Term
| What is the study of studies the fate of a drug after administration to an organism, i.e. How the body responds to a drug. |
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Definition
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Term
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Definition
dynamics of the movement of drugs within the biological system
Absorption
Distribution
Metabolism
Elimination
person's physiology affects these 4 steps |
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Term
What are the 2 routes to take a drug?
Which is the more convenient, economic and safe? |
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Definition
Enteral route (most, convenient, economic, and safe)
-oral (most common)
-sublingual
-rectal (least common)
Parental route
-subcutaneous
-intramuscular
-intravenous |
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Term
| What are the issues with taking a drug orally? |
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Definition
Variable absorption rates and unpredictable serum levels.
Drug degradation due to acidic environment of GI tract.
Low bioavailability due to the first pass effect (metabolism-usually inactivates) |
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Term
What are the positive to parental drug delivery?
What are the negatives? |
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Definition
Positives:
Rapid onset of action (directly in bloodstream)
Predictable and almost complete bioavailability
Avoidance of absorption phase as well as possible inactivation by first-pass metabolism by the liver.Drugs that are poorly absorbed and unstable in GIT
Unconscious patients (can't take orally)
Cons:
Not convenient (need expertise, needle, not economic)
Once injected, there is no stopping (must be careful) |
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Term
| What is a good route of administration for unconscious patients, that avoids problems with GI irritation, metabolism, etc., good for local delivery, but it diffuses slowly by the gradient between the high concentration in the delivery system and the zero concentration prevailing in the skin. |
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Definition
| Trans-dermal (ex: nictotine patch, estradiol patch) |
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Term
| What is a good route that avoids an injection, increases therapeutic efficiency, bypasses first pass metabolism, and higher patience acceptance? |
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Definition
Mucosal Drug delivery (buccal and sublingual routes)
-rapid absorption compared to oral administration
-ex: oxytocin, vasopressin analogues, calcitonin etc |
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Term
| What drug route is used for topical & systemic effects of a drug, rapid absorption, avoidance of first pass hepatic metabolism, no drug degradation as observed in the GI, Higher bioavailability for smaller drug molecules, convenient for patients |
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Definition
Nasal drug delivery
(not good if patient as nose problem) |
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Term
| What is is the movement of the drug from its site of administration into the bloodstream |
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Definition
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Term
| What are the 2 major mechanisms of Drug absorption? |
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Definition
A. Passive Diffusion (Concentration difference across membrane)
B. Active transport- requires energy expenditure and specific transport proteins
– Saturable
– Effectively transports highly polar compounds
– Transport against a concentration gradient |
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Term
Which is NOT a good characteristic of a drug for basic absorption?
neither too hydrophobic or too hydrophilic
uncharged
lipophilic
gradient of concentration from lower to higher
weak acid or weak base
small molecular weight |
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Definition
Gradient of concentration should be HIGHER to LOWER
Drugs should be neither too hydrophobic or hydrophilic (weak acid or weak base), uncharged (to pass intestinal lipid bilayer), small molecular weight |
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Term
| Which drugs absorb quicker? (capsule, tablet, solution, suspension) |
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Definition
solution (fastest)
suspension
capsule
tablet (slowest) |
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Term
| In the stomach, would a basic or acidic drug stay uncharged? |
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Definition
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Term
| Which is better for absorption? the stomach or intestine? |
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Definition
| Intestine- more blood flow, microvilli (large intestine has bacteria) |
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Term
Which is true and which is false about absorption of drugs in the intestines?
1. Intestines have a large surface area
2. Intestines have a more basic pH
3. Intestines absorb many uncharged drugs by passive diffusion
4. Intestines absorb some drugs by active transport or facilitated diffusion
5. Drug absorption is diminished if contact time is decreased, as in diarrhea
6. Food cannot affect drug absorption |
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Definition
T-Intestines have a large surface area
F-Intestines have a more neutral pH (6-8)
T-Intestines absorb many uncharged drugs by passive diffusion
T-Intestines absorb some drugs by active transport or facilitated diffusion
T-Drug absorption is diminished if contact time is decreased, as in diarrhea
F-Food can affect drug absorption (physical or chemical effect) |
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Term
What is hydrogen ion concentration?
What is a compound's propensity to give or accept hydrogen ions (a property)? |
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Definition
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Term
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Definition
| When 50% are protonated and 50% unprotonated, then log(1)=0, so pKa and pH will be equal. |
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Term
Are acids in ionized in the stomach, in the intestine, and the blood? Where is it absorbed?
