Drug Absorption - Issar

Question 1

What physiological factors influence drug absorption?

Answer 1

1. Route of administration
2. Area of absorbing surface
3. Blood flow or perfusion at site of administration
4. Disease states
5. Drugs affecting absorption of other drugs

Question 2

What physiochemical factors influence drug absorption?

Answer 2

1. Drug solubility and pH
2. Particle size
3. Polymorphic crystal and solvates
4. Drug lipophilicity

Question 3

Which routes of administration are parenteral?

Answer 3

1. Intravenous
2. Subcutaneous
3. Intramuscular

Question 4

Which routes of administration are enteral?

Answer 4

1. Buccal
2. Sublingual
3. Oral
4. Rectal

Question 5

Which routes of administration are topical/transdermal/inhaled?

Answer 5

1. Skin and mucosa

2. Lungs

Question 6

Intravenous (IV)

Answer 6

• 100% bioavailable
o Entire drug quantity enters vasculature
• Good for drugs with
o Narrow therapeutic index
o Poor, erratic or no absorption
o Rapid metabolism
o When circulation is poor to site of administration
• Disadvantages
o Neither removed nor its absorption retarded following overdose
o Introduction of air (embolism) or bacteria
o Precipitation of blood contents
o DO NOT give insoluble drugs or oils via this route

Question 7

Subcutaneous (SC)

Answer 7

• Less vascular than muscle tissue → sustained effect
• Rate of absorption affected by similar factors as IV
• Only for nonirritating drugs
o Can cause tissue necrosis

Question 8

Intramuscular (IM)

Answer 8

• Rate of absorption if better than SC
• Can give more irritating drugs and larger volumes
• Skeletal muscles show rapid absorption but can vary on vasculature and other properties
o Which muscle you administer the drug in matters
• If drug insoluble or in an oily vehicle àslower absorption

Question 9

Buccal

Answer 9

• Tablets or buccal lollipops
• Dissolve slowly
• Some goes into stomach via saliva but most is directly absorbed from gums

Question 10

Sublingual

Answer 10

• Small tablets
• Dissolve rapidly
• Ideal candidate
o Non-ionized, highly lipid soluble, rapid dissolution rate
o Ex: nitroglycerin
• Absorbed quickly due to extensive blood network under the tongue

Question 11

Oral

Answer 11

• Common, safe, convenient and economical
• Most oral drugs dissolve via passive diffusion
• Low stomach pH prevents ionization of weak acidic drugs
• Small intestine
o Large surface area, high blood perfusion → high capacity for absorption
o Diarrhea decreases extent of drug absorption
• Important considerations
o Efflux transporters –> reduce absorption
o Bacterial metabolism
o Effect of GIT secretion
• Stomach pH decomposes drug before it is fully absorbed
o Presence of food (slide 26)
• Can increase or decrease absorption
• High calorie, high fat content containing meals result in a larger effect on the bioavailability

Question 12

Rectal

Answer 12

• Irregular and incomplete absorption
• Partial avoidance of first pass effect
o Superior rectal V pours into hepatic portal V
• Drugs can irritate the rectal mucosa
• Advantages
o Labile drugs can bypass harsh environment
o Compliance with unconscious pts or pts with swallowing issues

Question 13

Skin and mucosa

Answer 13

• Stratum corneum (thick part of skin)
o Lipid soluble drugs diffuse slowly
o Water soluble drugs excluded
• Skin is not a perfect barrier
• Absorption through mucosa is rapid
• Absorption through skin is slow
o Enhanced in oily vehicle
• Skin permeation by passive diffusion follows Fick’s diffusion law
• Rate of diffusion across skin is relative to surface area (A) and inversely proportional to stratum corneum thickness (h)

Question 14

Lungs

Answer 14

• Advantages
    o Extensive surface area → rapid absorption
    o Local or systemic delivery
    o Rapid response
    o Bypass GI first pass
    o Similar therapeutic effect with lower dose
• Disadvantages 
    o Efficient aerodynamic filter
    o Mucociliary transporter
    o Low pulmonary deposition

Question 15

Which routes of absorption DO NOT have a first pass effect?

Answer 15

1. Intravenous
2. Subcutaneous
3. Intramuscular
4. Buccal
5. Sublingual
6. Skin and mucosa
7. Lungs

Question 16

Which routes of absorption DO have a first pass effect?

Answer 16

1. Oral

2. Rectal

Question 17

What is a first pass effect?

Answer 17

When a certain amount of the drug is broken down and metabolized in the liver so the amount of the drug that is actually active is lower than what was initially given

Question 18

What is an example of a drug whose absorption is highly affected by particle size?

Answer 18

Griseofuvin and steroids
 Highly lipophilic
 Poorly soluble in water hence show poor absorption.
 “Micronization” – increases surface area à ↑ dissolution