ICS Pharmacology Flashcards
Give an example of a proton pump inhibitor.
Omeprazole.
Give an example of a statin.
Simvastatin.
Give an example of an ACE inhibitor.
Enalapril.
Give an example of a COX inhibitor.
Aspirin and paracetamol.
Give an example of a β2 adrenoceptor agonist.
Salbutamol.
Give an example of a β1 adrenoceptor blocker.
Atenolol.
Give an example of a Ca2+ channel blocker.
Amlodipine.
Give an example of a broad spectrum antibiotic.
Amoxicillin.
Give an example of an opiate analgesic.
Tramadol.
What do most drugs target?
Proteins!
Name 4 receptors that drugs target.
- Ligand gated ion channels.
- GPCR.
- Kinase linked.
- Cytosolic/nuclear.
Give an example of a ligand gated ion channel.
Nicotinic Ach receptor.
Give an example of a GPCR.
Muscarinic and β2 adrenoceptor.
GPCR’s usually interact with adenylate cyclase or phospholipase C
Give an example of a kinase linked receptor.
Receptors for growth factors.
Give an example of a cytosolic/nuclear receptor.
Steroid receptors; steroids affect transcription.
What are agonists?
Agonists bind to a receptor and to activate it.
What are antagonists?
Antagonists decrease the effect of an agonist. They show no response at a receptor.
Describe the shape of a log dose-response curve.
Sigmoidal.
What does EC50 tell us about a drug?
Its potency!
What is EC50?
The concentration of drug that gives half the maximal response.
Would a drug with a lower EC50 have a lower or greater potency?
Greater potency.
What does Emax tell us about a drug?
Efficacy.
Which is more efficacious, a full agonist or partial agonist?
A full agonist is more efficacious because a full agonist can give a 100% response.
Would an antagonist shift a dose-response curve to the left or right?
The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent.
Drug action: define affinity.
How well a ligand binds to a receptor.
Drug action: define efficacy.
How well a ligand activates a receptor; how well it induces a conformational change.
What is the effect of fewer receptors on drug potency?
Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced.
What is the effect of fewer receptors on receptor response?
Receptor response is still 100% due to receptor reserve. (Partial agonists don’t have receptor reserve).
What is the affect of less signal amplification on drug response?
Less signal amplification gives a reduced drug response.
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
What is inverse agonism?
Where an agonist has a negative effect at a receptor.
Does an antagonist show efficacy?
No. An antagonist has affinity but zero efficacy. An agonist however demonstrates affinity and efficacy.
Pharmacology: define tolerance.
A reduction in the effect of a drug overtime. This can be due to continuous use of repeatedly high concentrations.
What 3 ways can a receptor be desensitised?
- Uncoupled (an agonist would be unable to interact with a GPCR).
- Internalised (endocytosis, the receptor is taken into vesicles in the cell).
- Degraded.
Can aspirin be described as a selective drug?
No. Aspirin is non-selective, it acts on COX1 and COX2.
What is the function of COX1 and COX2?
They cyclise and oxygenate arachidonic acid and produce prostaglandin H2.
What does prostaglandin H2 form when it interacts with synthases?
Prostanoids.
Define pro-drugs and give an example of one.
Drugs that need to be activated enzymatically e.g. ACE inhibitors, enalapril.
How do ACE inhibitors work?
Angiotensinogen is converted to angiotensin 1 via renin. Angiotensin 1 is then converted to angiotensin 2 via ACE. ACE inhibitors prevents angiotensin 1 binding and so you don’t get angiotensin 2 formation.
(Angiotensin 2 is a vasoconstrictor and so ACEi can be used in the treatment of hypertension).
Give an example of a β lactam antibiotic.
Penicillin and amoxicillin.
How do β lactam antibiotics work?
The inhibit transpeptidase and so prevent bacterial cell wall synthesis.
How do diuretics work?
They inhibit ‘synporters’ in the loop of henle. This leads to increased H2O excretion and decreased salt reabsorption and so BP decreases.
Give an example of loop of henle diuretics.
- Furosemide, act on the ascending loop.
- Thiazides, act on the distal tubule.
How can drugs be developed?
- Serendipity, by chance. e.g. penicillin.
2. Rational drug design. e.g. propranolol.
Describe how rational drug design works.
Rational drug design is focused on developing an antagonist from an agonist. It looks at solubility, electrostatic charge and bulk.
How do you determine whether insulin is long or short acting?
Small changes in amino acid sequence will determine whether insulin is long or short lasting - RECOMBINANT PROTEIN!
Name 3 things that the chemical properties of a drug can influence?
- Administration.
- Distribution.
- Elimination.
As the difference in concentration falls what happens to the rate of reaction?
The rate of reaction will slow down.
Rate is proportional to the concentration of drug
What is the association between diffusion and concentration gradient?
Diffusion is proportional to concentration gradient; this is a first order process and represents an exponential function.
How many litres of water are there in the following body compartments:
a) Plasma.
b) Interstitial space.
c) Intracellular space.
a) 3L.
b) 11L.
c) 28L.
What are the 5 ways by which fluid can move between compartments?
- Simple diffusion.
- Facilitated diffusion.
- Active transport.
- Movement through extra-cellular spaces.
- Non-ionic diffusion.
What can influence the degree of ionisation of weak acids and weak bases?
pH.
What equation can be used to determine the degree of ionisation at a specific pH?
Henderson Hasselbach.
pH = log[A-]/[HA] + pKa.
What can enhance non ionic diffusion?
Non ionic diffusion can be enhanced if adjacent compartments have pH difference.
In terms of ionisation, what happens to Aspirin in the stomach?
Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.
What is the advantage of aspirin becoming less ionised in the stomach?
This allows rapid non-ionic diffusion across the gut membrane into the plasma. Once in the plasma aspirin becomes more ionised again.
What is the effect of an increase in pH on a weak acid?
The weak acid will become more ionised.
What is the effect of an increase in pH on a weak base?
The weak base will become less ionised.
What is the effect of a decrease in pH on a weak acid?
The weak acid will become less ionised.
What is the effect of a decrease in pH on a weak base?
The weak base will become more ionised.
Define bioavailability.
The amount of drug taken up as a proportion of the amount administered. It is a reflection of uptake.
What route of drug administration has a bioavailability of 1?
IV infusion, all the drug administered will go into the plasma.
Explain what would happen to the bioavailability of aspirin if gastric pH increased.
The bioavailability would decrease. Aspirin would be more ionised and so wouldn’t diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease.
Give 2 factors that drug distribution in the plasma depends upon.
- Chemical properties.
2. Molecular size.