Cardiovascular Flashcards
Stage I (SBP 140-159 & DBP 90-99) HTN: med used
- Diuretics: thiazide-type
- May consider angiotensin-converting enzyme (ACEI), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), or combination
Stage II (SBP greater than or equal to 160/ DBP greater than or equal to 100) HTN: meds used
- Two-drug combination: thiazide-type & ACEI, ARB, BB, CCB
Heart Failure Stage A: meds used
ACEI are drug of choice
ARBs are considered but more expensive
Heart Failure Stage B: Meds used
ACEI in all patients, ARBs for those who cannot tolerate ACEI
BB in most
Heart Failure Stage C: Meds Used
ACEI and BBs (nonselective) in all patients
Diuretics, digoxin
Spironolactone
Heart Failure Stage D: Meds Used
Sacubitril/Valsartan (Entresto) in lieu of ACE or ARB
Inotrope: dobutamine
Ventricular assist device, transplantation, hospice
ACE Inhibitors: Pharmacodynamics
Inhibition of angiotensin-converting enzyme (ACE) activity results in decreased production o both angiotensin II and aldosterone
Can lower vascular resistance without decreasing CO or GFR
Does not produce reflex tachycardia
Strong evidence for CV & cerebrovascular risk reduction, HF, & slowing renal disease. Improves oxygenation to heart muscle, decreases inappropriate remodeling of heart muscle after MI or HF, reduces effects of diabetes on kidneys
Improves insulin sensitivity, does not affect glucose metabolism or raise serum lipid levels.
ACE Inhibitor: Clinical Uses
Younger caucasian patients:
- Patients w/ angina: prevent formation of AT II & decreases pulmonary vascular resistance by decreasing retention of NA & water & reduces extracellular fluid & preload
- Patients w/ diabetes: prevents or slows neuropathy
- After MR or HF, for ventricular remodeling
Not as effective in African American patients- when combined with diuretic, race no longer an issue
ACE Inhibitors: ADRs
3-4x greater risk of angioedema in African Americans & Asians
Dry cough (bradykinin-mediated), hypotension, loss of taste, angioedema, blood dyscrasias, teratogenicity, hyperkalemia, acute renal failure, cholestatic jaundice, pancreatitis, rash
ACE Inhibitor: Monitoring and Patient Education
Monitoring:
- Possible orthostasis within 1 hour of admin. when starting & with each dosage change
Patient education:
- Do not double dose if one is missed
- Hypotension most common ADR
- Cough common with older-generation agents
Function of RAAS (Renin-Angiotensin-Aldosterone System)
Regulator of BP and determinant of target-organ damage
It controls fluid and electrolyte balance through coordinating effects on the heart, blood vessels, and kidneys
Angiotensin II Receptor Blockers (ARBs): Pharmacodynamics
Prevent binding of AT II to receptors in kidney, brain, heart, and arterial walls
Inhibit the RAAS and cause fall in peripheral resistance
Evidence supports use in kidney disease until late stage and HF, but not all forms are renal protective like ACEI
No bradykinin-mediated cough like with ACEI
Considered alternatives for patients who cannot tolerate ACE or become resistant
Many combined with HCTZ
ARBs: ADRs, Monitoring, and Patient Education
ADRs:
- Similar to ACEIs but typically no problem with cough
Monitoring:
- Like ACEI, orthostasis with dose changes
Patient Education:
- Do not double dose if one is missed
- Hypotension most common ADR
Direct Renin Inhibitors (DRI)- Alsikiren (Tekturna): Pharmacodynamics
Works on the RAAS
Can be used for HTN, awaiting word on HF; not same MI indication as ACEI or ARB
Does not have the same renal protective properties as ACEI
For example, ACEI must stop when creatinine rises
Same issues in pregnancy, perhaps fewer issues with K+ and cough
Neprilysin Inhibitors (New Drug Class)
Sacubitril/valsartan (Entresto) decreases hospitalizations & death in chronic HF
- Ejection fraction (EF) < 40%
Taken in place of ACE or ARB
Not given with BBs, such as carvedilol
Increases renal blood flow & improves diuresis
Require 36-hour washout between ACE/ARB/BB
