Module 6 short notes

Chapter 15: Adrenergic Agonists

Overview
- Adrenergic Agonists: Activate adrenergic receptors, mimicking the sympathetic nervous system - Uses: Treat heart failure, asthma, preterm labor.
- Receptor Specificity: Low doses activate specific receptors; high doses reduce selectivity (e.g., Albuterol).
Clinical Effects
- Alpha-1 Activation
- Use: Hemostasis, adjunct to local anesthesia, blood pressure elevation.
- Adverse: Necrosis from extravasation, reflex bradycardia.
- Alpha-2 Activation: Peripheral - Minimal clinical significance / Central: Reduces sympathetic outflow, relieves pain.
- Beta-1 Activation: Improves cardiac performance in HF, shock, AV heart block, and cardiac arrest / Adverse: Tachycardia, dysrhythmias, angina pectoris.
- Dopamine Activation: Enhances renal blood flow, use in shock to prevent renal failure / Enhances cardiac performance thru beta-1 receptors. .
Treatment of Anaphylactic Shock with Epinephrine
- Mechanism: Alpha-1 Vasoconstriction, increased BP, reduced glottal edema / Beta-1 Increased cardiac output / Beta-2 Bronchodilation.
Patient Education on Epinephrine Auto-Injectors
- Prescription: Immediate fill and timely replacement / Emergency Use: Immediate use for severe reactions, followed by medical attention.
Patient-Centered Care Across the Lifespan - Pregnant Women Use Albuterol in emergencies despite potential risks.

Specific Drugs: Adrenergic Agonists

- Epinephrine (Receptors Alpha-1, Alpha-2, Beta-1, Beta-2)
- Uses: Vasoconstriction, cardiac support, bronchodilation, anaphylaxis / AE: Hypertensive crisis, dysrhythmias, angina, extravasation necrosis, hyperglycemia.
- Drug Interactions: MAO inhibitors, tricyclic antidepressants, general anesthetics, alpha/beta-blockers.
- Norepinephrine (Receptor Alpha-1, Alpha-2, Beta-1) / Uses: Like epinephrine; no Beta-2 activation.
- Dopamine (Receptor Dopamine, Beta-1, Alpha-1 (high doses)
- Uses: Shock, HF / AE: Tachycardia, dysrhythmias, anginal pain, extravasation necrosis / Drug Interactions: MAO inhibitors, tricyclic antidepressants.
- Dobutamine (Receptor Beta-1) / Uses: Heart failure / AE: Tachycardia / Drug Interactions: MAO inhibitors, tricyclic antidepressants.

Chapter 16 Adrenergic Antagonists

Alpha Blockade
TX - Essential HTN: Lowers BP by vasodilation / BPH: Improves urine flow / Pheochromocytoma: Manages HTN from adrenal tumors / Raynaud's D: Enhances blood
flow to extremities.
Adverse Effects of Alpha Blockade

- Orthostatic Hypotension: avoid sudden posture changes. . - Na Retention & Increased Blood Volume: May counteract BP lowering
- Reflex Tachycardia: Increased HR effects; use w diuretics.
- Nasal Congestion: d/t nasal vessel dilation. - Alpha2 Blockade: Increases NE release, reflex tachycardia.
- Inhibition of Ejaculation: Reversible sexual dysfxn.

Properties of Individual Alpha Blocking Agents

- Prazosin: For HTN and BPH; causes vasodilation. - Phentolamine: Non-selective; for pheochromocytoma, tissue necrosis
- Terazosin and Doxazosin: Like prazosin, longer duration. prevention.
- Tamsulosin and Alfuzosin: Selective for prostate/bladder; minimal - Phenoxybenzamine: Irreversible, non-selective; for
BP effect. pheochromocytoma, reflex tachycardia risk.
Patient Education about Alpha1 Adrenergic Antagonists

- First Dose Hypotension: Take initial dose at bedtime to prevent dizziness.

- Monitoring: Teach self-monitoring of HR and BP.

Key Prescribing Considerations for Alpha1 Adrenergic Antagonists

- Goals: Manage HTN, alleviate BPH sxs / Monitoring: Regular HR and BP checks / High-Risk Pts: Avoid in those w hypersensitivity.

Beta-Adrenergic Antagonists (BLOCKERS)

Treatment

- Angina Pectoris: Reduces cardiac workload. - HF: Effective w carvedilol, bisoprolol, metoprolol.
- HTN: Less preferred d/t newer data. - Hyperthyroidism: Suppresses tachydysrhythmias.
- Dysrhythmias: Reduces excessive electrical activity. - Migraine Prophylaxis: Reduces frequency, intensity.
- MI: Reduces pain, size, mortality. - Performance Anxiety: Prevents beta1-mediated tachycardia.

Adverse Effects

Beta-1 Blockade: heart Beta-2 Blockade: lungs

- Bradycardia: Treat with isoproterenol or atropine. - Bronchoconstriction: Hazardous for asthma patients.
- Reduced Cardiac Output: Caution in heart failure patients. - Hypoglycemia: Risk for diabetes patients; prefer beta1-selective agents.
- Heart Failure: Monitor for symptoms like shortness of breath. - Neonates: Monitor for bradycardia and hypoglycemia.
- AV Heart Block: Avoid in pre-existing block.
- Rebound Cardiac Excitation: Taper off dosage gradually.

