2. Hyperlipidemia
3
• Lipid is essential for our body structure
• Lipid is insoluble in blood (water vs lipid solubility)
• They require special carrier to facilitate their
transportation through blood
• Lipid source is from dietary intake
Chylomicrons facilitate lipid intake from
intestine
• In blood vessels, Very Low density Lipoprotein
(VLDL), Low Density Lipoprotein (LDL) and
High Density Lipoprotein (HDL) are
responsible to facilitate lipid transportation
3. Hyperlipidemia
(Atherosclerosis)
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• Atherosclerosis is an abnormal accumulation of lipids and
products resulting from an inflammatory response in the wall
of arteries
• A major cause of heart attacks, angina pectoris, stroke and
peripheral vascular disease
• Once plasma lipid profile has been improved prevent
atherosclerosis and decrease mortality risk
• Lipoproteins are responsible to distribute Cholesterol and
triglyceride to the body
• VLDL Triglyceride
• LDL and HDL Cholesterol
5. Functions of lipoproteins
Chylomicron:-
transport of exogenous dietary triglycerides
VLDL:-
transport of endogenous dietary triglycerides
synthesized in the liver to peripheral tissue
LDL:
transport of cholesterol to tissues (bad-harmful)
HDL:
transport of cholesterol out of tissues (good)
Triglyceride
7. Hyperlipidemia (Pharmacotherapy)
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• Diet is first line
• Omega-3 (fish oil) can reduce triglyceride
• Not omega-6 (in sunflower oil)
• Classes used for hyperlipidemia include
8. Hyperlipidemia (Statin)
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HMG-CoA inhibitors (simvastatin, atorvastatin, rosuvastatin, Pravastatin ,
Lovastatin,Fluvastatin)
• Mechanism of action
• They reduce hepatic hydroxymethylglutary-coenzyme (HMG-CoA)
• Reducing cholesterol, LDL and triglyceride plasma level
• Not used in pregnancy (class D teratogenic)
• Metabolized through liver to active metabolites
• Adverse effects: elevated liver enzymes (hepatotoxicity) , hyperglycemia, myopathy,
rhabdomyolysis
• Drug-drug interaction:
• They are CYP substrate for increased risk of hepatotoxicity and myopathy
• Should not be combined with fibrates (precipitate myositis)
9.
10. Hyperlipidemia (Bile Acid Resin)
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• Cholestyramine and Colestipol
• Mechanism of action
• These are large non-absorbable polymers bind to bile acid in the intestine and
stop reabsorption Force liver to used new cholesterol and to form new bile acid
• They reduce LDL and slightly increase HDL and triglyceride
• Can be used for adolescent patients (11 – 20 years)
• Adverse effects: Bloating, constipation, hypertriglyceridemia
• Drug-drug interaction:
• They reduce absorption of fat-soluble vitamins (K, D), and drugs (warfarin,
digoxin, diuretics)
11.
12. Hyperlipidemia (Nicotinic Acid (B-complex
vitamin)
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• Niacin
• Inhibits lipolysis of triglycerides in adipose tissue reduction
in LDL and VLDL
• Slight increase in HDL
• Used for managing hypertriglyceridemia and high LDL
plasma level
• Adverse effects: dyspepsia, facial and upper trunk flush,
hepatotoxicity, hyperglycemia
• Cautions and contraindications:
• Concurrent use with statin ↑ myopathy
• In diabetic patients ↑ blood glucose level
13. Hyperlipidemia (Fibric Acid Derivatives)
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• Fenofibrate and Gemibrozil
• Mechanism of action
• Not fully understood
• Suppress gene responsible for lipoprotein production and triglyceride
metabolism
• Used to lower LDL and mild hypertriglyceridemia
Adverse effect: rash, urticaria, hair loss, anemia, hepatotoxicity, myopathy
Drug interaction:
With statin ↑ myopathy
With warfarin ↑ bleeding
14. Hyperlipidemia (Other drugs)
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• Ezetimibe
• Mechanism of action
• Inhibits the enzyme responsible for cholesterol absorption from intestine
• It reduces LDL by 20%
• It is a pro-drug and undergoes enterohepatic circulation
• Adverse effects: hepatic toxicity
• Contraindications:
• Pregnancy
17. Coagulation disorders
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• Inside blood vessel, blood must remain fluid
• Clot to heal injury (thrombus formation)
• Dissolve clot to ensure fluidity (fibrinolysis)
