Drug Studies in the Elderly

Echocardiography
8. Radionuclide Techniques-Thallium 201
9. Radionuclide Techniques-Equilibrium Angiography
10. Electrocardiographic Changes
11. Conclusions
- References
6 The Effects of Age on Hepatic Drug Metabolism
1. Introduction
1.1. Hepatic Anatomical Changes with Age
1.2. Hepatic Physiological Changes with Age
2. Physiological Model of Hepatic Drug Metabolism
2.1. Clearance Concept
2.2. Intrinsic Clearance
2.3. Drug Binding
2.4. Classification of Drugs According to Extraction Ratio
2.5. Systemic Total Drug Clearance and Apparent Oral Drug Clearance
2.6. First-Pass Metabolism
2.7. Estimation of Hepatic Blood Flow and Intrinsic Clearance
3. Physiological Changes in the Liver with Age
3.1. Liver Blood Flow
3.2. Drug-Metabolizing Enzyme Activity
3.3. Drug Binding
4. Methodological Considerations
4.1. Subject Selection
4.2. Study Design
4.3. Protocol Selection
4.4. Data Analysis
5. Conclusions
- References
7 Hematological Effects of Aging: Considerations for Clinical Trials
1 Introduction
2. Effects of Aging on Blood Cells and Bone Marrow
2.1. Red Blood Cells
2.2. Leukocyte s
2.3. Platelets
2.4. Bone Marrow: Cellularity, Cytogenetics, and Function
3. Effects of Drugs on the Blood and Bone Marrow
3.1. General Considerations
3.2. Are the Elderly More Susceptible to Drug Effects on the Blood and Bone Marrow?
4. Methodological Considerations for Clinical Drug Trials in the Elderly
- References
8 The Aging Brain
1. Introduction
2. Brain Metabolism and Aging in the Rat
3. The Stressed Nervous System
4. Cerebral Metabolic Function and Aging in Humans
5. Cerebral Metabolic Function and Alzheimer's Disease
6. Receptor Function and the Aging Brain
7. Summary
- References

II Pharmacokinetics and Pharmacodynamics in the Elderly
9 The Tricyclic Antidepressants
1. Introduction
2. Diagnosis
3. Pharmacokinetic Factors
3.1. Drug Interactions
3.2. Coexisting Organic Pathology
4. Pharmacodynamic Factors
4.1. Intrinsic Drug Actions
4.2. Coexisting Organic Pathology
4.3. Additive Drug Effects
- References
10 Methodological Concerns for Clinical Trials in Geriatrics: Benzodiazepines
1. Introduction
2. Pharmacokinetic Trials
2.1. Selection of Subject Populations
2.2. Design of the Pharmacokinetic Study
3. Benzodiazepine Pharmacodynamic Studies in Geriatrics
3.1. Drug-Sensitive Pharmacodynamic Measures
3.2. Review of Benzodiazepine Pharmacodynamics in the Elderly
3.3. Pharmacodynamics in Elderly Patients with Underlying Disease
4. Conclusion
- References
11 Effect of Age on the Clinical Pharmacokinetics of Antiarrhythmic Drugs
1. Introduction
2. Major Antiarrhythmic Agents
2.1. Disopyramide
2.2. Lidocaine
2.3. Procainamide
2.4. Quinidine
3. New Antiarrhythmic Agents
3.1. Amiodarone
3.2. Cibenzoline
3.3. Encainide
3.4. Flecainide
3.5. Lorcainide
3.6. Mexiletine
3.7. Pirmenol
3.8. Propafenone
3.9. Tocainide
4. Commentary
- References
12 Beta Blockers in the Elderly
1. Introduction
2. Pharmacokinetics of Beta Blockers in the Elderly
3. Systemic Bioavailability
4. Distribution
5. Clearance
6. Sensitivity of Beta Blockers
7. Beta-Blocker Efficacy
8. Beta-Blocker Toxicity
9. Suggestions Regarding Pharmacokinetic Study Design
10. Concerns for Future Investigations
- References
13 Antiepileptic Drugs in the Elderly
1. Introduction
2. Studies of Antiepileptic Drug Efficacy and Toxicity
3. AED Pharmacology in the Elderly
- References
14 Pharmacokinetics and Bioavailability of Corticosteroids in the Treatment of Neurological Diseases of the Elderly
1. Introduction
2. Factors That Influence Clinical Responses to Administered Steroids
2.1. Normal Bioavailability and Pharmacokinetics
2.2. Pharmacokinetic Considerations of Steroids Administered in Geriatric Patients
3. Administration of Corticosteroids in Neuromuscular Diseases of the Elderly
3.1. The Aging Neuromuscular System
3.2. Common Neuromuscular Problems in the Aged That Need Steroid Therapy
3.3. Incidence of Side Effects from Therapeutic Doses of Corticosteroids in the Elderly
4. Conclusions
- References
15 Pharmacological Treatment of Parkinson's Disease
1. Introduction
2. Levodopa
3. Extracerebral Decarboxylase Inhibitors
4. Artificial Dopamine Agonists
5. Monoamine Oxidase Inhibitors
6. Anticholinergics
7. Amantadine
8. Conclusions
- References
16 Cognitive Enhancers in Alzheimer's Disease
1. Introduction
2. Empirical Therapy
3. Pharmacological Basis for Neurochemical Investigations
3.1. Cholinergic System
3.2. Noradrenergic System
3.3. Dopaminergic/GABAergic Systems
3.4. Serotoninergic System
3.5. Neuropeptidergic Systems
3.6. Glycolytic Enzymes
4. Brain Transplantation
5. Methodological Concerns
5.1. Subject Description
5.2. Description of Severity
5.3. Screening
5.4. Duration of a Therapeutic Trial
5.5. Role of Pilot Studies
5.6. Neuropsychological Measures
5.7. End-Organ Measures
6. Conclusion
- References