EX- Propranolol TX HTN, angina, dysrhythmias, MI.

- AE: Bradycardia, AV block, HF, rebound excitation, bronchoconstriction, hypoglycemia, CNS effects, neonatal effects.
Patient Education on Beta Blockers
- Masking Hypoglycemia: Teach alternative sxs.
- HF: Report sxs like SOB.
- Rebound Cardiac Excitation: Warn against abrupt discontinuation.
Black Box Warning - Abrupt Discontinuation increase risk of angina and myocardial infarction.
Intrinsic Sympathomimetic Activity (ISA) - ISA Beta Blockers (Pindolol; partial agonists) are preferred for bradycardia, not for myocardial infarction.
Vasodilation- Third-Generation Beta Blockers: Carvedilol, labetalol, nebivolol; dilate blood vessels.
Key Prescribing Considerations for Beta-Adrenergic Antagonists
- Goals: Manage HTN, angina, HF, dysrhythmias.
- Monitoring: Regular HR and BP checks.
- High-Risk Pts: Caution w HF, asthma, diabetes, depression, severe allergies.
- Minimizing AE: Gradually taper off, monitor sxs, use cardioselective drugs for asthma/diabetes, manage CNS effects w low lipid-solubility beta blockers.
Other Notes about Beta Blockers
- Beta-blockers prescribed for stage fright and test anxiety because they decrease the adrenergic surge that causes sxs assoc w anxiety.
- Beta-blockers can cause hypoglycemia because they block glucose production mediated by adrenergic activity.
- Beta-blockers can mask hypoglycemia because they prevent some s/s of hypoglycemia such as tachycardia, tremors, and anxiety.
 - Beta-blockers should be tapered off when discontinued. If stopped suddenly, rebound HTN can occur.

Summary Chapter 17: Indirect-Acting Antiadrenergic Agents

Purpose- Lower blood pressure by reducing norepinephrine (NE) in the CNS, decreasing peripheral adrenergic receptor activation.
Main Agents- Centrally acting alpha2 agonists primarily used for hypertension.
Mechanism of Action of Alpha2 Receptors: Located in CNS; reduces NE synthesis, leading to vasodilation and lower blood pressure.
Clonidine: HTN, severe pain, ADHD.
- How It Works: Activates CNS alpha2 receptors, reducing heart and blood vessel activity.
- Effects: Heart (Lowers HR and CO) / Vessels (Causes vasodilation, reducing BP)
- Adverse Effects:

- Drowsiness: Avoid hazardous activities initially. - Pregnancy: Avoid.

- Dry Mouth: Usually improves in a few wks. - Abuse: Potential for misuse among drug abusers.
- Rebound HTN: Risk if stopped abruptly.

- Key Patient Instructions:

- Dosing: Take most at bedtime d/t drowsiness. - Travel: Carry enough medication.
- Patch: Apply to hairless skin, change weekly, remove before MRI. - Side Effects: Manage drowsiness and dry mouth with gum/candy.
- Monitoring: Record BP daily. - Pregnancy: Not recommended; confirm you're not pregnant
-Discontinuation: Don’t stop abruptly.

** Methyldopa: Preferred for HTN during pregnancy due to safety profile. **

Lifespan Considerations
- Pregnant Women: Avoid Clonidine, Methyldopa preferred / Breastfeeding Women: Clonidine not recommended.
- Older Adults: Avoid centrally acting alpha-blockers in patients 65+ (BEERS).
Key Prescribing Points
- Goals: Lower BP & HTN
- Baseline Assessment: Check HR/BP/CV status / For Methyldopa check CBC and liver enzymes.
- Monitoring: Regularly check HR/BP, CBC, and liver enzymes.
- High-Risk Patients: Caution w bradycardia and CNS depressants / Avoid Clonidine in pregnancy / Methyldopa not for active liver dz pts.
- Evaluation: Monitor BP and HTN control.
- Minimizing AE: CNS Depression (Implement fall risk precautions) / Rebound HTN: Gradually stop Clonidine over 2-4 days / Abuse: Signs of misuse.

Chapter 37: Diuretics

Classification of Diuretics

1. Loop Diuretics (e.g., Furosemide) 4. Potassium-Sparing Diuretics: Aldosterone Antagonists (e.g.,

2. Thiazide Diuretics (e.g., Hydrochlorothiazide) Spironolactone) & Non-Aldosterone Antagonists (e.g., Triamterene,
3. Osmotic Diuretics (e.g., Mannitol) Amiloride)

Loop Diuretics - Furosemide (Lasix): TX Pulmonary edema, severe HF, HTN, renal impairment.
- MOA: Blocks Na & Cl- reabsorption in the loop of Henle / AE: Hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia, ototoxicity.
 - Special Considerations: Avoid in pregnancy, monitor closely in older adults.
Thiazide Diuretics - Hydrochlorothiazide (Microzide): TX HTN, mild to moderate HF, renal conditions.
- MOA: Inhibits Na & Cl- reabsorption in the distal convoluted tubule / AE: Like loop diuretics w/o ototoxicity.
- Considerations: Monitor electrolytes, especially potassium.
Potassium-Sparing Diuretics
- Spironolactone (Aldactone): TX HTN, edema, severe HF.
- MOA: Blocks aldosterone, promoting potassium retention and sodium excretion / AE: Hyperkalemia, endocrine effects (e.g., gynecomastia).
- Considerations: Avoid unnecessary use due to tumorigenic risk in animals.
- Triamterene and Amiloride:
- MOA: sodium-potassium exchange in the distal nephron / AE: Risk of hyperkalemia / Monitoring: Regular potassium checks necessary.
Summary of Key Points
- Loop Diuretics: Potent but riskier; monitor electrolytes closely.
- Thiazide Diuretics: Less potent, effective for hypertension; monitor potassium.
- Potassium-Sparing Diuretics: Moderate diuresis, focus on potassium balance; avoid hyperkalemia.

