Lec 8 Flashcards
The three major routes of elimination (clearance) are :
• Hepatic metabolism.
• Biliary elimination.
• Urinary elimination.
elimination processes decrease the plasma concentration exponentially . (T/F) ?
T
estimates the amount of drug cleared from the body per unit of time is called ?
Clearance (CL)
Total CL calculated as follows
CL= 0.7*Vd/ t1/2
Most drugs are eliminated according to zero-order kinetics . (T/F) ?
F—>( first-order kinetics)
aspirin in high doses, are eliminated according to ?
zero-order or nonlinear kinetics
Metabolism leads to production of products with ?
increased polarity, which allows the drug to be eliminated
the rate of drug metabolism and elimination is directly proportional to the concentration of free drug . This statement describe?
First-order kinetics (linear kinetics)
Constant fraction of drug is metabolized per unit of time (that is, with each half-life, the concentration decreases by 50%). (T/F) ?
T
With a few drugs the doses are very large such as :
● Aspirin.
● Ethanol.
● Phenytoin.
In the zero-order kinetics , the rate of drug metabolism = ?
Vmax
The enzyme is saturated by a high free drug concentration, and the rate of metabolism remains constant over time . This statement describe?
Zero-order kinetics (nonlinear kinetics)
The rate of elimination is constant and does not depend on the drug concentration in zero-order kinetics . (T/F) ?
T
The kidney cannot efficiently eliminate lipophilic drugs that readily cross cell membranes and are reabsorbed in the distal convoluted tubules. (T/F) ?
T
Lipid-soluble agents are first metabolized into more polar (hydrophilic) substances in the liver via two general sets of reactions mention them :
phase I and phase II
The function of Phase I Reactions is ?
Convert lipophilic drugs into more polar molecules by introducing or unmasking a polar functional group, such as –OH or –NH2.
Phase I Reactions Involve?
reduction, oxidation, or hydrolysis.
Phase I Reactions can’t increase, decrease, or have no effect on
pharmacologic activity. (T/F) .
F —>(May increase, decrease, or have no effect on pharmacologic activity) .
Phase I reaction have two forms, mention them:
- Involves P450 system
- Does not involve P450 system
The phase I reactions most frequently involved in drug metabolism are catalyzed by ?
the cytochrome P450 system (also called microsomal mixed-function oxidases).
The P450 system is important for:
● Metabolism of many endogenous compounds (such as steroids, lipids)
● For the biotransformation of exogenous substances
(xenobiotics).
Why there are many different P450 isoforms ?
Because there are many different genes that encode multiple enzymes
Four isozymes are responsible for the vast of P450-catalyzed reactions. They are:
• CYP3A4/5.
• CYP2D6.
• CYP2C8/9.
• CYP1A2.
CYP2D6, in particular, has been shown to exhibit
genetic polymorphism
CYP2D6 mutations result in very low capacities to metabolize substrates. (T/F) ?
True
Clopidogrel is a prodrug that can be active metabolite through?
CYP2C19
patients who are poor CYP2C19 metabolizers have a higher incidence of ?
Cardiovascular events (for example, stroke or myocardial infarction).
Some individuals obtain no benefit from the opioid analgesic codeine, because ?
they lack the CYP2D6 enzyme
Similar polymorphisms have been characterized for the CYP2C subfamily of isozymes . (T/F) ?
T
chemicals not normally produced or expected to be present in the body, for example, drugs or environmental pollutants is called ?
Xenobiotics
Xenobiotics may induce the activity of these enzymes . (T/F) ?
T
The functions of these drugs( Phenobarbital, rifampin, and carbamazepine) are ?
- inc. CYP isozymes synthesis
- inc. some drugs metabolism
- reduced effect
Consequences of increased drug metabolism include:
- Decreased Plasma Drug Concentrations.
- Decreased drug activity if the metabolite is inactive.
- Increased drug activity if the metabolite is active.
- Decreased therapeutic drug effect.
The most common form of inhibition is through?
competition for the
same isozyme which leads to serious adverse events
The effect of Omeprazole is .
inhibits three of the CYP isozymes responsible for warfarin metabolism —> accumulation Of warfarin —> increase anticoagulant effect—> bleeding
Mention the inhibitors drugs :
- Omeprazole
- erythromycin
- ketoconazole
- ritonavir
Grapefruit juice inhibits?
CYP3A4
Grapefruit juice inhibits CYP3A4 which leads to :
higher conc. Of nifedipine, clarithromycin, and simvastatin
Give me examples about phase I reactions that not involving the P450 system:
•Amine Oxidation (Oxidation of Catecholamines or Histamine)
•Alcohol Dehydrogenation (Ethanol oxidation)
•Esterases (metabolism of Aspirin in the liver)
•Hydrolysis (Procaine).
phase II reactions consists of ?
conjugation reactions
We have water-soluble compounds that are often therapeutically inactive , mention them:
((glucuronic acid )), sulfuric acid, acetic acid, or an amino acid .
notable exception is morphine-6-glucuronide, which is less potent than morphine . (T/F) ?
F—> (more)
Drugs already possessing an ?
–OH, –NH2, or –COOH group
These group may enter phase II directly and become conjugated without prior phase I metabolism. (T/F) ?
T
The highly polar drug conjugates are then excreted by ?
kidney or in bile
