Routes Of Administration Flashcards
Name and define the four different routes through which a drug can be administered?
ENTERAL - Drug administration involves any part of the GI tract/enteric system: Oral, Sublingual or Rectal
PARENTERAL - Drug administration avoids the GI tract: Subcutaneous, Intramuscular, Intravenous or Intrathecal (Into the spinal canal or subarachnoid space)
TOPICAL - Drug is administered via direct application onto an epithelial surface: Skin, Cornea or Nasal
INHALTION - Drug is administered to the respiratory tract via inhalation via a nebuliser, inhaler etc
Where does absorption occur when a drug is administered orally?
Within the stomach and small intestine.
Absorption of oral dugs involves transport across epithelial cell membranes in the GI tract.
Despite the stomach’s large epithelial surface, its thick mucous layer and short transit time limit drug absorption. The small intestine has a larger surface area for drug absorption and it’s membranes are more permeable than those within the stomach, due to this, most drugs are absorbed primarily in the small intestine.
What are two drug properties that favour absorption through the GI tract?
High Lipid Solubility - Once a drug is dissolved in the aqueous medium in the GI tract, it can pass into the capillaries of the GI wall. A drug must have a reasons amount of lipid solubility to enable absorption across the lipid membrane.
Low Ionization - For acids and bases, only the non-ionized molecules can be absorbed. At all physiological pH values, weak acids and bases mostly exist in the un-ionised form. The more the drug is in its un-ionized form, the more likely it is to be lipid-soluble and transferred by passive diffusion through the membrane. Meaning that weak acids and bases are typically well absorbed.
Strong acids (pKa <3) and bases (pKa >10) are highly ionized and are usually unable to penetrate lipid cell membranes are they hydrophilic and poorly lipid soluble, meaning they are absorbed poorly.
What percentage of a drug administrated orally is typically absorbed within 1-3 hours of ingestion?
75%
What four factors influence oral drug absorption?
GI Tract Perfusion
GI Tract Motility
Physiological Factors (Stomach acid concentration, Intestinal surface area)
Drug Formulation
Physiochemical Factors (Drug-Food Interactions)
How does GI tract perfusion affect oral drug absorption?
Once a drug is absorbed through the small intestine, it enters the hepatic portal vein and the liver via the mesenteric vessels prior to reaching the systemic circulation.
Blood flow to the GI tract can increase after eating, due to this some drugs can have increased absorption following meals
Reduced GI perfusion (can occur in heart failure, sepsis, shock, intestinal ischaemia etc) can reduce the systemic absorption of drugs from the intestines
How does GI tract motility affect oral drug absorption?
GI motility refers to the movement of food from the mouth, pharynx, esophagus, stomach, small and large intestines etc.
When GI motility is slow/reduced (can occur in diabetes related autonomic neuropathy, or due to medications that slow GI motility such as opioids, anticholinergics) , the rate of drug absorption is reduced
How does an orally administered drug’s formulation affect its absorption?
There are various ways in which drug formulation can be altered to control the process of absorption, typically in oral drugs a sustained release is desirable (as medicines used in emergent situations that require rapid-acting intervention i.e adrenaline for anaphylaxis, will often be delivered parenterally)
To achieve a sustained release, the active drug may be layered with an inert coating or suspended in a slowly dissolving matrix. Enteric release tablets have a coating layer that is insoluble to acid, but freely soluble under basic conditions and are therefore designed to allow drugs to reach the duodenum if they are ordinarily inactivated by stomach acid or have undesirable gastric effects. To achieve a rapid yet sustained absorption, a mixture of fast and slow release particles contained within a capsule may be used. To achieve a faster rate of absorption, typically a higher administrative dose of a drug will facilitate this by generating a bigger gradient for diffusion.
How do physiological factors such as stomach acid concentration and intestinal surface area affect oral drug absorption?
A higher proportion of an acidic drug is un-ionized in acidic conditions, allowing it to move more freely across the cell membrane, therefore acidic drugs should be more rapidly absorbed in the lower pH of the stomach. So if the production of stomach acid is reduced (i.e in old age, H.Pylori infection, with long term use of antacids or proton-pump inhibitors) absorption of certain medications that are primarily absorbed within the stomach will be affected.
Conditions such as coeliac disease or short gut syndrome result in reduced GI absorption due to reduced intestinal surface area.
How do Physiochemical factors such as drug food interactions affect oral drug absorption?
