Cardiac Meds: Antihypertensives & CHF

Cardiac Medications: Antihypertensives and CHF Medications

• Objectives include defining indications, MOA, adverse effects, pertinent PK/PD concepts, and PT implications for various medications.
• Includes Diuretics, Calcium channel blockers, Beta-blockers, Alpha-blockers, Dual alpha/beta blockers, Alpha-2 agonists, and Digoxin.
• Requires identifying potential adverse events or counseling points for patient cases.

Antihypertensive Drugs

• Some act at adrenergic receptors.

Antihypertensive Med Classes

• Diuretics, Beta-blockers, Alpha1 blockers, Dual alpha/beta blockers, and Alpha2 agonists are med classes.
• Types of diuretics are loop, thiazide, and potassium-sparing diuretics.
• Calcium channel blockers (CCB) is another med class.

Diuretics

• Recommended as initial therapy for all HTN patients.
• Act directly on the nephron to limit water and sodium reabsorption, increasing sodium and water excretion by kidneys.
• Forming more urine decreases the blood volume, making them inexpensive.

Types of Diuretics

• Loop diuretics act on the descending loop of Henle.
• Thiazide diuretics work on distal (early) tubules.
• Potassium-sparing diuretics affect distal (late) tubules.

Diuretics MOA and Examples

• Mechanism acts on renal tubules inhibiting Na+/K+/2Cl- reabsorption and preventing water reabsorption after electrolytes.
• Example drugs include furosemide (Lasix), hydrochlorothiazide (Microzide), and spironolactone (Aldactone).
• Adverse effects are dehydration and electrolyte imbalance (hypokalemia, hyponatremia).
• Supplemental K+ or K+ sparing diuretics reduce hypokalemia and metabolic alkalosis risk.

Diuretics: Adverse Effects

• Hypokalemia or hyperkalemia signs should be monitored, as both can trigger arrhythmias.
• Frequent potassium level monitoring is typical.
• Cardiac arrest can occur with either low or high potassium.
• Syncope may occur.

Diuretics: Hyperglycemia

• Can produce hyperglycemia, which is a concern if the patient has diabetes mellitus.
• Ability to control glucose levels may be adversely affected.
• Blood glucose level (normal: 70-130 mg/dl fasting) must be monitored.
• Signs of hyperglycemia: increased thirst, headache, blurred vision, difficulty concentrating, fatigue, and frequent urination.
• Patients should be educated on monitoring blood glucose and lipid levels.

Diuretics: Fluid Depletion

• Fluid depletion can cause orthostatic hypotension, dehydration → reflex ↑ CO and peripheral resistance → ↑ workload on the heart.
• This can also activate the renin-angiotensin cascade → further vasoconstriction.

Diuretics: Therapeutic Concerns

• Dehydration can cause significant confusion in the elderly.
• Orthostatic hypotension can lead to falls.
• Arrhythmias requires pulse check for irregularities.
• Drug-drug interaction with NSAIDs can make diuretics less effective; NSAIDs cause Na+ retention and decreased renal perfusion.

Calcium Channel Blockers

• MOA involves blocking Ca2+ entrance into vascular smooth muscles, reducing smooth muscle tone and vasodilation.
• Reduces Ca2+ flux into myocytes.
• Decreases contractility and CO, reducing cardiac function and energy demands.
• Originally for treating cardiac disease like HTN, angina, and arrhythmia.
• Useful when beta blockers are contraindicated.
• Examples include amlodipine (Norvasc).
• Significant adverse effects are headache, dizziness, hypotension, and constipation.

Adrenergic Receptor Antagonists

• Including Alpha Receptor Antagonists and Beta Receptor Antagonists.
• Further classified into Non-selective, a1-selective, a2-selective, B1-selective etc...

Adrenergic Receptors - Agonist vs Antagonist

• Alpha 1 receptor agonists cause vasoconstriction, leading to anti-hypotensive effects and nasal decongestion. Antagonists favor peripheral vasodilation to treat hypertension.
• Alpha 2 receptor agonists inhibit brainstem vasomotor centers, leading to anti-hypertensive and anti-spasticity effects. Antagonists have no significant clinical use.
• Beta 1 receptor agonists cause cardiac decompensation. Beta 1 receptor antagonists: treat hypertension, arrhythmia, angina pectoris, prevention of reinfarction.
• Beta 2 receptor agonists prevent bronchospasms. Antagonists have no significant clinical use.

