Pharmacokinetic and Pharmacodynamic Variations Flashcards
Define pharmacokinetic variation.
Variations in drug absorption, distribution, metabolism, and excretion that affect drug concentrations and responses.
Define pharmacodynamic variation.
Differences in the body’s response to a drug due to variations in receptor sensitivity, drug interactions, or disease states.
Provide a clinical example of pharmacokinetic variation.
In older adults, reduced renal function leads to slower excretion of morphine, increasing the risk of toxicity.
Provide a clinical example of pharmacodynamic variation.
Genetic absence of TPMT enzyme in some individuals increases toxicity risk with mercaptopurine.
What are the main causes of pharmacokinetic variation?
- Genetic differences in enzyme activity.
- Age-related physiological changes.
- Pregnancy and hormonal shifts.
- Obesity and altered body composition.
- Disease states affecting liver or kidney function.
Why do older adults experience pharmacokinetic variation?
- Reduced liver and kidney function.
- Decreased protein binding due to lower albumin levels.
- Altered body composition with increased fat stores.
How does pregnancy alter drug pharmacokinetics?
Increased renal clearance and changes in enzyme activity affect drugs like Metformin, leading to faster elimination.
How does obesity affect drug response?
- Increased fat alters drug distribution, especially for lipophilic drugs like Diazepam.
- Fatty liver disease can impact liver metabolism.
Why is understanding variability in drug response important?
It improves prescribing safety and efficacy, reducing risks of toxicity and treatment failure in vulnerable groups.
What factors cause pharmacokinetic variability in the elderly?
Reduced gastric acid and slowed gastric emptying.
- Lower serum albumin, affecting protein-bound drugs (e.g., Warfarin, Diazepam).
- Reduced liver size and hepatic enzyme activity, slowing phase 1 metabolism.
- Decreased renal function, reducing drug excretion (e.g., Morphine)
Provide an example of pharmacodynamic variability in the elderly.
Benzodiazepines, like Diazepam, may cause more confusion and less sedation due to altered receptor sensitivity.
How does pregnancy influence pharmacokinetics?
Slowed GI motility increases absorption.
- Increased plasma volume dilutes drug concentrations.
- Enhanced renal clearance increases excretion.
- Altered hepatic enzyme activity changes metabolism (e.g., Metformin).
How does obesity affect pharmacokinetics?
Increased fat alters drug distribution, prolonging the effect of lipophilic drugs (e.g., Diazepam).
Fatty liver disease impairs metabolism.
What role does genetic variation play in pharmacokinetics?
Variations in enzymes like CYP450 affect drug metabolism.
For example, CYP450 inhibitors like grapefruit juice slow drug clearance.
How do diseases impact pharmacokinetics?
Renal impairment reduces excretion.
- Liver diseases impair drug metabolism.
- Shock decreases muscle blood flow, slowing IM drug absorption.
How does renal decline in older adults affect drugs like Morphine?
Active metabolites accumulate, increasing the risk of prolonged effects and toxicity.
Why is Metformin excreted faster in pregnant women?
Increased renal blood flow and GFR enhance renal clearance.
Why does Diazepam remain longer in the body in obese individuals?
Its high lipophilicity leads to prolonged storage and release from fat tissues.
What is the clinical significance of adverse drug reactions (ADRs)?
Adverse drug reactions (ADRs) are harmful or unintended effects caused by drugs.
They are clinically significant because they can lead to patient harm, increased healthcare costs, longer hospital stays, and even death.
Recognizing and managing ADRs is crucial for patient safety.
How are common ADRs classified using the “A, B, C” system?
A (Augmented): Predictable reactions related to the drug’s known pharmacological effects (e.g., sedation from antihistamines).
B (Bizarre): Unpredictable reactions that are not related to the drug’s pharmacological effects (e.g., anaphylaxis from penicillin).
C (Chronic): Reactions that result from long-term drug use (e.g., corticosteroid-induced osteoporosis).
What factors determine the likelihood of adverse drug reactions (ADRs)?
Factors that increase the likelihood of ADRs include:
Age: The very young and elderly are more vulnerable.
Genetic factors: Certain genetic profiles may increase sensitivity to drugs.
Drug dose: Higher doses increase the risk of ADRs.
Polypharmacy: Using multiple medications can increase the risk of drug interactions and ADRs.
Comorbidities: Pre-existing conditions can affect how drugs are metabolized and excreted, influencing ADR risk.
What are some common adverse drug reactions (ADRs)?
Common ADRs include:
Allergic reactions (e.g., rash, anaphylaxis).
Gastrointestinal issues (e.g., nausea, diarrhoea from antibiotics).
Sedation (e.g., from antihistamines or benzodiazepines).
Hypotension (e.g., from antihypertensive).
Hepatotoxicity (e.g., from acetaminophen overdose).
Renal toxicity (e.g., from NSAIDs or ACE inhibitors).
What are some approaches to detecting adverse drug reactions (ADRs)?
Approaches to detecting ADRs include:
Patient reporting: Encouraging patients to report any unusual symptoms or reactions.
Spontaneous reporting systems: Using systems like the Yellow Card Scheme in the UK to collect ADR reports.
Clinical observation: Monitoring for signs of ADRs during treatment.
Epidemiological studies: Conducting studies to identify patterns and causes of ADRs.
Pharmacovigilance: Ongoing monitoring and assessment of drugs once they are marketed.
Why is variability in drug response a serious issue in terms of prescribing safety and efficacy?
Variability in drug response means that patients may respond differently to the same drug.
This can lead to ineffective treatment or harmful side effects, making it crucial to consider individual differences to ensure safety and efficacy in prescribing.
