Pharmacology and Patient Factors in Elderly Patients

Course number: 0201531, offering 3 credit hours
Prerequisites: Pharmacology (3), Biopharmacy and Pharmacokinetics, Clinical Biochemistry
Instructors: Dr. Alaa Hammad, Dr. Ameerah Hasan Ibrahim

Understand principles of therapeutics and individual patient factors impacting drug selection and dosing
Identify patient-specific factors influencing treatment efficacy
Describe therapeutic regimens for common diseases and assess treatment effectiveness
Apply pharmacotherapy principles in practical cases

Triad of Therapy: Requires knowledge of disease, patient, and drug factors.
Disease Factors: Includes etiology, pathology, severity, onset, natural history, symptoms/signs, and complications.
Patient Factors: Encompasses genetics, age, gender, physiological conditions (e.g., pregnancy), and comorbidities.
Drug Factors: Focus on pharmacodynamics, pharmacokinetics, adverse effects, and drug interactions.

Pharmacogenetics: Examines genetic determinants of drug action at cellular and subcellular levels.
Pharmacogenomics: Investigates how genetic variations influence an individual’s drug response.

Variations in enzyme activity can significantly affect drug metabolism:
- CYP3A4/5: Metabolizes calcium channel blockers, benzodiazepines, SSRIs, and more.
- CYP2D6: Influences metabolism of beta-blockers and many antidepressants.
- CYP2C9/19: Affects anticoagulants (e.g., warfarin) and NSAIDs.

Physiological changes in the elderly alter drug pharmacokinetics:
- Absorption: Slower due to higher gastric pH and reduced blood flow.
- Distribution: Changes in body fat percentage, water composition, and plasma proteins impact drug effectiveness.
- Metabolism: Decreased liver function and phase I metabolism slow drug clearance.
- Elimination: Reduced renal function increases risk of accumulation for renally-excreted drugs.

Risk factors for increased adverse reactions include polypharmacy, poor compliance, and altered pharmacodynamics.
Commonly affected responses include blunted reactions to beta-adrenoceptor agonists, increased CNS sensitivity, and reduced baroreceptor sensitivity leading to hypotension.

Avoid long-acting benzodiazepines and anticholinergic drugs to minimize confusion and sedation.
Use smaller doses due to altered pharmacokinetics, ensuring patient understanding for compliance.
Implement rigorous drug histories to avoid unnecessary polypharmacy and consider drug withdrawal when adding new medications.

Drug handling differs significantly in neonates and infants due to immature organ functions and body composition variations.
Clinical management requires awareness of these developmental changes to optimize therapeutic outcomes.

"Pharmacotherapy: A Pathophysiologic Approach" (11th edition) by Joseph DiPiro
"Pharmacotherapy: Principles and Practice" (5th edition) by Marie A. Chishol-Burns
"Applied Therapeutics: The Clinical Use of Drugs" (10th edition) by Koda-Kimble
"Clinical Pharmacy and Therapeutics" (3rd edition) by Roger Walker and Clive Edwards

This course focuses on the integration of knowledge areas to optimize therapeutic plans tailored to individual patient needs, highlighting the critical role of pharmacogenetics, patient factors, and age-related considerations in drug therapy.### Pharmacokinetics of Drugs in Infants

Gastric pH drops from 6-8 to 1.3 within the first 24 hours after birth.
Gastric emptying is slow in the initial day of life.
Immature pancreatic lipase secretion affects fat absorption.
Rectal absorption is highly efficient for drug administration.
Intramuscular injection absorption is unpredictable.
Transdermal absorption is enhanced due to a less developed skin barrier and good skin hydration.

Body water percentage in infants is approximately 78%, with extracellular fluid (ECF) around 25-35%.
Newborns have a higher apparent volume of distribution for water-soluble drugs due to increased body water and low fat content.
Premature infants contain only 1% fat of total body weight, versus 15% in mature infants.
Fat-soluble drugs exhibit lower apparent volumes of distribution in infants due to reduced fatty tissue.
Low plasma protein binding in newborns results from low plasma protein levels, binding capacity, and binding affinity.
Competing compounds like bilirubin can affect drug binding and distribution.
Drugs with low plasma protein binding include phenobarbital, salicylate, phenytoin, theophylline, propranolol, lidocaine, penicillin, nafcillin, and chloramphenicol.

Neonates show reduced activity of cytochrome P450 enzymes, affecting drug metabolism.
Low activity of glucuronide conjugation enzymes is present in neonatal life.
Sulfation and methylation pathways are well developed in infants.

Kidney function takes 6-12 months to mature fully.
Glomerular filtration rate (GFR) is 30-40% of adult levels in the first few days, increasing to 50-60% by 3 weeks of age.
Drugs reliant on renal excretion, such as aminoglycosides, penicillins, and diuretics, may require reduced doses before 6 months of age.

Drug effects can differ in infants due to unique pharmacodynamic factors.
Maintenance doses for digoxin are higher in infants compared to adults.
Propylene glycol may induce hyperosmolarity in infants.
Benzyl alcohol usage can lead to toxicity and potentially fatal outcomes.
Fluoroquinolones are linked to the risk of arthropathy in infants.
Aminoglycosides demonstrate reduced toxicity in this age group.
Prostaglandin analogues are used to maintain patency of the ductus arteriosus in newborns.