Chapter 38: Drugs Targeting RAAS

RAAS Drug Classes
1. ACE Inhibitors: Enalapril, Lisinopril, Ramipril / Tx: HTN, HF, diabetic nephropathy, post-MI / MOA: Block conversion of angiotensin I to angiotensin II.
2. ARBs: Losartan, Valsartan, Irbesartan / Tx: HTN, HF, diabetic nephropathy, CV event prevention / MOA: Block angiotensin II receptors.
3. DRIs: Aliskiren / Tx: Primarily HTN / MOA: Inhibit renin directly, reducing angiotensin I formation.
4. Aldosterone Antagonists:
-Eplerenone: Tx HTN, HF / MOA: Blocks aldosterone receptors.
- Spironolactone: Tx: Prevents diuretic-induced hypokalemia and treats hyperaldosteronism.
Physiology of RAAS
- Angiotensin Family: Includes Angiotensin I (inactive), Angiotensin II (active vasoconstrictor), and Angiotensin III (moderate activity).
- Actions: Vasoconstriction, aldosterone release, cardiac and vascular remodeling.
- Aldosterone Effects: Sodium retention, potassium excretion, impacts on cardiac and vascular health.
Clinical Considerations
- ACE inhibitors for HTN, HF, and renal protection. ARBs as alternatives. Aldosterone antagonists for potassium retention issues.
- AE: Hypotension, hyperkalemia, renal impairment. Specific issues like cough (ACE inhibitors) and gynecomastia (aldosterone antagonists).
- Monitoring: Renal function, electrolytes (especially potassium), blood pressure.
Clinical Relevance
- Indications: HTN, HF diabetic nephropathy, post-MI care.
- Monitoring: Regular assessment of renal fxn, electrolytes (especially potassium), and BP..
- Adverse Effects: Hyperkalemia, renal impairment, hypotension; Special considerations in pregnancy (avoid ACE inhibitors and ARBs).

Chapter 39: Calcium Channel Blockers (CCBs)

Table 39.1. Calcium channel blockers, classification sites of action and indications.

Classification. Sites of action. Hypertension. Angina. Dysrhythmias. Migraine. Others.

Dihydropyridines.
Nifedipine Arterioles. x x x
Amlodipine (Norvasc) Arterioles. x x
Felodipine Arterioles. x
Isradipine Arterioles. x
 Nicardipine Arterioles. x x
Nimodipine Arterioles. x
Nimodipine Arterioles. x
Non-Dihydropyridines.
Verapamil Arterioles/heart x x x X
Diltiazem Arterioles/heart x x x x

Mechanism: Prevent Ca ions from entering cells, primarily affecting the heart and blood vessels / Uses: HTN, angina pectoris, dysrhythmias.
- Safety Considerations: Controversies in patients with hypertension and diabetes.
Classification and Sites of Action
- Dihydropyridines: Act primarily on vascular smooth muscle (e.g., amlodipine).
- Nondihydropyridines: Act on both cardiac and smooth muscle tissues (e.g., verapamil, diltiazem).
Verapamil: Angina pectoris, essential HTN, dysrhythmias.
- Sites of Action: Acts on peripheral arterioles, arteries of the heart, SA node, AV node, and myocardium.
- Hemo Effects: Vasodilation, increased coronary perfusion, reduced HR, decreased AV nodal conduction, and decreased myocardial contractility.
- kinetics: Administered orally or intravenously, undergoes hepatic metabolism.
- AEs: Constipation, dizziness, facial flushing, headache, ankle/foot edema, bradycardia, AV block, decreased contractility.
- Drug Interactions: Interacts with digoxin, beta-blockers, and grapefruit juice.
Diltiazem: HTN, angina, dysrhythmias.
- Drug Interactions: Like verapamil, interacts with digoxin and beta blockers.
Dihydropyridines (e.g., Nifedipine)
- MOA: Acts mainly on vascular smooth muscle.
- Hemo Effects: Causes vasodilation, increases coronary perfusion without direct effects on HR or contractility.
- Uses: Angina pectoris, essential HTN (prefer sustained-release formulations to avoid reflex tachycardia).
- AE: Flushing, dizziness, headache, peripheral edema.
Summary of Key Prescribing Considerations
- Goals: Manage HTN, angina pectoris, and cardiac dysrhythmias.
- Monitoring: Assess BP, HR, liver and kidney fxn.
- High-Risk Pts: Avoid pts wi hypotension, sick sinus syndrome, and advanced AV block.
- AE: Manage common SE and monitor for serious cardiac effects and interactions w other meds.