What about bases in the stomach? |
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Definition
Acids ionizes none in stomach (protonated form), a little in intestine and more in blood; absorbed in stomach (passive when not in ionized form)
Bases in acidic environments will get protonated; it becomes ionized, and then less absorption. |
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Term
| Where does drug metabolism (process of inactivation) immediately start? |
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Definition
| In the GI tract (absorption site and elimination site) |
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Term
| What are the 2 phases of drug metabolism? |
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Definition
Phase I: conversion to lipophilic into more polar metabolites (oxidation, reduction, hydrolysis) - involves CytochromeP450 system
Phase II: many conjugation making more water soluble metabolites (glucuronidation, sulfation, methylation)
Makes it easier to eliminate
(can be excreted after Phase 1, doesn't have to go into phase II but some do) |
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Term
| What is the fraction of the parent compound/unchanged compound that exists in circulation. Very important |
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Definition
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Term
| How is bioavailability measured? |
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Definition
| Bioavailability is measured by comparing IV administration with other route (100% bioavailable when administered by IV, other routes less absorbed) |
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Term
| What is the equation for bioavailability? |
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Definition
| Bioavailability = (AUC)O/(AUC) IV. DoseIV/DoseO x 100 |
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Term
There is a (reversible/irreversible) transfer of a drug between blood and the extravascular and tissue of the body.
Is distribution of a drug uniform throughout the body? |
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Definition
reversible
Distribution of a drug is not uniform throughout the body and it depends on its size, capillary permeability, binding to plasma and tissue proteins etc. |
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Term
| What is volume of distribution (VD)? |
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Definition
It is not a real physiological volume, but takes into account how the drug distributes in the body, including tissues, organs, cells and other non-fluid compartments.
It is the volume in which the amount of a drug would be uniformly distributed to produce the observed blood conc. |
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Term
Are protein-bound drugs pharmacologically active?
Do they have a small or large volume of distribution? |
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Definition
Protein-bound drug can’t reach target receptors
Only free drug is pharmacologically active.
Drugs that bind to plasma protein will have small Vd |
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Term
| Drugs that bind extravascular tissue, will have a (small or large) volume of distribution? |
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Definition
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Term
| A large volume of distribution means that some of the drug is not in the circulation; therefore? |
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Definition
it will NOT be cleared by the kidney
This will result in a longer half-life for the drug |
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Term
| What is the formula for volume distribution? |
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Definition
| volume given divided by the plasma concentration (must have same units) |
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Term
| What is the most important route of a drug elimination? |
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Definition
| kidney-excretion into the urine |
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Term
Most drugs are eliminated by a _________ process?
Acidification of urine increases the excretion of _______ drugs
Alkalinization of urine increases the excretion of _______ drugs |
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Definition
First Order process
Acidification of urine increases the excretion of basic drugs
Alkalinization of urine increases the excretion of acidic drugs |
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Term
| What happens to drugs that are smaller in size than albumin when it enters the glomerulus? |
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Definition
| can be filtered into the lumen of the proximal tubule and be reabsorbed (drugs that are uncharged can be reabsorbed) |
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Term
How does the plot of drug concentration versus time look when a few drugs are administered at such high doses that the enzymes that metabolize them can be saturated?
What order kinetics is this? |
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Definition
linear (A constant amount of drug is eliminated per unit of time)
zero-order kinetics |
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Term
| Is the half-life constant in (zero-order or first-order) process? |
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Definition
For a first- order process, the half-life is a constant
while in zero-order it is not.
(It is a measure of the elimination processes: metabolism
and excretion) |
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Term
| Rate of elimination is (directly or indirectly) proportional to drug concentration? |
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Definition
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Term
Urine pH can be lowered by giving _____
Urine pH can be raised by giving ______ |
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Definition
Urine pH can be lowered by giving NH4Cl
Urine pH can be raised by giving NaHCO3 (this would increase aspirin or phenobarbital(acids) excretion) |
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Term
What is the ability of organs of eliminating a drug from the blood stream.
What is the formula for this? |
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Definition
clearance (Volume of fluid which is completely cleared of drug per unit of time)
clearance = rate of elimination/plasma concentration |
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Term
| What is the formula for rate of elimination? |
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Definition
rate of elimination = clearance x plasma concentration
(clearance=rate of elimination/plasma concentration) |
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Term
Half-life is (inversely or directly) proportional to volume distribution?
Half-life is (inversely or directly) proportional to clearance? |
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Definition
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Term
If a drug has a short duration of action, what would you do in regards to half-life and clearance?
If a drug is too toxic, what would you do in regards to half-life and clearance? |
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Definition
if a drug has a short duration of action, optimize it with larger t 1/2 & smaller clearance
If a drug is too toxic, modify it with
smaller t 1/2 & larger clearance |
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