Pharmacology of Medicines for Hyperlipidaemia and Angina

Question 1

what is atherosclerosis?

Answer 1

a slowly progressing arterial disease in which intima (the innermost membrane of an organ) is thickened by fibrous deposits that gradually narrow the lumen and gradually becomes a site of thrombus formation

Question 2

what is the earliest visible sign of atherosclerosis?

Answer 2

fatty streaks

Question 3

what is accumulated to form a fibrous plaque?

Answer 3

• monocytes
• macrophages
• foam cells
• T-lymphocytes
• connective tissue
• tissue debris
• cholesterol crystals

Question 4

what are foam cells?

Answer 4

• monocytes move to the subendothelium and are transformed into macrophages.
• these consume excess modified lipoproteins to become foam cells

Question 5

how does a atherosclerotic plaque evolve from a fatty streak?

Answer 5

• fatty streak present
• soft atherosclerotic plaque develops which is vulnerable to fissure (cracks/narrow opening) or haemorrhage
• interaction of soft atherosclerotic plaque with circulating cells (platelets and macrophages) and neurohumoral factors
• fibrous cap develops when smooth muscle migrates to intima producing a tough fibrous matrix gluing cells together

Question 6

what are unstable plaques?

Answer 6

• plaques with a lipid-core and substantial inflammatory cell infiltration.
• also has a thin fibrous cap
• prone to plaque disruption by ulceration (leading to thrombus formation)

Question 7

what are stable plaques?

Answer 7

plaques with a thick fibrous cap

Question 8

give an example of a local vasodilator?

Answer 8

nitric oxide

Question 9

what effect does a long-standing coronary heart disease caused by an atheroma have?

Answer 9

it leads to collateral vessels, around the atheromatous, narrowing

Question 10

what causes atherosclerosis?

Answer 10

1, hyperlipidaemia

2. smoking
3. hyperhomocysteinemia (as homocysteine favours plaque formation)

Question 11

at what site do plaques form?

Answer 11

sites of high mechanical stress (making hypertension a risk factor)

Question 12

what are the consequences of atherosclerosis?

Answer 12

• narrowing of the lumen leading to ischemia and coronary heart disease
• Stiffening of the vessel wall (calcification)
• Thrombus formation obstructing residual lumen and causing peripheral emboli (e.g. cerebral infarction, stroke)
• Bleeding into the plaques and vessel wall.
• Wall may be stretched, creating aneurysm, and even rupture

Question 13

What are some prophylactic interventions that may take place to prevent/reduce chances of developing atherosclerosis?

Answer 13

1. Dietary changes to reduce cholesterol & lipids
2. Cessation of Smoking
3. Control of Blood Pressure
4. Control of Diabetes
5. Regular, moderate exercise
6. Drugs to reduce plasma cholesterol

Question 14

explain how cholesterol is transported?

Answer 14

• chylomicrons transport lipids from the gut to the periphery
• in the liver, chylomicron remnants bind to LDL receptors via ApoE and are endocytosed producing new trigycerides and cholesterol which are exported as VDLP
• these activate LPL leading to fatty acid release
• some VLDL and IDL remnants leave as VLDL and LDLs
• this delivers cholesterol

Question 15

what happens when there’s a rise in intracellular cholesterol levels?

Answer 15

• Key enzyme of cholesterol synthesis inhibited (3-HMG-CoA reductase)
• Cholesterol is esterified to its storage form
• LDL receptor synthesis inhibited

Question 16

what do high density lipoproteins do?

Answer 16

• exchange certain apolipoproteins with chylomicrons and VLDLs and also take up excess cholesterol from extrahepatic cells and blood.
• Pass cholesterol and Chol-E to liver, and steroid hormone–producing glands

Question 17

what is the effect of an elevated cholesterol-rich LDL in the serum?

Answer 17

it increases the binding of LDLs to the scavenger receptor that mediates the incorporation of cholesterol in macrophages, skin and vessel walls

Question 18

what ways to drugs lower lipid levels?

Answer 18

1. inhibition of cholesterol synthesis (e.g. HMG -CoA reductase inhibitors)
2. prevent cholesterol reabsorption
3. reduce VLDL secretion (e.g. niacin)
4. Increase synthesis of lipoprotein lipase (e.g fibrates)

Question 19

how do statins work to inhibit cholesterol synthesis?

Answer 19

by inhibiting HMG-Co- reductase that blosck de novo synthesis of cholesterol

Question 20

what are some side effects to using statins?

Answer 20

• May damage skeletal muscle or liver

- Interfere with myelination of infants (contraindicated in pregnancy)

Question 21

how do resins prevent cholesterol absorption?

Answer 21

resins or non-absorbable macromolecules so they bind to cholesterol preventing absorption from the gut

Question 22

what are the side effects to using resins?

Answer 22

• Unpleasant gritty taste
• GI tract discomfort
• Interference of vitamin or drug absorption

Question 23

what are side effects to using niacin?

Answer 23

• Occasional flush with itching reduced with aspirin

- Rarely causes glucose intolerance

Question 24

How do Fibrates increase lipoprotein lipase synthesis?

Answer 24

Activate peroxisome proliferation-activated receptor-α (PPARα), increasing lipoprotein lipase synthesis and β-oxidation of lipids

Question 25

what are some side effects to using fibrates?

Answer 25

• Nausea
• Skin Rash
• Occasional increase risk of gallstones