Chapter 40: Vasodilators

Introduction to Vasodilators: Directly relax smooth muscles in arterioles/veins, leading to vessel relaxation; hydralazine, minoxidil, & sodium nitroprusside (emergency)
Selectivity of Vasodilatory Effects
- Hydralazine and Minoxidil: Selectively dilate arterioles.
- Sodium Nitroprusside: Dilates both arterioles and veins.
Hemodynamic Effects Based on Selectivity
- Arteriolar Dilators: Decrease cardiac afterload / Reduce cardiac work / Increase cardiac output and tissue perfusion.
- Venous Dilators: Reduce venous return / Decrease ventricular fill (preload) / Reduce force ventricular contraction /Decrease cardiac work, CO, tissue perfusion.
Therapeutic Uses: Essential HTN / HTN Crisis / Angina Pectoris / HF / MI
Adverse Effects Related to Vasodilation: Postural Hypotension - Minimizing Effect by lying down due to reduced influence of gravity.
Patient Education on Hypotension Risks
- Symptoms of Hypotension: Lightheadedness, dizziness.
- Advice: Sit or lie down if symptoms occur to prevent fainting.
- Prevention: Avoid abrupt position changes from lying or sitting to standing.
Key Prescribing Considerations
- Goal: Reduce BP in HTN, reduce afterload temporarily in HF pts.
- Baseline: Record weight and vital signs before starting therapy.
- Monitor: Patients should record daily BP, HR,, and those on minoxidil should also record daily weight.
- High-Risk Pts: Avoid use in pregnant patients if possible.
- Evaluating: Reduce BP, improvement in HF sxs (reduced dyspnea).
- Minimizing AE: Use low doses when combined w other antihypertensives to prevent hypotension. Caution pts to stand up slowly to avoid postural hypotension.

Chapter 41: Hypertension

Alpha1 Blockers (-sin) Beta Blockers (-olol) Combination Alpha + Beta Blockers

Untreated Hypertension Consequences: Heart dz / Kidney dz / Stroke

Treatment Benefits: Reduces BP / Lowers risk of long-term complications.
Challenges: Lifelong tx required / Nonadherence common
Blood Pressure Classification: Normal:<120 / <80 / Elevated: 120–129 / <80 / HTN: Stage 1 (130–139 / 80–89) / Stage 2 ( ≥140 / ≥90)
Types of Hypertensions: Primary (Essential) - No identifiable cause / Secondary - Identifiable cause that is possible to treat/cure
Diagnosis Procedure: Multiple BP readings across visits / Confirm high readings in both arms / Use ambulatory BP monitoring (ABPM)
Patient Evaluation Objectives: Identify HTN causes / Assess CV risk factors
Risk Factors for Hypertension: Target-organ damage (heart, kidney, etc.) / Major risk factors (smoking, inactivity, diabetes, etc.)
Diagnostic Tests: ECG, Urinalysis, Hemoglobin/hematocrit, & Blood tests for sodium, potassium, creatinine, etc.
Treatment Goals: Reduce CV and renal morbidity or mortality / BP target: SBP <130 mm Hg and DBP <80 mm Hg
Therapeutic Interventions: Lifestyle Modifications like Sodium restriction, DASH diet, Limit alcohol, Exercise, Healthy weight, Smoking cessation
Drug Therapy - Classes of Antihypertensive Drugs:

- Diuretics (Hydrochlorothiazide, Spironolactone) - RAAS Inhibitors: (ACE-prils), (ARB-sartans), Aliskiren (DRI), Eplerenone
- β-Blockers (-lol) (Aldosterone antagonist)
- Calcium Channel Blockers (-dipines, dilti-vera)

Determinants of Blood Pressure: Cardiac Output (HR, contractility, blood volume, venous return) / Peripheral Resistance (Arteriolar constriction)
Systems Regulating Blood Pressure: Sympathetic Nervous System, RAAS, Kidney
Antihypertensive Mechanisms
- Sympathetic Baroreceptor Reflex: Adjusts BP via heart and blood vessel stimulation
- RAAS Activation: Counteracts BP reduction; managed with β blockers, DRIs, ACEIs, ARBs, aldosterone antagonists
- Renal Regulation: Adjusts blood volume, targeted by diuretics
Sites of Drug Action

- Brain Stem: Clonidine suppresses sympathetic outflow - Vascular Smooth Muscle: Hydralazine causes vasodilation
- Cardiac β1 Receptors: Metoprolol reduces HR and contractility - Renal Tubules: Hydrochlorothiazide promotes diuresis
- Vascular α1 Receptors: Prazosin promotes vasodilation

Special Populations Considerations

- African Americans: Higher prevalence, respond well to diuretics and CCBs, less to β blockers and ACE inhibitors alone
 - Children/Adolescents: Avoid ACEIs/ARBs in sexually active young women due to fetal harm risk
- Older Adults: Start with low doses, gradual titration due to risk of orthostatic hypotension
Promoting Adherence

- Ed Pts: Explain risks and benefits - Simplify: Once or twice-daily dosing, consider combo pills
- Min. SEs: Report & manage SE - Support: Positive reinforcement, involve family, convenient appts,
- Collaborate: Involve pts in tx planning address cost concerns

