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For first order kinetics what is the elimnation rate equal to?
rate= v= [Drug plasma] * k
k= is the elimnation rate constant
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1st order kinetics what is drug elimnation equal to?
[drug plasma] * drug clearance
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What happens to the elimnation rate with a decrease in [drug] with 1st order kinetics?
the elimnation rate decreases with a decrease in [drug]
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What happens to t1/2 and cl with a decrease in [drug] 1st order kinetics?
half life and clearance remain the same if hepatic and renal function do not change
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What is t1/2?
the time it takes to decrease the plasma concentration by 50%
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t1/2= (equation we need to know)
t1/2= 0.693/k
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What are the factors that affect t1/2 ?
Drug clearance rate
Volume of distribution
Disease or age
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Cl = (equation we need to know)
Cl = Vd * K
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What is the rate emlination during zero order kinetics?
It is constant
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Are zero order reactions dependent on concentration?
INdependent of concentration of drug in plasma
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What are the things posted on Baskis slide about metabolism?
Drug molecules are metabolized by enzymes
Drug action may increase/decrease after metabolism
Genetic variations determine the fate of the drug
Several routes of metabolism for drugs
May or may not terminate the action of the drug
May take place anywhere but the liver is the prime site
Not contant, can be changed by other drugs basic of drug
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Where are the sites of biotranformation?
Where ever the appropiate enzymes occur, plasm, kidney,gut wall and the liver is the ideal place to metabolize drugs and has a major role in biotransformation
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What is the main enzyme for metabolism?
Cytohrome P450, had mix function of oxidases, there are 4 fmailies, six sub families, and 20 isoenzymes
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What is the order of phase 1 reactions?
Hydroxylation
Oxidation
- N-de-alkylation
- Oxidative deamination
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What does an oxidation reaction do?
increase in the proportion of oxygen
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What does a reduction reaction do?
decrease in the proportion of oxygen
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What does a hydrolysis reaction do?
Cleavage by the addition of water
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What is the phase 2 reactions?
Conjugations with glucuronide, sulphate
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What does conjugation of glucuronide, sulphate do?
Alters activity, made less lipid soluble so excreted
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What are the factors that effect biotransformation?
Race
Age
Sex
Species
- Clinical or physiological condition
- Other drugs administerd
Food
First pass metabolism
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What are high risk patients for drug interaction?
Elderly
Multiple Disease
Multiple drug therapy
Renal, liver impairment
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What are high risk drugs for drug interaction?
Narrow therapeutic index
Enzyme inhibitor or inducer
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What are some drugs with low therapeutics index?
Lithium
Carbamazepine
Phenytoin
Theophyline
Digoxin
Cylcosporin
Phenobarbitone
Warfarin
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What is the definition of drug interaction?
ONe drug may alter the extent of absorption, distribution, metabolism, or excretion of another drug
A change in blood concentration of one drug may cause a change in the drugs effect
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What is enzyme induction?
LEads to the production of more enzymes usually 3 to 4 days of exposure to an inducer
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What does the time course of an inducer depend on?
the half life of the inducer
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What are some drug interactions with excretion?
- Drug A can increase or decrease the excretion of drug B
- Which causes drug B fall below or rise above normal therapeutic range
Can lead the drug to be either toxic or ineffective
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What is drug displacement?
Drug binding to plasma protein and not allowing to drug to get to tissue
Only free drug can get to the target tissue
Another drug can bind to the plasma protein displacing the first drug from the plasma protein allowing more free drug available to bind to tissue
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Define bioavailability
the true rate and extent at which the therapeutically ative drug reaches the systemic circulation and is available at the site of action from an administered dosage form
The proportion of drug in a dosage form available to the body
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How much drug is bioavailable for an IV injection?
IV are 100 percent bioavailable
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What is the absolute bioavailability equal to?
[AUC]po * does IV divided by [AUC]IV * dose po
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What is the relative bioavailability?
[AUC]a *dose b divided by [AUV]b * dose a
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What is the pharmokinetic method of assessing bioavailability?
It is based on the plasma concentration of the drug and the assumption that the pharmokinetic profile reflects the therapeutic effectiveness of a drug
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What is the pharmodynamic method of assessing bioavailability?
Based on direct measurement of drug effect on a pathophysiologic process as a function of time
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What are some reasons for poor bioavailability?
Poor aqueous solubility
- Poor stability of the dissolved drug at physiological pH
- Poor permeation through the biomembranes
Extensive presystemic metabolism
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What are the methods of enhancing bioavailability?
Lipids based formulation
Size reduction, mirconization
Functional polymer technology
Porous microparticle technology
The hydrophilic solubilization technology
Controlled precipitation technology
Inclusion complexes
Solid Dispersions
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What is the lipid based formulation way to enhance absorption?
Lipid solution
high lipophilicity facilitates drug absorption
The presence of surfactant in such formulations enhances absorption due to increase permeability
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What is the size reduction micronization way to enhance absorption?
Increasing the surface area by decreasing the particle size gives a higher rate of dissolution
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What is the functional polymer technology way to enhance absorption?
Ion exchange resins interact and exchange ions with ionizable molecules of the surrounding medium reversibily
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What is the porous microparticle technology way to enhance absorption?
The hydrophobic drug delivery system
The poorly water soluble drug is embedded into a porous water soluble mircoparticle.
When in contact with water the matrix dissolves leaving a suspension of rapidly dissolving particles
The particle have a large surface area
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What is the hydrophilic solubilization technology way to enhance absorption?
THey are coated with lecithin-gelatin which form micelles to enhance dissolution
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What is the controlled precipitation technology way to enhance absorption?
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