Sometimes called “game changer medication”
Calcium Channel Blockers (CCBs): Pharmacodynamics
Functionally act as vasodilators, lowering calcium influx into smooth muscles
First choice for African Americans with HTN
- can be used as add-on medications for others
Two classes:
- Type I - Non-dihydropyridines
- Type II - Dihydropyridines
CCB Type I
Non-dihydropyridines
Affect conduction through the atrioventricular (AV) node and have negative chronotropic effects
- Used in treating supraventricular tachycardia
- Diltiazem (cardizem), verapamil (Calan)
CCB Type II
Dihydropyridines
Do not affect conduction through the AV node
- Nifedipine (procardia), amlodipine (Norvasc), felodipine (Plendil)
CCB: Metabolism, ADRs, Monitoring
Metabolized by the liver, CYP450 3A4
ADRs:
- very constipating and can cause dizziness, HA, edema, rash, and gingival hyperplasia
Monitoring:
- Verapamil has strongest negative inotropic effect and should be avoided in patients with HF
- CCB/ACE combination decreases peripheral edema by 50% vs high-dose CCB alone
CCBs: Patient Education
Pregnancy Category C
Avoid NSAIDs, alcohol, being in a jacuzzi alone
GERD symptoms get worse because of decrease esophageal tone
Cardiac Glycosides: dose
Serum concentrations greater than 1 mg/mL increase mortality
- Initiate therapy at the lowest dose possible
Cardiac Glycosides- Digoxin: pharmacodynamics
Highly selective inhibitor of adenosine triphosphatase (ATPase) system
- Inhibition of this pump results in sodium & calcium buildup inside the cell, which leads to increased contractility of heart muscle
New research shows it may increase mortality in women
Cardiac Glycosides- Digoxin: Use, Half-Life, Drug Interaction
Benefits are best in patients with severe HF, enlarged heart, & third heart sounds, & in patients who do not respond to ACEI & BBs
Well absorbed orally
Not extensively metabolized, excreted unchanged by kidneys
Half-life is 36-48 hours
- In the absence of oral or IV loading, steady state is achieved in four half-lives or 1 week
- Reduced clearance of digoxin with drug interaction- Quinidine, amiodarone, verapamil, diltiazem
Cardiac Glycosides- Digoxin: ADRs
GI most common: anorexia, N/V, diarrhea
CNS: fatigue, disorientation, depressio, hallucinations, visual disturbances (yellow vision & green halos around lights)
Toxicity: atrial arrhythmias/tachycardia in children
Cardiac: bradycardia, PVCs, junctional & atrioventricular (AV) block arrhythmias, & bigeminy
Avoid using in patients with normal left ventricular systolic function
Cardiac Glycoside- Digoxin: Monitoring and Patient Education
Monitoring:
- Diagnosis of toxicity is based on both clinical & lab data
- Toxicity commonly occurs with serum levels greater than 2 mg/mL
- Monitor Potassium levels (it can cause high potassium)
Patient Education:
- Take at same time each day
- Do not double dose
- Monitor for signs of toxicity
- Take pulse, hold for HR less than 60 or greater than 100 bpm
Absolute Refractory Period
Regardless of the strength of a stimulus, the cell cannot be depolarized
Relative Refractory Period
Stronger-than-normal stimulus can induce depolarization
Refractoriness
State of the cardiac cell which determines depolarization
Damaged heart cells may maintain a constant rate of refractoriness or may not be refractory at all
Class IA: Sodium Channel Blockers
Lengthen the duration of action potential (slows HR)
Class IB: Sodium Channel Blockers
Shorten the duration of action potential
Class IC: Sodium Channel Blockers
Minimally increase action potential
Class II: Beta blockers
Reduce adrenergic activity in the heart
Sotalol: considered a class II and III drug
Class III: Potassium Channel Blockers
Prolong effective refractory period and reduce speed of conduction
Amiodarone
Class IV: Calcium Channel Blockers
Block influx of calcium, reduce contractility (negative inotropism), decrease SA and AV code conduction
Significantly reduce afterload but little effect on preload