Beta-Adrenoceptor Blockers

• Act as adrenoceptor antagonists used to treat cardiovascular dysfunction: HTN, angina, arrhythmia, post-MI survival.
• Act as competitive antagonists of beta-adrenoceptors, causing negative inotropic and chronotropic effects.
• They exert a central inhibitory effect on sympathetic activity, reducing peripheral vascular resistance.
• Some are selective or nonselective for beta-adrenoceptors.
• Nonselective beta-blockers block both β₁- and β₂-adrenoceptors.
• Selective beta-blockers primarily block β₁-receptors.

Beta Blocker MOA

• Beta blockers reduce sympathetic influence, preventing normal ligand binding and competing for the site.
• Decreases HR, contractility, and conduction.

Beta 1 +2 Receptor Antagonists

• Target beta receptors are located in the heart (Beta 1) and bronchiole smooth muscle (Beta 2).
• Response when beta receptors are stimulated: B-1 ↑ HR and Contractility; B-2: Smooth muscle relaxation resulting in bronchodilation.
• Drugs primarily for B-1 antagonism reduce HR (rate) and contractility (strength of contraction) and workload of the heart.
• Useful for HTN and angina pectoris, as negative chronotropic and ionotropic effects reduce workload on the heart and O2 demand.

Non-Selective Beta Blockers

• These end in "lol"; see Carvedilol (Coreg) and Propranolol (Inderal).
• Related to receptor blocking action and causes: Bronchoconstriction, Bradycardia = potential heart block, Reduced exercise capacity/tolerance.
• Can trigger arrhythmia, angina, Ml with abrupt withdrawal.
• Other side effects are dizziness, OH, depression, fatigue, and sexual dysfunction.

Cardioselective Beta Blockers

• These end in "lol" and are Beta -1 specific
• Examples are Atenolol (Tenormin) and Metoprolol (Lopressor).
• Selectively block β -1 receptors without causing bronchoconstriction.
• Adverse effects: Same as nonselective but without pulmonary effects.

Beta Blockers: Therapeutic Concerns

• Depress HR and CO during exercise, reducing exercise tolerance.
• The HR indicator of patient's response exercise cannot be used.
• Orthostatic hypotension requires positional BP check with MD notification if systolic BP is < 90 mm Hg or HR < 60 bpm.
• Masks hypoglycemia symptoms in individuals with diabetes and may cause development of DM in individuals with HTN.

Alpha-1 Blockers

• These end in “azosin”.
• MOA reduces sympathetic tone of blood vessels = vasodilation = decreases peripheral vascular resistance (PVR).
• Selective α₁-blockers: doxazosin (Cardura), prazosin (Minipress).
• Used to lower BP by lowering PVR, reduces LDL and triglyceride levels.
• The medication is typically used as "add-on" drugs to reduce BP medication.
• Adverse effects are postural hypotension (OH), nasal stuffiness, reflex tachycardia, and arrhythmia.

Alpha-1 Blockers: Therapeutic Concerns

• First-dose syncope leads to significant drop in BP after initial dose.
• Bedtime dosing may alleviate this issue.
• Always take BP and watch for OH signs.
• FALLS precaution!
• Reflex increase in HR: Can cause angina in patients with poor cardiac perfusion.
• Increased incidence of Congestive Heart Failure is possible.
• Must be aware of S/S Congestive Heart Failure.

Dual Alpha- and Beta-Blockers

• Beneficial for individuals who have increased PVR with pure Beta-blockers.
• Examples of nonselective α₁- and β₁- receptor antagonists: labetalol (10:1 beta to alpha blockade) and carvedilol (4:1 beta to alpha blockade).
• Adverse effects are similar to those of beta-blockers and alpha-blockers.

