Med I: Drug Induced Diseases and Geriatric Considerations

Agonist

drug that activates a receptor by binding to it

has intrinsic activity

Partial agonist: doesn’t elicit maximum possible response produced by full agonists

Antogonist

drug that binds to receptor w/o activating receptos, while preventing agonist from exerting its effect

competitive v non-competitve

Competitive

most common

higher concentration WINS!

• binding reversible w/ competitor

Non-competitive

antagonist binds to receptor and stays bound

• agonist blocked

• NOT reversible w/ concentration

Absorption

acidity of GI tract affects absorption

adsorption: one element binds to another on surface and makes complex (lowers absorption)

• cations and binding resins

Absorption: GI motility/flora

affect rate of absorption NOT amt of drug absorbed

antibiotics/birth control can affect flora

Pharmacokinetics - Metabolism

(AKA biotransformation) change drugs into more hydrophilic metabolites (Phase I (oxidations); Phase II)

• generally results: more polar/inactive metabolites that can be exreted

• results: promote drug activity/ no change/ toxic metabolite

MAIN SITES: liver & small intestines, other tissues

• Cytochrome P450 (CYP) - protein in smooth ER

  • first pass effect!!

Metabolism inhibtion

competitve/nonocompetitive

• DECR metabolism of drug

• stops enzyme → substate builds up (active or prodrug?)

greatest affinity = inhibiting drug

Metabolism Induction

INCR metabolism

• number of enzymes available HIGHer (CYP more synth to metabolize)

• incr hepatic blood flow

Metabolism

Metabolism Characteristics

Affinity

Half-life: duration of interaction (typ complete elimination ~3-5 half lives)

Concentration: threshold concentration must be reached/exceed to inhibit enzyme

Drug interaction considerations

Toxic potential of drugs: check that other drugs don’t have strong affinity to same isoenzyme

Efficacy

PRODRUGS: first pass to active form

Drug-Food Interactions

Absorption/Adsorption: what is altering/changing

• food creates physical barrier and prevents

Metabolism: certain foods can affect the P450 enzymes

• CYP3A4: grape fruit juice is potent inhibitor

Excretion: alter urinary pH

• urinary pH

Pharmacodynamics: drug inhibits/induces smth

• warfarin inhibits vit K dep clotting factors → incr intake of leafy green veggies..

Nutrients:

• drugs able to precipitate when interact w/ foods

  • effect nutrient absorption and exertion

• metformin decr vit B12

• chronic laxatives decr absorption of fat-soluble vit

Pharmacokinetic: Excretion/Elimination

Primary modes! biliary and renal excretion

• affected by pH of urine and alterations of pathways

  • ionization state (lipophilic v hydrophilic): ionized drugs excreted via urine

  • acidic → ionized in alkaline urine (same for basic)

  • altered pH of urine MAY promote increase in reabsorption/excretion of another drug

P-glycoprotein Interactions (PGP)

efflux transporter in intestines, liver, and kidney

• intestines: absorbed thru intestinal wall into circultion

  • can pick up molecule and carry BACK to intestinal form

  • INHIBITED: more drug absorbed

  • INDUCED: less drug absorbed (via enterocytes)

Drug Disease Interactions

Absorption: GI (fast/slow/damaged)

• b12 req stomach acid to be absorbed

Distribution: Albumin levels!!

Metabolism/Excretion:

• disease affecting kidney/liver

  • monitor!! Cr clearance,

• Alcohol intake: DM hypoglycemia, Metronidazole: inhibits enzyme responsible for metabolizing alcohol

Adverse Drug Events (ADEs)

typ as # of drugs administered INCR

“harm cause by appropriate or inappropriate use of drug”

• cases of provider error, non-adherence, incorrect dosages

Adverse Drug Reactions

subset of ADE: har is directly cuase by drug under APPROPRIATE use (@normal dose)

ALLERGY

• drug may act as antigen and elicit one of several classic immune responses

• drug may directly interact with/ immune receptors and under certain circumstances, lead to activation of specific immune cells

• Sx:

  • hives, itching (skin/eyes), skin rash, swelling of lips/tongue/face, wheezing

  • ANAPHYLAXIS: diff breathing/ confusion/ dizziness/fainting/ lightheadedness/ hives spread out/ N/V/ rapid pulse/palpations

Adverse Event Reporting

FDA Adverse Event Monitoring System (AEMS)

• adverse event reports, medication error reports, reports of therapy quality issues resulting in adverse events

• MedWatch: public-friendly portal

  • - printable forms/ by phone/links to reporting syst for med devices/regu therapies

• FDA Safety Reporting Portal

  • by healthcare professionals; pt/fam/caregivers; manufacturers

Challenges of Geriatric Prescribing

CAUSE NON-ADHERENCE

• mult medical conditions (80% 2+; 60% 3+)

  • more medications = more drug interactions/side effects

• multiple medications/ “polypharmacy”

• Multiple Prescribers

• Different metabolisms/responses

• Cost

• Self-medication (herbal/OTC)

• physical & mental changes

Geriatric ADME

Absorption: not from normal aging

• altered by food/drug (antacids/iron); disease (lack of intrinsic (b12 absorp; delayed gastic emptying); incr gastric pH

Distribution:

• less water = less volume = higher conc of water solube drugs

• more fat = higher volume = prolonged action of fat soluble drug (higher half life)

• lower serum proteins (albumin!!) = incre unbound drugs more fat

Metabolism

• slowed

• drug-drug interactions

Elimination:

• Hepatic: decr size and hepatic blood flow SLOW clearance

• Renal: redu renal clearance (sCr not accurate)

• Active drug metabolites may accum

AGS Beers Criteria

Guideline to weight risk/benefit

Anticholinergic Medications (replace w/ diphenhhydramine)

• adverse events more pronounced (confusion/drowsiness/constipation/dry mouth)

• clearance reduced

• tolerance developed when used a hypnotic

Cardiovascular Medicatons

• Avoid:

  • Alpha agents risk (orthostatic hypotension, CNS effected)

  • Anti-arrhythmic → favor rate control

  • Decr elim of digoxin

  • Spironolactone: risk of hyperkalemia

Benzodiazepines

• Incr sensitivity (slow metabolism/sim neurocog to alc)

• incr risk of adverse clinical effects (fall/cognitive/delierium)

• AVOID or use lowest dose

Sedative-Hypnotics

• sim to benzodiazeprines

Antipsych Medications

• avoid → dementia!

• Arrhythmias (QT prolong)

• Abnormal Mvmt (parkinsons..)

Pain

• non-COX-selective NSAIDs (GI bleeding/peptic ulcer disease)

  • avoid chronic use

• indomethacis and keterolac (toraldol)

  • risk of GI/renal/CNS effects

• Merperidin (demerol)

  • cause neurotoxicity. Safer alternatives!!