Pharmacology

Question 1

What 4 corticosteroids are used in the treatment of asthma?

Answer 1

Oral - prednisolone
IV - hydrocortisone
Inhaled - beclomethasone
- fluticasone

Question 2

What are the cellular targets of glucocorticoids?

Answer 2

Immune cells of the lung - Macrophages
T-lymphocytes
Eosinophils

Question 3

What are the molecular targets of glucocorticoids?

Answer 3

Intracellular glucocorticoid receptor (GR).

Activated GR interacts with selected nuclear DNA sequences and influences the expression of genes:
-suppression of pro-inflammatory mediators (TH2 cytokines e.g. IL3 and IL5)

• expression of anti-inflammatory products (secreted leukocyte peptidase inhibitor)

Question 4

What are the side effects of glucocorticoids?

Answer 4

Moon face, weight gain, osteoporosis, hyperglycaemia

Question 5

Name 2 short acting and 2 long action B2 adrenoreceptor agonists

Answer 5

Short term
Salbutamol
Terbutaline

Long acting
Salmeterol
Formoterol

Question 6

Describe the mechanism of action of B2 adrenoreceptor agonists

Answer 6

B2 adrenoreceptor agonist stimulate B2 adrenergic receptors on bronchiolar smooth muscle cells. This activation increases the action of the enzyme adenylate cyclase, increasing cAMP production from ATP. cAMP activates protein kinase A which drives Ca2+ into storage vesicles away from the cytoplasm, reducing smooth muscle contractility. PKA inactivates MLCK and drives dephosphorylation on myosin light chain

Question 7

Name 2 methylxanthines

Answer 7

Theophylline

Aminophylline

Question 8

Describe the mechanism of action of methylxanthines

Answer 8

Methylxanthines block the enzyme phosphodiesterase in the bronchiolar smooth muscle cells. This increases the levels of cAMP levels, promoting uptake of calcium into vesicles and promoting bronchodilation.

Question 9

What are the side effects of beta 2 agonists?

Answer 9

Tremor
Tachycardia
Cardiac arrhythmia

Question 10

What is the cellular target of Beta -2 adrenoreceptor agonist

Answer 10

Bronchiolar smooth muscle cells

Question 11

What are the molecular targets of beta2 agonists

Answer 11

Stimulation of B2 adrenergic receptors

Question 12

What are the cellular targets of anti-cholinergics in asthma treatment?

Answer 12

Bronchiolar smooth muscle cells

Question 13

What are the molecular targets of anti-cholinergics?

Answer 13

Blockade of M3 muscarinic acetylcholine receptors

Question 14

What are the side effects of anti-cholinergics?

Answer 14

Dry mouth, constipation, urinary retention

Question 15

Describe the mechanism of action of anti-cholinergics

Answer 15

The blockade of the M3 muscarinic acetylcholine receptors reduces the action of phospholipase C enzyme (PLC), reducing the release of Ca2+ into the cytoplasm.
This reduces smooth muscle contraction, resulting in bronchodilation and resolution of asthma symptoms

Question 16

Name 2 anti-cholinergic drugs

Answer 16

Ipratropium (short acting)

Tiotropium (long acting)

Question 17

Name 2 leukotriene receptor antagonists

Answer 17

Montelukast

Zafirlukast

Question 18

What are the cellular targets of leukotriene receptor antagonists?

Answer 18

Eosinophils in the lungs

Bronchiolar smooth muscle cells

Question 19

What are the molecular targets of leukotriene receptor antagonists?

Answer 19

Blockade of CysLT1 leukotriene receptors

Question 20

Describe the mechanism of action of leukotriene receptor antagonists

Answer 20

Blockade of intracellular signals on smooth muscle cells –> inactivation of PLC –> bronchodilation

Blockade of receptors on eosinophils - less chemotaxis to site of inflammation

Question 21

What are the side effects of leukotriene receptor antagonists?

Answer 21

Abdominal pain

Headache

Question 22

What releases leukotrienes?

Answer 22

Mast cell IgE complex

TH2 releases IL-4, IL-13, this activates B cells to secrete IgE which then binds to mast cells

Question 23

Describe the mechanism of action of ACE inhibitors

Answer 23

Block conversion of Angiotensin I to Angiotensin II by angiotensin converting enzyme.
Decreased vasoconstriction in peripheral blood vessels because of reduction of release of Ca2+ into the cytoplasms –> reduced cardiac afterload –>reduction in BP
Aldosterone secretion reduced –> less water retention –> lower plasma volume –> reduced preload

Question 24

Describe the mechanism of action of angiotensin receptor blockers

Answer 24

Directly blocks the activation of the angiotensin receptors.
Decreased vasoconstriction in peripheral blood vessels because of reduction in IP3 which reduces release of Ca2+ into cytoplasm –> reduced cardiac afterload –>reduction in BP
Aldosterone secretion reduced –> less water retention –> lower plasma volume –> reduced preload

Question 25

What are the common side effects of ACEi

Answer 25

Persistent cough

Question 26

What are the main treatment strategies for chronic heart failure?

