Pharmacological Treatment Options for Coronary Artery Disease #2
Molly Roberts, PharmD Candidate 2007
ACEI / Morphine / Antithrombotic Agents / LDL-C Lowering Therapy / GP IIb/IIIaInhibitors
Product Availability
Generic (Brand) /
- benazepril (Lotensin)
- captopril (Capoten)
- enalapril (Vasotec)
- fosinopril (Monopril)
- lisinopril (Prinivil, Zestril)
- moexipril (Univasc)
- perindopril (Aceon)
- quinapril (Accupril)
- ramipril (Altace)
- trandolapril (Mavik)
- enalaprilat (parenteral)
- Capsule-SR: (Kadian)
- Injection
- Infusion
- Solution
- Suppository
- Tablet-CR: (MS Contin)
- enoxaparin (Lovenox)
- daltiparin (Fragmin)
- ardeparin (Normiflo)
- rosuvastatin (Crestor)
- pravastatin (Pravachol)
- lovastatin (Mevacor)
- simvastatin (Zocor)
- atorvastatin (Lipitor)
- fluvastatin (Lescol)
- abciximab (ReoPro)
- tirofiban (Aggrastat)
- eptifibatide (Integrelin)
Mechanism
of Action / ACE inhibition prevents the conversion of angiotensin I to angiotensin II which is a potent vasoconstrictor. Decreased angiotensin II decreased vasopressor activity and decreased aldosterone secretion / Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression / Potentiates the action of antithrombin III and thereby inactivates thrombin (as well as activated coagulation factors IX, X, XI, XII, and plasmin) and prevents the conversion of fibrinogen to fibrin; heparin also stimulates release of lipoprotein lipase (lipoprotein lipase hydrolyzes TG to glycerol and free fatty acids). / Competitive HMG-CoA reductase inhibitor that decreases intracellular cholesterol levels through reversible inhibition of HMG-CoA reductase activity. This reduction leads to an increased LDL receptors and improved clearance of LDL. It also blocks the production of LDL by inhibiting the synthesis of VLDL in the liver / Inhibits the glycoprotein IIb/IIIa receptor, which is the final common pathway for platelet aggregation
EFFICACY
(Indication/Use, Clinical Data Support) / ACEI use is recommended in all patients with CAD who also have diabetes and/or LVSD (Class I Recommendation, Level-A Evidence)
ACEI use is also recommended in all patients with CAD or other vascular disease (Class IIa Recommendation, Level-B Evidence) / Effective in the relief of moderate to severe acute and chronic pain; relief of MI; relief of dyspnea of acute LV failure and pulmonary edema / Studies have shown a lower incidence of MI or death among patients treated with both lmw heparin and aspirin when compared to aspirin alone.
Advantages of lmw heparin over unfractionated heparin include high bioavailability, long plasma t ½ , ease of administration and predictable pharmacokinetic profile. In addition, no need to monitor the PTT when using lmw heparin. / The LDL-C treatment goal is <100mg/dL. Persons with established CAD who have a baseline LDL-C 130mg/dL should be started on a cholesterol-lowering drug simultaneously with therapeutic lifestyle changes and control of nonlipid risk factors. (Class I Recommendation, Level-A Evidence)
Most potent: rosuvastatin
Least potent: fluvastatin
Not met. by P450: pravastatin
Only statins shown to reduce MI:
- Pravastatin*+
- Simvastatin*
- Lovastatin
+proven to reduce risk of stroke / A platelet GP IIb/IIIa receptor antagonist should be administered, in addition to ASA and heparin, to patients in whom catheterization and PCI are planned. The GP IIb/IIIa antagonist may also be administered just prior to PCI.
