Lecture: 30 Pharmacokinetics

Question 1

Orally ingested drugs mechanism

Answer 1

CNS –>The wall of the intestine–> The walls of the capillaries that perfuse the gut –> The blood-brain barrier

Effects felt and drug eliminated

Question 2

Drug mechanisms of permeation

Answer 2

1) Aqueous diffusion (PARACELLULAR PATHWAY)

2) LIPID DIFFUSION (TRANSCELLULAR
PATHWAY)

3) SPECIAL CARRIERS
4) ENDOCYTOSIS & EXOCYTOSIS (TRANSCYTOSIS)

Question 3

Absorption

Answer 3

Absorption = Site of administered –> bloodstream

• IV= absorption complete (total dose reaches systemic circulation)
• Every other drug delivery routes (besides IV) gives partial absorption

Question 4

Enteral Routes

Oral

Sublingual

Rectal

Answer 4

Oral:

• Maximum convenience, but slower/less complete absorption
• First-pass effect= Some of the drug is metabolized in the gut wall and liver = not reaching circulation

Sublingual:
(under the tongue)
-Drug enters the systemic circulation directly, drug bypasses first-pass effect

Rectal:
(up the ass)
-Partial avoidance of the first pass-effect

Question 5

Parenteral routes (routes not by mouth)

Answer 5

1) Intravenous- in veins
2) Intramuscular- in muscles
3) Subcutaneous- under skin
4) Intradermal- shallow, under skin

Question 6

Other routes

Answer 6

1) Oral inhalation (in mouth)
2) Nasal inhalation (in nose)
3) Topical (top of skin)
4) Transdermal (Through the skin)

Question 7

Factors that influence drug absorption

Answer 7

1) Effects of PH on drug absorption
-The protonated form of a weak acid is the
more liposoluble form (no charge)
-The unprotonated form of a weak base is the
more liposoluble form.

2) Surface area available for absorption
3) Blood flow to absorption site
4) Contact time at absorption surface
5) P-Glycoprotein

Question 8

Henderson Hasselbach equation

Answer 8

pH - pK = log [Unprotonated form]/[Protonated form]

-When PH= pK [Unprotonated] = protonated][

Question 9

What will happen if If a drug is in a liposoluble form during its passage down the renal tubule

Answer 9

A significant fraction will be reabsorbed by passive diffusion

(To avoid this can adjust PH of the urine to ionize the drug, “trapping” it in the urine)

Question 10

Why does most drug absorption occurs at the small

intestine

Answer 10

Because of its large surface area and greater blood flow

Question 11

P-glycoprotein (MDR1)

Answer 11

• Transporter Protein, Transports drugs across a cell membrane
• Reduces drug absorption

Question 12

BIOAVAILABILITY (F)

and AUC

Answer 12

-Fraction of administered dose of a drug that
reaches the systemic circulation
-Plot plasma concentrations of the drug vs.
time, the area under the curve (AUC)

-Determined comparing the AUC after a particular route of administration with the AUC after IV injection

• AUC = extent of absorption
• AUC= AUC Oral/AUC IV X 100

Question 13

Drug distribution

Answer 13

-It is the process by which a drug leaves the
blood stream and enters the extracellular fluid
and /or the cells of the tissues.

Determined by:

1) Blood flow
2) Drug binding to plasma and tissue proteins
3) Capillary permeability
4) Drug hydrophobicity

Question 14

Where can drugs accumulate

Answer 14

Tissues, fat

Accumulation can prolong drug action

Question 15

The blood brain barrier

Answer 15

• Restricts the penetration of polar molecules
• Endothelial cells contain tight junctions
• P-glycoprotein actively transports drugs back into the systemic circulation.
• To enter the CNS drugs must be highly liposoluble or have an active transporter

Question 16

Drug elimination

Two routes

Answer 16

1) Metabolism
-Lipophilic drugs can pass across cell membranes and
gain access to their site of action, (not easily excreted bc they are reabsorbed through the tubular membranes)

2) Excretion
-Enhance the hydrophilicity of drugs and their metabolites,
enabling them to be excreted
• Renal excretion (most common)
• Bile excretion (less common)

Question 17

Metabolism of Drugs

Organs that metabolize

Organs involved in the first pass

Answer 17

• Liver = main organ of drug metabolism
• More polar, inactive metabolites = excreted easier from body
• Particularly active sites include the GI tract, the kidneys, the skin and the lungs.
• First pass= liver, Gi tract

Question 18

Cytochrome P450 system

Drugs

Answer 18

• Metabolizes majority of clinical drugs
• Can be inductibles = increases transcription (Enzyme induction)

Drugs that increase P450:
• Rifampin
• Phenobarbital
• Carbamazepine
-may reduce drug plasma concentrations below therapeutic levels

Drugs that inhibit P450:
• Cimetidine
• Erythromycin
• Chloramphenicol
• Grapefruit juice
-Inhibition can lead to toxic concentration due to lack of metabolism