Verapail, diltiazem, bepridil
Beta Adrenergic Blockers: Pharmacodynamics
Various types include nonspecific beta antagonists, selective beta antagonists, and those with or without intrinsic sympathomimetic activity (ISA)
- In post-MI patients, cardioselective agents without ISA are preferred
- Some are used as antiarrhythmics
- Drugs with ISA may help avoid a decrease in cardiac output (CO) and HR. May be preferred for patients who experience bradycardia with other BBs
More effective in African Americans & older patients
BBs may not be abruptly withdrawn, because it will increase beta receptor sensitivity
No longer first-line HTN drug choice
Amiodarone: Pharmacodynamics/kinetics
Class III antiarrhythmic
Onset of action: oral- 2 days to 3 weeks
Duration of action: 7 to 50 days
Excreted in feces, 1% urine
Dosing: watch out for use in grapefruit juice
- Ventricular arrhythmias: 800-1600 mg BID for 1-3 weeks, then decreased to 300-400 mg BID, maintenance 400 mg/day
Amiodarone: ADRs, drug interaction
ADRs:
- Thyroid, neurological, blue skin discoloration, bradycardia, lung damage not evident until advance
Many drug interactions
Monitoring and Patient Education for all Antiarrhythmics
Monitoring:
- Potassium, blood urea nitrogen (BUN), creatinine, therapeutic drug levels
- ECG
Patient Education:
- Take exactly as prescribed; do not double dose
- Be aware of food-drug interactions
- Monitor HR for regularity of rate and rhythm
- Monitor BP at home
Nitrates: ADRs
HA, orthostatic hypotension w/ potential for syncope & tachycardia (direct extensions of therapeutic vasodilation)
HA may be severe & persists in up to 50% of patients
Hypotension may lead to decrease in diastolic filling pressure & tachycardia may lead to decrease in diastolic filling time, which may lead to myocardial ischemia, arrhythmias, and rebound HTN
Contact dermatitis can occur with transdermal patches
Nitrates: Drug Interactions
Concurrent use with vasodilators or with erectile dysfunction drugs sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra) contraindicated
Additive hypotension with antihypertensives, alcohol, BBs, CCBs
Nitroglycerin: Use, & Dosing
Clinical Use:
- Acute angina attack (use NTG)
- —-sublingual NTG, a short-acting form, 0.4-0.6 mg every 5 minutes for up to 3 doses
- Stable or Predictable angina (use isosorbide):
- —-Isosorbide dinitrate: 10-40 mg orally 2-3 times daily; sustained-release form 40-80 mg daily
- —-Isosorbide mononitrate: dosing is 20 mg BID
- —-Eccentric scheduling to avoid development of tolerance
Nitroglycerin: Patient Education
Take the drug exactly as prescribed
- Eccentric dosing schedule is separated by 7 hours because of need to have nitrate-free period
- Take at 7 to 8 am and 2 to 3 pm rather than “usual” twice daily regimen
- A nitrate-free interval of 10-12 hours is needed
If anginal symptoms occur at night, have a daytime nitrate-free interval
Storage of NTG
- Adhere to the expiration date on bottle, usually 6 months
- Do not open bottle frequently or keep bottles of tabs nest to body (e.g., in a shirt pocket)
Peripheral Vasodilators: Pharmacodynamics
Hydralazine and Minoxidil
There are NOT used as first line HTN
Minoxidil is more potent vasodilator and has more dramatic compensator response
These drugs act by direct relaxation and dilation of arteriolar smooth muscle, decreasing peripheral vascular resistance
Peripheral Vasodilators: ADRs, Drug Interactions, & Dosing
ADRs: related to compensatory responses in the sympathetic nervous system & RAAS- tachycardia, increased cardiac contractility & output, sodium & water retention, HA
Drug interactions: additive effects with other antihypertensive; NSAIDs may decrease their effect
Dosing:
- HTN: hydralazine 25-100 mg QID; max dose 200 mg/day
Peripheral Vasodilators: Monitoring & Recommendations
Most patients should return for follow-up & adjustment of meds at monthly intervals or until the BP goal is reached.
