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6 Cards in this Set

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Describe how a determination of bioavailability is made.
The determination of Bioavailability is determined by comparing the AUC (IV) to the AUC (other route of administration). IV is determined to be the “gold standard’ thus all other modes of ingestion fractions of that percentage. Bioavailability can be affected by enzymatic destruction, remaining soluble enough to pass throughout the body, but also having enough lipophilicity or specificity to cross plasma membranes. Drugs with low oral bioavailability due to being affected by first pass factors are not suitable oral drugs and alternate forms of administration must be utilized(Other forms of administration
include: Intramuscular, Subcutaneous, Inhalation, Transdermal, Oral, and Topical)
Describe the relationship between a drug's volume of distribution and its distribution in various body fluids
The relationship of a drug’s volume of distribution (Vd) and its distribution in body fluids is determined by its lipophilicity/hydrophilicity, charged/uncharged, and big/small. The Vd is a method to determine a relative proportion of the drug that is dispersed in the plasma versus the tissues.

It is calculated as the total amount of drug in the body divided by the drug plasma concentration (Cp)
Explain the difference between zero-order and first-order rates of elimination and apply concepts appropriate to patient care.
First order kinetics: rate of elimination is proportionate to the plasma concentration Cp, and thus is continuously changing. Cp decays exponentially over time.

Zero order kinetics: rate of elimination is constant, regardless of concentration

Clinical relevance??:
Maintenance dosing?
Ease of achieving a particular Cp?
Rate of elimination in case of overdose?
For zero-order drugs, small changes in dose can cause disproportionate changes in Cp, whereas first-order drugs can accommodate changes in dose more easily (vary elimination rate accordingly)
Explain the concept of clearance.
The volume of plasma from which the kidneys can completely remove a substance per unit. Thus, renal clearance specifies how much plasma the kidneys can "clear" per minute or per hour. This concept can be extended to include all organs, not just the kidneys.

Clearance equals the ratio between the rate of elimination and the plasma drug concentration (Cp) or the fraction of total Vd being cleared p/unit time irrespective of drug concentration

rate of elimination of drug [mg/hr]
plasma drug concentration [mg/L]
Units: [L/hr]

These values can be affected if the organs related to drug metabolism/elimination are diseased (i.e.liver, kidney), impaired blood flow (i.e. CHF), drug-drug interactions (can "or # clearance) then drug clearance will be significantly reduced.
Use a drug's volume of distribution and clearance to calculate its half-life.
Half-life is the time it takes for the Cp of a drug to reach half of its original concentration at time zero.

t1/2 = (0.693 x Vd)/CL
Extra Information
1) to account for differing rates of absorption into the blood, the concentration appearing in the plasma must be integrated over time to obtain an integrated total area under the plasma concentration curve (AUC)
2) Cp is a function of the rate of input of the drug into the plasma, the rate of distribution to the peripheral tissues (including the target organ), and the rate of elimination from the body
3) F=1 for IV administration; F=AUC(route)/AUC(IV); unitless
4) Some drugs bind to divalent cations such as calcium in milk and form complexes in the GI tract that can’t be absorbed → watch what you eat when you take medications!
5) Elimination: amt of drug that is removed from the body per unit of time (different from “metabolized”)
6) Zero order kinetics: occurs when the drugs saturate their elimination mechanisms even at low concentrations
7) Most drugs are eliminated via first order elimination