Chapter 42: Heart Failure

Signs and Sxs: Reduced exercise tolerance, fatigue, dyspnea (pulm edema), wt gain (fluid retention) / Physical Signs Cardiomegaly, JVD, peripheral edema
Overview of Drugs Used to Treat Heart Failure: Diuretics, RAAS Inhibitors, Beta Blockers, & Inotropic Agents
Angiotensin-Converting Enzyme Inhibitors (ACEIs) / MOA: Inhibit ACE, reducing angiotensin II production and preventing vasoconstriction and aldosterone release
- Benefits: Improve sxs, reduce cardiac remodeling, lower mortality rates
- AE: Hypotension, hyperkalemia, cough, angioedema; contraindicated in pregnancy
Angiotensin II Receptor Blockers (ARBs) / MOA: Block angiotensin II receptors, providing similar benefits as ACEIs w/o increasing bradykinin levels
- Benefits: Improve sxs, decrease hospitalizations, reduce mortality
- Usage: Alternative to ACEIs in patients with intolerable cough
Angiotensin Receptor Neprilysin Inhibitor (ARNI - Sacubitril/Valsartan) / MOA: Combines ARB (valsartan) w neprilysin inhibitor (sacubitril) to enhance natriuretic
peptides and block harmful RAAS effects.
- Benefits: Reduces mortality, improves sxs, enhances quality of life
Aldosterone Antagonists (Spironolactone, Eplerenone) / MOA: Block aldosterone receptors, reducing sodium and water retention
- Benefits: Improve sxs, reduce hospitalizations, prolong survival
- AE: Hyperkalemia, gynecomastia (spironolactone); contraindicated in severe renal impairment
Beta Blockers / Role: Improve left ventricular function, reduce hospitalizations, prolong survival by blocking excessive sympathetic stimulation
Digoxin / MOA: Positive inotropic action by inhibiting Na+, K+,-ATPase, increasing myocardial contractility
- Benefits: Improves sxs and exercise tolerance / Limitations: Narrow therapeutic index, risk of toxicity, not first-line due to limited survival benefits
- AE of Digoxin: Cardiac Dysrhythmias (requires close monitoring) / GI disturbances, visual disturbances, fatigue
- Drug Interactions and Monitoring: Diuretics (Increase risk of hypokalemia and digoxin toxicity)
- Pharmacokinetic: Half-life 1.5 days, requires careful dosing and monitoring.
Key Prescribing Considerations: Goals: Manage sxs and improve o/c in HF pts / Monitoring: Regular assess of sxs, e-, renal fxn, and drug levels.
- High-Risk Pts: Avoid in severe dysrhythmias and renal impairment; caution in hypokalemia.
Management of Heart Failure - Stage C: Drugs to Avoid: Antidysrhythmics (except amiodarone, dofetilide), CCBs (except long-acting dihydropyridines), NSAIDs
(except when clinically indicated).
Chapter 43 - Antidysrhythmic Drugs
Classified into four Vaughan Williams classes:
Class I: Sodium Channel Blockers: Effective for ventricular and some supraventricular arrhythmias.
- Mechanism: Sodium channel blockers
- Primary Effect: Slow conduction through atria, ventricles, and His-Purkinje system.
- IA: Moderate sodium channel blockade, moderate delay in repolarization - Examples: Quinidine, Procainamide, Disopyramide.
- Quinidine:
- Effects on Heart: Slows impulse conduction and delays repolarization in the atria, ventricles, and His-Purkinje system - ECG: Wide QRS, Prolong QT.
- Adverse Effects: Cinchonism (ototoxicity) & cardiotoxicity. - Cinchonism Sxs: Tinnitus, hearing loss, vertigo, N/V, HA, visual disturbances.
- Black Box Warnings: Increased mortality risk in atrial flutter and fibrillation.
 - Quinidine and Digoxin - Effect: Reduces digoxin excretion, leading to dig toxicity - Action: Monitor digoxin levels closely if given together.
- Risk of Torsades de Pointes: Characterized by twisting QRS complexes on EKG. Common with Class Ia and Class III antidysrhythmics. TX: Magnesium
- Increases AV Conduction: Risking higher ventricular rates. Often digoxin is given first to control ventricular rate.
- IB: Fast sodium channel blockade, minimal effect on repolarization - Examples: Lidocaine, Tocainide, Mexiletine.
- Selectivity: Highly selective for abnormal tissue, especially areas affected by ischemia.
- CNS Effects: Anxiety, agitation, confusion, psychosis, seizures (due to blood-brain barrier crossing).
- IC: Marked sodium channel blockade, minimal effect on repolarization - Examples: Flecainide, Moricizine, Propafenone.
- CAST Study Findings: Extensive proarrhythmic effects. Slows conduction to critical levels, especially in AV node, increasing risk of reentrant dysrhythmias.
Class II: β-Adrenergic Blockers: Treat supraventricular arrhythmias and control heart rate in atrial fibrillation.
- Mechanism: Beta-adrenergic blocking agents, reducing calcium entry.
- Primary Effects: Reduced SA node automaticity, slowed AV node conduction, reduced myocardial contractility.
- Examples: Atenolol, Metoprolol, Propranolol.
- Primary Uses: Control rate of supraventricular tachyarrhythmias.
- Other Indications: Hypertension, angina, reduction of post-MI reinfarction, migraine prevention, glaucoma, tremors, stage fright.
- Adverse Effects: Bradycardia, heart block, hypotension, heart failure, asthma issues, impotence.
- Selective vs. Nonselective Beta Antagonists:
- Selective: Block beta1 receptors (cardioselective).
- Nonselective: Block both beta1 and beta2 receptors, leading to pulmonary problems.
Class III: Potassium Channel Blockers: Effective in both supraventricular and ventricular arrhythmias.
- Mechanism: Block potassium channels, prolonging action potential duration and effective refractory period.
- Primary Effect: Delayed repolarization and prolonged action potential duration.
- Examples: Amiodarone, Sotalol, Dofetilide, Ibutilide.
- Amiodarone: Treat and prevent ventricular fibrillation and unstable ventricular tachycardia.
- Unique Feature: Half-life of 10 seconds, requires rapid IV administration.
- Amiodarone Toxicity: Pulmonary toxicity (pneumonitis, alveolitis, pulmonary fibrosis).
- Adverse Effects: Bradycardia, heart failure, corneal microdeposits, optic neuropathy, blue-gray skin discoloration, CNS effects.
- Monitoring: Cardiovascular, respiratory, hepatic, and thyroid function.
- Black Box Warnings for Amiodarone: Risk of pulmonary and liver toxicity; requires regular monitoring.
Class IV: Calcium Channel Blockers: Slowing of SA nodal automaticity, delay of AV nodal conduction, reduction of myocardial contractility.
- Mechanism: Block L-type calcium channels, reducing calcium entry.
- Examples: Verapamil, Diltiazem.
- Primary Use: Slow ventricular rate in atrial fibrillation or flutter, convert supraventricular tachycardia.
- Other Indications: Hypertension management, treatment of angina (especially vasospastic angina).
- Adverse Effects: Bradycardia, heart block, hypotension, peripheral edema, heart failure.
- CYP450 3A4 Interactions:
- Inducer Effect: Faster metabolism, inadequate drug levels.
- Inhibitor Effect: Slower metabolism, elevated drug levels.
- Avoid Grape juice! Increases CCB
Other Antidysrhythmic Drugs
- Digoxin:
- Mechanism: Inhibits Na+/K+ ATPase, increasing intracellular calcium.
- Use Control supraventricular tachydysrhythmias, particularly atrial fibrillation and flutter.
- Toxicity Concerns: Low therapeutic index, risk of toxicity- Half-Life: 36 hours, making toxicity management challenging.
- Magnesium: Treating Torsades de Pointes.
 Chapter 44 - Atherosclerotic Cardiovascular Disease (ASCVD)
Drug Therapy for Improving Plasma Lipid Levels
*Rhabdo Triad symptoms: Muscle pain, Weakness characteristic, Dark red to brown urine
- Statins: Inhibit cholesterol synthesis, reduce LDL, increase HDL, improve endothelial fxn, and stabilize plaques. Risk: muscle toxicity and hepatotoxicity.
- Bile Acid Sequestrants (prefix of chole or cole): Bind bile acids, modestly reduce LDL. Can cause GI effects.
- PCSK9 Inhibitors (have “ocumab” as a suffix): Increase LDL receptor recycling, reduce LDL. Administered via subcutaneous injections.
***Risk for upper respiratory infection!
- Ezetimibe: Inhibits cholesterol absorption, reduces LDL. Used alone or with statins. Expensive!
- Fibrates (contain the stem “fibr”): Reduce triglycerides, increase HDL. Used for severe hypertriglyceridemia. Risk of muscle toxicity and GI effects.
*Patient-Centered Care Across The Life Span Treating Dyslipidemia