Serum potassium & creatinine should be monitored at least one to two times per year
After BP is at goal & stable, follow-up visits can usually be at 3-6 month intervals
Co-morbidities such as HF, associated diseases such as diabetes, and the need for lab tests influence the frequency of visits
Other CV risk factors should be monitored & treated to their respective goals, and tobacco avoidance must be promoted vigorously
Low-dose aspirin therapy should be considered only when BP is controlled because of increased risk of hemorrhagic stroke when BP high
Pathophysiology of Hyperlipidemia
Atherosclerosis is a major cause of CAD
Lipoproteins: all contain triglycerides (TGs), phospholipids, & cholesterol
- Low density (LDL), high density (HDL), very low density (VLDL), TGs
Exogenous pathway: involves absorption of lipids via intestine
Endogenous pathway: lipids originate from liver
Statins- HMG CoA Reductase Inhibitors: Pharmacodynamics
- Block synthesis of cholesterol in liver by competitively inhibiting HMG CoA reductase activity
- Decreases levels of LDL by 25-65%
- Modest decreases in TGs (10-40%) and very modest increases in HDL (5%-17%) may occur
- Pregnancy: old category X; fully contraindicated
Statins: CYP3A Interactions
- All statins (except fluvastatin & rosuvastatin) are metabolized at least in part by CYP3A
- CYP3A inhibitors may increase statin concentrations
- –Verapamil, diltiazem, azole antifungals, erythromycin, fluoxetine, nefazodone, protease inhibitors
- CYP3A inducers may decrease statin concentrations
- –Rifampin, phenytoin, phenobarbital
- Statins may also interact with other CYP channel substrates; for example cyclosporine
Statin ADRs
Common: HA, myalgia, fatigue, GI intolerance, flu-like symptoms
Myopathy: occurs in 0.2-0.4% of patients, some agents more likely
- Reduced by using lowest effective dose; cautiously combining statins with fibrates; avoiding drug interactions
Increase in liver enzymes NOT ENOUGH to warrant frequent lab tests
- Active liver disease is a contraindication; occurs in 0.5-2.5% of cases & is dose-dependent; serious liver problems are rare; manage by reducing dose or stopping until levels return to normal
Statins- HMG CoA Reductase Inhibitors: Dosing
Start with lower dose & increase, as needed, according to LDL response; absolute levels of LDL not as closely monitored now
Rosuvastatin most potent: 5-20 mg daily
Atorvastatin next most potent (Best ADR profile): 10 mg/day initially, increase no fewer than 2-4 weeks
Simvastatin: 20-40 mg/day
Lovastatin: (IR) 20 mg/day, (ER) 40-60 mg
Provastatin: 40 mg/day; pediatric dosing for children 8-13 years: 20 mg/day
Doses often are given traditionally in evening/bedtime
May need to decrease dose occasionally: when adding potentially interacting drug; profound drop in LDL
Statin: Monitoring and Patient Education
Monitoring:
- Lipid levels in 4-6 weeks then ever 3-4 months until controlled
- LDL levels guide dose increases
- LFTs before starting therapy & 3-6 months later only if suspected issues or underlying hepatic issues
Patient Education:
- Lifestyle changes (diet, exercise)
Fibrates- Fibric Acid Derivatives: Mechanism of Action (MOA)
Inhibition of cholesterol synthesis
Decreased triglyceride synthesis
Inhibition of lipolysis in adipose tissue
Decreased production of VLDL/increased clearance
Increased plasma & hepatic lipoprotein lipase (LPL) activity
Effects on lipids
- Decreases total cholesterol (TC), LDL, TGs
- Increases HDL
Fibrates- Fibric Acid Derivatives: Pharmacodynamics
Effective TG-lowering drugs that modestly lower LDL & raise HDL for only some patients
Work for patients with very high TG levels, such as patients with type 2 diabetes & with familial dysbetalipoproteinemia
These drugs do NOT produce substantial reduction in LDL, so are not appropriate as initial or monotherapy
Fibrates: Dosing, ADRs, Drug Interactions
Dosing:
- Gemfibrozil: 600 mg BID
- Micronized Fenofibrate: 67 mg QID, max 201 mg
- Clofibrate: 2 g daily in divided doses
ADRs:
- nausea, diarrhea, cholelithiasis, phototoxicity
