Absorption

Systemic absorption of drug (regardless of route) depends on:

• Solubility of the drug
• Blood flow to the site
• Area of surface available for absorption

 

Oral administration

Most absorption occur in small intestine due to greater surface area

Advantages

• Convenient
• Economical

Disadvantages

• Emesis caused by irritation of GIT mucosa
• Destruction of drug by enzymes or gastric acid
• Irregularities in absorption (also influenced by presence of food)
• Potential metabolism by enzyme or bacteria in GIT

First-pass hepatic effect

Drug absorbed from GIT goes into portal venous blood
--> Goes through liver
--> Drugs undergo hepatic metabolism before going into systemic circulation

 

Oral transmucosal administration

Sublingual or buccal route permits rapid onset due to bypassing of hepatic metabolism

 

Sublingual area drains directly into SVC
* e.g. GTN

 

Nasal mucosa - also an effective route (?? bypass hepatic metabolism)

 

Rectal administration

Superior hemorrhoidal vein drains into portal venous system

Lower rectal area drains directly into systemic circulation (bypassing liver)

(???) Dentate line = cut off

Transdermal administration

Rate-limiting step in absorption
--> Diffusion across stratum corneum of the epidermis

 

Examples:

• Scopolamine
• Fentanyl
• Clonidine
• Nitroglycerin

 

NB:

Postauricular zone has thin epidermal layer and slightly higher temperature
--> The only site where scopolamine is absorbed transdermally predictably

Advantages

• Sustained therapeutic plasma concentration
• Lower incidence of side effects (due to lower dosage used)

Disadvantages

• Contact dermatitis
• 7 days limit for one application
  * Due to sloughing of stratum corneum
• Tolerance for some drugs
  * e.g. scopolamine and nitroglycerin

Factors influencing transdermal absorption

Transdermal absorption is increased where:

• High combined water and lipid solubility
• MW < 1000
• pH 5-9 in a saturated aqueous solution
• absence of histamine-releasing effects
• Daily dose requirement < 10mg

Tolerance

Sustained plasma concentration provided by transdermal administration of scopolamine and nitroglycerin can lead to tolerance

 

===

 

More notes on sublingual

PR paracetamol and indocid