Outline pharmacology

Question 1

What is pharmacology

Answer 1

Science of drugs
Covers the precise mechanisms of drug action- including drugs (statins, aspirin) and endogenous mediators (acetyl choline, noradrenaline)
Explains how body deals with drugs- pharmacokinetics (metabolised secreted and path around the body from ingestion orally or intravenously)
And how body uses drugs- clinical pharmacology

Question 2

Explain terms agonist and antagonist and give e.g.

Answer 2

Agonist- activate receptors e.g. beta-agonists in asthma

Antagonist- block receptors e.g. beta-blockers in heart disease

Question 3

Explain other modes of actions of drugs (apart from agonist and antagonists)

Answer 3

• Interact with ion channels
– Calcium channel blockers- restrict entry of C making muscle less excitable
• Activate enzymes
• Inhibit enzymes
– Statins- inhibit first enzyme in statin synthesis
– Penicillins- inhibit cell wall formation in bacteria
• Inhibit transporters/ pumps
– Proton pump inhibitors- good for gastrointestinal problems
• Interact with DNA
– Anticancer drug- kill of cells in bone marrow as also fast growing
• Monoclonal antibodies- target certain targets

Question 4

How does salbutamol lead to a pharmacological response?

Answer 4

B2 adrenoceptor lying in the membrane of the cell
Transduction system of a G protein- made up of a beta, gamma and alpha subunit
Alpha subunit has GDP bound to it
Adenylyl cyclase (enzyme) embedded in membrane

1) Salbutamol (agonist) that binds to receptor to activate it
2) Causes the receptor to couple with G protein
(chemical reversible interaction) forming a G-coupled protein receptor
3) Alpha subunit dissociates and swaps GDP with GTP so it is now GTP bound
Once it is GDP bound this activates adenylyl cyclase (enzyme)
4) Adenylyl cyclase concerts ATP into cAMP
(2nd messenger system)
5) cAMP is the intracellular signal which interacts with the contractile apparatus causing relaxation of airways
6) Activates protein kinase which phosphorylates some contractile proteins

Question 5

Explain how the concentration of agonist changes the pharmacological response (graph)

Answer 5

• When plotting log [agonist] against pharmacological response we see a sigmoidal shaped curve
• Showing most drugs are concentration dependent and have a certain concentration over which they have the biggest effect on body
• In presence of competitive agonist curve shifted to right as competes for agonist binding
• In presence of non-competitive agonist this will block a receptor downstream so if we increase agonist you cant overcome the blockade and so have lower level of pharmacological response

Question 6

Explain how we now use aspirins

Answer 6

• low dose aspirin prevents MI
• Recommended for secondary prevention
• Reduces incidence of stroke (as antiplatelet drug)
• Works by irreversibly inhibiting cyclo-oxygenase

Question 7

Explain how aspirin works

Answer 7

1) In all cell membranes 20C arachidonic fatty acid
2) Broken out of membrane by phospholipase A2
3) Releases free arachidonic acid
4) Cyclo-oxygenase converts this to endoperoxides
5) Converted to prostaglandins

Question 8

What do prostaglandins do?

Answer 8

Pain inflammation, pain, control stomach, control uterus (female) control of platelets

Question 9

Effect of aspirin after 3 years

Answer 9

• decreased vascular events
• Increase major extranial bleeding (causing bleeds in stomach)
• Decreases cancers

Question 10

Outline how statins work

Answer 10

• HMG-CoA reductase inhibitors
• Inhibiting synthesis of LDL cholesterol, hence lowering chance of CV disease
• Recommended in over 1- % chance of CV disease in next 10 yrs