Drug Induced Diseases Geriatric Considerations

ID and recognize mechanisms for PK interactions: pH interaction on absorption

Drug changes acidity of stomach, changing absorption of other drugs

Ex. proton-pump inhibitors increase gastric pH decreasing absorption

ID and recognize mechanisms for PK interactions: Adsorption interaction on absorption

Two drugs bind together (make complex), leading to drug-drug interactions

Ex. Calcium binds to Fluoroquinolones, preventing it from binding to receptors

ID and recognize mechanisms for PK interactions: GI Motility interaction on absorption

Drugs may interact w rate of gastric emptying, impacting absorption (faster motility = faster rate of absorption)

Reglan speeds rate of gastric emptying

Opiates decerase rate of gastric emptying

ID and recognize mechanisms for PK interactions: Gut Flora interaction on absorption

Dysfunctions impact metabolism and absorption - Gut bacteria are responsible for the metabolism of some drugs during absorption, disrupting gut flora (antibiotics) influences absorption

Antibiotics change gut flora will decrease con (effectiveness) of active ingredient of Birth Control

ID and recognize mechanisms for PK interactions: First Pass Effect on absorption

Oral drugs metabolized prior to entering circulation (decreases absorption amount and distribution)

Physiological dysfunctions (leading to increased first pass effect) may require higher drug con

ID and recognize mechanisms for PK interactions: Antagonism for Protein Binding interaction on distribution

Drugs compete for protein binding, influencing distribution

Drugs w higher affinity wins and binds to protein / Drugs w lower affinity remain unbound and in circulation

ID and recognize mechanisms for PK interactions: CYP Isoenzymes on metabolism interactions

Drugs can inhibit/induce CYP Isoenzymes, slowing or increasing rate of metabolism (influenced via affinity). If the parent compound has toxic potential, check that other drugs don’t have a strong affinity to the same Isoenzyme

Genetic Variation in CYP Isoenzymes + Isoenzyme Induction (increase # of enzymes, increase met) + Isoenzyme Inhibition (decrease met of drugs)

Prodrugs are useless if no isoenzymes

ID and recognize mechanisms for PK interactions: Renal pH on Elimination

Reabsorption from kidneys into bloodstream (type of elim reabsorption). Renal pH = the pH of urine and kidneys affects reabsorption of drugs from kidneys into the bloodstream. pH affects ionized state.

Define and differentiate competitive and noncompetitive inhibition and induction of an enzyme

Competitive: antagonist competes w agonist for receptor sites. Concentration dependent (highest affinity wins). Binding can be reversible

Non - antagonist binds to receptor and stays bound (blocks other drugs, no affect on receptor

Enzyme Induction - Increasing the # of enzymes, increasing metabolism

Recognize the impact of affinity and concentration on metabolic drug interactions

Affinity: Determines “winner” in competitive inhibitor interactions. Drugs with higher affinity will bind to plasma proteins and CYP450 enzymes over drugs with lower affinity. The other drug will remain unbound, continue circulation, increasing rate of distribution, metabolism, and excretion

Concentration: Drugs must reach a threshold to exceed or inhibit enzyme action (metabolism interaction) Ex. Cimetidine a weak inhibitor at low dose, but inhibits 2 isoenzymes at high dose

ID the impact of P-Glycoprotein on drug interactions

P-Glycoprotein: An efflux transporter in intestines, liver, and kidney that pick up drugs absorbed through intestines and carry it back INSIDE to intestine (RECIRCULATION)

Inhibit - more drug absored

Induce - less drug absorbed

ID and recognize mechanisms of pharmacodynamic interactions

Synergistic Effects: Two drugs acting together, their actions add together. Ex: 2 sedatives have synergistic effects

Changes in body chemistry: Drug interactions may affect body chemistry, causing adversity (electrochemical potentials/gradients): Arrhythmias - ACE inhibitors and K sparing diuretics raise potassium lvls

Opposing Effects: drug interaction cancels out the effect of a drug or botch drugs

ID the impact of and common “drug-food”, and drug-disease interactions

Drug Food Interactions:

