2. Drug Absorption

Question 1

What is generic substitution?

Answer 1

Generic substitution occurs when a different formulation of the same drug is substituted. All generic versions of a drug are considered by the licensing authority to be equivalent to each other and to the originator drug.

Question 2

What is therapeutic substitution?

Answer 2

Therapeutic substitution is the replacement of the originally-prescribed drug with an alternative molecule with assumed equivalent therapeutic effect. The alternative drug may be within the same class or from another class with assumed therapeutic equivalence

Question 3

Name the advantages and disadvantages of drug administration via oral route?

Answer 3

Advantages
– Cheap
– Safe
– Convenient
Disadvantages
– Patient compliance
– Variation in bioavailability of drug

Question 4

Particle size and formation, what is contained in a drug capsule?

Answer 4

Drug
Excipients
Binding agents
Lubricants
Coatings

Question 5

List the advantages of the different forms of oral route:
Buccal / sublingual mucosa
Gastric mucosa
Small intestine
Large intestine / colon
Rectal mucosa

Answer 5

Buccal / sublingual mucosa
– Direct absorption into bloodstream 
– Avoids first pass metabolism
– Not ideal surface for absorption
Gastric mucosa
– Enteric coating
Small intestine
– Main site of drug absorption
– Large surface area, more neutral pH
Large intestine / colon
– Poor absorption, long transit times
Rectal mucosa
– Direct to systemic circulation

Question 6

4 ways small molecules cross cell membranes

Answer 6

1) Diffusing directly through the lipid
-Lipid solubility highly important
2) Diffusing through aqueous pores
-More likely important for diffusion of gases
3) Transmembrane carrier protein
– e.g. solute carriers
4) Pinocytosis
– Mostly macromolecules, not drugs

Question 7

What is the physicochemical factor affecting drug absorption?

Answer 7

Drug ionisation

Question 8

What is the henderson-hasselblach equation for a weak base?

Answer 8

pKa - pH = Log10 [BH+]/[B]

ionised on top

Question 9

What is the henderson-hasselblach equation for a weak acid?

Answer 9

pKa - pH = Log10 [AH]/[A-]

note ionised on bottom
weak acid are more likely to be absorbed by SI than weak bases

Question 10

Weak acid are ____likely to be absorbed by SI than weak bases

Answer 10

Weak acid are more likely to be absorbed by SI than weak bases

Question 11

Effect of food on gastric emptying?

Answer 11

Slows the rate

Question 12

Effect of decreased absorption on drug absorption

Answer 12

Intestinal motility
Interactions with food, acids
Presystemic metabolism

Question 13

Effect of delayed absorption on drug absorption

Answer 13

Gastric emptying
Clinically important
Cmas may decrease

Question 14

Increased absorption effect on drug absorption

Answer 14

Poorly water soluble drugs
increased solubilisation
Decreased pre systemic metabolism

Question 15

What is process of first pass metabolism in levodopa uptake?

Answer 15

Levodopa: Prodrug in treatment of Parkinson’s disease
Rapidly taken up from stomach and small intestine. Large neural amino acid transport carrier (LNAA)
DOPA decarboxylase present in gastric mucosa

Question 16

Effect of intestinal disease in drug absorption?

Answer 16

Altered rate of drug absorption due to disease state
– E.g. Increased GI motility, compromised GI integrity
– What about reduced motility? (e.g. diabetic gastroparesis)

E.g. Crohn’s and coeliac disease

Question 17

Factors that affect oral absorption?

Answer 17

1. Particle size and formulation
2. GI motility
   3, First pass metabolism
   – First pass metabolism by gut wall or hepatic enzymes
3. Physicochemical factors
   – Direct drug interactions, dietary factors, varying pH
4. Splanchnic blood flow
   – Increased flow increases drug absorption
5. Efflux pumps
   – P-glycoprotein

Question 18

Name 2 parenteral routes and their properties?

Answer 18

Subcutaneous:
Slow absorption due to blood flow
Intramuscular:
-Lipophilic drugs rapidly
-Polar drugs via bulk flow and endothelial cell junctions
-High MTW or very lipophilic drugs via lymphatics

Question 19

What determines the rate of onset when using parenteral routes?

Answer 19

Extent of capillary perfusion
Drug vehicle
Affected by factors that alter perfusion

Question 20

Inhalation as a method of drug administration:
Where is the drug absorbed via?
Systemic effects?
Local effects achieved by:

Answer 20

Where is the drug absorbed via: Alveolar epithelium and bronchial mucosa
Systemic effects:
-Lipid-soluble drugs
-Drugs of abuse
-Accidental poisoning
Local effects achieved by:
-Modifying structure e.g. ipratropium
-Changing the particle size e.g. salbutamol
-Selectivity for receptors e.g. salbutamol
-Rapid breakdown in circulation e.g. fluticasone

Question 21

Intranasal drug administration:
Advantages?
Limitations?

Answer 21

Advantages:

• Easily accessible
• Rich vascular plexus
• Avoids hepatic first pass metabolism
• Ease, convenience, safety

Limitations:
-Limited drugs suitable as it requires concentrated drug

Question 22

What are the local and systemic uses for drug administrations via the topical route?

Answer 22

Local uses:

• Corticosteroids for eczema e.g. hydrocortisone
• Antihistamines for insect bites e.g. mepyramine
• Local anaesthetics

Systemic uses:

• Transdural patches (HRT, GTN, nicotine)
• Accidental poisoning (AChEsterase insecticides)

Question 23

What are difference in weak acid and base absorption?

Answer 23

Weak bases:

• Ionised in acidic pH
• Absorbed in SI
• Ionisation in plasma

Weak acids

• Unionised in acidic pH
• BUT also absorbed in small intestine due to large SA