Week 5: Heme

Introduction to Heme and Pharmacology

• Focus: Drugs affecting cholesterol and lipids in pharmacology class.

• Definition of hyperlipidemia: High lipid levels in blood.

• Importance of understanding normal serum levels to discuss drug effects.

Understanding Cholesterol and Lipids

• Cholesterol:

  • Necessary component of human cells.

  • Essential for forming steroid hormones and cell membranes.

  • Produced in cells and obtained through diet.

• Lipids classification:

  • Triglycerides:

  • Composed of three fatty acids and one glycerol molecule.

  • Primarily used for energy and metabolized in the body.

  • Phospholipids: Involved in cell membrane structure.

  • Cholesterol:

  • Exists in "good" (HDL) and "bad" (LDL) forms.

• HDL (High-Density Lipoprotein):

  • Transports cholesterol from tissues to liver for elimination.

  • Protective against cardiovascular diseases.

• LDL (Low-Density Lipoprotein):

  • Main molecule that transports cholesterol and associated with cardiovascular risk.

Cardiovascular Disease and Cholesterol Levels

• High serum lipid levels correlate with increased risk of cardiovascular disease, the leading cause of death in adults.

• Desirable lipid levels:

  • Total cholesterol: 150 - 200 mg/dL

  • Triglycerides: 40 - 150 mg/dL

  • LDL: < 100 mg/dL

  • HDL: 45 - 60 mg/dL

Risk Factors for Cardiovascular Disease

• Non-modifiable factors:

  • Genetics, age, sex.

• Modifiable factors:

  • Cigarette smoking.

  • Sedentary lifestyle.

  • High stress levels.

  • Hypertension.

  • Obesity.

  • Diabetes (manageable).

Hyperlipidemia and Treatment

• Hyperlipidemia: Elevated blood lipid levels.

• Treatment methods: Dietary modifications and medication if dietary changes are ineffective.

• Three classes of lipid-lowering agents:

  1. HMG-CoA inhibitors (Statins)

  2. Fibrates

  3. Cholesterol absorption inhibitors

HMG-CoA Inhibitors (Statins)

• Overview:

  • Statins lower cholesterol by inhibiting HMG-CoA reductase.

  • Prototype drug: Atorvastatin.

• Mechanism of action:

  • Decreases serum levels of LDL and triglycerides while increasing HDL.

  • Predominantly acts during hepatic metabolism, preferably taken at night.

• Cautions:

  • Contraindications include pregnancy and active liver disease.

  • Monitor liver function with tests like ALT and AST.

• Nursing implications:

  • Advise low-fat diet regardless of medication.

  • Report muscle tenderness (risk for rhabdomyolysis).

  • Do not co-administer with grapefruit juice.

• Monitoring:

  • Lipid profile requires fasting for 12 hours before a blood draw.

  • Monitor every 6-8 weeks initially, then every 3-6 months.

• Adverse effects:

  • Gastrointestinal symptoms (gas, pain, nausea, vomiting).

  • Muscle cramps and potential for liver failure.

Cholesterol Absorption Inhibitors

• Ezetimibe (Zetia):

  • Works by inhibiting cholesterol absorption in the intestines.

  • Often used in combination with statins.

• Adverse effects:

  • Headache, dizziness, abdominal pain, diarrhea.

  • Monitor cholesterol and liver function.

Fibrates

• Example: Fenofibrate.

• Mechanism:

  • Reduces triglycerides and LDL levels by inhibiting triglyceride synthesis in the liver and promoting triglyceride breakdown.

• Adverse effects:

  • Typically not listed; requires monitoring and assessment.

  • Important to adhere to a strict low cholesterol diet.

Coagulation and Hemostasis

• Cardiovascular system maintains blood in a liquid state:

  • Coagulation refers to blood forming a solid state (clotting) when necessary.

• Definitions:

  • Hemostasis: Blood stopping (clot formation after injury).

  • Thrombosis: Abnormal clotting in the blood vessels.

  • Bleeding disorders: Result from failure to clot.

Anticoagulants

• Function: Prevent new clot formation and the extension of existing clots.

• Main indication: Management of thromboembolic disorders.

• Adverse effects: Primary risk is bleeding.

• Types of anticoagulants:

  • Heparin:

  • Administered via IV or subcutaneously.

  • Monitored through aPTT (should be 1.5-2.5x control).

  • Antidote: Protamine sulfate (to reverse excessive anticoagulation).

  • Enoxaparin (Lovenox):

  • Low molecular weight heparin, monitored differently than heparin.

  • No specific antidote.

  • Warfarin (Coumadin):

  • Monitored via PT/INR (therapeutic range is 2-3).

  • Requires daily lab checks to establish therapeutic levels.

  • Antidote: Vitamin K (important to counsel patients about dietary vitamin K intake).

Managing Anticoagulant Therapy

• Educate patients about bleeding precautions:

  • Use soft toothbrushes, electric razors.

  • Report any signs of unusual bleeding (e.g., blood in urine/stool).

Antiplatelet Agents

• Function: Decrease platelet aggregation to prevent clot formation.

• Examples: Aspirin, Clopidogrel (Plavix).

• Mechanism:

  • Aspirin reduces risk of myocardial infarction (MI) and stroke, especially in patients with a history of vascular events.

  • Clopidogrel specifically blocks a receptor on platelets, reducing aggregation.

• Adverse effects:

  • Pruritus (itching), purpura (bruising), diarrhea, and potential for severe hematologic issues (e.g., thrombocytic purpura).

Conclusion

• Effective management of cholesterol levels and coagulation requires in-depth knowledge of various pharmacological agents and their implications for patient care. Regular monitoring for both efficacy and potential side effects is essential.