Drug Interactions:
- Increased risk of hepatotoxicity and/or myalgias with concurrent statins and/or niacin
- Protein-binding displacement (e.g., warfarin)
Fibrates: Monitoring & Patient Education
Monitoring:
- Lipid levels in 4-6 weeks, then every 3-4 months until controlled
- LDL levels will drop when triglycerides drop
- LFTs before starting and PRN
Patient Education:
- Take as directed
- ADRs: constipation & flatulence
- Lifestyle changes (diet & exercise)
Bile Acid Sequestrants: Pharmacodynamics
By promoting an increase in bile acid excretion, they enhance conversion of cholesterol to bile acids by the liver & increase uptake of LDL
Bind with cholesterol in the intestine and are NOT metabolized by liver
Excreted in bound form in feces
May use with patient with active liver disease
Lower TC, LDL, and TG, and increases HDL, in theory
Bile Acid Sequestrants: Use
Strong record of efficacy & safety
Most useful for patients with moderately elevated LDL levels & low coronary heart disease (CHD) risk profile
Patients who are not able to reduce their LDLs with lifestyle modifications
Can be used together with fibrates
Bile Acid Sequestrants: ADRS, Dose, Drug Interactions
ADRs:
- GI- constipation, bloating, abdominal pain, unpleasant taste & texture; HA
- Reduced folate levels with long-term use
Dosing:
- Initial dose: one packet mixed with juice; never swallow in dry form
Drug Interactions:
- Interfere with absorption of other medications
Bile Acid Sequestrants: Monitoring and Patient Education
Monitoring:
- Lipid levels
- Bowel issues
Patient Education:
- Taken with meals mixed with 4-6 oz of fluid
- Other drug absorption impaired if taken at the same time
- ADRs: constipation, may need stool softeners
- Lifestyle changes (diet & exercise)
Niacin
- No longer approved by FDA for use in lipid management
- Previous touted effects on lipids (lower TC, LDL, TG, & elevate HDL)
- Increased risk CV events if taken at doses to change lipids. Adverse events STRONGER than any benefit
- OTC doses are not sufficient to lower LDL (flush-free have no CV effect)
- Does not raise enough of the HDL to counter the increase in CV events without evidence of benefit
- No evidence (yet) that actually increasing HDL is helpful
Ezetimibe (Zetia)
- Selectively inhibits intestinal absorption of cholesterol & related phytosterols
- Has been shown to reduce TC, LDL, & TG while increasing HDL-C
- No good outcome data yet, but most effective in combination with statin
- Dosing: 10 mg/day
- Pregnancy category C; not for children younger than 10 years of age
Thiazide Diuretics
- HCTZ, chlorthalidone, indapamide, metolozone
- High dose therapy (HCTZ greater than 50) has increased risk of hypokalemia, increase in uric acid levels, and serious CV outcomes; use in combination vs. pushing high doses
- Watch with patients with hyperlipidemia
Loop Diuretics
Potential for cross-sensitivity with sulfa
Furosemide, bumetanide, torsemide
Potassium Sparing Diuretic
Often used in combination with thiazide to reverse low potassium effect
Triamterene, Spironlactone, Eplerenone (Inspra)
Eplerenone (Inspra)- next generation aldosterone agent
- Potassium sparing, selective aldosterone blocker
Diuretics: ADRs
Hypotension, decreased GFR, hypokalemia/hyperkalemia, electrolyte abnormalities, metabolic alkalosis, hyponatremia
Diuretics: Metabolism and Cost
Major CYP3A4 substrate
- Decreased effects with NSAIDs
- Drug effects increase with grapefruit juice, azoles, CCBs
- Increases effects of ACEI, ARB, BB, potassium replacement
Cost:
- Approximately $110 to $125/month without superior outcomes
Diuretics: Monitoring & Patient Education
Monitoring:
- BP, HR, edema, weight gain, dyspnea, cough, urine output
- Prior to initiating therapy- BUN, creatinine, electrolytes (sodium, potassium, calcium, magnesium), uric acid, & glucose levels
- Ongoing monitoring of electrolytes
Patient Education:
- Take as directed early in day if there are urination issues
- Do not skip or double dose
- Monitor weight
- Must drink fluids!!
