Pharmacology: Principles Flashcards
What is pharmacodynamics?
What the drug does to the body
What is pharmacokinetics?
What the body does to the drug
What can drugs target?
Enzymes (e.g. ACE inhibitors, aspirin, neostigmine)
Carrier Molecules (e.g. flavonoid – Pgp antagonist, digoxin)
Ion channels (e.g. verapamil - L-type calcium channel antagonist)
Receptors (e.g. benzodiazepine – GABA receptor agonist, adrenoceptor agonists and antagonists )
Structural proteins (e.g. Taxol – Tubulin “agonist”)
DNA (e.g. anti cancer agents like Doxorubicin)
What are receptors?
Receptors are Protein molecules whose function is to recognise and respond to endogenous chemical signals.
Chemicals which mimic the endogenous signals (i.e. drugs) will also elicit an effect.
What us an agonist?
molecule/drug that binds and activates the receptor
What is affinity?
the tendency of a drug to bind to the receptor
What is efficacy?
the tendency of a drug to activate the receptor once bound
If the activation is 100%, namely each time a drug interacts with its target there is a response then the agonist is said to be a “full agonist”, If the activation is <100%, the agonist is said to be a ….
Partial agonists, which have lower efficacy than full agonists – even with maximal occupancy of receptors.
What is EC50?
Effective concentration. The dose required for an individual to experience 50% of the maximal effect.
What is ED50?
Effective dose. The dose for 50% of the population to obtain the therapeutic effect.
What is the therapeutic index?
Therapeutic index = toxic dose (TD50)/ Effective dose (ED50)
What therapeutic index does the ideal drug have?
A high one
What is potency?
The amount of drug required to produce 50% of its maximal effects. Used to compare drugs within a chemical class (usually expressed in milligrams/kg).
What is efficacy?
The maximum therapeutic response that a drug can produce (example: morphine vs buprenorphine)
What is specificity?
Describes the capacity of a drug to cause a particular action in a population (for example, a drug of absolute specificity of action might decrease or increase, a specific function of a given gene or protein or cell type, but it must do either, not both).
What is selectivity?
Relates to a drugs ability to target only a selective population i.e. a cell/tissue/ signalling pathway, protein etc in preference to others
Do antagonists have efficacy and affinity?
Antagonist have affinity but zero efficacy (as they block the target activity)
What are the two main types of antagonism?
Competitive, Non-competitive and Irreversible
How does competitive antagonism work?
Competitive agonists compete with agonists for the receptor binding site.
The chemical structure of the agonist and competitive antagonist are often similar (lock and key hypothesis).
Antagonist binds to receptor in such a way as to prevent agonist binding
Competitive antagonism is surmountable – additional agonist can overcome the receptor blockade.
How does non-competitive antagonism work?
Non-competitive antagonists either bind to a different receptor site OR block the chain of events “post” binding - acting “downstream” of the receptor.
How does irreversible antagonism work?
Antagonist dissociates from the receptor only very slowly or not at all.
The antagonist forms covalent bonds with the receptor.
Irreversible antagonism is insurmountable – additional agonist cannot overcome the receptor blockade
What is IC50?
Concentration of antagonist to inhibit 50% of the agonist maximal
What is inverse agonism?
An agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist.
What is tachyphylaxis?
(“rapid protection”): Reduction in drug tolerance which develops after a short period of repeated dosing (decrease in response). Not common. Often due to a lack of a co-factor.
What is self-antagonism?
When a drug becomes antagonistic to its own effects
What can cause loss of target sensitivity?
Change in receptors (become resistant to drug stimulation/conformational changes)
Loss of receptors (endocytosis)
Exhaustion of mediators (degradation/low re-expression level)
Increased metabolic degradation (higher concentration of drugs are needed)
Physiological adaptation (crosstalk between body systems, one takes over)
Drug transporters (drug removed from receptor sites)
What is drug-drug interaction?
Altered pharmacologic response to one drug caused by the presence of a second drug
What are the possible outcomes of drug-drug interaction?
Action of one or more drugs is enhanced
Development of totally new effects
Inhibitory effects on one drug on the other
No change
What does pharmaceutical interaction mean?
Interaction prior to administration
Because of chemical or physical incompatibility/interaction
– Sodium bicarbonate and calcium
– Insulin is denatured by glucose
– Diazepam binds to plastics
What does pharmacokinetic interaction mean?
Related to interactions within ADME (absorption, distribution, metabolism, and excretion)
What are some possible mechanisms of pharmacokinetic interaction?
Absorption - one drug binding another
Decreased gastric emptying – metaclopramide
Chemical changes
– pH: Stability of drugs is often pH dependent: penicillin G is inactivated by sulphonamide (alkaline)
Oxidation/reduction
Loss of drug potency: e.g. tetracyclines are oxidised by riboflavin
Complex formation
Some drugs reduce circulation and may therefore reduce clearance and elimination E.g. alpha-2 agonists
Competition for binding sites on plasma proteins: Most are bound to albumin
Physical incompatibility: Insolubility
What does pharmacodynamic interaction mean?
The action of one drug is altered by another due to interactions within receptor signalling
What is summation interaction?
( 1 + 1 = 2)
When two drugs are administered together the effect seen is equal to the sum of the individual effects of each drug
What is potentiation interaction?
(1 + 0 = 2)
When a drug or food increases the effect of another drug, but has no effect when administered alone
What is synergism reaction?
(1 + 1 = 3)
When two drugs are administered together produce effects that are greater than would be produced if either drug were administered individually or would be seen with summative (additive) effects. This can be toxic or enhanced.
