ICPP 7 Flashcards
What are the major routes of drug delivery?
Oral Intravenous Intramuscular Transdermal Intranasal Sublingual Subcutaneous Inhalation Rectal
Where does most enteral drug absorption take place?
Small intestine
What is parenteral drug administration?
Delivery via other route not involving GI
The pH of the small intestine is weakly acid, how does this affect drugs?
Determines ratio of molecules in ionised and unionised state
What are the 4 major absorption mechanisms?
Passive diffusion
Facilitated diffusion
Active transport
Pinocytosis
What drugs are able to absorb via passive diffusion?
Lipophilic drugs - steroids
Drugs that are weak acids or weak bases
Can ionised drugs diffuse through the lipid bilayer?
No, only the unionised form.
What equation can you use to determine the ratio of ionised:unionised drug?
Henderson-hassleback equation
What molecules can diffuse by facilitated diffusion?
Charged molecules with low lipid solubility
What transports are widely expressed commonly used for facilitated transport?
Solute carrier transport (SLC)
What are the 2 types of SLC?
Organic anion transporters
Organic cation transporters
What molecules are absorbed by endocytosis and exocytosis?
large molecules
What are some GI factors affecting drug absorption?
SA Length Density of SLC expression Blood flow Gi motility Food presence
Where does first pass metabolism occur?
in liver
What affect does first pass metabolism have on bioavailability?
Decreases
Define bioavailability.
The relative amount of the drug that reaches the greater systemic circulation.
What enzymes are responsible for phase 1 metabolism?
CYP450 enzymes
What enzymes are responsible for phase II of metabolism?
Conjugating enzymes
What is the first stage of drug distribution?
Bulk flow via arterial system
How does blood flow affect rate of delivery?
Drugs will reach well vascularised organs more rapidly
What other factors affect distribution?
Capillary permeability - varies
How does plasma protein binding affect drug absorption?
Protein-bound drugs are unable to diffuse across membranes and unable to bind receptors. Decrease bioavailability
What are the body fluid compartments?
Plasma water
Extracellular = plasma water + interstitial fluid
Total body = plasma + interstitial fluid + intracellular
What is the ‘apparent’ volume of distribution?
Describes how the drug will distribute within the body compartments
What does a small Vd indicate?
Less penetration of interstitial and intracellular compartments
What does a large Vd indicate?
Greater penetration into interstitial and intracellular compartments
What can Vd be affected by?
Renal failure, pregnancy, changes in blood flow
What do phase I and II enzymes do?
Increase the ionic charge in order to increase renal elimination
What sort of reactions does Phase I metabolism involve?
redox
Aklylation
Hydroxylation
What sort of reactions does Phase II involve?
Sulhation, glururonidation
What enzyme does grapefruit juice inhibit?
CYP3A4
What enzyme metabolises verapamil?
CYP3A4
Codeine is a prodrug, activated by which CYP enzyme?
CYP2D6
Where does most drug elimination take place?
Kidney
What are the 3 processes that take place during renal elimination?
- Glomerular filtration
- Active tubular secretion in proximal tubule -OAT and OCT transport drug into tubule
- Passive tubular resorption of lipophilic drugs in distal tubule
What is clearance?
The rate of elimination of a drug from the body
Total body clearance = hepatic clearance + renal clearance
What is half life, t 1/2?
The amount of time which the concentration of a drug in plasma decrease to one half of its original concentration.
What influences t 1/2?
Vd and total clearance
What is first order kinetics?
Linear relationship where the rate of metabolism and excretion is proportional to the concentration of druhg
What happens when elimination processes are saturated?
They become rate-limited and kinetics show zero-order.
What are the consequences of zero order kinetics?
More likely to have ADR’s and toxicity
