3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.1. Pharmacokinetics
 3.1.3.1.1.2. Absorption 

Absorption

[SH4:p8]

 

=== Unfinished ===

More notes on sublingual

PR paracetamol and indocid

===

 

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
  • Drugs absorbed from suppositories in the lower rectum go into inferior vena cava
    --> Bypass the liver [BGK9:p43]

Transdermal administration

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

 

Examples:

  • Scopolamine
  • Fentanyl
  • Clonidine
  • Nitroglycerin
  • Oestradiol
    * [Examiner's report 1996A13]
    * [???]

 

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)
  • Enhanced compliance

 

Disadvantages

  • Contact dermatitis
  • 7 days limit for one application
    * Due to sloughing of stratum corneum
  • Tolerance for some drugs
    * e.g. scopolamine and nitroglycerin
  • Slow onset [???]
  • Transdermal preparation requires special formulation

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

 

Other factors which may influence absorption

  • Blood flow
  • Body site (determines the thickness of the epidermal layer)
  • Skin temperature
  • Skin integrity
  • Ethnic group [???]
  • Age [???]

 

 

Tolerance

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