Individualized Drug Dosing: Narrow Therapeutic Range
Why Must Drug Doses Be Adjusted Individually for Drugs with a Narrow Therapeutic Range?
Drug dosage must be adjusted individually due to variations in:
- Pharmacokinetic Processes: Differences in absorption, distribution, metabolism, and excretion. These are the main determinants of inter- and intra-individual variability.
- Pharmacodynamic Processes: Changes in drug-receptor binding. This may be due to genetic factors, environmental factors, or disease.
Why is Health Education Important for Side Effects of Drugs with a Narrow Therapeutic Range?
No two people are alike. A single dose of a drug causes very similar effects in most people, but in some, it may not produce the desired effect. The same dose may be insufficient, ineffective, cause an exaggerated response, or be toxic.
Impaired Drug Absorption in Neonates
- Oral: Peristalsis is slowed, so drugs may take longer to reach circulation.
- Topical: The skin is thinner and more supple, leading to greater drug absorption.
- Intramuscular: Reduced blood flow to less-developed muscles can result in slower absorption. Proper muscle selection for injections is crucial (e.g., gluteal muscles are not adequate until 7 years old).
Impaired Renal Drug Elimination in Neonates
The renal system is immature, with lower glomerular filtration and tubular function. Reduced kidney function increases the risk of toxicity as drugs and metabolites accumulate in the blood.
Altered Drug Metabolism in Older Adults
Blood supply to the liver and liver function diminish with age. Some drugs have an increased half-life (e.g., verapamil, propranolol, salbutamol) due to slower metabolism.
Factors Increasing Medication Errors in Older Adults
- Visual impairment
- Complicated regimens
- Polypharmacy
- Memory difficulties
- Difficulty managing blisters and small tablets
- Long-term treatments (e.g., for hypertension)
Effect of Renal Impairment on Drug Elimination
Renal impairment limits the kidney’s ability to remove drugs or their metabolites, potentially leading to accumulation. It also causes a decrease in albumin, and plasma substances like fatty acids compete with drugs for protein binding. Consequently, the free fraction of the drug is much greater, as it is difficult to eliminate and not bound to plasma proteins.
Effect of Hepatic Impairment on Drug Metabolism
Hepatic impairment increases the half-life of many drugs in the blood because their metabolism slows. Therefore, a person with liver failure may experience an exaggerated response or intoxication with the same drug quantity.
Monitoring for Drug Toxicity in Heart Failure Patients
Reduced cardiac perfusion in heart failure affects the digestive system, tissue perfusion, and liver and kidney perfusion. It is crucial to monitor for signs of drug toxicity.
Populations at Increased Risk of Drug Toxicity
The following patients are at *increased* risk of drug toxicity:
- Infants
- Elderly
- Patients with hepatic impairment
- Patients with renal impairment
- Patients with cardiac impairment