Variation in Individual Responses to Drugs

Why must therapy be tailored to each patient?

Because individual variations in drug responses can significantly affect treatment outcomes.

How does body weight and composition affect drug effects?

Body size can be a significant determinant of drug effects.

What is the relationship between drug concentration and response intensity?

The higher the concentration, the more intense the response.

What is a more accurate method for adjusting drug doses?

Using body surface area, which takes into consideration adipose tissue.

How does age affect drug sensitivity?

Drug sensitivity varies with age, with infants and older adults being especially sensitive.

What effect does kidney disease have on drug responses?

It can reduce drug excretion, causing drugs to accumulate in the body and potentially reach toxic levels.

How does liver disease affect drug metabolism?

It can cause drugs to accumulate because the liver is the major site of drug metabolism, and declining liver function reduces the rate of metabolism.

How does acid-base imbalance influence drug accumulation?

By altering pH, a drug will accumulate on the side where the pH most favors ionization.

What role do electrolytes play in drug responses?

Electrolytes are crucial for cell physiology, and disturbances can disrupt cellular processes.

How does potassium level affect digoxin's effect on cardiac rhythm?

Low potassium levels increase the tendency of digoxin to induce dysrhythmias.

What type of drug is digoxin?

Digoxin is a cardiac glycoside.

What is tolerance in drug responses?

Decreased responsiveness to a drug as a result of repeated drug administration.

What is pharmacodynamic tolerance?

A type of tolerance associated with long-term administration of drugs such as morphine and heroin, involving adaptive processes in response to chronic receptor occupation.

What is metabolic tolerance?

Tolerance resulting from accelerated drug metabolism.

What is tachyphylaxis?

A reduction in drug responsiveness brought on by repeated dosing over a short time.

What is an example of tachyphylaxis?

Transdermal nitroglycerin, where effects are lost in less than 24 hours if not replaced.

How often should a transdermal nitro patch be changed?

Every 6 hours.

What is the placebo effect?

A response based solely on the patient's psychological reaction to the idea of taking a medication, not due to any direct physiological or biochemical action of the placebo.

What does variability in absorption refer to?

The rate and extent of drug absorption can vary among patients.

What is bioavailability?

The amount of active drug that reaches the systemic circulation from its site of administration.

When is bioavailability a greater concern?

With drugs that have a narrow therapeutic window, primarily with oral preparations rather than parenteral preparations.

How can a patient's genetic make-up affect drug responses?

A patient's unique genetic make-up can lead to drug responses that are different from the population at large.

What genetic variant can reduce the effects of tamoxifen?

Variants in the gene that codes for cytochrome P450-2D6 can reduce the effects of tamoxifen.

What genetic variant increases the risk of bleeding from warfarin?

Variants in the gene that codes for CYP2C9 can increase the risk of bleeding from warfarin (Coumadin).

How can genetic variations alter drug targets?

Genetic variations can alter the structure of drug receptors and thereby influence drug responses.

How does warfarin work and what genetic variant affects its efficacy?

Warfarin works by inhibiting vitamin K, and variant genes can produce a form of the enzyme that can be easily inhibited, allowing anticoagulation with low warfarin doses.

What is pharmacogenomics?

Pharmacogenomics is the study of how genetic variants affect drug responses.

How can genetic variations influence drug responses?

Genetic variations can alter the structure of drug receptors.

What is an example of a drug affected by genetic variants?

Warfarin.

How does Warfarin work?

Warfarin works by inhibiting vitamin K.

What effect can variant genes have on Warfarin dosage?

Variant genes can produce an enzyme that can be easily inhibited, allowing for anticoagulation with low Warfarin doses.

What can genetic variants that affect the immune system increase the risk of?

Severe hypersensitivity reactions to drugs.

What drug used for epilepsy and bipolar disorder can cause life-threatening skin reactions in some patients?

Carbamazepine (Tegretol).

What specific genetic factor can trigger life-threatening skin reactions to Carbamazepine?

An unusual human leukocyte antigen (HLA).

What type of response is triggered by the hypersensitivity reaction to Carbamazepine?

A cellular response.

How do therapeutic and adverse effects of drugs differ between genders?

Therapeutic and adverse effects of drugs may differ between males and females.

How is alcohol metabolized differently between genders?

Alcohol is metabolized more slowly by women than by men.

What is the effect of Digoxin on women compared to men?

Digoxin may increase mortality in women while having no effect in men.

Is race a good predictor of drug responses?

Race is a poor predictor of drug responses.

What factors should be considered instead of race when predicting drug responses?

Specific genetic variations and psychosocial factors should be considered.

How can diet affect drug responses?

Diet can affect responses to drugs primarily by affecting the patient's general health.

What can a good diet do for drug therapy?

A good diet can enable drugs to elicit therapeutic responses and increase the patient's capacity to tolerate adverse effects.

What is an example of a drug that has dietary restrictions?

Monoamine Oxidase (MAO) inhibitors, such as phenelzine (Nardil), are used to treat depression.

What can happen if MAO inhibitors are taken with tyramine-rich foods?

Taking MAO inhibitors with tyramine-rich foods can lead to malignant hypertension.

What types of foods should be avoided when taking MAO inhibitors?

Foods that contain tyramine, including cheeses and cured meats, should be avoided.

What is a common cause of variability in the response to a prescribed dose?

Failure to administer medication as prescribed.

