Pharmacology

Question 1

1. describe the stages that lead to the formation of prostaglandins, prostacyclins and thromboxane
2. When is COX1 expressed? What does it produce?
3. when is COX2 expressed? what does it produce?

Answer 1

1. phospholipids are metabolised by arachidonic acid by phospholipase A2.
   Arachidonic acid is metabolised to lipoxins by lipoxygenase (which is important for the resolution of the immune response) or to prostaglandins, prostacyclins and thromboxane.
2. constitutively expressed (housekeeping gene). priduces prostaglandin 2, thromboxane A2 and prostacyclins which have physiological functions
3. expression is induced by inflammatory stimuli. produces inflammatory prostaglandins, proteases and ROS.

Question 2

1. How does Asprin bind to COX enzymes?
2. what does low dose aspirin have a preferential effect over?
3. what does high dose aspirin have a preferential effect over?
4. Why does aspirin need to be given before iboprufen for it to exert it’s antiplatelet effects?
5. Describe the effects of NSAIDs on platelets and vascular endothelial cells
6. What are Coxibs?
7. What are NO-NSAIDS?

Answer 2

1. binds irreversibly to both cox1 and 2
2. thromboxane (antiplatelet)
3. prostacyclin (anti-inflammatory)
4. because ibuprofen blocks the activity of aspirin
5. COX1 inhibition leads to decreased thromboxane A2 production, preventing platelet aggregation and vasoconstriction.
   COX1 and 2 inhibition in endothelial cells decreases the production of prostacyclins, a vasodilator (thus causing vasoconstriction)
6. class of drugs that selectively inhibit COX2. They were introduced to minimise gastric problems, by only targeting prostaglandin production. There in an increase of MI/stroke/cardiovascular disease
7. a new class of NSAIDS that have gastro-protective effect and increased anti-inflammatory effect

Question 3

1. How do steroidal anti-inflammatories (glutocorticoids) work?
2. Name side effects of steroidal anti-inflammatories (3)

Answer 3

1. drive the expression of anti-inflammatory genes or prevent the expression of inflammatory genes
2. prolonged use leads to a decrease in the size of the adrenal gland thus decreased production of endogenous steroids - can lead to cushing syndrome (exogenous steroid dependency)
   suppressed immune response
   osteoporosis

Question 4

1. Name 4 physiological effects of histamine
2. name 2 sedating anti-histamines
3. name 3 non-sedating antihistamines
4. name 2 clinical indications of antihistamines

Answer 4

1. stimulation of gastric secretion; contraction of smooth muscle; cardiac stimulation; vasodilation
2. clorphenamine, promethazine
3. cetrizine, fexofendadine
4. allergic responses - alergic rhinitis, urticaria, insect bites, drug sensitivities
   as an adjunct to adrenaline in emergency treatment of anaphylaxis.

Question 5

1. when are immunosupressants used?
2. how do calcineurin inhibitors work?
3. name 2 calcineurin inhibitors
4. What are the side effects of calcineurin inhibitors?
5. how does rapamycin work?
6. how do immunosupressant antibodies function?

Answer 5

1. a drug of last resort
2. calcineurin is stimulated by a rise in Ca in response to antigen-T helper cell interraction. Calcineurin then initiates IL-2 synthesis, thus T cell activation. Calcineurin inhibitors prevent this IL-2 synthesis and T cell activation
3. ciclosporin and tacrolimus
4. nephrotoxicity, hepatotoxicity and hypertension
5. inhibits mTOR which is critical for various cellular functions, including protein synthesis, DNA replication and cell migration
6. inhibit cytokines or adhesion molecules

Question 6

1. What type of drug is aspirin?
2. how does it work?
3. name 2 adverse effects of aspirin usage
4. what is low dose aspirin used for?
5. what is high dose aspirin used for?

Answer 6

1. anti platelet drug
2. THROMBOXANE INHIBITOR
   - by inhibiting COX1, it inhibits the synthesis of thromboxane A2. As a result platelets can’t become activated and aggregate.
3. GI bleeding. Haemorrhagic stroke
4. daily dose to inhibit platelet activity
5. initial treatment of acute symptoms such as MI

Question 7

1. What type of drug is clopidogrel?
2. how does it work?
3. what is it used for?
4. how is clopidogrel a pro drug? what are the implications of this?
5. what are the side effects of clopidogrel?

Answer 7

1. antiplatelet
2. prevents ADP binding to P2Y2, P2Y1 and P2X, which is required for platelet aggregation
3. reduce thrombotic events in people with recent MI/stroke/peripheral arterial disease., and to prevent the blockade of stents
4. gets metabolised by cytochrome P450 enzymes in the liver. Some people carry mutations in these enzymes meaning that they are unable to metabolise clopidogrel well and require another ADP antagonist.
5. bleeding. thrombocytopenia purpura

Question 8

1. what type of drug is heparin?
2. how does heparin work?
3. what is the difference in function between fractionated and unfractionated heparin?
4. when is heparin used?

Answer 8

1. anti-coagulant
2. it inhibits factor Xa and or thrombin, by potentiating the action of anti-thrombin
3. unfractionated hepatin binds to antithrombin, causing a conformational change which increases its binding affinity for factor Xa and thrombin
   fractionated hepatin can only inactivate factor Xa
4. prophylaxis and treatment of venous thromboembolism.
   prophylaxis and treatment of atrial fibrillation with systemic embolism
   prevention of clotting in cardiac surgery

Question 9

1. what type of drug is warfarin?
2. how does it work?
3. what is it used for?

Answer 9

1. anticoagulant
2. antagonises vitamin K, which is required for the formation of clotting factors III, VII, IX and X
3. preventing clotting following heart attacks, strokes and major surgery