2Pharmacokinetics~Excretion

Distribution

The transport of a drug in the body by the bloodstream to its site of action.

Distribution

The extent to which the drug passes into different tissues and fluid compartments in the body

Distribution

Drug inside the blood stream in order to the drug to be able to target the active site

Central and Peripheral Compartment

Distribution

2 Compartments

▪ Volume of Distribution

▪ Protein Binding

▪ BBB and Placental Barrier

DISTRIBUTION

Parameters

Volume of Distribution

Amount of medication available to distributed in the entire bloodstream (Vd)

Regulatory and Serum Protein

2 Types of Protein Binding

❌ No action

Inactivation

Serum Protein

If drug binds to the protein

Anticoagulant

Warfarin use

99%

% of Warfarin making it highly protein bounded and inactivated

1%

Warfarin %

Potent making it active causing anticoagulation

Excessive bleeding

Warfarin ADR

Receptor / Enzymes

Regulatory molecules

Cardiac Output

Regional Blood Flow

DISTRIBUTION

Physiologic Factors Affecting Distribution

Cardiac Output

The amount of blood heart pumps in every minutes

Stroke volume × Heart rate

Cardiac output equation

2.2-3.5 liters/min/square meter

Normal Cardiac Output

Liver, kidneys, and Brain

25% CO

Lungs

100% CO

Adipose tissues and Bones

<1 % CO

7-14 days treatment because 100%

CO

Pneumonia

6 weeks to 6 months Tx (very low CO)

Osteomyelitis

Osteo = bones

mye = muscle

litis = inflammation

Osteo

Mye

Litis

Regional Blood Flow

fraction of cardiac output that is delivered to specific tissues/organs

heart, liver, kidneys, brain

Areas of ⬆high blood flow:

muscle, skin, fat, bone

Areas of ⬇ low blood flow:

Volume of Distribution (VD)

The hypothetical volume of body fluid necessary to dissolve a given amount or dose of a drug to achieve a concentration equal to that of the drug plasma concentration

basic drugs

⬆ High VD

acidic drugs

⬇ Low VD

atropine, chloroquine -chlorpropamide

-raloxifene

⬆ High VD

-basic drugs -acidic drugs

-examples:

Anticholinergic

Atropine use

⬇😉 mucus

⬇ Secretion

Constipation

Atropine ADR

Antimalarial

Chloroquine

Evista

Raloxifene BN

Osteoporosis

Raloxifene (Evista) for

chlorpropamide

tolbutamide

⬇ Low VD

-acidic drugs

examples

chlorpropamide

tolbutamide

Increase the release of Insulin from the Pancreas

• To control diabetes

Protein Binding

It is the phenomenon that occurs when a drug combines with plasma (particularly albumin) or tissue protein to form a complex.

Albumin

Most abundant type of serum protein

Albumin

Alpha acid glycoprotein

globulin

lipoproteins

erythrocytes

Protein binding

Albumin

Major binding protein available

Albumin

Protein binding

Acidic drugs

lipoproteins

Protein binding

Lipids or proteins

Alpha acid glycoprotein

Protein binding

Basic dugs

Orosomucoid

Alpha acid glycoprotein example

globulin

Protein binding

Hormones

erythrocytes

Protein binding

Exogenous/endogenous compounds

a1 globulin

bind to a number of steroidal drug cortisone, prednisolone $ thyroxine, cynocobalamine

y-globulin

Bind to antigen

B1-globulin

(transferrin) bind to ferrous ion

B2-globulin

Bind to carotinoid