In the aging population, how does absorption change?
How does the peak serum concentration change in the older population?
Peak serum conc. may be lower and delayed
Exception: Drugs with extensive first-pass effect may increase because less drug is extracted by the liver which is smaller with reduced blood flow
What are the three factors that affect absorption?
- Route of admin
- Concurrent drugs
- Comorbid illness
What are the effects of aging on volume of distribution?
Decreased body water - Lower VD for hydrophilic drugs
Decreased lead body mass - Lower VD for drugs that bind to muscle
Increased fat stores - Higher VD for lipophilic drugs
Decreased plasma protein - higher percentage of drug that is unbound
Factors causing decreased liver metabolism?
- Aging decreases liver bloodflow, size, mass
What drugs based on metabolism are preferred in older patients? Why?
Phase II (conversion drugs to inactive metabolites) because active metabolites can be dangerous
Why are benzos highly contraindicated in elderly patients?
Benzos have highly active metabolites!
What common drug metabolized through hepatic metabolism should be avoided if possible?
What organ eliminates most drugs from the body?
Why can kidney failure be problematic when dosing drugs?
Reduced kidney fuction = reduced elimination = drug accumulation and toxicity
General effects of aging on the kidney
- Decreased kidney size
- Decreased renal blood flow
- Decreased number of functioning nephrons
- Decreased renal tubular secretion
And therefore decreased GFR
What changes in serum creatinine occur with aging?
Lean body mass decreases resulting in lower creatinine production, BUT, GFR decreases too resulting in Cr in normal range
What is the usual method to measure Cr clearance?
Estimate using the Cockroft and Gault equation
What are pharmacodynamics?
Time course and intensity of pharmacologic effect of a drug
What are the four goals of a successful drug diagnosis?
- Use the correct drug
- Prescribe correct dosage
- Target correct condition
- Drug is appropriate for patient
What medications are most commonly associated with adverse drug interactions?
- Cardiovascular meds
- Meds with narrow margin of saftey
What are the RFs for ADEs?
- 6 or more concurrent chronic conditions
- 12 or more doses of drugs/day
- 9 or more medications
- Prior adverse drug rxn
- Low body weight/BMI
- > 85 yo
- Cr clearance < 50 mL/min
What is the ADE prescribing cascade?
Prescribing a drug and then prescribing another drug to Tx the previous drug's SEs
Factors that increase risk of drug-drug interactions?
- Increased number of meds
- Multiple prescribers
- Multiple pharmacies
What are some key facts about drug drug interaction?
- Absorption can be up or down
- Drugs with similar/opposite effects can have exaggerated/diminished effects
- Metabolism may be inhibited/induced
- Herbal preparations can fuck things up
What are the most common adverse effects of drug-drug interaction?
- Cognitive impairment
- Arterial hTN
What are common drug-disease interactions?
- Obesity alters VD of lipophilic drugs
- Ascites alters VD of hydrophilic drugs
- Dementia may increase sensitivity, induce paradoxical rxns to drugs with CNS or antiCh activity
- Renal or hepatic impairment may impair detox and excretion of drugs
What is the basic principle for dosing drugs?
Start low and go slow. Don't start two drugs at once.