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29 Cards in this Set
- Front
- Back
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What is biotransformation?
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Process of drug elimination that alters a drug to a state that is no longer present as such in the body.
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What is excretion?
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Process of drug elimination that transports a drug outside the body by the kidney or other organs.
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What is the pharmacokinetic parameter that gives a quantitative measure of drug elimination?
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Clearance
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This is defined as the VOLUME of a biological fluid (generally plasma) from which that drug is removed "cleared" /time?
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Clearance
Important distinction is that clearance is defined as volume NOT AMOUNT!! |
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How do you calculate total systemic clearance?
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CLt= CLh+CLr+CLo
h=hepatic r=renal o=other |
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If bioavailability is 0 what may be happening?
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The drug may not be absorbed or the liver clears ALL blood of the drug.
The latter assuming that Liver Clearance (CLh) is equal to the blood flow to the liver. So CLh=Blood Flow |
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What organ plays a major role in eliminating water-soluble substances?
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The kidney
However, since many drugs are NOT water soluble, biotransformation is the way to turn drugs into more polar and readily excretable products. |
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Concerning biotransformation, there are two phases. Generally describe each.
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Phase 1 reactions:
(nonsynthetic reactions) The primary reaction being oxidation reactions=oxygen is added to a compound or the proportion of oxygen in a compound is increased by removal of other groups. Other phase 1 reactions include reduction and hydrolyses. Phase 2 reactions (synthetic reactions) when drugs are conjugated/ main process being glucuronidation. Other phase 2 rxns are acetylation, methylation, and sulfation. |
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What is the common feature to both phase 1 and phase 2 biotransformation reactions?
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The products of biotransformation are more water soluble than the original drug, enhancing excretion.
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Phase 1 biotransformation oxidation reactions may lead to highly reactive intermediates that can combine COVALENTLY and cause tissue necrosis and blood dyscrasias. What are the two main monooxygenases that are responsible for these actions?
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NADPH-cytochrome P450 reductase (flavoprotein)
cytochrome P450 (hemoprotein) |
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What is the most common conjugation (phase 2) reaction of xenobiotics?
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Glucuronidation with glucuronic acid
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What enzyme is responsible for glucoronidation and where?
What the effect? |
UDP-glucuronosyltransferase in the liver
UDP-glucuronosyltransferase conjugates a drug to a more water soluble form which can then be excreted with the bile. |
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These enzymes are located mainly in the SER of liver cells andare mainly monooxygenases devoted to biotransformation of xenobiotics. They have VERY LOW substrate specificity but is compensated by their abundance. They can ONLY catalyze reactions of compounds that are lipid soluble.
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Microsomal enzymes
These enzymes catalyze mainly oxidations and glucuronidations |
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What gene family is responsible for the majority of all drug biotransformation?
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the cytochrome P450 family
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Barbiturates and rifampin are STRONG inducers of...
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Barbiturates and rifampin are strong inducers of metabolizing enzymes, especially the CYP family.
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Which CYP family isoenzyme is responsible for metabolism of 50% of all drugs?
A.) 3A4 B.) 2D6 C.) 2C19 D.) 2C9 E.) 1A2 |
A.) CYP 3A4
CYP 3A4 is the biggest player |
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Which microsomal drug enzymes are involved in the majority of all drug biotransformation?
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cytochrome P450 1,2 and 3 gene families
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How are non-microsomal drug-metabolizing enzymes different than microsomal ones?
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Variable (usually moderate) level of substrate specificity.
-located mainly in cytosol or mitochondria of liver cells and also in extracellular fluids. -catalyze mainly conjugation (phase 2) reactions EXCEPT glucuronidations CAN be inhibited BUT CANNOT be induced by xenobiotics. |
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What are some factors that affect drug biotransformation?
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-Individual differences
-Age -Nutrition -Genetic factors -Drug-drug interactions -Disease |
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What are 4 routes for drug excretion?
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1.) Renal *most important
2.) Intestinal a.Biliary excretion b.Fecal excretion(drugs that do not cross gut wall) 3.) Pulmonary 4.) Others(saliva, sweat, skin) |
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How much plasma water is filtered across the glomerular capillary membrane each minute?
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125 (+/- 26)
each minute |
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(T/F) All drugs free in plasma will not be filtered.
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False
Free drugs in the plasma will be filtered as long as their molecular size, charge and shape are not excesively large. |
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(T/F) Filtration rate of drugs is dependent upon the hydrostatic pressure in the glomerular capillaries.
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True
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Will a drug be filtered if it is bound to its corresponding plasma protein?
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No, drugs bound to plasma proteins (or MW>6500) will NOT be filtered.
ONLY free drugs are filtered |
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What is Renal clearance?
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Volume of plasma from which the kidney removes the drug per unit of time.
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What is the equation of renal clerance?
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CLr= (FxUd)/Pd
F=urine flow rate Ud=Urine concentration of drug Clearance=(UxV)/ Px Pd= Plasma conc of the drug |
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Renal clerance depends on which of the following renal factors:
-GFR -tubular fluid pH -passive absorption of the drug -active absorption of the drug |
Renal clearance depends on ALL of these renal factors!
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Clearance can be used as a marker of the process of renal drug elimination. What does each clearance rate indicate?
1.) CLr= 100-150 2.) CLr> 150 3.) CLr<100 |
1.) CLr= 100-150 ml/min indicates glomerular filtration
2.) >150 indicates tubular secretion 3.) <100 indicates tubular reabsorption (or protein building) |
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Biliary excretion plays a major role in drug removal of three kinds of compounds:
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-Anions
-cations -some nonionized molecules These compounds are brought to the liver and into the bile. |
