Pharmcokinetics

Question 1

Drug efficacy is defined as

Answer 1

A drug in its therapeutic concentration.

Question 2

Pharmacokinetics

Answer 2

Gets the drug there so pharmacodynamics (drug action) happens

Question 3

Pharmacokinetics in Four easy Pieces

Answer 3

1. Absorption
2. Distribution
3. Metabolism (drug molecule altered: activated/inactivated, made toxic or nontoxic).
4. Elimination (broken down or excreted)

Question 4

Non-absorption, why would you want this?

Answer 4

Drug given for localized effect, don’t want it to be absorbed.
May be well tolerated b/c it doesn’t have systemic effects
**GI infection drugs, skin and mucosal infections, lung infections (inhalants), or local anesthetics

Question 5

Basic pharmacokinetic plot

Answer 5

X-axis is time
Y axis is [drug] (C) in blood (expressed as a log)
Absorption is the up slope: the appearance and increase of drug in blood

Question 6

Factors that affect absorption:

Answer 6

1. Drug Molecule
2. Site of Administration
3. Patient Factors
4. Miscellaneous Factors

Question 7

Chemical nature of the drug determines what?

Answer 7

Absorption, elimination, distribution, and metabolism.

Question 8

Most important property of the drug:

Answer 8

Lipophilicity

1. Lipophilic=fat-soluble=hydrophobic (goes better through cell membrane)
2. Hydrophilic=water soluble=lipophobic

Question 9

Lipophilic drug life cycle

Answer 9

Easily pass through cell membranes and tissue barriers.
Are generally more readily absorbed and better distributed throughout the body.
Generally must be metabolized before elimination by the kidneys.
***Easy in, easy around, hard out (stored in body fat)

Question 10

Weak Acids/Weak Bases

Answer 10

60% of drugs

Can exist in either charged or uncharged forms.

Question 11

Charged or uncharged weak acids/bases: What determines this?

Answer 11

The its pKa and the pH of the environment

Question 12

Henderson-Hasselbach for weak acids/bases

Answer 12

1. Weak acid: log HA/A-=pKa-pH
   weak acid @low pH=more unionized so more cross the barrier.
2. Weak base: log H+A/A=pKa-pH
   weak base @high pH=more unionized so cross barrier

Question 13

Example of a weak acid with a pKa of 7.3

Answer 13

1. In breast milk (pH 6.3): log HA/A-=7.3-6.3=1
2. Log 10^1 HA/A=10 parts HA (unionized), 1 part ionized
   Basically, a weak acid in a strong acid has more unionized, and vice versa.

Question 14

Ion trapping

Answer 14

When drugs are charged they have difficulty passing through tissue barriers, they are trapped.
**Will be trapped in an environment opposite its pKa

Question 15

Ion trapping of a weak acid

Answer 15

(Amphetamines)

Will be trapped in a basic environment.

Question 16

Ion trapping of a weak base

Answer 16

(Barbituates)

Will be trapped in an acidic environment.

Question 17

Other properties of drugs that affect absorption

Answer 17

1. Size: smaller drugs are more easily absorbed
2. Formulation: more easily absorbed if they are easily dissolved
   Liquid suspensions more quickly absorbed, some are give in forms that delays or prolongs absorption (XR capsule

Question 18

Site of Absorption

Answer 18

Second most important determinant of absorption.
Tight junctions: skin, mucous membranes, sublingual, stomach (excludes better)
Open junctions: intestines, subcutaneous, intramuscular, intrapleural (absorbs better)

Question 19

Blood flow and surface area:

Answer 19

Higher the blood flow to absorptive site, the more quickly the drug gets absorbed.
Larger surface area=more rapid drug transfer (alveoli for example).