Lipid lowering drugs Flashcards
What are statins?
- They –|HMG - CoA reductase
- Competitive and reversible
- More effective at reducing cholesetrol than other drugs.
- Not great for moderate to high TG
What is the MOA of statins?
Decreases cholesterol synthesis upregulates LDL recptor synthesis, leading to LDL-C clearance from plasma to liver. Reduces plasma LDL-C, decreases plasma TG & increases HDL-C
What other protective effect does statins have?
- Plaque stability
- Increases neovascularisation of ischemic tissue
- Anti-thrombotic
- Anti-oxidant
- Anti-inflammatory
What are fibrates?
Derivative of fibric acid - structually related to thiozolidones (Bezafibrate, Ciprofibrate, Fenofibrate, Genfibrozil)
What is the MOA of Fibrates?
- Agonsit of PPAR-α
- Increases LDL-C uptake, form LDL with higher affinity to LDL
- Increases fatty acids uptake & conversion to acyl-coA by the liver, therefore fatty acids arent available for TG synthesis.
- Decrease in VLDL from liver & hence TG lvls reduced.
- Anti-inflammatory effects.
What is ezetimibe?
–| of cholesterol absorption, used where statin is C/I or in addition to statins.
What is the MOA of ezetimibe?
- Specifically block absorption of cholesterol without affecting absorption of fat-soluble vitamins, TG or bile acids.
- Conjugated in the intestine to ezetimibe glucuronide & excreted in stools.
- Lowers LCL-C 17%
What is the MOA of Nicotinic Acid?
- Mobilisation of FFA
- Decrease TG synthesis
- Decreases APoB and decreases VLDL
- Decreased serum VLDL results in lipolysis to LDL
- Decreased LDL
- Increased HDL
What are Nicotinic Acid Derivatives?
Lowes both LDL-C & TG by –|of synthesis
Increases HDL-C
–| Hepatic TG production & VLDL secretion
What is Inclisiran ?
Small interfering RNA treatment that –| the translation of PCSK9 mRNA.
What are PCSK9?
Bind to hepatic LDL receptors & promote their lysosomal degradation.
Prevents recycling of LDLR back onto cell surface of hepatocytes -> limits LDL uptake into the liver
What is the MOA of PCSK9?
–| PCSK9 -> Increases receptor number & LDL uptake.
What is the MOA of Inclisiran?
- Interacts with RICS complex which degrades mRNA of PCSK9
- Less PCSK9 therefore less likely to interfere with LDL receptor expression.
What is the mechanism of platelet adhesion, activation & secretion?
- Exposed to dmg & becomes activated. Exposure of the basement membrane to the ECM - they combine & cab cause platelet adhesion.
- Soluble factors, TXA2, ADP binding of the ligands can cause platelet activation
- Platelet aggregation -> platelet activation. Receptors will bind to fibrin & fibrin will form links between platelets & cause aggregation & further stimulation.
How can you influence platelet aggregation?
- –| either TXA2, or ADP
- By stimulating g prostacyclin / nitric acid.
What molecules activate platelets?
- Serotonin
- Epi
- PAF
- Thrombin
- ADP
- TXA2
- Collagen
What do antiplatelet drugs do?
Decrease platelet aggregation & –| thrombus formulation in arterial circulation.
Name some antiplatelet drugs?
Aspirin
Thienopyridines (Clopidogrel)
Ticagrelor
Glycoprotein 11b/11a –|(Eptifibatide, Tirofiban, Abciximab)
How does aspirin work as an antiplatelet?
Irreversibly inactivates COX-1 in platelets.
* Decreases TXA2 formation
* Reduces platelet aggregation
Irreversibly inactivates COX-2 in Endothelium
* Decreases prostacyclin formation
* Increases platelet aggregation.
Endothelial cells can synthesise new COX-2
Lower doses just –| platelet
Higher doses –| both
How does clopidogrel work?
- Pro-drug additive effects to aspirin, but work on different pathways
- –| ADP induced aggregation
- Antagonises the platelet P2Y12 receptor.
How does ticagrelor work?
- Nucleoside analogue like adenosine.
- Blocks p2y12 ADP receptors on platelets.
- Diff binding site than ADP so allosteric –| & Blockage is reversible _. acts faster for a short period of time.
What are the side effects of Ticagrelor?
More non-lethal bleeding, effects more quickly.
How do glycoprotein 11b/11a work?
–| all pathway of platelet activation be it binds to glycoprotein 11b/11a receptors, blocking fibrinogen binding -> –| aggregation.
