4: Basic Principles IV

Question 1

______ OF TOXICANTS Can have a widespread influence on drug use by terminating the Effect of a Drug, which is Desirable.

1. Route of administration
2. Dose
3. Effectiveness
4. Toxicity, safety
5. Duration of effect

Answer 1

BIOTRANSFORMATION OF TOXICANTS Can have a widespread influence on drug use by terminating the Effect of a Drug, which is Desirable

1. Route of administration
2. Dose
3. Effectiveness
4. Toxicity, safety
5. Duration of effect

Question 2

Clearance = removal of something from the ______ in ml/min

Answer 2

Clearance = removal of something from the plasma in ml/min

Question 3

Biotransformation clears drug from the plasma and its rate will depend on endogenous enzyme systems. There are two purposes of biotransformation:

1. Drug ______ changes the structure which changes the drug’s intrinsic activity
2. Prepare Drug for ______ by reducing the characteristics that made it easy to absorb. i.e., Make drug ______, Add positive or negative ______, Make drug more water ______- especially important- transform drug from lipid soluble form to water soluble form.

Answer 3

Biotransformation clears drug from the plasma and its rate will depend on endogenous enzyme systems. There are two purposes of biotransformation:

1. Drug Detoxification changes the structure which changes the drug’s intrinsic activity
2. Prepare Drug for Excretion by reducing the characteristics that made it easy to absorb. i.e., Make drug larger, Add positive or negative charges, Make drug more water soluble- especially important- transform drug from lipid soluble form to water soluble form.

Question 4

Sites of ______ include the liver’s SER, mitochondria, and cytoplasm. It can also occur anywhere else in the body.

Answer 4

Sites of biotransformation include the liver’s SER, mitochondria, and cytoplasm. It can also occur anywhere else in the body.

Question 5

Liver Microsomal Drug Metabolizing Systems does Both Phase I and Phase II processes of:

Induction: ______ metabolism of the primary drug or other drugs, might be observed as an ______ in first pass metabolism

Inhibition: use a drug to ______ the metabolism of another drug or endogenous compound

Answer 5

Liver Microsomal Drug Metabolizing Systems does Both Phase I and Phase II processes of:

Induction: increase metabolism of the primary drug or other drugs, might be observed as an increase in first pass metabolism

Inhibition: use a drug to block the metabolism of another drug or endogenous compound

Question 6

Non-microsomal Systems include other organs, plasma, red cells & Usually does Phase I. eg: acetyl cholinesterase, alcohol dehydrogenase.

______ only- intentional or accidental, “polypharmacy”.

Answer 6

Non-microsomal Systems include other organs, plasma, red cells & Usually does Phase I. eg: acetyl cholinesterase, alcohol dehydrogenase.

Inhibition only- intentional or accidental, “polypharmacy”.

Question 7

What is the most common phase 1 rxn?

Answer 7

Oxidation = the addition of Oxygen

Question 8

Components of Hepatic Mixed Function ______ System:

1. NADPH
2. Cytochrome P450 reductase (flavoprotein)
3. Cytochrome P450 (hemoproteins)
4. Mg++
5. Phospholipid
6. O2

Usually metabolize ______ soluble drugs

The drug as a [substrate] will concentrate in the ______

Answer 8

Components of Hepatic Mixed Function Oxidase System:

1. NADPH
2. Cytochrome P450 reductase (flavoprotein)
3. Cytochrome P450 (hemoproteins)
4. Mg++
5. Phospholipid
6. O2

Usually metabolize lipid soluble drugs

The drug as a [substrate] will concentrate in the SER (smooth endoplasmic reticulum)

Question 9

12 P450 groups in humans - some for toxins (drugs) - others for endogenous compounds:

1. ______ specificity
2. very ______ genetic variations
3. catalyzes primarily ______, but does some reductions.

Answer 9

12 P450 groups in humans - some for toxins (drugs) - others for endogenous compounds:

1. low specificity
2. very large genetic variations
3. catalyzes primarily oxidations, but does some reductions.

Question 10

CYP2D6 has substatian genetic variation.

Phenotypes of patients for metabolic activity

1. poor → potential ______
2. intermediate
3. extensive
4. ultrarapid → potential no ______ effect- high first pass metabolism

Answer 10

CYP2D6 has substatian genetic variation.

