Drug Absorption and Distribution

Question 1

What are the factors affecting rate of absorption?

Answer 1

• Route of administration
• Dosage
• Lipid solubility

Question 2

What are the 3 major routes of administration?

Answer 2

• TOPICAL - applied directly where it is needed. Reduced risk of side effects. Less absorbed in circulation e.g ointments and lotions
• PARENTERAL - When administration avoids the gut. Acts rapidly. e.g IV, IM
• ENTERAL - Drug reaches target after absorption from gut. Crosses several barriers and metabolised. SIDE EFFECTS - unwanted pharmacological (in)activation

Question 3

What are some issues during drug absorption from gut?

Answer 3

• Binding to food - may cause pharmacological inactivation
• Metabolised by gut enzymes
• First pass metabolism by liver - cause drug to be broken down
• Drug needs to enter systemic circulation - issues during perfusion/heart defects

Question 4

Describe drug movement across the bilayer.

Answer 4

• Proportional to the size and lipid solubility of drug
• Un-ionised molecules (B) pass through much
  easier than those that are ionised (BH+).
• Ionised molecules have a ‘shell’ of water so require transporter

Question 5

What happens when pH=pKa?

Answer 5

• Fifty percent in unionised format (can cross membrane)
• Fifty percent ionised

Question 6

When will drugs tend to exist in ionised(water-soluble) state?

Answer 6

• When exposed to solution with pH opposite to the drug’s own pH

Question 7

Aspirin is a weak acid with a pKa of 3.5. Describe its behaviour in the stomach, plasma and urine.

Answer 7

• STOMACH - pH 2. More drug in neutral form so greater absorption
• PLASMA - pH 7.4 - more drug in ionised form
• URINE - pH 8 - more in ionised form. Cannot cross membrane

Question 8

Morphine is a weak base with pKa 8. Describe its behaviour in the stomach, plasma and urine.

Answer 8

• STOMACH - pH 2. More drug in ionised form. Cannot cross membrane
• PLASMA/URINE - more drug in neutral form
• Most absorption occurs at ileum

Question 9

What can separation of solutions with differing pHs do to the drug?

Answer 9

ION TRAPPING
- Limits movement - because solutions on either side of membrane have different pHs.
- Differing fraction of drug found ionised/neutral.

Question 10

Describe drug distribution and the body compartments it can occur across.

Answer 10

• Reversible transfer of drug from one location to another
• Usually by passive diffusion of the unionised form
• Affected by barriers e.g blood-brain barrier
• COMPARTMENTS - Plasma, Muscle, Fat

Question 11

Describe bioavailability

Answer 11

• Proportion of a drug that passes into the systemic circulation after administration.

Question 12

What is the difference between derivates and conjugates?

Answer 12

DERIVATIVES - pharmacologically active
CONJUGATE - pharmacologically inactive

Question 13

What are the factors affecting rate of distribution?

Answer 13

• Membrane permeability
• Blood perfusion - drug reaches highly vascularised tissues faster

Question 14

What are the factors affecting extent of distribution?

Answer 14

• Lipid solubility
• Plasma protein binding (not bioavailable when bound)
• Tissue binding

Question 15

Describe drug-plasma protein binding.

Answer 15

• Some are more plasma protein bound than others
• Bind reversibly
• Albumin binds acidic drugs
• Acid-glycoprotein/beta-globulin binds basic drugs
• Slows drug action and elimination. Highly plasma protein bound drugs - slower acting and prolonged therapeutic effects

Question 16

Describe tissue binding.

Answer 16

• Due to composition - lipid soluble drugs accumulate in fat
• Bind to cellular components i.e proteins
• Tetracyclines accumulate at bone or teeth - high calcium affinity

Question 17

What is the formula for volume of distribution?

Answer 17

Administered dose/Initial plasma concentration

Question 18

What happens when Vd close to plasma volume?

Answer 18

• Remains confined to plasma

Question 19

What happens when Vd is greater than plasma volume?

Answer 19

• Equilibration within tissues

Question 20

Describe the Vd of acidic, neutral and basic drugs.

Answer 20

• ACIDIC - greater plasma protein binding. Low Vd
• NEUTRALS - Equilibrate, not necessarily retained by tissues. Greater Vd
• BASES - High affinity for membrane phospholipids. Highest Vd

Question 21

What does it mean for a drug to be bioavailable and when does this occur?

Answer 21

• Becomes bioavailable upon reaching systemic circulation
• 100% bioavailability when given IV
• Less with other routes

Question 22

What is the equation for dug and plasma protein binding?

Answer 22

FREE Drug + plasma protein ⇋ Drug - plasma protein complex

Question 23

What factors does distribution affect?

Answer 23

• Rate of onset
• Drug effects
• Duration of action