Term
| What is the predominant mechanism of how drugs cross membranes? |
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Definition
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Term
| What do drugs need for passive diffusion? |
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Definition
| Enogh lipid solubility to pass through the lipid portion of cell membranes |
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Term
| What is the driving force for movement in passive diffusion? |
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Definition
| concentration gradient across the membrane |
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Term
| What are the 5 other mechanisms (besides passive diffusion) that drugs may cross the membrane? |
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Definition
1) Ion channels
2) skeletal muscle capillary fenestrations
3) active pumps or co-transporters
4) facilitated diffusion carriers
5) cellular endocytosis |
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Term
| What equation is used to calculate the pH? |
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Definition
|
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Term
| -What is the Henderson-Hasselbalch equation? |
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Definition
| pH = pKa + log (unprotonated/protonated) |
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Term
| Where do acids accumulate? |
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Definition
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Term
| Where do bases accumulate? |
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Definition
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Term
| Are acids or bases absorbed from the stomache? |
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Definition
| Acids. They are trapped by the more alkaline plasma, where bases are trapped to the acidic stomache. |
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Term
| What drug types are NOT effected by pH? |
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Definition
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Term
| What 3 routes of administration give immediate effect? |
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Definition
Sublingual
Inhalation
Intravenous |
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Term
| How fast does oral administration take effect? |
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Definition
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Term
| Which 2 administration routes take effect in minutes to hours? |
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Definition
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Term
| How long before topical agents take effect? |
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Definition
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Term
| What route of administration has the most variable effect? |
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Definition
| Intramuscular - minutes to days. |
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Term
| Which 3 routes of administration are more convenient? |
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Definition
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Term
| Which 2 drug administration routes avoid 1st pass metabolism? |
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Definition
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Term
| What is the alternative to oral administration? |
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Definition
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Term
| Which administration route allows for the most control? |
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Definition
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Term
| Which administration route could be given in a long-term depot? |
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Definition
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Term
| Which 3 routes of administration must be given in small amounts? |
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Definition
Sublingual
Topical
Subcutaneous |
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Term
| Which 2 routes of administration are irreversible? |
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Definition
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Term
| What is the disadvantage to oral administration? |
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Definition
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Term
| Besides small quantity, what is a disadvantage to topical administration? |
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Definition
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Term
| What is the disadvantage to inhalation administration? |
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Definition
| Gas, vapor, or small particles are needed. |
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Term
| Why is first pass metabolism a disadvantage? |
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Definition
| Blood from stomach & intestines flows first thru the liver => significant amount of a drug could be chemically altered (perhaps inactivated) before it reaches the systemic circulation. |
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Term
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Definition
| measure of the percent or fraction of the orally administered dose of a drug that enters systemic circulation. |
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Term
| How do drugs compensate for low bioavailability? |
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Definition
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Term
| How do you monitor drug therapy? |
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Definition
| Determine Volume of Distribution (Vd) for the drug and relate it to the concentration in the blood. |
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Term
| How do you determine the Volume of Distribution (Vd) |
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Definition
1) Administer known amount of drug IV
2) Take blood samples intermittently & measure [drug].
3)Plot log concentration vs. time
4) Extrapolate straight line back to t=0 |
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Term
| **What is the equation for Vd? |
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Definition
| Vd = (amount administered)/([t=0]) |
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Term
| What does the distribution phase depend on? |
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Definition
Distribution out of plasma & therefore lipid solubility.
