Factors Affecting Drug Therapy

How Age and Body Weight Affect Drug Therapy

• Infants and the very old are typically most responsive to drug effects.
• The aging process causes changes in body composition and organ function.
• Overweight patients may need a higher drug dosage to get the same therapeutic effects.

How Gender and Metabolic Rate Affect Drug Therapy

• Men and women function differently in almost every body system and experience disease differently.
• Patients that have a higher-than-average metabolic rate tend to metabolize drugs more rapidly.
• Chronic smoking enhances the metabolism of some drugs.

How Illness and Psychology Affect Drug Therapy

• Pathologic conditions may change the rate of absorption, distribution, metabolism, and excretion of a drug.
• Patients who have kidney failure usually excrete drugs at a slower rate.
• Attitudes and expectations play a big role in a patient's response to therapy and willingness to take medication as prescribed.

Placebo and Nocebo

• Placebo effect occurs when a patient's positive expectation can positively affect the outcome.
• Nocebo effect occurs when a patient's negative expectations can result in a less-than-optimal outcome.

Drug Tolerance

• Drug tolerance occurs when a person begins to require a higher dosage of a medication to produce the same effects that a lower dosage once provided.
• Drug tolerance can be the result of psychological dependence.

Drug Dependence

• Drug dependence occurs when a person is unable to control their ingestion of drugs.
• Physiologic drug dependence involves a person developing withdrawal symptoms if the drug is withdrawn.
• Psychological drug dependence involves a person being emotionally attached to a drug.

Cumulative Effect

• Drug accumulation occurs when the next dose is given before the previously given drug has been metabolized or excreted.
• Drug accumulation may cause drug toxicity.
• Carcinogenicity is the ability of a drug to induce living cells to mutate and become cancerous.

Factors That Influence Absorption

• Absorption is the process by which drugs are absorbed in the body.
• Drugs are most commonly absorbed through the GI tract, but can also be absorbed through parenteral and topical routes.
• Premature infants: Slower gastric emptying time may allow increased absorption.
• Neonates: IM absorption erratic, reduced gastric acidity.
• Infants: Topical absorption increased.
• Geriatric patients require special considerations, including:
  • Erratic IM absorption
  • Reduced salivary flow that makes swallowing difficult
  • Transdermal absorption which is hard to predict
  • Timed-release/enteric-coated tablets cannot be crushed
  • Reduced GI acidity affecting absorption
  • Slower gastric emptying time
  • Decreased GI motility and blood flow
• Gender considerations:
  • A woman's stomach empties solids more slowly than a man's.
  • Slower gastric emptying time may allow drugs to stay in contact with absorptive tissue longer.
  • Body weight may aggravate the higher blood alcohol level and state of intoxication in women and men.

Factors That Influence Distribution

• Distribution are the ways in which drugs are transported to the site of action.
• Distribution depends on pH, body water concentrations, fat tissues, protein binding, cardiac output, and blood flow.
• Infants considerations:
  • Higher total body water content, requiring higher dose on mg/kg basis
  • Lower body fat
  • Reduced protein binding in neonates
• Geriatric patients have a total body water content decrease.
• Females have a higher total body fat higher.

Factors That Influence Metabolism

• Metabolism is the process whereby the body inactivates medications, primarily in the liver.
• Infants' enzymes take several weeks to a year to develop.
• Older adults have decreased liver cells and blood flow.
• Factors that affect metabolism for all ages include: genetics, smoking, diet, other medications, and liver disorders.

Factors That Influence Excretion

• Drug metabolites and the drug itself are excreted from the body.
• Preterm infants have 15% of the renal capacity of an adult.
• Neonates have 35% of the renal capacity of an adult.
• Full adult function occurs at 9 to 12 months.
• Geriatric considerations must be made when considering their:
  • Decreased renal blood flow
  • Reduced cardiac output
  • Loss of glomeruli
  • Decreased tubular function
• Serum creatinine levels give estimate of renal function

Therapeutic Drug Monitoring

• Therapeutic drug monitoring involves the measurement of drag concentration in blood samples.
• It is essential in neonates, infants, and children.
• Dosage and frequency of medications can be adjusted to maintain therapeutic levels of potentially toxic drugs

Monitoring Parameters

• All medicines have a number of parameters including: expected therapeutic actions, common adverse effects, serious adverse effects, and any drug interactions
• Crucial that normal values for monitoring parameters and laboratory tests be related to the age of the monitored patient.

Pediatric Patients

• Dosage adjustments expected during growth
• Measure liquid medications using mL
• Use appropriate dilution
• Verify dosage prior to giving
• Aspirin use linked with Reye's syndrome
• Allergic reactions occur rapidly

Geriatric Patients

• Obtain a complete drug history, including prescription, OTC, herbal medications, and nutritional status.
• Evaluate vision and motor skills.
• When evaluating a new symptom, determine whether it was induced by a medication already prescribed.
• Start with smaller doses and gradually increase.
• Keep multidrug regimen simple.
• Review if any medications can be discontinued.
• Assess ability to pay for medications.
• Polypharmacy is multidrug therapy.

Potentially Inappropriate Medications for Geriatric Patients

• Includes medications that should be avoided and those that are rarely appropriate, like some barbiturates, benzodiazepines, and some narcotics.
• Some are considered appropriate to give only with certain indications, but may have potentially adverse reactions.

Pregnant Patients

• The fetus is exposed to substances in mother's blood.
• Teratogens are drugs that cause abnormal development of fetal tissues.

Use of Monitoring Parameters: Pregnant Women

• Avoid drugs if at all possible
• When taking woman's history, be alert to possibility of pregnancy
• Instruct patient to avoid drugs, alcohol, and tobacco
• Try nonpharmacologic treatments before using medicines
• Avoid herbal medicines

Drugs Known to be Teratogenic

• Androgenic and estrogenic hormones
• ACE inhibitors, ethanol, tetracycline
• Thalidomide, vitamin A, warfarin
• Angiotensin II receptor antagonists
• Anticonvulsants, antimanic agents, antithyroid
• Chemotherapy, statins, cocaine

Use of Monitoring Parameters: Breastfeeding Infants

• Some drugs are known to enter breast milk and harm the nursing infant
• Discuss all medications health care provider
• Take medicine immediately after breastfeeding or just before infant's longest sleeping period

Genetics and Drug Metabolism

• Genetics: Study of how living organisms inherit the traits of their ancestors, including function of metabolic pathways
• Genome: Complete package of genetic coding of an organism.
• Pharmacogenetics: Study of how drug response may vary according to inherited differences.
• Significant differences can occur among racial and ethnic groups.
• Most studies to date have concentrated on cardiovascular and psychiatric drugs, analgesics, antihistamines, and ethanol.
• Monoclonal antibodies are early examples of medicines that were synthesized to attack certain types of cancers.

Drug therapy is affected by several physiological and psychological factors. Age, weight, and gender are important physiological elements in drug response. Body composition and organ function changes can affect how drugs are metabolized and excreted, influencing therapeutic outcomes.