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daynuhmay
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what the body does to the drug
(description of changes in drug concentrations over time)
pharmacokinetics (PK)
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the study of ADME
pharmacokinetics (PK)
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rate and extent to which an unchanged drug leaves its site of administration
absorption
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movement of drug from the systemic circulation to the body tissues and intended site of action
distribution
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chemical alteration of a drug through an enzymatic process
metabolism
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elimination of drugs and metabolites from the body (form of drug upon elimination)
excretion
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what the drug does to the body
pharmacodynamics (PD)
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relationship between drug concentration and drug effect/response
pharmacodynamics (PD)
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determines therapeutic effect (response, non-response, toxicity)
pharmacodynamics
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factors of pharmacokinetics (3)
- 1) drug dose
- 2) biological fluid concentration
- 3) effect site concentration
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factors of pharmacodynamics (2)
- 1) effect site concentration
- 2) pharmacologic effect
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the magnitude of the desired therapeutic response, and likelihood for potential toxicity, are a function of...
the drug concentration at its site of action
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2 reasons drug therapy fails
- 1) therapy is ineffective bc concentrations are too low
- 2) unacceptable toxicity bc concentrations are too high
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between upper & lower limits of concentration where region of desirable concentrations lie
window OR range OR index
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PD parameters out of our control (2)
- 1) intrinsic ADME properties of drug
- 2) pharmacodynamics
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similar to adverse reaction, but usually fairly mild
side effect
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unwanted/unexpected negative reaction to a medication/treatment that is used in an approved manner
adverse reaction
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adverse reaction which is more severe in nature with potentially more severe consequences
toxicity
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dose regimens (dose & frequency) are determined by... (2)
- 1) width of therapeutic range
- 2) ADME characteristics of drug
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results in standard dosing regimens being effective for some pts and ineffective or unacceptably toxic for others
pharmacokinetic variability
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from a PK standpoint, absorption is defined by... (2)
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extent of absorption of intact drug from the site of administration into the systemic circulation
bioavailability (F)
expressed as % or fraction of administered dose which achieves intact absorption
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drug distribution is a _____ process
reversible
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smaller Vd = ____ concentration in blood
- higher concentration in blood
- (doesn't distribute well into body)
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units of Vd
volume (L, mL)
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"apparent volume of distribution" can be calculated from ... (2)
- 1) measured dose administered
- 2) measured resultant concentrations
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important determinant of Vd
- drug binding
- (assumed that only unbound drug is pharmacologically active/free to distribute throughout body)
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most important plasma drug-binding proteins (2)
- 1) albumin (for acidic drugs)
- 2)
 1-acid glycoprotein (for basic drugs)
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2 processes of elimination
- 1) metabolism
- 2) excretion
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loss of drug activity
detoxification
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Type I drug metabolism
modifications in molecular structure of drug (oxidation, hydrolysis)
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Type II drug metabolism
"conjugation" of drug molecule with other compounds (sulfation, glucuronidation)
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most common family of metabolizing enzymes
CYP450
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active process of kidney excretion
tubular secretion
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passive process of kidney excretion
tubular reabsorption
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serves as index of drug elimination; reflects intrinsic ability of organs to metabolize/excrete drug
clearance (CL)
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T1/2 is influenced by... (2)
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where in kidney drug reabsorption occurs
distal convoluted tubule
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where in kidney drug secretion occurs
proximal convoluted tubule
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volume of plasma filtered across the renal glomerulus per unit of time
GFR (glomerular filtration rate)
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renal excretion of drugs correlates best with...
GFR
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commonly used together to assess renal function (2)
- 1) BUN
- 2) serum creatinine
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BUN
- blood urea nitrogen
- metabolism of amino acids into urea
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SCr
- serum creatinine
- breakdown product of creatine & phosphocreatine in skeletal muscle tissues; primarily filtered through glomerulus
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frequently used as an estimate of GFR
clearance of creatinine (CrCL)
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Cockcroft-Gault Equation for determining CrCL
 mL/min
*0.85 for females
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male IBW (kg)
50+(2.3 * inches>60)
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female IBW (kg)
45.5+(2.3*inches>60)
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if obese (>130% IBW)...
- use adjusted dosing weight (ADW)
- ADW=IBW+[0.4*(ABW-IBW)]
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limitations of CG equation (3)
- 1) accurate only in adult pts w/ stable kidney fcn
- 2) CrCL calc overestimates actual GFR3) not accurate in pts w/ liver disease
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measurement of prothrombin time (PT) is an assessment of...
- protein synthetic fcn
- clotting
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measurement of albumin is an assessment of...
protein synthetic fcn
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measurement of bilirubin is an assessment of...
secretory function
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measurement of alkaline phosphatase is an assessment of... (3)
- 1) hepatocyte integrity
- 2) secretory fcn
- 3) inflammation
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measurement of aspartate aminotransferase/alanine aminotransferase (AST/ALT) is an assessment of... (2)
- 1) hepatocyte integrity
- 2) inflammation
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Child-Pugh scored for worst liver function
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