3)Drug Absorption/ Pharmacokinetics Flashcards
Route Administration
Determined by:
- Properties of Drug - water/lipid solubility
- Therapeutic objectives - eg desirability of rapid onset of action
2 major routes: Enteral + Parenteral
Enteral Route
- Via the mouth
- Can be swallowed - oral delivery OR placed under tongue - direct absorption into blood stream
Oral Administration
- Easily self-administered
- Drug is exposed to GI environment - this limits its absorption
- major entry site into systemic circulation ⇢ Duodenum - due to large S/A
- After absorption ⇢ entered into portal circulation + liver ⇢ Then general circulation
Sublingual Administration
- Allows drug to diffuse into capillary network + directly into systemic circulation
- rapid absorption
- convenient
- Low incidence of infection
- Avoids harsh GI environment
- Avoidance of 1st pass metabolism
Parenteral Route
This avoids the GI tract by going directly across the body’s barrier defences into systemic circulation
- Intravenous
- Intramuscular
- Subcutaneous
Used for:
- Drugs that are poorly absorbed in GI tract
- Patients who are unconscious
- Topical administration
Differences between enteral + parenteral
- Enteral must first pass through liver - 1st pass effect
- Due to liver portal system (drains venous blood from gastro-enteral system)
Absorption of drugs after administration
Absorption = Transfer of drug from site of administration into the bloodstream
- Rate of efficiency depends on route of administration
- eg for I.V ⇢ complete absorption as total dose reaches systemic circulation
- eg for Oral ⇢ requires drug to dissolve in GI fluid + penetrate epithelila cells of intestinal mucosa
Transport of drug from GI tract
Drugs are absorbed into GI tract via passive diffusion OR active transport
Passive Diffusion
- Driving force = conc gradient across membrane separating 2 body compartments
- From high conc ⇢ low conc
- low structural specificity = how most drugs gain access to body
- Lipid soluble drugs are better absorbed
- Passive = no energy/atp required
Active Transport
- Uses specific carrier proteins to transport substances across membrane
- This is used by drugs that closely resemble structure of natural metabolites
- It is energy dependent - ATP
- Endocytosis + Exocytosis ⇢ Transports large drugs across membrane via vesicular transport
Effect of PH on drug absorption
Most drugs are either WEAK ACIDS/WEAK BASES
Passage of uncharged drug through membranes occurs more Readily
- Weak base ⇢ unchraged form (B) penetrates cell membrane, but BH+ doesnt
- Absorption of drug is determined by ⇢ relative concs of charged + uncharged forms
- Ratio between 2 forms is determined by ⇢ PH at site of absorption + pKa ⇢ strength of acid/base
- Determination of how much drug will be found on either side of membrane ⇢ Henderson-Hassel Bach equation:
pH = pK + log ( [A+] ÷ [HA])
Physical factors influencing absorption
Blood flow to absorption site
- blood flow to intestine > blood flow to stomach ⇢ intestine absorption is favoured
Total S/A available for absorption
- Intestine has surface that is rich in microvilli ⇢ Giving it a surface area that is 1000x that of stomach
- This makes drug absorption across intestine more efficient
Contact time at absorption surface
- If a drug moves through the GI tract very quickly = Not well absorbed
- Anything that delays transport of drug from stomach to intestine = Delayed absorption rate
- Presence of Food in stomach = dilutes drug + slows gastric emptying ⇢ Drugs taken w/meals are absorbed more slowly
Bioavailability
This is the Fraction of administered drug that reaches systemic circulation
Influenced by:
First Pass Effect
- Drug is absorbed in GI tract
- Enters Portal circulation before S.C
- Drug is rapidly metabolised in liver
- This means amount of unchanged drug that reaches S.C is Decreased
Solubility of Drug
- Very Hydrophilic drugs are poorly absorbed due to inability to cross lipid bilayer
- Very Hydrophobic drugs are poorly absorbed due to being totally insoluble in aq body fluids
- The drug mist be Largely hydrophobic + have some solubility in aq solutions
Chemical Instability
- some drugs are unstable in pH of gastric contents
- Others are destroyed by degradative enzymes
Nature of Drug formulation
- eg Particle Size