Absorption - food in gut and gut motility alters extent of absorption, altering rate

Adsorption - Milk based products and Fluoroquinolones

Food creating physical barrier, preventing absorption - Azithromycin has reduced bioavailability when taken with food and should be taken 2 hours apart

Metabolism - Certain foods may alter P450 enzyme (grapefruit juice is inhibiter of 3A4 enzyme

Excretion - Fruit juices may alter urinary pH (acidic juices increase urinary pH)

ID the impact of and common drug-food, and “drug-disease” interactions

Drug-disease Interactions:

Absorption - GI function (fast/slow) affects absorption (B12 needs stomach acid to be absorbed, stomach surgery indicative)

Distribution - Disease causing albumin lvls to fluctuate, affecting protein binding (burn patience have decreased albumin)

Metabolism/Excretion - Liver and Kidney disease impact metabolism and excretion / Alc intake potential for hypoglycemia in diabetics if drug interact w alc met

Define and differentiate between adverse drug reactions, side-effects, and medication error

Adverse Drug Event: Adversity resulting during inappropriate or appropriate use of drug. May be caused by reactions or med errors

Adverse Drug Reaction: A type of adverse drug event of a physiological adverse reaction/harm despite appropriate dosing. USUALLY PREVENTABLE. ID high risk patients, comm w other providers, extensive med history, special patient populations

Medication Errors: Inappropriate med dosing, administration, adherence, or other factors. PREVENTABLE

ID reporting program for drug interactions and adverse drug reactions

FDA

ID and describe the physiologic changes that occur in older adults that impact pharmacokinetic and pharmacodynamic responses

ID and describe the goal of and the commonly prescribed med classes on the AGS BEERS criteria

AGC BEERS criteria - guideline for prescriptions of geriatric patients, allows view of risk to weigh risk vs therapeutic effect

AGS Beers Drug Classes:

1. Anticholinergic Meds - risk of confusion, constipation, and urinary retention

2. Cardiovascular Meds - hypotension, CNS effects

3. Benzodiazepines - increased risk of falls and cognitive impairment, increased sensitivity sim effects to alc

4. Sedative-Hypnotics - Nonbenzodiazepine Hypnotics

5. Antipsychotic Meds - risk of stroke and mortality in dementia patients (avoid for dementia)

6. Pain Meds - risk of sedation, falls, and constipation (opiods)

ID and describe the mechanism of at least four potentially harmful medications for geriatric patients

Anticholinergic Agents - block acetylcholine receptors, leading to decreased secretions and muscle contractions. Can cause confusion, dry mouth, constipation, and urinary retention

Cardiovascular Meds - avoid alpha-1 blockers, alpha agonists (high risk of hypotension / CNS effects) & Spironolactone - higher risk of hyperkalemia

Benzodiazepines - enhance the effect of the GABA neurotransmitter, leading to sedation effects. Increased risk of falls, fractures, and cognitive impairment

Sedative Hypnotics - similar to benzos

Antipsychotic Meds - avoid using for problems associated w dementia

Pain Meds - NSAIDS - GI bleeding, peptic ulcer, & Indomethacin

ID and recognize factors that contribute to non-adherence of medications in the older population

Multiple medical conditions

Multiple medications/polypharmacy

Adverse Drug Reactions

Multiple Prescribers

Cognitive Decline

Recognize potential medication adverse events when an older adult presents with a new condition or complaint on a new medication

Adverse Drug Reactions - symptoms may be misattributed to aging rather than medication effects

Drug interactions - Increased risk due to polypharmacy

Exacerbation of Existing Conditions - New meds may worsen pre-existing health conditions

Given a clinical scenario that includes a geriatric patient, apply guidelines for safe prescribing to avoid adverse reactions

Start Low, Go Slow - begin w lower doses, titrate slowly to minimize adverse effects

Review Meds Regularly - conduct regular med review to asses necessity and effectiveness of each drug

Consider non-pharm options

Educate patients and caregivers - provide clear instructions, strategies for adherence

Monitor for adverse effects - be vigilant for signs, especially when starting a new med