.

Question 33

amiodarone

Answer 33

• Amiodaroe has a t1/2 of weeks to months in the elderly. ADRs will take months to resolve.
• Increased body fat in this geriatric patient will result in months before steady state dosing is reached.
• Amiodarone inhibits many CYP enzymes which can cause drug-drug interactions.
• Amiodarone will cause problems with warfarin and blood monitoring of warfarin will be extra important (drug-drug interact).
• Switch to dabigatran which does not require blood monitoring (thrombin inhibitor anticoagulant)
• Amiodarone at 2x day will further complicate the patient’s drug regimen.
• Patient has major problems with Medicare Part D (drug insurance). It will take 10 Wall St lawyers to figure it out.
• Beers Criteria indicates that amitriptyline for migraine is bad news. See if metoprolol will prevent the migraines.