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
Why don’t drugs absorbed in the buccal cavity and rectum undergo the first pass metabolism
they are absorbed straight into the vena cava
Gives examples of drugs that can be given intravenously
Tubocurarine - muscle relaxant during surgery
Pyridostigmine - reverses the effects of tubocurarine
Thiopental(thiopentone) - general anaesthetic
How does perfusion affect intramuscular absorption
Larger the blood flow, faster the absorption.
Give examples of drugs that can be given through rectal administration
Prochlorperazine - vomiting
Diazepam - epilepsy in children
Aminophyline - asthma
Indomethacin - arthritis, esp. morning stiffness
Give examples of drugs that can be given by transdermal administration
Trinitrin - sticking plaster or ointment
Hyoscine - sticking plaster - motion sickness
Nicotine - sticking plaster - smoking cessation
Give examples of drugs that can be given by inhalation
Halothane - gaseous/volatile anaesthetics
Salbutamol - local bronchodilators
Name the factors that the rate of passive drug diffusion depends on
- conc gradient across the membrane
- surface area involved
- membrane thickness
- partition coefficient of the drug (measure of lipophilicity)
- Diffusion coefficient of the drug (product of drug size and shape)
What does amphoteric mean
A molecule/drug with both basic and acidic groups
If the dose of the drug is known what can the Vd indicate
Vd can indicate which body compartments it has distributed to.
What are drugs often bound to as they’re distributed
Plasma proteins, tissue proteins or DNA
Why do local pH differences affect Vd
Can trap drugs in ionised/un-ionised forms
How can dissolution in lipids affect Vd
Lipophilic drugs can become concentrated in adipose tissue fat droplets