Phenotypes of patients for metabolic activity

1. poor → potential toxicity
2. intermediate
3. extensive
4. ultrarapid → potential no theraputic effect- high first pass metabolism

Question 11

65 commonly used drugs metabolized by CYP2D6
Potential drug interactions when various drugs are metabolized by the ______ type of cytochrome P450 enzymes - ______ metabolism

1. competition with inhibition - potential ______
2. Induction → ______ effectiveness for a given dose

cP450 System also influenced by:

A. ______ factors - liver disease, liver perfusion

B. Age and sex - fetal → geriatric

Answer 11

65 commonly used drugs metabolized by CYP2D6
Potential drug interactions when various drugs are metabolized by the same type of cytochrome P450 enzymes - slow metabolism

1. competition with inhibition - potential toxicities
2. Induction → decrease effectiveness for a given dose

cP450 System also influenced by:

A. Disease factors - liver disease, liver perfusion

B. Age and sex - fetal → geriatric

Question 12

Types of Drug Biotransformations Carried Out
by Hepatic Mixed Function Oxidase System:

Drug oxidation = add ______

Drug reductions = add ______ or change the proportion of hydrogen in the molecule

Answer 12

Types of Drug Biotransformations Carried Out
by Hepatic Mixed Function Oxidase System:

Drug oxidation = add oxygen

Drug reductions = add Hydrogen or change the proportion of hydrogen in the molecule

Question 13

PHASE II REACTIONS occur in the ______.

______ = synthesis of a new molecule. Enzymes using endogenous substrates. Covalent bond of drug to another molecule.

As a result of ______, Molecule is: Larger, Charged, Water Soluble, & Inactive.

Answer 13

PHASE II REACTIONS occur in the liver.

Conjugation = synthesis of a new molecule. Enzymes using endogenous substrates. Covalent bond of drug to another molecule.

As a result of conjugation, Molecule is: Larger, Charged, Water Soluble, & Inactive.

Question 14

______ order enzyme kinetics = concentration of drug is less than Km so = constant x [drug]—velocity is responsive to drug concentration.

______ order enzyme kinetics = v = Vmax & inefficient since it saturated so always working @ Vmax. Velocity is not responsive to drug concentration.

Answer 14

First order enzyme kinetics = concentration of drug is less than Km so = constant x [drug]—velocity is responsive to drug concentration.

Zero order enzyme kinetics = v = Vmax & inefficient since it saturated so always working @ Vmax. Velocity is not responsive to drug concentration.

Question 15

Concerning hepatic enzymes:

______ = increases metabolism caused by the drug in question or by other drugs.

______ = decreases metabolism caused by another drug.

Answer 15

Concerning hepatic enzymes:

Induction = increases metabolism caused by the drug in question or by other drugs.

Inhibition = decreases metabolism caused by another drug.

Question 16

______ enzymes can do inhibition and saturation only.

______ enzymes can do induction, inhibition, and saturation.

Answer 16

Non-microsomal enzymes can do inhibition and saturation only.

Microsomal enzymes can do induction, inhibition, and saturation.

Question 17

Amount of Drug Excreted by kidney =

Answer 17

Amount of Drug Excreted by kidney = (glomerular filtration + active tubular secretion) - (passive reabsorption + active reabsorption)

In more simple way:

Excreted = filtration + secretion – reabsorption (passive or active)

Question 18

Enhancing Renal Excretion:

1. Forced ______ = give a ton of fluid
2. Manipulate the ______ of the urine - trapping of ionized drug

Answer 18

Enhancing Renal Excretion:

1. Forced diuresis = give a ton of fluid
2. Manipulate the pH of the urine - trapping of ionized drug

Question 19

Biliary Excretion:

Amount of Drug Excreted =

Answer 19

Biliary Excretion:

Amount of Drug Excreted = (Amount of drug entering bile) - (Amount of drug reabsorbed)

Question 20

ELIMINATION OF DRUGS FROM SITE OF ACTION = ______ the concentration in the plasma

Redistribution = changes ______ of the drug

Biotransformation is primarily ______, metabolically changes the drug to metabolites & causes a ______ of the drug from the plasma.

Excretion is primarily ______, produces a clearance of the drug from the plasma and the body.

Answer 20

ELIMINATION OF DRUGS FROM SITE OF ACTION = Decrease the concentration in the plasma

Redistribution = changes location of the drug

Biotransformation is primarily hepatic, metabolically changes the drug to metabolites & causes a clearance of the drug from the plasma.

Excretion is primarily renal, produces a clearance of the drug from the plasma and the body.

Question 21

Clearance is a combination of ______ and excretion. It is a volume of plasma that is cleared of drug per unit of time in ______.

Answer 21

Clearance is a combination of biotransformation and excretion. It is a volume of plasma that is cleared of drug per unit of time in ml/min.