Pregnant women Statins are contraindicated in pregnancy. Ezetimibe and fibrates can be used in pregnancy, but benefit should outweigh risk.

Chapter 45 - Drugs for Angina Pectoris

Main Antianginal Agents - Organic nitrates, β blockers, CCB, and Ranolazine enhance the effects of primary drugs.
Angina Pectoris: Pathophysiology and Treatment Strategy
Chronic Stable Angina
- Patho: Insufficient oxygen during exertion d/t CAD / Tx: Reduce anginal attacks by increasing oxygen supply or decreasing oxygen demand.
Variant Angina (Prinzmetal, Vasospastic Angina)
- Patho: Coronary artery spasm limits blood flow / Sxs: Occur at rest or during sleep / Tx: Increase oxygen supply via vasodilators.
Organic Nitrates - Nitroglycerin, effective for acute attacks.
- MOA: Vasodilation via nitric oxide production.
- Effects: Reduce angina by decreasing oxygen demand (stable angina) or preventing spasms (variant angina)
- AEs: HA, hypotension, reflex tachycardia.
- Tolerance: Managed by intermittent dosing.
- Interactions: Risk of hypotension w other drugs.
β Blockers - First-line for exertional angina; not effective for vasospastic angina.
- MOA: Decrease oxygen demand by reducing HR, contractility, and arterial pressure / AE: Bradycardia, AV conduction reduction, bronchoconstriction.
Calcium Channel Blockers (CCBs) - Verapamil, diltiazem, nifedipine / Use Stable and variant angina.
- MOA: Block calcium channels, dilating arterioles, reducing resistance. Relaxes coronary artery spasm and reduces afterload.
Ranolazine – Combo Therapy w nitrates, β blockers, CCBs, and other drugs.
- Use: Reduces angina episodes and increases exercise tolerance w/o affecting HR or BP / AE: Prolong QT interval, risk of dysrhythmias.
Management of Variant Angina

- Step 1: Use a CCB or long-acting nitrate.

