PDPK - Therapeutic Variability

01/16/2025

Intensity of response can be different among patients due to _______

Differences in pharmacokinetics and pharmacodynamics

Nature of response may vary due to ______

Alteration of physiological and pathological conditions

What is interpatient variability?

Therapeutic variability between different people

What is intrapatient variability?

Drug response changes for patient at different times

Genetic variability is the primary cause of ______

Altered drug response

What is a drug interaction?

One drug influences behavior of another drug contributes to variability in response

What are 4 common predictable factors?

Pharmacokinetic, pharmacodynamic, immunological, non-drug related factors

What is a pharmacokinetic factor?

Differing concentrations of drug at target

What is a pharmacodynamic factor?

Different pharmacological response to the same drug concentration at target

What is an immunological factor?

Results in allergic response

What is a non-drug related factor?

Personality, beliefs, attitudes of both patient and clinician

What are some factors that produce pharmacokinetic variability in children?

Smaller body weight, physiological differences, increased tissue permeability, more water, lower blood flow, decreased biotransformation, decreased renal clearance

Aspirin is contraindicated in children due to the risk of _____

Reye syndrome

Chloramphenicol is contraindicated in newborns due to the risk of _____

Grey baby syndrome

What decreases in the elderly population?

Organ system, muscle mass, ADME

What hepatic effects are present in elderly patients?

Decreased hepatic mass, blood flow, enzyme activity

What renal effects are present in elderly patients?

Reduced nephrons, functioning glomeruli, renal blood flow

Plasma and tissue concentration higher

Increased drug sensitivity

What is a pharmacokinetic variability risk in pregnancy?

Teratogenicity (birth defects)

What kind of drugs distribute readily into breast milk?

Lipophilic drugs

What are the 2 important organs in metabolism and elimination?

Liver and kidneys

What is the result of impaired hepatic or renal function?

Reduced elimination, high plasma levels, potential toxicity

What are some causes for pharmacodynamic variability?

Sex, idiosyncrasy, circadian rhythm, drug tolerance, drug resistance

In idiosyncrasy, response to drugs is in a _____

Highly unusual or unpredictable manner

What is the circadian rhythm?

Recurrence of a biological process in cycle of 24 hours; biological clock; response to recurring daylight and darkness

Circadian rhythms are important in _____

Receptor function, signaling pathways, hormones, enzyme activity

What is drug resistance?

Insensitivity or decreased sensitivity of cells to drugs that inhibit cell growth or cause cell death

What is intrinsic resistance?

Cell is inherently insensitive to the drug and predisposed to respond poorly to it

What is acquired resistance?

Cells initially respond to the drug, eventually some or all fail to respond

What is cross resistance?

Cells become resistant to drugs that are chemically related or have some mechanism of action

What is multi-drug resistance?

Cells become resistant to a broad range of structurally and functionally unrelated drugs

Drug resistance is a serious problem in ______ therapies (List 5)

Chemo, anti-bacterial, anti-protozoal, anti-viral, anti-fungal

What is mono-drug resistant?

Resistant to only one anti-TB drug

What is MDR?

Simultaneously resistant to the two most effective first-line drugs

What are the 2 most effective first-line drugs?

Isoniazid and Rifampin

What is extensively drug resistant?

MDR is resistant to most effective second-line drug and 1/3 injectable second-line drug

What is the most effective second-line drug?

Fluoroquinolones

What are 3 injectable second-line drugs?

Amikasin, Kanamycin, Capreomycin

What is drug allergy?

An allergic reaction to a drug that is a result of previous exposure to the same drug

What is the most important cause of drug-related immediate hypersensitivity?

Antibiotics

What is one of the most common cause of allergies?

Penicillin antibiotics

What are some common allergic symptoms?

Rashes, hives, itchy eyes, swollen lips, tongue, face

What are anaphylactic symptoms?

Dizziness, loss of consciousness, diarrhea, wheezing, nausea, vomiting

What are emergency treatments of anaphylaxis?

Epinephrine, antihistamines, corticosteroids

What drug is associated with red man syndrome?

Vancomycin

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