P3: Drug Administration and Distribution Flashcards
Name the 8 administration routes. O I.v I.m/S B R T I I.c.v
- Oral (per os; p.o.)
- Intravenous (i.v.)
- Intramuscular (i.m.)/ Subcutaneous
- Buccal
- Rectal
- Transdermal
- Inhalation
- Intracerebroventricular (i.c.v.) stick injection in brain
Advantages with Oral Administration (5)
- Easy
- No sterile preparations
- No special skills nor apparatus
- Convenient
- Generally accepted by the patient
Problems with Oral Administration (4)
- Could be altered by stomach acidity
- Could be digested by proteolytic enzymes
- Potential poor/no absorption
- Potential first pass metabolism
What affects first-pass metabolism in regards to a metabolite?
Depends on whether or not the metabolite(s) is active
Advantages with Intravenous Administration (3)
- No absorption problems (enters systemic circulation)
- All of the dose enters the systemic circulation
- Can be given by slow injection or infusion
- Can be stopped if necessary
Problems with Intravenous Administration (2)
- Needs sterile apparatus
- Certain skill required
Advantages with Intramuscular and Subcutaneous Administration (3)
- Low skill required (insulin, s.c.)
- Allows slower sustained release
- Avoids problems with oral administration
Problems with Intramuscular and Subcutaneous Administration (2)
- Sterile conditions required
- Not suitable for all drugs because too slow (E.g. diazepam)
- slow to reach peak conc.
What administration route does glyceryl trinitrate take?
What is it used for?
- Sublingual, absorbed from the Buccal cavity
- Rapidly absorbed to give relief from angina
What is an advantage of sublingual administration route?
Drugs absorbed from buccal cavity do not enter the portal vein so they avoid first-pass metabolism
What are the benefits and reasons for using rectal administration
When other routes are unsuitable or for sustained action
What type of drugs use transdermal administration?
Limited to Potent, lipohillic drugs (through skin)
What is an advantage of inhalation as an administration route?
Large Surface Area
Rapid absorption and onset of affect
Name the 5 possible mechanisms of drug absorption
1) Passive diffusion
2) Filtration through channels
3) Facilitated diffusion
4) Active transport
5) Pinocytosis
(most drugs are passive)
What are the two major families of drug transporters?
- Solute carriers (SLC)
- ABC transporters
(ATP-binding cassette)
What do ABC transporters do?
ABC transporters are primarily active efflux pumps
What do SLCs do?
- Gets rid of waste and carries out nutrient transport
- Drugs can hijack them
- Use active transport and facilitated diffusion
(second largest category of membrane proteins after GPCRs)
What are the 4 things that transport across membranes depend on?
- Lipophilicity
- Size
- Ionisation
- Rate of diffusion
Explain the movement of ionised molecules across membranes
Ionised molecules cannot cross membranes
Name the factors effecting absorption from the GIT
- pH
- Gastric emptying
- Transporter expression
- Motility of GIT
- Interaction of food and drug
What is volume of distribution (Vd)?
The volume of fluid required to dissolve the amount of drug in the body to give the same concentration as that in the plasma
Name the factors that affect Vd (5)
- Local pH differences
- Binding to macromolecules
- Dissolution in lipids
- Active transport
- Irreversible binding
Name some problems encountered with oral administration
- Stomach Acidity
- Proteolytic enzymes
- Poor Absorption
- No absorption
- Pre systemic metabolism (broken down in first pass)
Describe the route of the first pass (pre-systemic) metabolism
- Drugs absorbed from GI tract enter the mesenteric capillary network
- Absorbed drug is carried via the portal vein to the liver
- Undergoes hepatic metabolism
- Metabolites but not parent drug enters the systemic circulation
