Term
| Number of Membrane Barriers Crossed |
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Definition
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Term
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Definition
must occur in order to achieve
a drug effect. |
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Term
| The Capillary Endothelial Membrane |
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Definition
Most common type of multicellular membrane
Must be crossed by all drugs (unless IT route)
Passage of drugs out of the vasculature is by bulk flow of water plus solutes due to osmotic and hydrostatic forces |
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Term
| Site-specific differences |
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Definition
Brain 8 A: The BBB ↓↓ movement of large or charged molecules as most must move through the lipid phase of the membranes.
Kidney (50+A) allows filtration of big molecules which enhances renal excretion |
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Term
| MOLECULAR SIZE and diffusion |
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Definition
| MAKES A LOT OF DIFFERENCE FOR WATER-SOLUBLE DRUGS. |
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Term
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Definition
Weak acids will accumulate in the more
basic medium while weak bases will
accumulate in the more acid medium |
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Term
| Active transport is involved in |
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Definition
absorption of a few drugs
relatively nonspecific excretion of many anionic and cationic drugs and metabolites
It can occur in both the kidney and the choroid plexus |
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Term
| VARIABLES IN DRUG ABSORPTION |
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Definition
Aqueous drug solubility
�� The rate of drug dissolution
�� The concentration of a drug at the site
�� Blood flow to the site of administration
�� Area of the absorbing surface |
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Term
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Definition
| Injected into the spinal cord. Bypasses BBB |
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Term
| Drug enters GI tract by what three sources of administration |
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Definition
a. Oral
b. Sublingual
c. Rectal
Last two somewhat avoid first pass hepatic metabolism |
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Term
| first phase in drug distribution |
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Definition
proportional to tissue blood flow with
highly perfused organs receiving the most drug |
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Term
| Second phase in drug distribution |
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Definition
• The second phase involves both blood flow and the drug’s ability to leave the vasculature.
• A drug that can leave readily is said to be (only) flow-limited |
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Term
| PROTEIN BINDING and drug storage |
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Definition
♦ Protein binding slows drug excretion by glomerular filtration but may or may not slow hepatic metabolism or excretion by active transport.
♦ Protein binding can, in some instances, prolong the drug effect. (EX: SURAMIN) |
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Term
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Definition
| DEALS WITH THE ACTIONS OF A DRUG ON THE BODY. |
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Term
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Definition
| DEALS WITH THE ACTIONS OF THE BODY ON THE DRUG |
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Term
| The effect of an antagonist depends |
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Definition
the degree of “tone” normally present.
Tone is the amount of transmitter released |
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Term
| Antagonist activity is minimum or absent when? |
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Definition
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Term
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Definition
RECEPTOR IS STABILIZED IN “NON-LEAKY” OR INACTIVE CONFIGURATION
1. A drug cannot be defined as an inverse agonist unless its receptor is constitutively “leaky”, that is exhibits some agonist-independent activity.
2. In the absence of agonist-independent activity, the drug will appear to be a standard competitive antagonist. |
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Term
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Definition
| Very important as most drugs bind in ionic form; strength varies as [1/d] |
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Term
| BINDING AFFINITY AND DRUG EFFICACY |
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Definition
| ARE SEPERABLE. Tight binding does not mean activation |
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Term
| EFFECT OF AN IRREVERSIBLE ANTAGONIST |
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Definition
| MAX EFFICACY CANNOT BE ACHIEVED WITH ANY AMOUNT OF AGONIST |
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Term
| EFFECT OF A REVERSIBLE COMPETITIVE ANTAGONIST |
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Definition
| MAX EFFICACY CAN ALWAYS BE ACHIEVED WITH ENOUGH AGONIST |
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Term
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Definition
| Concentration when have the drug is bound to receptors |
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Term
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Definition
| Not the same as efficacy. Defines the size of the dose needed to produce a response in 50% of the population |
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Term
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Definition
| Binds to the same receptor but is unable to achieve the full effect. Less than maximal efficacy. |
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Term
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Definition
TI = TD50 / ED50
TD = Toxic dose
ED = effective dose
The larger number the better |
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Term
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Definition
CSF = TD1 / ED99
The higher the better |
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Term
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Definition
SSM = ([TD1 - ED99] * 100) / ED99
Once again, the higher the better |
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Term
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Definition
| steady state concentration (Css) that is approximately reached (94%) in 4 half-lives (t1/2) of the drug |
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Term
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Definition
Effective Dose = F x Actual Dose
F is the bioavailability, 1 for IV |
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Term
| A. Zero-Order Elimination |
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Definition
| occurs when the rate of change of the amount of drug in the body is independent of the amount of drug present. |
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Term
| B. First-Order Elimination |
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Definition
| occurs when the rate of change of amount of drug in body is proportional to the amount of drug present |
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Term
| C. Saturable (Michaelis–Menten) Elimination |
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Definition
| The rate of change of drug present follows first-order kinetics at low doses and zero-order kinetics at higher doses |
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Term
| C. VOLUME OF DISTRIBUTION (Vd) |
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Definition
apparent volume of fluid into which a drug is distributed after maximal absorption and maximal distribution and typically does not represent an actual physiologic space
Vd = (F x dose) / CPo
expressed as either ℒ or ℒ/kg
Don't forget to divide by Kg if it's given |
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Term
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Definition
amount of drug needed to fill up the entire Vd to a desired Cp
LD = (Cp x Vd) / F
Don't forget to multiply by Kg of the patient if the Vd is in L/Kg |
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Term
| As Vd increases what happens to T1/2 |
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Definition
| It also increases. Directly proportional |
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Term
| As Cl increases what happens to T 1/2 |
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Definition
| it decreases. Inversely proportional |
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Term
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Definition
fractional elimination constant (KF) can be calculated by normalizing clearance for the volume of distribution in a particular patient and for a particular drug
KF = Cl/Vd |
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Term
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Definition
RE = KF × dose it simplifies to
RE = Cl × CPo |
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Term
| How does congestive heart failure change Cl and Vd |
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Definition
| It decreases both of them. Because they are both decreased t 1/2 stays about the same |
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Term
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Definition
| Pump stuff from the plasma into the cell. Use secondary active transport. OAT and OCT pump anions and Cations respectively |
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Term
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Definition
| Pump stuff out of cell into lumen or other places. MDR pumps cations MRP pumps anions. ABC = Primary active transport. |
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