7: Pharmacology, Pharmacokinetics, Metabolism

Question 1

drugs not synthesized within the body

Answer 1

xenobiotics

Question 2

Who said the dose makes the poison?

Answer 2

Theophrastus Von Hohenheim (Paracelsus)

Question 3

actions of the drug on the body; group in which drug belongs

Answer 3

pharmacodynamics

*think Drug’s effect on the body = D

Question 4

actions of the body on the drug (absorption, distribution, metabolism, and elimination ) aka ADME

Answer 4

pharmacokinetics

Question 5

Flux (molecules per unit time) = (c1-c2) x ((area x permeability coefficient))/thickeness

Answer 5

Fick’s Law of Diffusion

Question 6

category of drug absorption expressed as fraction of dose administered; also known as the fraction of unchanged drug reaching circulation

Answer 6

Oral Bioavalability (F)

(area under curve)

Question 7

How are most toxicants absorbed by the body?

Answer 7

Simple diffusion

Question 8

True/False:
Only the unbound drugs (those not bound to proteins) distribute into tissues and receptors, exert pharmacological effects, and are metabolized

Answer 8

True

Question 9

The elimination rate constant; a function of clearance and volume of distribution

Answer 9

KEL

Cl = Vd x KEL

Question 10

A constant relating to drugs rate of transfer/elimination from plasma; units are mL/min

Answer 10

Clearance

Cl = kel/Cp

Question 11

Is clearance used for zero order or first order eliminated drugs?

Answer 11

first-order

Question 12

Type of elimination where processes are saturated (going as fast as they can

-Constant rate of elimination; think of a tub; linear

Answer 12

zero-order elimination

i.e. Ethanol

Question 13

Type of elimination where processes are not saturated; not linear

Answer 13

first-order elimination

Question 14

Time for plasma concentrations to become ½

Answer 14

half life, T1/2

Question 15

Is clearance used for zero order or first order eliminated drugs?

Answer 15

first-order

Question 16

Calculation for half-life

Answer 16

T1/2 = 0.693/KEL

Question 17

hypothetical volume of body fluid (plasma) necessary to contain all of the drug at a concentration equal to the plasma concentration

Answer 17

Apparent Volume of Distribution, Vd

Question 18

Vd of ethanol

Answer 18

0.7 L/kg male and 0.55 L/kg females

Question 19

Route of Administration –>
Put in order of speed of delivery starting w/ fastest:
subcutaneous, IM, IV, Oral

Answer 19

(fastest) IV, Intramuscular, subcutaneous, oral (slowest)

Question 20

when the quantity of drug eliminated in the unit of time equals the quantity of the drug that reaches the systemic circulation in the unit of time.

Answer 20

Steady State

Question 21

How much accumulation/loss is achieved in 1 half life?
4 half lives?
5-6 half lives?

Answer 21

1 = 50%
4 = 90%
5-6 = 95-99%

Question 22

What three factors influence clearance?

Answer 22

1) dose (timing, was absorption complete)
2) organ blood flow
3) intrinsic function of liver and kidneys

Question 23

range of target plasma concentrations effective for most patients;

Answer 23

Therapeutic Range

Question 24

chemical transformation of any xenobiotic

Answer 24

Biotransformation

Question 25

Where does biotransformation primarily occur?

Answer 25

Liver

Question 26

Step in biotransformation where drugs are converted to more polar metabolite (oxidation, reduction, hydrolysis)

Answer 26

Phase I

Question 27

Step in biotransformation where drugs are conjugated w/ larger molecule (endogenous substance) to yield a more easily excreted conjugate; examples: glucuronidation acetylation, sulfation, methylation

Answer 27

Phase II *Most common is glucuronidation

Question 28

Where are drug metabolizing enzymes primarily located?

Answer 28

endoplasmic reticulum of liver

Question 29

Common enzymes responsible for biotransformation of drugs

Answer 29

Cytochrome p450 family CYP 1-3 w/ different isoforms CYP3A inhibition: grapefruit juice

Question 30

The two most important sites for drug elimination are:

Answer 30

Liver and Kidney

Question 31

An antagonist is a type of drug that: Has maximal efficacy Has affinity for a receptor but poor efficacy Binds to a receptor and activates it Has efficacy but poor affinity Decreases the concentration of an agonist required to produce an effect

Answer 31

Has affinity for a receptor but poor efficacy

Question 32

An agonist is a type of drug that: Prevents the metabolism of other drugs Binds to a receptor without activating it Simulates the metabolism of other drugs Competes noncompetitively Binds to a receptor and activates it

Answer 32

Binds to a receptor and activates it

Question 33

True or False: Most drugs are either strong acids or strong bases.

Answer 33

False. Most are weakly basic or acidic

Question 34

True or False: In alkaline urine, acidic drugs are more readily ionized.

Answer 34

True.

Question 35

True or False: Ionized substances are also referred to as polar substances.

Answer 35

True.

Question 36

True or False: The plasma half-life of a drug is directly proportional to total clearance.

Answer 36

False. Think of this equation --> T1/2 = 0.693/KEL

Question 37

True or False: Drugs bound to albumin are inactive

Answer 37

True.

Question 38

A classic example of a drug with a high Vd is: Cocaine THC Alprazolam Ethanol Isopropanol

Answer 38

THC

Question 39

One of the major physiological factors that determines the variability in the rate of drug excretion into the urine is its: pH Protein content Temperature Volume

Answer 39

pH

Question 40

In biotransformation, Oxidation, hydroxylation, dealkylation and sulfoxide formation are examples of...

Answer 40

Phase I reactions

Question 41

With few exceptions, the metabolites of drugs are more __________ than the parent drug. Polar or Non-Polar

Answer 41

Polar

Question 42

The primary site for drug absorption is: Stomach Small intestine Muscle Kidney Liver

Answer 42

Small Intestine

Question 43

Metabolism is the __________ conversion of one chemical substance to another.

Answer 43

Chemical

Question 44

This metabolite is highly reactive and responsible for acetaminophen-induced hepatotoxicity:

Answer 44

NAPQI

Question 45

The following is an inactive metabolite: Dihydrocodeine Delta-9-Carboxy-THC Morphine 6-glucuronide 11-OH-THC Nordiazepam

Answer 45

Delta-9-Carboxy-THC

Question 46

In contrast to drugs after phase I biotransformation, drugs after phase II have: Less pharmacological activity and lower water solubility More pharmacological activity and greater water solubility Less pharmacological activity and greater water solubility More pharmacological activity and less water solubility

Answer 46

Less pharmacological activity and greater water solubility

Question 47

Cocaine undergoes this to form benzoylecgonine: Demethylation Reduction Hydrolysis Glucuronidation Oxidation

Answer 47

Hydrolysis

Question 48

Cytochrome p450 is a family of: Mixed function monoamine oxidase inhibitors Mixed function glutathione transferases Mixed function transferases Mixed function oxidases Mixed function isozymes

Answer 48

Mixed function oxidases

Question 49

True or False: Lorazepam has no active metabolites.

Answer 49

True

Question 50

1,4-butanediol is a metabolic precursor to: GHB PCP LSD GBL alpha-PVP

Answer 50

GHB