Pharmacodynamics Flashcards
Difference between pharmacodynamics and pharmacokinetics
DYNAMICS - what the drugs do to the body
KINETICS - what the body does to the drug
Explain the difference between intracellular and extracellular drug targets
cellular receptor on the cell membrane
intracellular receptor exerting an effect on the nucleus, an enzyme, transport proteins or even a specific nucleic acid sequence.
Name the 4 types of cellular drug target
Ion channel
G-protein coupled receptor (GPCR)
Tyrosine Kinase Receptors
Nuclear Receptor
Explain how drugs act on ion channels
- Drug binds to receptor
- Channel is either opened or closed dependent upon the action of the drug (agonist or antagonist)
Local anaesthetics (e.g. lidocaine) work on which ion channel?
voltage-gated sodium (Na+) channels.
Explain how drugs act on GPCRs
- drug binds to the target
- causes a sequence of events within the G-protein subunits
- leads to production of secondary messenger such as cyclic AMP or a protein phosphorylation cascade
These second messengers are actually responsible for causing the effect.
Give an example of G-protein coupled receptors
Adrenoreceptors
Explain how drugs act on Tyrosine Kinase receptors
- Drug binds
- series of steps within the cell, involving phosphorylation of targets
- affects cell growth/differentiation
Give an example of a drug which acts on Tyrosine kinase receptors
Insulin
Explain how drugs act on nuclear receptors
- located within nucleus of the cell
- activation/inhibition typically causes increased or decreased gene transcription
Why must drugs working on nuclear receptors be lipid soluble?
To penetrate the cell membrane
(after which it forms a complex with a receptor protein before exerting an effect)
Give examples of drugs which work on nuclear receptors
steroids e.g. prednisolone
other hormone replacements e.g. levothyroxine.
Describe the difference between Agonists and Antagonists
Agonists - activates the receptor.
Antagonists - block a receptor and PREVENT activation
**they do not deactivate a receptor
Describe the difference between a competitive and non-competitive antagonist
Competitive - binds to same site as agonist and blocks activation
Non-competitive - binds to alternative site which changes shape of original site, and therefore agonist cannot bind
Binding affinity
how readily a drug will bind to the specific receptor.
> More receptors occupied by a drug = greater effect produced.
efficacy
how effective an agonist is at producing a response
once it has bound to the receptor
therapeutic index
Ratio of the drug dose which causes an undesired effect compared to that at which it produces the desired effect.
e.g. Gentamicin has a narrow therapeutic index => monitoring
potency
concentration at which a drug is effective
Most drugs exhibit ‘first-order’ elimination kinetics. What does this mean?
the rate of drug elimination is proportional to drug concentration
i.e. more drug ingested = more drug excreted
Explain ‘zero-order’ kinetics
rate of excretion is constant despite changes in plasma concentration (graph plateaus)
*due to saturation of the metabolic process
Give examples of drugs which exhibit zero-order elimination kinetics
phenytoin
salicylates (e.g. aspirin)
Drug metabolism usually involves phase I and phase II reactions. Describe what happens in each
Phase I reactions:
- oxidation, reduction, hydrolysis
- usually P450 enzymes (some exceptions)
Phase II reactions:
- conjugation
- Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved
Where do most Phase I + II metabolism reactions take place?
Liver
Are products of Phase I or Phase II metabolic reactions usually active and potentially toxic?
Phase I
In Phase II the products are often inactive and excreted in urine/bile
What is meant by First Pass Metabolism?
concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism
=> larger oral doses needed than if given by other routes
Give examples of drugs which exhibit first pass metabolism.
aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone
Describe zero-order kinetics
Metabolism not proportional to concentration of drug. I.e. graph plateaus once metabolic process to eliminate that drug is saturated
Therefore constant amount of drug eliminated per unit time
Give examples of drugs which exhibit “zero-order” kinetics
phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol
50% of the UK population are deficient in hepatic N-acetyltransferase.
What drugs are affected by acetylator status?
isoniazid
procainamide
hydralazine
dapsone
sulfasalazine
