week 5 Flashcards
(23 cards)
absorption
when the drug enters the systemic circulation from the site of administration.
distribution
once in the bloodstream, drugs are distributed to organs + tissues
metabolism
most drugs undergo metabolism in the liver, where enzymes transform them into more water-soluble compounds
excretion
the drug and its metabolites are excreted from the body through the kidneys and liver.
inactive metabolites
most drugs produce inactive metabolites
active metabolites
inactive prodrug is administered; liver enzymes transform it into active metabolites (e.g. codeine into morphine)
toxic metabolites
low percentage of paracetamol is transformed by liver enzymes into liver toxic metabolites.
passive diffusion
Most drugs cross membranes by passive diffusion, which is the transfer of the drug across the membrane from a region of higher concentration to a region of lower concentration until equilibrium is established on either side of the membrane
Passive diffusion is influenced by the surface are of the membrane exposed to the drug, the concentration gradient of the drug and its lipid solubility. For acidic and basic drugs, diffusion is also influenced by the ionisation state.
Nonpolar drugs dissolve freely in the membrane lipids and consequently diffuse readily across cell membranes, in contrast to polar drugs
carrier mediated transport
Requires the involvement of a membrane protein for the movement of a compound across a biological membrane
Carrier mediated transport may be active (require energy) or facilitated (not requiring energy)
- Important in the kidney, GI tract, liver, and the blood brain barrier
factors influencing drug absorption
Surface area
The surface area available for absorption is a major determinant of rate of absorption. The larger the surface area, the faster absorption will be. Orally administered drugs are usually absorbed from the small intestine rather than the stomach. The small intestine has larger SA b/c of its lining of microvilli
Blood flow
Drugs are absorbed most rapidly from sites where blood flow is high, like the sublingual route. This is because blood containing a newly absorbed drug will be replaced rapidly by drug free blood, thereby maintaining a large gradient between the concentration of the drug outside the blood and the concentration of the drug in the blood required for passive diffusion.
formulations
- Some formulations are modified to delay absorption (enteric coated tablets)
- Sustained release formulations are designed to achieve absorption over a period of time. The capsules are filled with tiny spheres containing the drug, individual spheres have coatings that dissolve at variable rates
- Immediate release are designed to have faster absorption
Lipid solubility
Highly lipid soluble drugs are absorbed more rapidly than drugs with low lipid solubility. Because lipid soluble drugs can readily cross the phospholipid bilayer.
routes of administration
Enteral – through GI tract
Parental
Topical
orally administered drugs
- pass through GI tract before being absorbed in the bloodstream
disintegration and dissolution
- For the body to process a tablet or capsule, it has to DISINTEGRATE into small particles and combine with a liquid to form a solution – process known as dissolution – before it can b absorbed from the GI tract into the bloodstream.
- The rate of dissolution is the time it takes for a drug to disintegrate and dissolve to become available for the body to absorb.
- The faster the rate of dissolution, the faster the drug can be absorbed.
- Drugs in liquid forms are more rapidly absorbed than tablet and capsules.
Factors influencing the absorption of orally administered drugs
- Presence of food can delay absorption
- Delays in gastric emptying
- GI motility/peristaltic activity of the intestines
- Digestive enzymes/ stomach pH can break down some drugs
first - pass metabolism
After oral drugs are absorbed from the GI tract, they pass from the intestinal lumen to the liver via the portal vein. In the liver, some drugs are metabolised to an inactive form and excreted, reducing the amount of active drug available to exert a pharmacological effect. – first pass effect/ first pass metabolism.
GI tract -> portal vein -> liver -> inferior vena cava -> heart -> general circulation
Orally administered drugs pass through the liver before they enter systemic circulation, making them highly susceptible to first pass metabolism. This affects the amount of the intact drug that reaches systemic circulation when administered orally.
bioavailabilty
Bioavailability (F) is the fraction of the drug that reaches the systemic circulation after absorption compared to IV bolus administration.
The bioavailability of an orally administered drug can be calculated from the area under the curve (AUC) of a plasma drug concentration-time curve, as shown below.
Oral drug ->- absorption ->- first pass metabolism ->- blood (body)
bioavailability formula
Dose (route) = dose (IV)/ F (route)
Factors influencing bioavailability of orally administered drugs
- Absorption – the fraction of the drug dose absorbed from the GIT
- First – pass metabolism – the fraction of absorbed drug that escapes first-pass metabolism by the liver.
The bioavailability of ORAL drugs is always less than 100%
The bioavailability of IV drugs is always 100%
Bioequivalence
2 drugs will be considered bioequivalent if they have similar bioavailabilites and show no clinical differences in their therapeutic or adverse effects.
Parental administration
- Avoids GI tract
- Most parental administrations involve the administration of drugs by injection (small volume) or infusions (large volume).
- Most common parental administration routes are intravenous (IV), intramuscular (IM) and subcutaneous (SC)
inhalation
For systemic (anaesthetics) or local effects (bronchodilators).
Avoids first pass metabolism
Total alveolar surface area + capillary network facilitate rapid absorption.
sublingual or buccal administration
- Sublingual – placed under the tongue
o Absorbed from the oral mucosa - Buccal – placed between the teeth and mucous membrane of the cheek.
Both passes directly into the systemic circulation, avoiding first pass metabolism.
Preferred route when rapid response is required.