What percentage of patients do not adhere to their prescribed medication regimen?

30 to 60%

What factors should be considered regarding medication adherence?

Manual dexterity, visual acuity, intellectual capacity, psychologic state, attitude toward drugs, financial concerns.

What is another source of individual variation in medication response?

Medication errors.

Is drug therapy during pregnancy common?

Yes, drug therapy during pregnancy is common.

What percentage of pregnant patients take at least one medication?

About 2/3 of pregnant patients take at least one medication.

What are some drugs used to treat pregnancy-related conditions?

Drugs used to treat nausea, constipation, and preeclampsia.

What chronic conditions may require drug therapy during pregnancy?

Hypertension, diabetes, and epilepsy.

What types of conditions may require drug therapy during pregnancy aside from chronic conditions?

Invasive conditions such as infectious diseases or cancer.

What is a major concern regarding drugs used during pregnancy?

Drugs used during pregnancy can be risky, and the risk-benefit ratio must be considered.

What does the health of the fetus depend on?

The health of the fetus depends on the mother's health.

Why is there a lack of information on drug safety during pregnancy?

There is a lack of clinical trials, necessitating retrospective studies for information.

How can physiologic changes during pregnancy affect drug disposition?

Physiologic changes can alter drug disposition, requiring dose adjustments.

What specific changes in the body during pregnancy are of particular interest for drug dosing?

Changes in the kidney, liver, and GI tract.

What happens to renal blood flow by the third trimester?

Renal blood flow is doubled, leading to increased glomerular filtration rate and accelerated drug clearance.

How does pregnancy affect intestinal transit time?

Tone and mobility of the bowel decrease, increasing intestinal transit time and drug absorption.

Can all drugs cross the placenta during pregnancy?

Yes, all drugs can cross the placenta, especially lipid-soluble drugs.

What is a potential adverse reaction of warfarin during pregnancy?

Warfarin during pregnancy can cause fetal hemorrhage.

What complications can benzodiazepines cause when taken late in pregnancy?

Benzodiazepines may cause hypoglycemia and respiratory complications in the neonate.

What is teratogenesis?

Teratogenesis refers to the development of birth defects.

What are some causes of congenital anomalies?

Genetic predisposition, environmental chemicals, and drugs.

What percentage of all birth defects are caused by drugs?

Less than 1% of all birth defects are caused by drugs.

When do gross malformations occur due to teratogen exposure?

Gross malformations are produced during the embryonic period.

What is an essential intervention to decrease risk during pregnancy?

Review all prescription drugs, over-the-counter medications, herbal supplements, and recreational drug use at every visit.

What is the FDA Pregnancy Risk Category?

The FDA Pregnancy Risk Category classifies the safety of drugs used during pregnancy.

Have most drugs used in pediatrics been tested in children?

No, the majority of drugs used in pediatrics have never been tested in children.

Why are young patients highly sensitive to drugs?

Organ system immaturity makes young patients highly sensitive to drugs.

How do drug responses in neonates and young infants compare to adults?

Drug responses may be unusually intense and prolonged.

How does the absorption of IM drugs in neonates compare to adults?

Absorption of IM drugs in neonates is slower than in adults.

How does the absorption of IM drugs in infants compare to adults?

IM injections in infants are more rapid than in adults.

What is the protein-binding capacity like early in life?

Protein-binding capacity is limited early in life, leading to high free concentrations of some drugs.

How developed is the blood-brain barrier at birth?

The blood-brain barrier is not fully developed at birth.

Why are neonates especially sensitive to CNS-affecting drugs?

Neonates are especially sensitive to drugs that affect the CNS due to an underdeveloped blood-brain barrier.

What is the drug-metabolizing capacity of neonates?

The drug-metabolizing capacity of neonates is low.

How does renal excretion of drugs in neonates compare to adults?

Renal excretion of drugs is low in neonates.

How do children aged 1 to 12 years differ pharmacokinetically from adults?

Children metabolize drugs faster than adults.

How reliable are initial pediatric doses?

Initial pediatric doses are at best an approximation.

Are older patients more or less sensitive to drugs compared to younger adults?

More sensitive

What can aging-related organ decline change in terms of drug processing?

Drug absorption, distribution, metabolism, and excretion

How does the rate of drug absorption in older adults compare to younger adults?

Slowed rate of absorption, but extent of absorption is unchanged

What is the plasma concentration of lipid-soluble drugs in older adults?

May be low

What is the plasma concentration of water-soluble drugs in older adults?

May be high

How does reduced liver function affect drug effects in older adults?

Prolongs drug effects

What is the most important cause of adverse drug reactions in older adults?

Reduced renal function with resultant drug accumulation

What should be determined for all patients taking drugs?

Creatinine clearance

Are adverse drug reactions more or less common in older adults?

Much more common

What factors contribute to the increase in adverse drug reactions in older adults?

Polypharmacy, severe illness, comorbidities, and treatment with dangerous drugs

Is nonadherence common among older adults?

Yes

What are some causes of unintentional nonadherence in older adults?

Complex regimens, awkward drug packaging, forgetfulness, side effects, low income, and failure to comprehend instructions

Are most cases of nonadherence among older adults intentional or unintentional?

Intentional

What are some reasons for intentional nonadherence among older adults?

Expense, side effects, and belief that the drug is unnecessary or dosage too high

How does priority treatment shift for older adults?

From disease prevention and management to provision of comfort measures