Antihypertensive and Antihypotensive

• These refer to different mechanisms and outcomes.
• Alpha 1 antagonist = antihypertensive
• Alpha 1 agonist = antihypotensive (↑ BP)
• Alpha 2 agonist = antihypertensive (↓ BP)

Alpha Agonists

• Alpha₁ receptor agonists cause nasal congestion (pseudoephedrine (Sudafed), phenylephrine (Sudafed PE)).
• Vasoconstrict mucosal membranes.
• Alpha₂ receptor agonists decrease spasicity (tizanidine (Zanaflex)) and antihypertensive (clonidine, guanfacine, methyldopa).

Central-Acting α₂ Agonists

• Central-Acting α₂ Agonists treat HTN; Clonidine (Catapres), Guanfacine, Methyldopa
• Mechanism works on presynaptic neurons in CNS which reduces NE production and peripheral resistance, renal vascular resistance, HR, BP.
• Common adverse effects are dizziness, drowsiness, fatigue, and headache and reserved for resistant HTN.
• Concerns with this class: Possible orthostatic hypotension, particularly in the elderly, increases falls risk, rebound hypertension.
• Should be critically tapered after use.

Additional Therapeutic Concerns of Antihypertensive Agents

• Orthostatic hypotension can lead to syncope and falls.
• Educate patients about rising slowly and performing LE exercises to improve peripheral circulation.
• Monitor BP in supine, sitting, and standing positions.
• Assess the frequency of nighttime bathroom trips.
• Dehydration affects BP; educate patients about adequate hydration and offer water during PT sessions.
• Caution with heat modalities due to vasodilation, which can cause syncope.

Therapeutic Concerns About Antihypertensive Agents

• Beta-blockers prevent the heart from responding to increased activity demand.
• HR should not be used to determine patient's activity tolerance; use Borg Rate of Perceived Exertion (RPE).
• Increase activity no more than 20 bpm over resting heart rate.
• Diuretics can deplete electrolytes: K+ depletion, muscle fatigue, cramping, arrhythmia, dehydration, hypovolemia, and compromised thermoregulation.
• Polypharmacy is common due to HTN's comorbidity with other conditions like DM, PVD, CAD, CHF, and kidney disease.

Congestive Heart Failure

• Heart can't pump a sufficient supply of blood.
• Clinical manifestations is caused by inadequate pump performance of either the myocardium or the heart valves.
• CHF is chronic can include: structural changes, reduced cardiac output, Cardiac hypertrophy, lower stroke volume.
• No cure to the disorder. The patient will need a heart transplant or death.

Previously Discussed Medications

• HF specifics includes Diuretics.
• Furosemide provides symptom relief.
• Can be a combo loop with Thiazide diuretic or Aldosterone antagonists (AKA: potassium sparing diuretics) to prove mortality benefit.
• Beta-blockers are specific to HF treatment and proves patient mortality at target doses.
• Other medication classes to treat HF will be discussed during the Renal System unit in a few weeks.

Digoxin

• Derived from foxglove plant.
• Only if the symptoms are not controlled on other therapy; does not reduce mortality.
• inhibits Na+/K+ ATPase pump in myocardial cells leading to higher intracellular sodium and higher Ca2+ contractility.

CHF: Goals and Corresponding Medications

• Diuretics can help edema and congestion.
• Positive inotropic drugs (digoxin) increase contractility
• Vasodilators can lower preload and afterload.
• Outcomes improve QoL by↓ decreasing fatigue/SOB, reducing hospitalizations, and prolonging survival

Digoxin: Therapeutic Concerns

• Narrow Therapeutic Index means toxicity can occur even when concentration in therapeutic range.
• Signs of Toxicity includes hypokalemia, hypomagnesaemia, hypercalcemia, MI, hypoxemia, acid-base imbalance.
• GI Symptoms if toxic: nausea, vomiting, diarrhea, abdominal pain, anorexia.
• CNS: blurred vision, confusion, lethargy.
• Cardiac: arrhythmia, which results from increased intracellular calcium = increased cardiac contractility.
• Mainly cleared by kidneys, so watch in individuals with impaired renal function and considered a medical emergency!