Answer 26

Improve contractility using ionotropes - sympathomimetics (Dobutamine, adrenergic stimulants) Reduce oedema with diuretics - furosemide Reduce preload and afterload - ACEi and ARBs

Question 27

Give an example of an ACEi

Answer 27

Ramipril

Question 28

Give 2 examples of ARBs

Answer 28

Losartan | Valsartan

Question 29

Describe the mechanism of action of calcium channel blockers

Answer 29

Prevent opening of voltage-gated calcium channels on vascular smooth muscle Reduce Ca2+ influx Vasodilator effect on resistance in vessels --> reduces afterload (easier for heart to pump) Coronary artery dilation

Question 30

What are the side effects of CCBs?

Answer 30

Ankle swelling, palpitations

Question 31

Give 2 examples of CCBs

Answer 31

Nifedipine | Amlodipine

Question 32

Give 2 examples of nitrate vasodilators

Answer 32

``` Glyceryl Trinitrate (GTN) Isosorbide Mononitrate (ISMN) ```

Question 33

Describe the mechanism of action of nitrate vasodilators

Answer 33

Metabolised to release nitric oxide (NO) NO stimulates soluble guanylate cyclase This causes an increase in cGMP in vascular smooth muscle cells Drives dephosphorylation of MLC via activation of MLC phosphatase Inhibits influx of Ca2+ into smooth muscle cells Drives vascular smooth muscle relaxation Promotes venodilation --> reduces preload Promote coronary artery vasodilation --> increased blood supply to myocardium

Question 34

Give an example of a beta blocker

Answer 34

Atenolol

Question 35

What are the side effects of beta blockers

Answer 35

Dizziness | Constipation

Question 36

Describe the mechanism of action of beta blockers

Answer 36

Beta blockers competitively inhibit adrenaline and noradrenaline at B1-adrenoceptor sites on cardiac smooth muscle cells, thereby inhibiting sympathetic stimulation of the heart muscle. Reduce heart rate and cardiomyocyte contractility Reduce the workload of the heart and relieve oxygen demand

Question 37

How does activation of a beta receptor give a different response in cardiomyocytes and smooth muscle?

Answer 37

The bronchiolar smooth muscles contain beta 2 adrenergic receptors. This activates the cAMP cascade, which in bronchiolar cells drives Ca2+ into storage vesicles in the cells, reducing contractility. In cardiomyocytes, activation of the B1 adrenoreceptors drives muscle contractility by activation of cAMP, increasing PKA levels and stimulating release of Ca2+ from intracellular stores and increasing uptake of Ca2+ from extracellular sites

Question 38

What diuretic is used to treat HF?

Answer 38

Spironolactone (potassium sparing) Increase water and sodium output in urine Reduce plasma volume and reduce cardiac preload Review block 1 drugs

Question 39

Give an example of a neprilysin inhibitor

Answer 39

Sacubitril

Question 40

Describe the mechanism of action of neprilysin inhibitors

Answer 40

Inhibits the action of neprilysin - therefore inhibits the inactivation of natriuretic peptides. Inhibition of neprilysin prolongs the presence & activity of NPs, which promote water & sodium excretion

Question 41

What drug is used in the treatment of sinus bradycardia?

Answer 41

Atropine

Question 42

Describe the mechanism of action of atropine

Answer 42

Blocks muscarinic-type M2 acetylcholine receptors on cardiomyocytes. This inhibits the parasympathetic cholinergic vagus nerve transmission, which normally decreases heart rate Atropine also accelerates the repolarisation rate in cardiac muscle, leading to an increased heart rate

Question 43

Name 2 antiplatelet drugs

Answer 43

Aspirin (COX inhibitor) | Clopidogrel (ADP receptor blocker)

Question 44

Describe the mechanism of clopidogrel (ADP receptor blocker)

Answer 44

Binds to and blocks the function of ADP receptors on platelet surfaces. This inhibits platelet activation and subsequent thrombus formation

Question 45

Describe the mechanism of action of aspirin (COX inhibitor)

Answer 45

Blocks the enzyme action of platelet COX enzyme | This leads to a reduction in TXAs synthesis which inhibits platelet activation and thrombus formation

Question 46

Give 2 examples of HMG-CoA Reductase Inhibitors

Answer 46

Atorvastatin (Any time) | Simvastatin (night time)

Question 47

Describe the mechanism of action of HMG-CoA Reductase Inhibitors

Answer 47

Cholesterol is produced in the liver. The enzyme HMG-CoA Reductase rate limits cholesterol. HMG-CoA Reductase inhibitors reduce circulating cholesterol levels and can promote uptake of excess cholesterol into the liver