Pharmacology Flashcards
What does the plasma concentration of a drug allow you to do?
Create a dosing regimen for each specific patient as it dictates the ability of a drug to reach its target organ in an effective concentration
First Order Kinetics
The rate of elimination is directly proportional to the concentration of drug
Half life is constant
Kel
Kel represents the fraction of drug eliminated per unit of time
Zero Order
Rate of elimination is independent of drug concentration
Half life is not constant
Drug could build up in body leading to toxic side effects
Volume of Distribution
Proportionality factor that relates the amount of drug in the body to the concentration of drug measured in the plasma
What is Vd affected by?
Drug permeability across tissue barriers
Binding within compartments
pH partition
Why is Vd important?
Used to calculate drug dose
High Vd - accumulated in peripheral tissues
Low Vd - confined to the plasma
Drug with a higher Vd tends to require a higher initial dose
How can we calculate Vd and C0 from a graph?
By measuring and then plotting plasma concentrations of drug over time
How is half life useful?
It allows the clinician to estimate the frequency of dosing
Plasma Clearance
The volume of plasma cleared of drug per unit time
Steady State
The equilibrium point where the amount of drug administered exactly replaces the amount of drug excreted
What does optimal therapeutic dosing regimens seek to maintain?
The steady state plasma drug concentration within the therapeutic window for that drug
What does the time required to reach steady state depend on?
Half life
The shorter the half life, the quicker steady state is reached (usually given IV)
What must be given if the therapeutic concentration must be achieved rapidly?
A large loading dose
Vd Equation
Dose / C0
Clearance Equation
(0.693 / t1/2) x Vd
Loading Dose Equation
Vd x desired plasma concentration
Why can the duration of drug action for a given dose vary between individuals?
Certain drug metabolising enzymes display polymorphic expression of activity –> increased or decreased enzyme activity / levels of metabolism
Fast metabolisers
Possess wild type enzyme
Lower plasma concentration
Higher concentration of the metabolite
Generally a normal therapeutic effect
Slow metabolisers
Possess either a defective enzyme or don’t express enzyme at all
Higher plasma concentration
Lower concentration of the metabolite
Exaggerated therapeutic effect at normal doses –> reduced drug dose
Polymorphic Drug Metabolising Enzymes for Alcohol
Alcohol - alcohol dehydrogenase
Acetaldehyde - aldehyde dehydrogenase
Acetate
Water and carbon dioxide
Treat alcoholics by inhibiting aldehyde dehydrogenase –> flushed skin, vomiting, blurred vision, SOB, throbbing headache, confusion, palpitations
Liver disease affecting metabolism
The healthy liver facilitates rapid metabolism of lipid soluble drugs
In chronic liver disease this capacity is reduced for many drugs
First pass metabolism is reduced and so bioavailability is much greater
Cardiac disease affecting metabolism
Rate of metabolism is dependent on drug delivery to the liver via the bloodstream
Reduced blood flow in cardiac failure
Dose of a drug may need to be decreased for cardiac failure
Disease and Altered Excretion (Renal)
Rate of renal elimination is the main factor that determines the duration of action of these drugs
Alteration of renal function will alter renal elimination rate
These drugs have to be used with special care in individuals whose renal function may be impaired
What does reduced glomerular flow rate result in?
Less drug filtered
Longer lasting drug action in body
Lower drug dose, increase dose interval
What does pharmacodynamics depend on?
Concentration of drug at the receptor
Response at the receptor
Postsynaptic response within cells
All affected by ageing
Tolerance
Reduction in response to a drug after repeated administration
Can be pharmacokinetic or pharmacodynamic
Pharmacokinetic Tolerance
Altered drug metabolism
Pharmacodynamic Tolerance
Receptor internalisation
Receptor down regulation
Decreased activity of intracellular signalling pathways and ion channels
This is desensitisation
Factors affecting drug metabolism and excretion
Age
Disease
Genetics
Other drugs taken
Diet
Environmental pollutants
