Basic Principles

Question 1

What is a drug?

Answer 1

Chemical substance used for the Dx, prevention or Tx of disease, and for the prevention of pregnancy

Question 2

What is pharmacokinetics? What are the four major steps?

Answer 2

How a drug enters the body, circulates w/in the body, is changed by the body, and leaves the body.
Absorption
Distribution
Metabolism
Excretion

Question 3

What is pharmacodynamics?

Answer 3

Biochemical and physiologic actions of drugs, and their mechanisms of drug action at the cell level and sub-cell level

Question 4

What is a succinct difference between pharmacokinetics and pharmacodynamics?

Answer 4

Movement VS Action

Question 5

What are the characteristics of drug molecules?

Answer 5

Lipid solubility, Degree of ionization, Molecular size, and Shape

Question 6

How do drug molecules cross membranes?

Answer 6

Diffusion, Filtration, and Specialize transport

Question 7

How does pKa affect the ionization of weak acid drugs and weak base drugs?

Answer 7

Weak Acid in acidic environment is lipid soluble.
Weak Acid in basic environment is water soluble (dissociates).
Weak base in acidic environment is water soluble (dissociates).
Weak base in basic environment is lipid soluble.
THEREFORE, a weak acid or a weak base in its native environment is lipid soluble, otherwise it is water soluble and dissociates

Question 8

Are charged molecules lipid soluble?

Answer 8

No

Question 9

Is aspirin an acid or a base?

Answer 9

Weak acid pKa = 4.4

Question 10

What happens to aspirin in stomach?

Answer 10

It is dissociated 1000 uncharged:1 charged molecules. The uncharged aspirin is lipid soluble and can cross the wall of stomach into plasma. Once in plastma the pH is 7.4 and it’s ratio is reversed 1000 charged to 1 uncharged.

Question 11

What are the routes by which drugs are administered in the body?

Answer 11

Everything other than oral and rectal is a parenteral route. The parenteral route is inhalation, insufflation, intravenous, intramuscular, topical subcutaneous, sublingual, and transdermal

Question 12

What are the mechanisms by which drugs penetrate biological membranes?

Answer 12

Diffusion, filtration, and specialized transport

Question 13

How do most drugs cross membranes?

Answer 13

By diffusion

Question 14

What are the forms of specialized transport?

Answer 14

Facilitated diffusion and Active transport

Question 15

What is the first pass effect?

Answer 15

Only an issue with oral route drugs. Drugs must go thru liver first before reaching systemic circulation. Intestinal epithelium and liver have P450 enzymes that metabolize (a certain percentage) the drug to inactive forms

Question 16

What is bioavailability?

Answer 16

The fraction of the administered drug that becomes available in the plasma

Question 17

What does bioavailability often depend on in generic drugs?

Answer 17

The “vehicle” that carries the drug into the system. Active drug molecule may be the same but vehicle may differ in generics

Question 18

How do drugs get transported from the plasma to the tissue sites?

Answer 18

Drugs are either bound or unbound to plasma proteins. Only “free” unbound drug molecules can cross cell membranes to tissue sites.

Question 19

What happens to the bound drug as unbound drug leaves the plasma into interstitial fluid?

Answer 19

The bound/unbound ratio of a drug stays the same, so bound drugs become unbound to maintain that ratio

Question 20

What are the various body fluid compartments where drugs can pass? (3)

Answer 20

Plasma, interstitial fluids, and intracellular fluids

Question 21

What are the potential barriers to drug distribution in the body?

Answer 21

Two main barriers are the BBB and placenta.

ALSO,

1. Another drug may induce the metabolism of a drug, thereby reducing action of the first drug.
2. First pass effect.
3. Not being lipid soluble
4. large size
5. charged molecules cannot cross
6. shape

Question 22

What is a drug inducer? What is a drug inhibitor?

Answer 22

An inducer decreases the action of another drug, by increasing drug metabolism.
An inhibitor increases the action of another drug, by slowing down the metabolism of a drug; makes it stay around for longer.

Question 23

What is drug redistribution?

Answer 23

Movement of the drug from the site of action to nonspecific sites of action

Question 24

How does drug redistribution affect termination of drug activity?

Answer 24

When drug does from specific sites to nonspecific sites, the drug’s action will be terminated

Question 25

What is drug biotransformation?

Answer 25

Body’s way of changing a drug so that it can be more easily excreted by the kidneys. Such as, conversion of lipid soluble drugs to water soluble metabolites

Question 26

What are the phases of drug Biotransformation?

Answer 26

Two phases.
Phase 1 drug is modified by oxidation, reduction, or hydrolysis. Exposes site that can be further altered by Phase 2 reaction
Phase 2 drug is modified by conjugation to a larger endogenous molecule (eg, glucuronide, sulfate, glutathione)

Question 27

Are Phase 2 metabolites pharmacologically active?

Answer 27

No, phase 2 metabolites are inactive. In contrast, phase 1 can still be active, but is usually rendered inactive also.

Question 28

What are the characteristics of the microsomal oxidation enzyme system?

Answer 28

Cytochrome P450 enzymes metabolize the drugs. Microsomes are organelles in hepatocytes where most drug transformation takes place.

Question 29

Where does drug metabolism also occur besides the liver?

Answer 29

Kidneys, lungs, nerves, plasma, and the intestines. But, all drugs are processed by liver eventually (?)

Question 30

What is the principal organ of drug excretion?

Answer 30

The kidneys, they are the great “equalizers”.

Question 31

All drugs in the blood are filtered by what organ?

Answer 31

Kidneys

Question 32

What are the 6 ways for drug excretion from the body?

Answer 32

1) Kidney to urine
2) Bile to GI tract to feces
3) Sweat
4) Saliva
5) Lungs
6) Breast milk

Question 33

What happens if a drug is still lipid soluble when it reaches the kidneys?

Answer 33

Drug will be reabsorbed by the kidneys a placed back into the bloodstream.

Question 34

What is the biological “half-life” of a drug?

Answer 34

Amount of time needed for the plasma concentration of a drug to fall to one half its blood level

Question 35

How many half-lives does it take for most drugs to be eliminated? How many half-lives to build up to a steady state level in the body?

Answer 35

4-5 half lives. Same amount of half-lives, 4-5

Question 36

What is the difference between first order and zero order elimination?

Answer 36

First order elimination depends on a constant fraction that is eliminated per unit of time; most have a constant half-life; 50% eliminated per unit of time.
Zero order elimination is a given or set amount of drug eliminated per unit of time; as in alcohol is eliminated 1 g per hour regardless of initial amount of alcohol

Question 37

What is distribution half-life? How is it related to first order drug elimination?

Answer 37

Rapid decline in plasma drug concentration as 50% of drug distributed throughout the body. It is a type of first order elimination

Question 38

What is elimination half life? How is it related to first order drug elimination?

Answer 38

Time required to excrete 50% of drug from the system. It is a type of first order elimination.