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Flashcards in ADME of Medicines Deck (38)
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What are the oral routes of administration of drugs?

What does this mean for their absorption?

  • Buccal / sublingual
    • Direct absorption into the blood stream.
    • Avoids first pass metabolism.
    • Not ideal surface for absorption. 
  • Gastric mucosa
    • Enteric coating.
  • Small intestine
    • Main site of drug absorption.
    • Large surface area, more neutral pH.
  • Large intestine
    • Poor absorption, long transit times. 
  • Rectal mucosa
    • Direct to systemic circulation. 


What are the 4 ways in which small molecules cross cell membranes?

  • Diffusing directly through the lipid.
    • Lipid solubility is highly important. 
  • Diffusing through aqueous pores.
    • More likely important for diffusion of gases.
  • Transmembrane carrier protein.
    • E.g. solute carriers.
  • Pinocytosis.
    • Mostly macromolecules, not drugs.


Drugs have physiochemical factors which affect their ionisation. 

What does this mean for weak bases and weak acids and their absorption?

  • Weak bases
    • Ionised in acidic pH
    • Absorbed in the small intestine 
    • Possibly ionised in plasma. 
  • Weak acids
    • Unionised in acidic pH.
    • BUT also absorbed in small intestine.
      • Large surface area. 
  • Weak base will accept a proton, weak acid will donate a proton. In an acidic environment, weak acids are less likely to be ionised; in a basic acid weak bases are less likely to be ionised. But, in an acidic environment a weak base will be ionised.

  • This means that in the small intestine, a weak acid will be favourably absorbed (because an unionised drug will move across the membrane more freely), but a weak base in the small intestine will also be absorbed because the SI is specialised for absorption. So, by being ionised a weak base drug is not at a great disadvantage.


What is the effect of food on drug absorption?

  • In general, food tends to slow the rate of gastric emptying.


What direct or indirect effects do antacids and proton pump inhibitors have on absorption?

Causes changes in gastric or intestinal pH. 


What direct or indirect effects do laxatives and anticholinergics have on absorption?

Causes changes in gastrointestinal motility. 


What direct or indirect effects do vasodilators have on absorption?

Causes changes in gastrointestinal perfusion.


What direct or indirect effects does neomycin have on absorption?

Interferes with mucosal function.


What direct or indirect effects do tetracycline, calcium and magnesium have on absorption?

Causes chelation


What direct or indirect effects does cholestyramine have on absorption?

Causes resin binding


What direct or indirect effects does charcoal have on absorption?

Causes adsorption


List the factors that affect oral absorption.

  • Particle size and formulation
  • GI motility 
  • First pass metabolism
    • First pass metabolism by the gut wall or hepatic enzymes. 
  • Physicochemical factors
    • Direct drug interactions, dietary factors, varying pH. 
  • Splanchnic blood flow
    • Increased flow increases drug absorption.
  • Efflux pumps
    • P-glycoprotein.


List the parenteral routes by which drugs can be absorbed. 

  • Subcutaneous
    • Slow absorption due to blood flow. 
  • Intramuscular 
    • Lipophilic drugs rapidly absorbed
    • Polar drugs via bulk flow and endothelial cell junctions. 
    • High MWT or very liphphobic drugs via lymphatics.


What factors affect the rate of onset of drugs which are administered parenterally?

  • Extent of capillary perfusion. 
  • Drug vehicle.
  • Affected by factors that alter perfusion. 


Describe inhalation as a mode of administration of drug. 

  • Drug absorbed by the alveolar epithelium and bronchial mucosa. 
  • Systemic effects
    • Lipid-soluble drugs
      • Volatile / gaseous anaesthetics
    • Drugs of abuse
    • Accidental poisoning
  • Local effects
    • Modify structure (ipratropium)
    • Particulate size (salbutamol)
    • Selectivity for receptors (salbutamol)
    • Rapid breakdown in circulation (fluticasone)


Describe intranasal administration of drugs.

  • Easily accessible, rich vascular plexus. 
  • Advantages
    • Avoids hepatic first pass metabolism. 
    • Ease, convenience, safety.
  • Limitations
    • Limited drugs suitable.
      • Requires concentrated drug.


Describe the use of the topical route for administration of drugs.

  • Healthy skin as a barrier
    • Stratified, squamous epithelium
    • Keratinised layer
    • Sebaceous gland secretions
  • Local effects
    • Corticosteroids for eczema (hydrocortisone)
    • Antihistamines for insect bites (mepyramine)
    • Local anaesthetics (EMLA)
  • Systemic effects
    • Transdermal patches (HRT, GTN, nicotine)
    • Accidental poisoning (AChEsterase insecticides)
  • Surface area / volume ratio


List the different types of intravascular devices (IVDs).

  • Peripheral venous catheters
  • Central venous catheters (CVCs)
    • Peripherally inserted CVCs
    • Skin-tunneled CVCs (e.g. Hickman and Broviac lines)
  • Arterial catheters


What are the 3 methods of administering intravenous medications?

  1. Continuous infusion
  2. Bolus injection
  3. Intermittent infusion


Describe continuous IV infusion. 

  • Stable drugs
  • Short half life
  • Time dependent effects
  • Needs dedicated IV site


Describe bolus injection.

  • Rapid response required
  • Incompatibilities
  • Unstable drugs


Describe intermittent infusion.

  • Unstable drugs
  • Long half life
  • Concentration dependent effects
  • Less compatibility concerns


What are the complications of IV drug administration?

  • Fear / phobia / pain
  • Infection / sepsis
  • Thrombophlebitis 
  • Extravasation / infiltration 
  • Emboli
  • Anaphylaxis / hypersensitivity
  • Overdose
  • Insufficient mixing 
  • Stability of medicines in solution must be considered:
    • Light [total parenteral nutrition (TPN)]
    • Temperature (e.g. insulin, TPN)
    • Concentration (e.g. amiodarone)
    • pH (e.g. midazolam)
    • Interaction of medicines with the syringe or bag


Describe extravasation and infiltration with respect to IV cannulation. 

  • In both - the needle tip has gone into a tissue space. 

  • Extravasation is when there is something which is ‘irritant’ but infiltration is just adding volume to the tissue space. 

  • They can both be dangerous but extravasation is associated with more tissue damage.


List the factors which affect distribution of a drug.

  • Cardiac output and blood flow
  • Plasma protein binding 
  • Lipid solubility
  • Degree of drug ionisation 
  • pH of compartments 
  • Capillary permeability


What effect does organ perfusion have on distribution of drugs?

  • Initial rate of distribution of drugs depends heavily on blood flow. 


Describe the effect of albumin binding on the distribution of drugs. 

  • Albumin is a predominate plasma binding protein (40g/L).
  • Lipid-soluble drugs bind non-specifically.
  • Weak acids bind to a specific, saturable site. 


List the sites of drug metabolism.

  • Gut lumen
  • Gut wall
  • Plasma
  • Lungs
  • Kidneys
  • Nerves
  • Liver


List the potential results of drug metabolism.

  • Pharmacological deactivation
  • Pharmacological activation
  • Type of pharmacological response
  • No change in pharmacological activity 
  • Change in drug uptake
  • Change in drug distribution


Describe phase 1 and phase 2 of drug metabolism.

  • Phase 1 metabolism
    • Generally oxidation, reduction or hydrolysis.
      • Introcude / reveal a reactive chemical group.
      • "Functionalisation".
    • Products are often more reactive
  • Phase 2 metabolism
    • Synthetic, conjugative reactions.
    • Hydrophilic, inactive compounds generated (usually).