ICPP Flashcards
Kd and relationship to affinity
The higher the Kd the lower the affinity
Definition of Bmax
The maximum number of free receptors that can be saturated
Affinity
The degree to which the drug tends to bind to the receptor
Efficacy
The ability to produce the desired response
EC50
The effective concentration that gives 50% of the maximal response - known as drug potency
Emax
The maximal response that can be given
Concentration
The concentration refers to the known concentration of a drug at the site of action
Dose
The concentration at site of action is generally unknown
Spare receptors
Spare receptors don’t add to the size of a response
They increase the sensitivity and potency - allow responses at lower concentrations
Partial agonist
They bind to receptor and don’t elicit a maximal response
They have a lower intrinsic activity as lower efficacy
Reversible antagonist
Compete with agonist for receptors.
This inhibition is surmountable
Causes shift to the right
Irreversible antagonism
The antagonist dissociates slowly or not at all
This is non-surmountable
This will cause a a right ward shift and a smaller response with high antagonist concentrations
Non-competitive antagonist
The antagonist binds to an allosteric site
No competition for biding site
Similar effect to irreversible competitive antagonists
Main processes in drug therapy
Absorption
Distribution
Metabolism
Excretion
Drug administration
Oral Sublingual Rectal Intravenous Subcutaneous Intramuscular
Drug absorption - lipophilic drugs
Passive diffusion - cross GI epithelia
Steroids
Drug absorption - charged and hydrophilic drugs
Facilitated diffusion using solute carrier proteins
Passive process
Solute carrier proteins - active process
SLC can also enable drug transport in GI using secondary active transport
They don’t utilise ATP but rather a pre-existing electrochemical gradient
Factors affecting drug absorption
Physicochemcial factors - GI length and SA
GI physiology - blood flow, pH
First pass metabolism - enzymes can denture the drugs-liver
First pass metabolism
Reduces availability of drug reaching systemic
circulation - therefore affects therapeutic potential
Bioavailability
Fraction of dose which reaches the specific body compartment intended
Factors affecting drug distribution
Drug lipophilicity or hydrophilicity
Capillary permeability
Degree of drug binding to plasma or proteins
How does Vd - volume of distribution - affect the penetration
Smaller Vd values = less penetration
Larger Vd values = more penetration
Where does drug metabolism usually occur
Liver
Which enzymes do Phase 1
Cytochrome P450 enzymes
What do cytochrome P450 enzymes do?
They are versatile generalists which catalyse the drugs
This causes the drugs to have an increased ionic charge
Phase 2 metabolism
Carried out by hepatic enzymes - mainly cytosolic
Generalists but faster
Enhance hydrophilicity by increasing ionic charge further
Factors affecting drug metabolism
Age
Sex
General health
Certain drugs can inhibit or induce cytochrome P450 enzymes
CYP450 induction
Constant use of certain drugs can induce CYP450 isozymes
This will cause slower degradation
If another drug is metabolised using these enzymes its rate if elimination will increase
Drug levels will fall
CYP450 inhibition
Constant use of cortina drugs can inhibit CYP450 isozymes
This will cause a slower rate of elimination in drug by these enzymes
This will cause drug levels to increase
Main route of drug elimination
Kidney
Three processes of drug elimination.
Glomerular filtration
Active tubular secretion
Passive tubular reabsorption
Glomerular filtration
Unbound drug enters Bowman’s capsule
20% renal blood flow
Proximal tubular secretion
Remaining 80% of blood enters by organ cation and anion transporters
Distal tubular reabsorption
Passive reabsorption of lipid soluble and uncharged drugs
Clearance
The volume of plasma that is completely cleared of the drug per unit of time
Drug half life
The amount of time over which the concentration of a drug in the plasma has decreased to a half of that when first measured
If Vd increases so does half life
If clearance increases half life decreases
isoelectric point
The isoelectric point of a protein is the pH at which there is no overall net charge
