Pharmacology Flashcards
Define pharmacodynamics?
What a drug does to the body (biological effects and mechanisms of action)
Define pharmacokinetics?
What the body does to a drug (absorption, distribution, metabolism and excretion of drugs and their metabolites)
What is the medical definition of a drug?
Any synthetic or natural substance used in the treatment, prevention or diagnosis of disease
What are receptors?
Macromolecules that mediate the biological actions of hormones and neurotransmitters
What are agonists?
Drug that binds to receptor to produce a response
What are antagonists?
Drug that blocks the action of agonists
What is the affinity of a drug?
Binding step
Strength of association between ligand and receptor
What is the efficacy of a drug?
Activation step
The ability of an agonist to evoke a cellular response
Do agonists possess affinity or efficacy?
Both
Do antagonists possess affinity or efficacy?
Affinity only
What is the speed of reaction of a drug with low affinity?
Slow
What is the speed of reaction of a drug with high affinity?
Fast
What is the level of response of a drug with low efficacy?
Low
What is the level of response of a drug with high efficacy?
High
What is the relationship between agonist concentration and receptor occupancy?
Hyperbolic relationship showing saturation
What is the EC50?
Concentration of agonist which produces a half maximal response
What is the relationship between agonist concentration and response?
Sigmoidal, semi-logarithmic plot
Why is the sigmoidal plot better than that of the hyperbolic plot?
Encompasses a greater range of values
Gives a more accurate reading of the EC50
What is the potency of a drug?
The concentration of a drug required to produce an effect
i.e. the more drug needed, the less potent it is
How would a partial agonist be distinguished on a sigmoidal plot?
It will have less than 100% maximal response
How does competitive antagonism occur?
Agonist and antagonist bind to the same site (orthosteric)
How does non-competitive antagonism occur?
Antagonist binds to a separate allosteric site
Causes a conformational change in receptor change - even if agonist binds, receptor remains inactive in presence of antagonist
What is the effect of adding a non-competitive antagonist on the agonist-response curve?
No shift
Maximal response depressed
Slope clearly flattened
What is the effect of adding a competitive antagonist on the agonist-response curve?
Parallel shift to the right
No depression of maximal response
What are the four phases involved in drug disposition?
Absorption
Distribution
Metabolism
Excretion
What is absorption?
The process by which a drug enters the body, where the GI tract is considered outside
What is distribution?
The process by which a drug leaves the circulation an d enters the tissues perfused by blood
What is metabolism?
The process by which tissue enzymes catalyse the chemical conversion of a drug to a more polar form that is more readily excreted
What is excretion?
The processes that remove the drug from the body
How does solubility affect drug absorption?
Drug must dissolve in order to be absorbed
How does chemical stability affect drug absorption?
Protein based drugs would be digested before absorption and so cannot be given orally
How does the lipid to water partition coefficient affect drug absorption?
Drug must be able to dissolve in both lipid and water (amphipathic)
Drugs with higher lipid solubility will have a higher membrane concentration and so cross the membrane quicker
How does the degree of ionisation of a drug affect drug absorption?
Only unionised forms will diffuse readily across membrane
What is the Henderson-Hasselbalch equation?
Acid
pKa - pH = log(HA/A-)
Alkali
pKa - pH = log(BH+/B)
Calculates the proportions of ionised and unionised drugs
In what environment do acid drugs become less ionised?
In an acidic environment
In what environment do basic drugs become less ionised?
In a basic environment
What factors affect GI absorption?
GI motility pH of absorption site Blood flow to site Way in which the tablet has been manufactured Physiochemical interactions Presence of transporters in the membrane
What is the oral availability of a drug?
The fraction go the drug that reached the systemic circulation after oral ingestion
What is the systemic availability of a drug?
The fraction of the drug that reaches the systemic circulation after absorption
What are the enteral routes of drug administration (GI)?
Oral
Sublingual
Buccal
Rectal
What are the parenteral routes of drug administration (non GI)?
Intravenous Intramuscular Subcutaneous Inhalation Topical
What is the therapeutic ratio?
Maximum Tolerated Dose / Minimum Effective Concentration
The higher the ratio, the safer the drug
What is Kabs?
The absorption rate constant
What is Kel?
The elimination rate constant
How is the initial dose of an IV drug calculated?
Mass / Volume
C0 = D / Vd
By how many half lives will the majority of drugs have left the body?
Five
What drives the rate at which drugs leave the body?
Drug concentration
For drugs exhibiting first order kinetics, what is the effect of doubling the dose of a drug?
Adds one half life to its duration of therapeutic effect
Doubles the steady state plasma concentration
Does not alter the time for a drug to reach steady state
What is the clearance of a drug?
The volume of plasma cleared of drug in unit time
Why is clearance important?
Determines the maintenance dose rate
How is rate of elimination calculated?
Clearance x Plasma Concentration
What is the steady state of a drug, and how long does it generally take to reach?
Rate of drug administration = rate of drug elimination
Approximately 5 half lives
What is the volume of distribution of a drug?
The volume into which a drug appears to be distributed with a concentration equal to that of the plasma
What is the loading dose?
An initial higher dose of drug given at the start of treatment before stepping down to a lower maintenance dose
Why is a loading dose used?
To decrease the time to steady state for drugs with long half loves
What is the half life of a drug?
The time taken for the concentration of drug in the plasma to halve
What are first order kinetics?
Where the rate of elimination is directly proportional to drug concentration
What are zero order kinetics?
Where the rate of elimination is constant, rather than proportional to the concentration of the drug
What are the aims of drug metabolism?
Convert drugs to more polar metabolites which are not readily absorbed in the kidney, and so are excreted
Convert drugs to metabolites that are usually less pharmacologically active
What is the main organ of drug metabolism?
Liver
What occurs during phase 1 of metabolism in the liver?
Oxidation, reduction, hydrolysis
Makes drugs more polar
Adds chemically active group permitting conjugation in phase II
What occurs during phase 2 of metabolism in the liver?
Conjugation
Adds an endogenous compound increasing polarity
What are the cytochrome P450 family of Monooxygenases and what is their role in metabolism?
Haem proteins located in the ER of the liver
Mediate oxidation reactions in phase I of metabolism
How does the Monooxygenase P450 cycle cause oxidation?
Drug enters as substrate
Molecular oxygen enters cycle
One atom of oxygen is added to drug to yield the hydroxyl product
The other oxygen atom gives water
What is glucuronidation?
Common phase II reaction involving the transfer of gulcuronic acid to electron wish atoms of the substrate
What three basic processes are involved in renal excretion of drugs?
Glomerular filtration
Active tubular secretion
Passive reabsorption by diffusion across the tubular epithelium
How can a drug avoid glomerular filtration?
By binding to a large plasma protein
What are the two independent transporter systems which actively secret drugs into the lumen of the nephron?
Organic anion transporter = Acidic drugs
Organic cation transporter = Basic drugs
What is potentially the most effective mechanism for drug elimination by the kidney?
Tubular secretion
How can drugs which are highly protein bound be excreted?
Tubular secretion
What factors influence tubular reabsorption of a drug?
Lipid solubility
Polarity
Urinary flow rate
Urinary pH