- Step 2: Combine CCB and nitrate if needed.
- Step 3: Consider CABG surgery if combination therapy fails. β blockers are not effective.

Therapeutic Goals - Reduce freq and intensity of anginal attacks / Use nitroglycerin and long-acting preparations appropriately to avoid tolerance and adverse effects.

Module 6 PPTs
Central Alpha2 Agonist Antihypertensives
Agonists stimulate receptors & Antagonists block receptors (adrenergic receptors: alpha1, alpha2, beta1, and beta2)
- Adrenergic stimulation: Fright/Flight response; Adrenergic stimulation results in elevated blood pressure.

Adrenergic Antagonists as Antihypertensives: A number of antihypertensive drugs capitalize on the actions of adrenergic antagonism.

Alpha1 Blockers (-sin) Beta Blockers (-lol) Combination Alpha + Beta Blockers
doxazosin (Cardura) terazosin (Hytrin) nadolol (Corgard) propranolol (Inderal) metoprolol (Lopressor) carvedilol (Coreg) labetalol (Normodyne)
prazosin (Minipress) atenolol (Tenormin) metoprolol (Toprol) labetalol (Trandate)

But wait! Your textbook says that central alpha2 adrenergic agonists (not antagonists) are antihypertensives!

What are some examples of alpha2 agonist antihypertensives? Here are examples of common alpha2 agonists.

Alpha2 Agonists
clonidine (Catapres), guanfacine (Tenex), guanabenz (Wytensin), methyldopa (Aldomet)

What effect will these alpha2 agonists have on BP? They will decrease blood pressure!

DRUGS FOR HYPERLIPIDEMIA: THERAPEUTIC GOALS FOR MANAGEMENT OF LIPIDS

Total Cholesterol Want

HDL Increase
LDL Decrease
Triglycerides Decrease

PHARMACOLOGIC THERAPY
What drug categories are used to manage hyperlipidemia?

• HMG-CoA reductase inhibitors (AKA “statins”) • Fibric acid derivatives (AKA fibrates)
• Bile acid sequestrants (AKA bile acid-binding resins) • Cholesterol absorption inhibitors
• Niacin (AKA nicotinic acid)* • PCSK9 inhibitors

*Niacin is no longer recommended by experts in the cardiovascular specialty, but you may still see it used.
DRUG OF CHOICE
Which is the drug of choice for patients who can tolerate them (if there are no contraindications)?

• HMG-CoA reductase inhibitors (AKA “statins”) • Fibric acid derivatives (AKA fibrates)
• Bile acid sequestrants (AKA bile acid-binding resins) • Cholesterol absorption inhibitors
• Niacin (AKA nicotinic acid) • PCSK9 inhibitors

HMG-COA REDUCTASE INHIBITORS (AKA STATINS)

• What is the MOA for statins? The liver requires HMG–CoA reductase to produce cholesterol, so HMG-CoA reductase inhibitors decrease cholesterol production.
• What do the generic names of statins have in common? They have a suffix of statin (e.g. atorvastatin, pravastatin, simvastatin)
• Are there any groups for which statins are contraindicated? Pregnant women & Patients with liver disease.
• What are the major adverse effects of statins?
• Muscle pain! (In some instances, progressed to rhabdo, muscle necrosis! Breakdown of muscle protein can cause serious renal injury.)
• Liver injury (Liver enzyme elevations are common during the first three months
HMG-COA REDUCTASE INHIBITORS (CONT’D)
• We need to monitor for signs and symptoms of liver injury in patients taking statins. What are some of these s/s?

• Continuing rise of liver enzymes (ALT, • Jaundice (yellow skin and eyes) • Dark urine
AST) • Clay colored stools • Excessive fatigue

• We need to monitor for s/s of rhabdomyolysis in patients taking statins. What are some of these s/s?

• Elevated creatine kinase (CK) – usually 5 • Myoglobin in the urine • Weakness characteristic *
times the normal range • Muscle pain * • Dark red to brown urine *