These agents reduce early death and MI in unstable angina, with the greatest benefit shown in high risk patients in whom PCI is planned (PRISM trial)
SAFETY
(Major Drug Interactions,
Pre-cautions, Contra-indications,
Adverse Effects,
Pregnancy Risk Category) / DI: alcohol, diuretics, K-containing medicines
CI: angioedema related to previous treatment with an ACEI, bilateral renal artery stenosis, pregnancy (2nd and 3rd trimesters)
AE: dry cough, headache, dizziness
Pregnancy: C (1st)/D (2nd & 3rd) / Do Not Use With Alcohol
Precautions: CNS depression, drug abuse, hepatic/renal impairment, obesity, thyroid dysfunction, respiratory disease
CI: increased intracranial pressure; severe resp. depression; acute/severe asthma
AE: hypotension, bradycardia, drowsiness, dizziness, pruitus, nausea, constipation
Pregnancy: C/D / DI: drugs which affect coagulation/platelet function
Precautions to watch for: bleeding, HIT, hyperkalemia
CI: severe thrombocytopenia, uncontrolled active bleeding, suspected intracranial hemorrhage
AE: chest pain, thrombosis, vasospasm, fever, headache, chills, bruising, hemorrhage
Pregnancy: C / DI: avoid Grapefruit juice when taking atorvastatin, lovastatin, or simvastatin
Precaution: rhabdomyolysis
CI:active liver disease, pregnancy
AE: very few, headache, GI upset
Pregnancy: X / Precautions: known thrombocytopenia, concomitant warfarin use, hemorrhagic retinopathy
CI: active internal bleeding, CVA in past 30 days, uncontrolled HBP, concomitant use of another GP IIb/IIIa inhibitor
AE: hypotension, chest pain, nausea, bleeding, back pain
Pregnancy: B/C
ACEI / Morphine / Antithrombotic Agents / LDL-C Lowering Therapy / GP IIb/IIIa
Inhibitors
Dosage & Administration
(Include renal and/or hepatic adjustments) / Dosing varies/patient, the following are dosage ranges:
benazepril
- 10-40mg QDay
- 12.5mg-100mg up to TID
- 2.5mg-40mg QDay
- 10-40mg QDay
- 10-40mg QDay
- 7.5-30mg QDay
- 4-16mg QDay
- 10-80mg QDay
- 2.5-20mg QDay
- 1-4mg QDay
- 1.25mg Q6hrs into a vein
The following are usual doses:
Oral: 10-30mg Q3-4 hrs
IM: 5-20mg Q3-4 hrs
Rectal: 10-20mg Q3-4 hrs
IV: 2.5-5mg Q3-4 hrs
Clcr 10-50mL/min: Admin 75% of normal dose
Clcr <10mL/min: Admin 50% of normal dose / Unstable Angina:
Initial bolus of 60-70 units/kg (max 5,000 units), followed by an initial infusion of 12-15 units/kg/hr (max 1,000 units/hr) / Dosing depends on baseline LDL, the following are dosage ranges:
rosuvastatin (Crestor)
- 10-40mg QDay in evening
- 10-80mg QDay in evening
- 20-80mg QDay in evening
- 5-80mg Qday in evening
- 10-80mg QDay in evening
- 20-80 mg QDay in evening
Renal impairment:
dose should be cut in ½
eptifibatide: IV only - bolus of 180 μg/kg/min followed by an infusion of 2.0 μg/kg/min – administer with ASA and heparin
Monitoring
(Efficacy and Toxicity Parameters) / Efficacy:
BUN, serum creatinine, renal function, WBC, potassium
Toxicology:
Hypotension, bradycardia, hyperkalemia / Efficacy:
pain relief, respiratory/mental status, BP
Toxicology:
Sx of respiratory depression, miosis, hypotension, bradycardia, apnea, and pulmonary edema / Efficacy:
Platelet count, hemoglobin, hematocrit, signs of bleeding, aPTT
Toxicology:
Bleeding / Efficacy/Toxicity:
Lipid levels after 2-4 weeks of therapy; LFT, CPK / Efficacy:
aPTT (due to concomitant use of heparin), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products
Toxicology:
Bleeding transfusion requirements, signs of hypersensitivity reactions, guaiac stools
Patient Education / Captopril, enalapril, lisinopril, moexipril: take on an empty stomach
Ramapril: if trouble swallowing capsule, you may open the capsule and mix it with applesauce, water or apple juice.
Do not use potassium supplement or salt substitutes without telling your doctor. May cause dizziness, headache, or a cough. Report any chest pain, mouth sores, fever/chills, or swelling of extremities, face, mouth, or tongue. / May cause physical &/or psychological dependence. While using this medication, do not use alcohol and maintain adequate hydration. May cause itching, hypotension, dizziness, drowsiness, blurred vision, vomiting or constipation. Report chest pain, slow or rapid heartbeat, acute dizziness, or persistent headache / This medication can only be administered by injection or infusion. You may have a tendency to bleed easily following this medication – use caution to prevent injury. Report immediately chest pain, difficulty breathing, unusual bleeding or bruising, blood in stool, urine or vomitus, bleeding gums / May take these medications without regard to food.* It is best to take them in the evening. You will need laboratory evaluation during therapy. The most common SE is a headache. Report unresolved diarrhea, unusual muscle cramping or weakness. Do not get pregnant during therapy.
*Lovastatin should be taken with evening meal / This medication can only be administered IV. You will have a tendency to bleed easily following this medication – use caution to prevent injury. If bleeding occurs, apply pressure to bleeding spot until bleeding stops completely. Report unusual bleeding or bruising, blood in stool, urine or vomitus, bleeding gums, or vision changes
Cost
(1-month) / Lisinopril 2.5mg #30: $12.99
Mavik 1mg #30: $37.93
Captopril 12.5mg #100: $12.99 / Lovenox: 30mg/0.3mL #3: $210.99 / Atorvastatin 10mg #30: $68.99
Crestor 5mg #30: $93.56
References
(Guidelines, Drug Info Sources) / ACC/AHA guidelines
Lexi-Comp
/ ACC/AHA guidelines
Lexi-Comp
/ ACC/AHA guidelines
Lexi-Comp
/ ACC/AHA guidelines
Lexi-Comp
/ ACC/AHA guidelines
Lexi-Comp
Molly Roberts, PharmD Candidate 2007Pharmacotherapy Presentation – Pharmaceutical Care Rotation
University of MarylandSchool of PharmacyHappy Harry’s PharmacyPatientCareCenter, Perryville, MD