Absorption

Describe absorption and factors that will influence it.

Absorption is dependent on the route of administration. Routes of administration are selected based on:

• Effect site of the drug
• Drug factors
  • Bioavailability
  • Available preparations
• Patient factors
  • Ability to take or absorb oral medications
  • Preference

Key Concepts

Bioavailability is the proportion of drug given which reaches the systemic circulation unchanged, compared to the IV form. It is affected by:

• Formulation
• Physicochemical Interactions
  Interactions with other drugs and food.
• Patient Factors
  • Malabsorption syndrome
  • Gastric stasis
• First-pass metabolism

First-pass (pre-systemic) metabolism is the extent to which drug concentration is reduced after its first passage through an organ, prior to reaching the systemic circulation. First pass metabolism is:

• Typically used when referring to passage of orally-administered drugs through the liver
  May also refer to metabolism by the:
  • Lungs
    First pass of intravenously injected drugs prior to entering the arterial side of the circulation, e.g. fentanyl.
  • Vascular endothelium
• Relevant in:
  • Understanding differences between PO and IV dosing
    • Alternative routes of administration for drugs with low PO bioavailability
  • Delivery of prodrugs via PO mechanisms
    Increases active drug concentration.
  • Understanding enzyme interactions
  • Understanding the effects of hepatic disease
    • Porto-systemic shunts decrease first pass metabolism
    • Altered bioavailability of drugs with high hepatic extraction ratios

Routes of administration

Intravenous

• Rapid Onset
• 100% bioavailability
  Some drugs may still undergo metabolism in the pulmonary circulation, such as fentanyl, lignocaine, propofol, and catecholamines.

Oral

• Absorption is through gut mucosa, through either:
  • Transport mechanisms
  • Unionised (lipid soluble)
    • Acidic drugs are absorbed more rapidly in the stomach
    • The small bowel absorbs both acid (despite being ionised) and alkaline drugs due to high surface area
• Lowest bioavailability of any route due to:
  • First-pass metabolism
  • Gut metabolism of drugs
  • Bacterial metabolism of drugs
• Drugs must be lipid soluble enough to cross cell-membranes and water soluble enough to cross interstitium

Factors affecting GIT Absorption

• Drug Factors
  • Molecular Weight
  • Concentration Gradient
  • Lipid Solubility
    • pH and pKa
  • Pharmaceutical Preparation
  • Physiochemical Interactions
    • Food
    • Other drugs

• Patient Factors
  • GIT blood flow
  • Surface Area
    • Small bowel has the largest surface area of any GIT organ
  • pH
  • Motility
  • Digestive Enzymes
  • GIT bacteria and subsequent metabolism
  • Disease
    • Critical Illness
    • Bowel Obstruction
    • Emesis/Diarrhoea

Epidural

• May be via bolus or infusion
• Onset determined by proportion of unionised drug available
  Lignocaine has a more rapid epidural onset than bupivacaine as it has a pKa of 7.9 (compared to 8.4) and therefore a greater unionised portion at physiologic pH.

• Additional factors include additives and intrinsic vasoactive properties of the delivered drug

Subarachnoid/Intrathecal

• Very small dosing
• Minimal systemic spread
• Extent of subarachnoid spread is dependent on volume and type of solution
• Appropriate positioning of the patient, with higher-specific gravity solutions, is required to avoid superior spread of the block
• Additional factors include additives and intrinsic vasoactive properties of the delivered drug

Inhalation

• Systemic absorption dependent on particle size
  • Large particles reach the bronchioles
  • < 1 micron diameter particles may reach the alveolus
• Rapid diffusion to circulation due to high surface area and no first-pass metabolism

Transdermal

• Systemic absorption dependent on:
  • Dose requirement
    • Large dose requirements cannot be effectively given transdermally
  • Fick Principle
    • Amount of drug given
    • Amount of drug in skin
      • Regional blood flow
        • Histamine release
    • Surface Area
    • Skin thickness
    • Lipid solubility
      • pH of skin and emulsion
      • pKa of drug
    • Molecular weight
  • Advantages
    • Convenient
    • Painless
    • No first pass metabolism
    • Steady plasma concentration once established
  • Disadvantages
    • Slow onset
    • Variable plasma concentration initially
    • Overdose and abuse potentials

Subcutaneous

• Absorption dependent on regional blood flow

Sublingual

• Rapid onset
• Bypass portal circulation (drains into SVC)

Rectal

• Variable absorption
  • Distal rectal absorption bypasses portal circulation
  • Proximal rectal absorption does not and may result in hepatic first pass metabolism
  • Small surface area for absorption

Intramuscular

• Bioavailability close to 1
• Absorption dependent on regional blood flow
• Potential local complications:
  • Abscess
  • Haematoma

References

1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
2. Chong CA, Denny NM. Local anaesthetic and additive drugs.
3. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.