3 Medical Mathematic: Distribution of Drugs

Question 0

What factors affect the distribution of drugs?

Answer 0

Physicochemical properties of the drug (Lipid solubility, degree of ionization) 
Concentration gradient
Plasma protein binding
Blood flow
Tissue barriers
Affinity of drugs to certain tissues

Question 1

What is distribution of drugs?

Answer 1

Is the transport of drugs from the plasma to the tissues (site of action, site of storage, site of biotransformation)

Question 2

Describe plasma binding proteins

Answer 2

Acidic drugs bind mainly to albumin.
Basic drugs bind mainly to acid alpha 1-glycoproteins and lipoproteins.
Some drugs bind to globulin (e.g., steroids).
Generally reversible.
Prolongs the half-life of the drug.
The bound form is inactive, can not be distributed, metabolized or excreted by glomerular filtration.
The rate of binding depends mainly on the amount of the drug.
Binding can be modified by disease.
Drugs can compete on the binding sites.
Plasma protein binding depends on the species.

Question 3

Describe blood flow as it affects the distribution of drugs

Answer 3

The rate of tissue perfusion relative to the tissue mass
	– Highly perfused tissues
		 Brain, liver, kidney, endocrine glands
	– Moderately perfused tissues 
		Muscle, skin
	– Poorly perfused tissues 
		Bone, adipose tissue
• Alteration of blood flow 
	– Physiological factors
	– Drugs
	– Disease

Question 4

List the tissue barriers

Answer 4

The blood-brain barrier 
Eye
Testicles
Placenta
Mammary gland

Question 5

Describe The blood-brain barrier

Answer 5

Tight capillary endothelial junctions
The presence of glial cells
Flow of the CSF into venous drainage
Active transport mechanisms for extrusion of organic acids or bases

Question 6

What factors influence the blood-brain barrier?

Answer 6

Age
Inflammation (meningitis)
Trauma
Allergic reactions
Severe hypotension
Hypoxia
High doses of organic solvents (alcohol)
High doses of heavy metals (lead, mercury)

Question 7

Examples of the Affinity of drugs to certain tissues

Answer 7

Tetracycline to calcium in skeletal tissues
Aminoglycosides to kidney tissue
Trapping of iodine by the thyroid gland

Question 8

What is the Redistribution of drugs?

Answer 8

Is the movement of the drug from the tissues to the blood

The example of thiopental versus phenobarbital