III General Perspectives
17 Dosage Form Considerations in Clinical Trials Involving Elderly Patients
1. Introduction
2. Dosage Control and Flexibility
3. Compliance
4. Dosage Form Performance in Elderly Patients
5. Conclusions
- References
18 Clinical Trial Design-Industry Perspective
1. Introduction
2. Industry-Sponsored Drug Studies
3. Elderly Issues
4. Phase I: Pharmacokinetics
5. Phase II
6. Subject Selection
7. Phase III
8. New Therapeutic Objectives
9. Conclusions
- References
19 Methodological Issues: A Regulatory Perspective
1. Introduction
2. Domestic Drug Regulation: Its Aims and Requirements
3. Drug Development Program Design
4. Safety, Efficacy, and Directions for Use
4.1. Efficacy Issues
4.2. Outcome Assessment Measures
4.3. Safety
5. Special Studies
6. Conclusion
- References
20 Statistical Analysis of Drug Disposition Data
1. Introduction
2. Deterministic Approach
2.1. Model Development
2.2. Data Analysis
2.3. Parameter Estimation
2.4. Weighting of Data
2.5. Model Validity
2.6. Model Discrimination and Selection
2.7. Variance Estimates for Model Parameters
2.8. Correlation of Model Parameters
3. Nondeterministic Approach
3.1. Markovian Approach
3.2. Population Statistics
3.3. Kalman Filtering
- References
21 Analytical Methods
1. Introduction
2. Instrumentation
3. Method Development
4. Quality Control
5. Specimen Collection and Storage
6. Metabolite Measurement
7. Plasma Protein Binding
- References
22 Nursing Perspectives on Clinical Trials in Geriatrics
1. Introduction
2. Planning the Protocol
3. In-Service Education
4. Subject Screening
5. Informed Consent
6. Preservation of Patient Comfort and Safety
7. Administration of the Investigational Agent
8. Scheduling and Collection of Data
9. Documentation
10. Controlling Variables
11. Compliance
12. Discharge Planning and Follow-Up
13. Patient Teaching and Counseling
14. Clinical Nurse Specialist
15. The Nursing Administrator
16. Conclusion
- References