Elimination from body |
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Term
| What does the elimination phase depend on? |
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Definition
|
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Term
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Definition
| The apparent volume of plasma that would have yielded the extrapolated concentration at t=0 upon dose administration |
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Term
| When is the drug entirely in the plasma for an IV dose? |
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Definition
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Term
|
Definition
|
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Term
| What 2 properties of a drug determine it's Vd? |
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Definition
1) Lipid solubility: high lipid solubility => low plasma concentration => large Vd
2) Binding to plasma proteins: high binding => trapping of drug in blood => low Vd |
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|
Term
Vd value range
>40 liters
5-10 literss |
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Definition
>40: highly lipid soluble
5-10: highly charged/bound to plasma protein |
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Term
| What 2 places do highly lipid soluble drugs have access to that other drugs don't? |
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Definition
1)Liver cells - access to CYP450
2) CNS |
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Term
| How are CNS drugs usually excreted? |
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Definition
|
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Term
| Why does blood flow from the stomach to the liver? |
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Definition
| To protect us from lipid soluble compounds in the diet from becoming CNS toxic |
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Term
| Why do drugs extensively plasma bound have slower elimination? |
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Definition
| Renal & Hepatic excretion depends on free, unbound drug. |
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Term
| What is an advantage to extensively bound plasma drugs? |
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Definition
| They act like a depot. As the small amount of free drug is eliminated, bound drug unbinds and replenishes. |
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Term
| When can plasma binding drugs have DDI? |
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Definition
| When there's another plasma bound drug competing for plasma proteins. |
|
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Term
|
Definition
Vd = 1400 mg/(40 mg/L)
= 35 L |
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Term
| What is the purpose of drug metabolism? |
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Definition
| To convert non-polar molecules not excreted by the kidney to polar metabolites which can be excreted by the kidney. |
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Term
|
Definition
| Enzymatic reactions involving oxidation, reduction or hydrolysis. |
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Term
|
Definition
| biosynthetic reactions where a functional group is attached to the drug molecule. |
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Term
| Can Phase II Metabolism preceed Phase I? |
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Definition
|
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Term
| Do all compounds have to go thru both Phase I & Phase II metabolism? |
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Definition
| No. Can go thru, I, II or both. (if both, I usually preceeds II, but isn't necissary) |
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Term
| How is drug metabolism controlled? |
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Definition
Chronic exposure => faster metabolism
or
Substrates can induce metabolism |
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Term
With chronic exposure, how long before maximum induction of metabolism is reached?
to return to normal levels? |
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Definition
| Same for both: several days to a week |
|
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Term
| What can cause inhibition and toxic accumulation of a drug? |
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Definition
| If drugs metabolized by CYP3A4 are co-administered and are therefore competitive => inhibition of eachother's metabolism. |
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Term
| What contributes to individual variations in metabolism? |
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Definition
|
|
Term
| Why can other P450 isoforms increase in activity when one P450 substrate induces it's own metabolism? |
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Definition
|
|
Term
| How are most drugs eliminated from the body? |
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Definition
| Renal excretion, liver metabolism, or a combination. |
|
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Term
| What is the most important organ for excretion of drugs and/or their metabolites? |
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Definition
|
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Term
| Via what other bodily fluids may drugs be excreted? |
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Definition
| Bile, sweat, saliva, exhaled air, milk |
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Term
| What is the ultrafiltrate of the kidney, allowing small molecules & water to pass thru, but retaining cells & large molecules in the blood? |
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Definition
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Term
| Which molecules are not reabsaorbed by the renal loops & tubules & are therefore excreted? |
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Definition
|
|
Term
| What are the 3 factors of renal excretion? |
|
Definition
1) Glomerular Filtration
2) Tubular Secretion (active)
3) Tubular Reabsorption (passive) |
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Term
| How does golmerular filtration affect drug excretion? |
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Definition
Only allows passage of free drug
Increased filtration rate increases rate of elimination |
|
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Term
| How can tubular secretion affect drug elminiation? |
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Definition
| It can select certain drugs & actively transport them against a concentration gradient, even if protein bound. |
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Term
| How does tubular reabsorption affect elimination? |
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Definition
Enhanced lipid solubility favors reabsorption
Urine pH affects drug reabsorption - same as in the gut
Slow renal flow favors reabsorption |
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|
Term
| When is biliary excretion an option? |
|
Definition
High molecular wt.
glucouronidated drugs |
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Term
| How can urinary excretion be increased in cases of overdose of a weak acid or base? |
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Definition
|
|
Term
| How do you cause urinary alkalinization? |
|
Definition
| IV administration of sodium bicarbonate. |
|
|
Term
| How do you cause urinary acidification? |
|
Definition
| administer ammonium choloride. |
|
|
Term
| What is the range of pKa when urinary acidification or alkalinization will work? |
|
Definition
|
|
Term
| What can provide active secretion of compounds from CSF to blood? |
|
Definition
|
|
Term
| When is hepatic drug metabolism useful? |
|
Definition
| Nonpolar compounds, since urinary excretion doesn't work well due to reabsorption. |
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