• This process is known as Hemostasis
• Alteration to hemostasis coagulation
disorder
• It is a complex process involving platelets
and coagulation cascade
• Fibrinolysis is the removal of a blood clot
19. Coagulation disorders (Platelet
Aggregation)
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• Aspirin (non-steroidal anti-inflammatory drugs)
• Mechanism of action:
• It inhibits formation of prostaglandins (including thromboxane), by
inhibiting the enzyme cyclooxygenase (COX) inhibiting platelet
aggregation
• Clinical use: prophylaxis of MI, cerebrovascular diseases and AF
• Adverse effect: bronchospasm, bleeding, dyspepsia and GI disturbance
• Contraindications: peptic ulcer, bleeding disorder and hypersensitivity
20. Coagulation disorders (Platelet
Aggregation)
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• ADP receptor inhibitors (Clopidogrel, Ticlopidine)
• Mechanism of action
• They irreversibly inhibit ADP receptor inhibiting ADP-medicated platelet aggregation
• Affected platelet will be affected for the reminder of their lifespan (10 days)
• Clinical use: acute coronary syndrome, acute angina, prophylaxis in atherosclerotic patients, patient with
hypersensitivity to aspirin
• Adverse effects: Bleeding, neutropenia and gastric ulcer
• Pharmacokinetic: These are prodrug, activation through CYP enzyme
• Caution: stop clopidogerl 7 days prior of surgery
21. Coagulation disorders (Coagulation
Cascade)
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• Extrinsic factors (TF and factor VII)
• Intrinsic factors (IX and VIII)
• Each factor will activate next based on numerical order
• These factors are produced by the liver and known by vitamin K
dependent factors
23. Anticoagulants (Indirect Thrombin Inhibitors)
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• Bind to antithrombin and enhance the inactivation of clotting
factor Xa
• These are classified into
• High Molecular Weight (unfractionated) heparin
• It inhibit thrombin formation and promote thrombin degradation
• Administered parenterally (IV or SC) not IM ↑ risk of
hematoma
• Low Molecular Weight (fractions) heparin (enoxaparin,
fondaparinux)
• They inhibit thrombin formation, but has no effect to degrade
formed thrombin
24. Anticoagulants (Indirect Thrombin Inhibitors)
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• Heparin efficacy is monitored through activated partial thromboplastin time
(aPTT) and partial thromboplastin time (PTT)
• Not required with LMW heparins
• Clinical use
• In emergency: deep vein thrombosis, pulmonary embolism, MI
• Can be used with pregnancy don’t cross placenta
• Adverse effects: bleeding, hemorrhagic stroke, thrombocytopenia (more with
HMW), osteoporosis with prolong use
• ANTIDOTE (PROTAMINE)
25. Anticoagulants (Direct Thrombin Inhibitors)
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• Dabigatran binds directly to thrombin inhibit fibrin clot formation
• Monitor efficacy through aPTT
• Clinical use: patients affected with heparin induced thrombocytopenia,
prevention of stroke, systemic embolism in AF patients
• Pharmacokinetics:
• Used orally
• Predictable pharmacokinetics allows better dosing than heparin
26. Anticoagulants (Coumarin Anticoagulants)
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• Warfarin inhibits Vit K dependent clotting factors synthesis in liver
• Warfarin efficacy is monitored with thrombin time (PT) and INR( 2-3)
• Clinical use: prophylaxis and treating of DVT in valvular diseases and AF,
PE
• Takes longer time to be activated consider using heparin as bridging
• Adverse effects: bleeding, hypersensitivity, hepatic dysfunction, skin
necrosis (Purple toe syndrome)
• Pharmacokinetic
• Drug-drug interaction CYP substrate, high protein binding
• Teratogenic avoid in pregnancy
• Narrow therapeutic index – dose adjusted based on INR
• ANTIDOTE Vit K (PHYTONADIONE)
27. Anticoagulants (Direct Oral Factor Xa
Inhibitors)
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• Rivaroxaban and Abixaban bind directly factor Xa ↓ fibrin clot formation
• Better than warfarin: used in fixed dose, no monitor is required, short half
life
• Clinical use: prevention of stroke in patients with AF (not valvular heart
diseases) and prevention of DVT after hip or knee surgery
• Adverse effects: bleeding
