2: Routes of Administration and Absorption Flashcards
What is transcellular passive diffusion?
The passive diffusion of drugs across cell membranes. This happens with drugs that have been administered enterally (orally, sublingually, rectally), as they must pass through the cell membranes of the G.I. tract (e.g. small intestines) to enter the bloodstream.
What is the epithelial lining?
The epithelial cells of the GI tract have tight junctions between them; hence to penetrate this layer of cells and to access the blood, the molecules of drugs that have been administered enterally (orally, sublingually, rectally) must pass through cell membranes before entering the bloodstream for distribution.
What is an epithelial cell?
Epithelial cells constitutes one of the four basic types of tissue, along with connective tissue, muscle tissue and nervous tissue cells. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs.
Enterally and transdermally/topically administered drugs must cross the membranes of epithelial cells in order to enter the bloodstream for distribution.
What is the structure and role of the cell membrane (in terms of drug absorption)?
Cell membranes consist of a phospholipid bilayer, i.e. a double layer of hydrophobic fat. In order for drugs to cross this membrane, they must be lipid soluble (lipophilic), i.e. readily dissolvable in fat. This applies to most enterally administered drugs.
Lipophilic drugs can passively diffuse across cell membranes down the concentration gradient, i.e. from a high to a low concentration.
This rate of diffusion is described by Fick’s law: Diffusion rate = (concentration gradient x surface area x lipid solubility of drug) / thickness of cell membrane.
In short, the higher gradient, larger surface area, and higher drug solubility, the faster diffusion will be; and the thicker the cell membrane, the slower. The single-cell thickness of the small intestine therefore results in the quickest diffusion in the gastrointestinal tract.
If drugs are not lipophilic but hydrophilic, they may be transported across the cell-membrane by carrier-mediated transport.
What is Fick’s Law?
Fick’s law describes the rate that lipophilic drugs diffuse down the concentration gradient across cell membranes:
Diffusion rate = (concentration gradient x surface area x lipid solubility of drug) / thickness of cell membrane.
In short, the higher gradient, larger surface area, and higher drug solubility, the faster diffusion will be; and the thicker the cell membrane, the slower.
For enterally administered drugs, the single-cell thickness of the small intestine therefore results in the quickest diffusion in the gastrointestinal tract.
What does oral administration of a drug entail?
This is an enteral drug route; absorption happens through the gastrointestinal tract, and the drug must therefore cross the tight barrier created by epithelial cells.
Oral administration is the most common route – good for self-dosing, cost-effective to make, easy to dose.
Onset is rapid (10-20 min) but the drug must dissolve first.
Most drugs are absorbed via the small intestine, so large quantities can be absorbed due to large surface area (small intestine = 200 m2) and good blood supply.
However, orally administered drugs must be designed to survive gastric acid, digestive enzymes, food, and gut bacteria. This can be done by way of an enteric coating - i.e. a coating that prevents disintegration (and therefore release) in the stomach, and instead allows the tablet to pass to the small intestine before being dissolved and absorbed.
As insulin and other peptide drugs cannot survive the digestive enzymes in the stomach, they cannot be given orally.
What does sublingual administration of a drug entail?
This is an enteral drug route; absorption happens through the gastrointestinal tract, and the drug must therefore cross the tight barrier created by epithelial cells.
During sublingual administration, a drug is placed under the tongue. Absorption is rapid due to good blood supply under the tongue, which drains into the jugular vein and then the heart, resulting in no first pass effect.
Sublingual absorption happens via transcellular diffusion – drugs must be lipophilic.
Glyceryl trinitrate (to treat angina) is a sublingual drug.
What does rectal administration of a drug entail?
This is an enteral drug route; absorption happens through the gastrointestinal tract, and the drug must therefore cross the tight barrier created by epithelial cells.
Absorption via transcellular diffusion – drugs must be lipophilic.
Useful when oral route is compromised (e.g. due to vomiting or gastric acid sensitivity) and if drug can damage the stomach lining (e.g. non-steroidal anti-inflammatory (NSAID) drugs).
Minor hepatic first pass effect for rectal administration.
Paracetamol & aspirin (pain relief) and promethazine (nausea/motion sickness) can be administered rectally.
What does intravenous administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
Hydrophilic drugs (e.g. gentamicin), large molecular mass drugs (e.g. insulin) and poorly soluble drugs (in suspension) can be delivered by this route of administration.
What does intramuscular administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
Hydrophilic drugs (e.g. gentamicin), large molecular mass drugs (e.g. insulin) and poorly soluble drugs (in suspension) can be delivered by this route of administration.
What does subcutaneous administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
Hydrophilic drugs (e.g. gentamicin), large molecular mass drugs (e.g. insulin) and poorly soluble drugs (in suspension) can be delivered by this route of administration.
What does inhaled administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
The lungs have a large surface area (100 m2), are very permeable and have low metabolism.
Anaesthetics are often given via inhalation. They are gaseous drugs that are absorbed into the pulmonary circulation … and then into the systemic circulation.
What does intranasal administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
What does topical administration of a drug entail?
A topically administered drug is a drug applied directly to a surface of the body (whether inside or outside), and can there be both parenteral and enteral.
It may be applied topically directly to skin (e.g. for transdermal drugs) or specific organs (e.g. the orally administered drug sulphasalazine, which is administered orally but only breaks down in and is absorbed by the colon after metabolization by bacteria).
What does transdermal administration of a drug entail?
This is a parenteral drug route; absorption does NOT happen through the gastrointestinal tract.
