Drug Absorption

Drug Absorption

1. Oral Route Journey

   • Bioavailability
     • Gut destroy
     • X absorbed
     • Gut wall destroy
     • Liver destroy
   • Formulations
     • Excipient
       • Make pill bigger
     • Binding agent, Coatings, Capsule
       • Keep together
     • Lubricants
       • moulds
     • Interact, affect absorption
       • Psychotics- X change once settled -> affect response
   • Particle Size
     • Must become suspension, dissolute
     • Time in stomach may aid dissolution

2. Oral Route

   • Pros
     • Cheap, Safe, Convenient
   • Cons
     • Patient Compliance
       • Take, Amt.
       • Conscious
     • Bioavailability variation
   • Buccal/ Sublingual
     • Bypass Hepatic
     • Limited S.A., epithelium capacity
     • Taste
     • Direct to blood
   • Gastric Mucosa
     • Enteric coat
       • prevent drug dissolution in stomach
   • Small intestine
     • Main site absorb
       • Large S.A.
       • More neutral pH
   • Large intestine
     • Absorb
       • Slow transit
       • Poor, Variable
   • Rectal Mucosa
     • Direct to blood
       • Bypass hepatic

3. Small molecules across cell membrane

   • Diffuse aqueous pores
     • Gases, v. small
   • Pinocytosis
     • Macromolecules, X drugs
   • Direct diffuse thru lipid
     • Lipid solubility
       • Ionized X even if lipid soluble
       • Lipophilic
   • Transmembrane Carrier Protein
     • Active transport
       • Ions
     • Solute Carriers

4. Ionisation

   • Weak bases
     • Ionised in acidic pH
     • Absorbed small intestine
   • Weak Acid
     • Unionised acid pH
     • Absorbed small intestine
       • Large S.A.
   • Henderson-Hasselbach
     • Refer notes
     • Plasma flowing
       • X equilibrisation, straight-away circulated
         • Weak base absorbed slow rate

5. GI Motility

   • Food
     • Protect GI from side-effects eg NSAIDS, asparin
     • Tend slow gastric emptying
     • before: Penicillin V
       • Longer time stomach acid environment, > degrade
     • Type
       • solid, liquid
       • Protein, Fat content
   • < absorb
     • Intestinal motility
     • Interact food, acid
     • Presystemic metabolism
   • > absorb
     • increase solubility
     • < presystemic metabolism
   • Delayed absorb
     • Gastric emptying change
     • May X clinical impt
       • Bioavailability same, effect delayed
   • 1st pass metabolism: Levodopa
     • Pro-drug, treat Parkinson's
       • Dopamine
         • might X cross BBB
         • hard get systemic
         • Levodopa cross BBB, effect
     • Stomach, Small intestine: Rapid
       • Large Neutral Amino Acid transport carrier (LNAA)
     • DOPA decarboxylase @ gastric mucosa
       • change to dopamine
         • Effect on GI --> nausea, vomit
           • combine with DOPA Decarboxylase inhibitor @ GI - co-careldopa
   • Intestinal disease
     • change absorb
     • Crohn's
       • Ulceration
         • Absorb affected
       • > motile
         • < time
     • Coeliac disease
       • autoimmune
         • gluten
         • Diet
       • < absorb capacity

6. Definition

   • Bioavailability
     • Fraction unchanged reach systemic circulation
     • IV 100%
       • Compare IV vs. other routes drug exposure
     • Wary other factors affect
   • Bioequivalence
     • Generic
       • 80 - 125% bioavailability reference product
       • Diff formulation; equivalent
     • Therapeutic
       • Assumed = therapeutic effect

7. Parenteral

   • Subcut,
     • slow cos bloodflow
   • Intramuscular
     • Lipophilic rapid
     • Polar
       • Bulk Flow
       • Endothelial cell junctions
     • High MWT, lipophobic
       • Lymphatics
     • Exercise
   • Rate onset
     • Capillary perfusion
     • Drug vehicle
     • factors alter perfuse

8. Inhalation

   • Alveolar epithelium, bronchial mucosa
   • Systemic effects
     • Lipid soluble
       • Volatile/ Gaseous Anaesthetics
     • Drugs abuse, Accident poison
   • Local effect
     • Modify structure
       • Ipratropium
       • > ionised
     • Particulate size
       • Salbutamol
     • Selectivity for receptors
       • Salbutamol
     • Rapid breakdown in circulation
       • Fluticasone

9. Intranasal

   • y access, rich vascular plexus
   • Pros
     • X hepatic
     • Ease, convenient, safe
   • Cons
     • Limited drugs ok
       • high conc

10. Topical

    • Adjust amt for child --&gt; smaller size!
    • skin barrier
      • Stratified squamous epithelium
      • Keratinised
      • Sebaceous secretions
    • Local
      • Corticosteroid eczema
        • Hydrocortisone
      • Antihistamins
        • Insect bite
      • Local anaesthetics
        • EMLA
    • Systemic
      • Transdermal patch
        • HRT, GTN, nicotine
      • Accidental poison
        • Lipophilic
        • AChEsterase insecticides