L40: Lipid Lower Drugs Flashcards Preview

CPRS > L40: Lipid Lower Drugs > Flashcards

Flashcards in L40: Lipid Lower Drugs Deck (12)
Loading flashcards...
1
Q

Risk factors of atherosclerosis

A
  • Age
  • Family history
  • Diabetes
  • Hypertension
  • ↓HDL, ↑LDL, ↑TAG
  • ↑Coagulation factors
  • ↑Inflammation
  • Lifestyle
2
Q

IDL, LDL, Chylomicron uptake by liver

A

IDL: Apo E mediated

Chylomicron remnant: Apo E mediated

LDL: Apo B100 mediated

3
Q

Risk assessment of CVD risk

A
  • 10 year Coronary Heart Disease risk (CHD risk)
  • Primary target: LDL-C
  • Secondary target: Non-HDL-C (for patients with fasting TAG > 200 mg/dL)
  • Risk ↑ —> goals for LDL-C ↑ (lower threshold)
  • TC:HDL-C ratio for treatment of low HDL-C patients
4
Q

Managment of lipoprotein disorder

A
  1. ↓ cholesterol intake
    - dietary restriction
    - cholesterol absorption inhibitor
  2. ↓ LDL plasma level
    - statins
    - niacin
    - resins (bile acid sequestrants)
    - PCSK9 inhibitor
  3. ↓ VLDL plasma level (TAG)
    - omega-3
    - fibrates
    - niacin
  4. ↑ HDL plasma level
    - niacin
5
Q

Statins

A

HMG CoA reductase inhibitor

  • ↓ LDL (due to ↓ cholesterol synthesis in liver)
  • ↓ LDL (due to ↑ LDL receptor synthesis —> ↑ LDL clearance)
  • small ↑ HDL (due to LDL clearance)
  • little ↓ TAG

Use:
- prevention of atherosclerosis in elevated LDL
- NOT for pregnancy, nursing, children
- homozygous familial hypercholesterolaemia: Attenuated response
- Short half life (1-4 hours): Pravastatin (taken at bed)
- Intermediate half life (12 hours): Simvastatin (taken at bed)
- Long half life (20 hours): Atorvastatin, Rosuvastatin (taken anytime)
(Hepatic cholesterol synthesis is maximal between 12am to 2am)

Adverse effects:

  • Safe (GI disturbance)
  • Hepatotoxicity (↑ALT, malaise, anorexia)
  • Myopathy / Rhabdomyolysis —> Renal failure (↑creatine kinase)

Factors increasing statin plasma level:

  • age
  • hepatic and renal dysfunction
  • small body size
  • drugs inhibit hepatic uptake (Gemfibrozil)
  • drugs inhibit CYP450 enzymes / glucuronidase (Gemfibrozil, Warfarin, Erythromycin, Itraconazole)
6
Q

Niacin

A

Vitamin B3

  • ↓ VLDL (inhibition of hormone-sensitive lipase in adipose tissue —> ↓ fatty acids to liver —> ↓ hepatic synthesis of TAG; ↑VLDL clearance by enhancing LPL activity)
  • ↓ LDL (due to ↓ VLDL)
  • ↑ HDL (due to ↓ clearance of Apo A1 in liver)

Use:

  • Most effective in ↑ HDL
  • Hypertriglyceridemia —> Effective in ↓ TAG
  • Normalize LDL level irrespective of LDL-R level
  • limited by adverse effects
  • NOT for pregnancy

Adverse effects:

  • flushing (reversed by aspirin, tachyphylaxis)
  • skin rash
  • GI disturbance (avoid in peptic disease)
  • Hepatotoxicity
  • birth defects
  • ↓ glucose tolerance, ↑ uric acid
7
Q

Fibrates

A

PPAR-α activator (clofibrate, fenofibrate, gemfibrozil)

  • ↓ VLDL (↑ LPL synthesis, ↑ fatty acid oxidation by liver —> ↓ TAG)
  • **- ↓/↑ LDL (due to ↓ VLDL / ↑ TAG —> fatty acid)
  • little ↑ HDL (↑ Apo A1, A2 production)

Use:

  • Hypertriglyceridemia
  • NOT for pregnancy, children

Adverse effects:

  • Safe (GI disturbance)
  • Myopathy (caution with statin)
  • ↑ Liver enzyme
  • ↑ cholesterol gallstone (caution with biliary tract disease)
  • ↑ Warfarin action
8
Q

Resins (Bile acid sequestrant)

A

(cholestyramine, colesevelam)

  • ↑ Bile acid excretion (by binding to bile acid —> ↓ reabsorption —> ↑ liver conversion of cholesterol into bile acid)
  • ↓ LDL (by ↑ LDL receptor synthesis in liver, offset by up-regulation of HMG CoA reductase —> ↑ cholesterol synthesis)

Use:

  • conditions with ↑ LDL
  • may cause ↑ hepatic TAG
  • relieve pruritis (in cholestasis)
  • bind digoxin (in digoxin toxicity)

Adverse effects:

  • no systemic toxicity
  • GI disturbance (diverticulitis, relieved by increase fibre intake)
  • ↓ fat-soluble vitamin and drug absorption in GI tract (1 hour before, 3-4 hours after)
9
Q

Cholesterol absorption inhibitor

A

Ezetimibe

  • ↓ cholesterol absorption (by binding to NPC1L1 + inhibit ACAT2)
  • ↓ LDL (by ↑ LDL receptor synthesis in liver, offset by up-regulation of HMG CoA reductase —> ↑ cholesterol synthesis)

Use:
- plasma concentration increased by fibrates, decreased by resins

Adverse effects:
- Safe

10
Q

PCSK9 inhibitor

A

Monoclonal Ab against PCSK9 (Alirocumab, Evolocumab)
- ↓ LDL (by binding to PCSK9 —> prevent binding to LDL receptor —> ↓ LDL receptor degradation —> ↑ LDL clearance)

Use:

  • 2nd line in refractory to diet change / maximum statin therapy
  • familial hypercholesterolaemia
  • CVD —> prevent cardiovascular events

Adverse effects:
- Safe

11
Q

Combination therapy

A
  • Lowest effective dose
  • Close monitoring for potential toxicity
  • Statin + Fenofibrate (Myopathy, Hepatotoxicity)
12
Q

Summary of all lipid lowering drugs

A

Statin:

  • ↓ cholesterol synthesis in liver —> ↓ LDL
  • ↑ LDL receptor synthesis —> ↓ LDL

Niacin:

  • ↓ Apo A1 clearance —> ↑ HDL
  • ↓ hepatic TAG synthesis —> ↓ VLDL

Fibrates:
- ↑ LPL synthesis + ↑ fatty acid oxidation in liver —> ↓ VLDL

Resins:
- ↑ bile acid excretion —> ↑ cholesterol utilisation —> ↓ LDL

Ezetimibe:
- inhibit NPC1L1 —> ↓ cholesterol absorption —> ↓ LDL

PCSK9 inhibitor:
- ↓ degradation of LDL receptor —> ↓ LDL

Decks in CPRS Class (75):