* Triad symptoms: Muscle pain, Weakness characteristic, Dark red to brown urine
NIACIN (AKA NICOTINIC ACID AKA VITAMIN B3)
• Can a person just take a daily multi-vitamin with B3 to achieve the same effect? No, the niacin used to treat hyperlipidemia is at a much higher dose.
• What are the major adverse effect of niacin? The major adverse effect – and a reason many stop taking it – is flushing. Pruritis may also occur in some patients.
• What can the NP do to minimize flushing? Advise the pt to take an NSAID about 30 mins b4 niacin admin to decrease flushing. It helps to give it w a snack.
• Why is niacin and some other anti-lipidemic drugs prescribed to be taken at bedtime? Most cholesterol synthesis occurs at night.
BILE ACID SEQUESTRANTS (AKA BILE ACID-BINDING RESINS)
• What is the MOA for bile acid sequestrants?
• Bile acids are required for the absorption of cholesterol from the small intestine.
• Bile acid sequestrants bind to bile acids so they cannot be reabsorbed. As a result, they are sequestered in the intestine and end up being excreted.
• What do the generic names of bile acid sequestrants have in common? They have a prefix of chole or cole (e.g. cholestyramine, colestipol, colesevelam)
• Are there any groups for which these drugs are contraindicated?
• Pts w bile duct obstruction or bowel obstruction
• Pts w phenylketonuria should not take brand names containing phenylalanine
• What are the major adverse effects of bile acid sequestrants? GI sxs such as constipation, heartburn, and bloating.
BILE ACID SEQUESTRANTS (CONT’D)
• What are the major adverse effects of bile acid sequestrants? GI sxs such as constipation, heartburn, bloating. (the drug is sequestered in the GI system!)
• What can the nurse practitioner do to manage this problem?
• Encourage intake of increased fluids, fiber, and activity.
• Remind them that the symptoms are usually temporary. (This is important because many people quit taking them because of the GI side effects)
• What problem do bile acid sequestrants (other than Colesevelam) create for other drugs?
• They may prevent absorption of other drugs and they may decrease absorption of fat-soluble vits (vits A, D, E, K)
• How can the NP prevent this interaction? Have the pt take other drugs at least 1 hr b4 and 4-6 hrs after bile acid sequestrants.
FIBRIC ACID DERIVATIVES (AKA FIBRATES)
• What is the mechanism of action of fibric acid derivatives? They have multiple actions:

(1) breaks down cholesterol, (3) inhibit synthesis of triglycerides

(2) suppresses release of free fatty acids from adipose tissue, (4) increase secretion of cholesterol into the bile.

• What do the generic names of fibric acid derivatives have in common? They contain the stem “fibr” (e.g. gemfibrozil, fenofibrate)
• Are there any groups for which fibric acid derivatives are contraindicated?
 • Pts w liver dz
• Pts w gallbladder dz (They can cause cholelithiasis because they increase secretion of cholesterol in the bile)
• Why should these drugs be avoided in patients who take a statin? Taking a fibric acid derivative w a statin increases rhabdomyolysis risk!
CHOLESTEROL ABSORPTION INHIBITORS
• What is the mechanism of action for cholesterol absorption inhibitors? Cholesterol absorption inhibitors inhibit the absorption of cholesterol.
• What is the name of the only cholesterol absorption inhibitor currently available? ezetimibe (Zetia)
• Are there any significant adverse effects? About 4% of those taking it will have GI discomfort. Others occur at less than 4%.
• Are there contraindications? Not when taken alone.
• Why don’t more people take ezetimibe given that it is safer? It costs about $935.87 for a bottle of 90 10mg tablets.
PCSK9 INHIBITORS
• What is the mechanism of action of PCSK9 Inhibitors? PCSK9 is an enzyme produced in the liver that increases LDL cholesterol, so inhibiting PCSK9 will lower LDL.
• What do the generic names of PCSK9 inhibitors have in common?
• The currently approved ones have “ocumab” as a suffix (e.g. evolocumab, alirocumab).
• The “mab” is typical for monoclonal antibodies
• What are the most common adverse reactions? Up to 11% develop an upper respiratory infection (nasopharyngitis)
• Are there any contraindications to PCSK9 inhibitors? Allergies to the drug, but then that is true for all drugs.
• Why aren’t more people on this very effective drug? It is given by injection + cost is about $650.77 - $672.00/mL
ANOTHER LOOK AT EXAMPLES FOR EACH DRUG CATEGORY

• HMG-CoA Reductase Inhibitors (statins): atorvastatin (Lipitor) • Fibric acid derivative: gemfibrozil (Lopid)
• Bile acid sequestrant: cholestyramine (Questran) • Niacin: niacin (Niacor)
• Cholesterol absorption inhibitor: ezetimibe (Zetia) • PCSK9 inhibitors: evolocumab (Repatha)

ANTIHYPERTENSIVE – HYPERTENSIVE
How to Decrease BP - We can decrease blood pressure by…

- Decreasing force of cardiac contraction - Dilating vessels

- Decreasing systemic vascular resistance (SVR) by - Decreasing circulatory volume

Antihypertensive Drug Classes

- Adrenergic antagonists: Alpha & Beta-blockers - Angiotensin II receptor blockers (ARBs) - Vasodilators
- Centrally acting adrenergic agonists - Direct renin inhibitors (DRIs) - Diuretics
- Angiotensin-converting enzyme (ACE) inhibitors - Calcium channel blockers (CCBs)

DRUGS THAT DECREASE EXPRESSION OF SYMPATHETIC NERVOUS SYSTEM ACTIVITY

* These are more often simply called alpha-blockers. Alpha1 Antagonists, Alpha2 Agonists, Selective and Nonselective Beta Antagonists

Review Effects of Alpha-Adrenergic Stimulation - This table illustrates the effects of alpha-adrenergic stimulation in the periphery.

TYPE ORGAN TISSUE RESPONSE TO ALPHA AGONIST The Agonist Paradox (or so it seems initially)
 Alpha-1 Eye Mydriasis (pupil dilation) Notice the location of the alpha-1 and alpha-2 receptors in relation to the synapse between these two neurons. This location is important.
Heart Strength of contraction - The alpha-1 receptors are located on the postsynaptic neuron. When they are stimulated by a neurotransmitter, they are stimulated to
Blood vessels Vasoconstriction produce an adrenergic response.
Urinary Bladder Contraction of sphincter
Prostate Contraction of sphincter
Sexual Response Promotes ejaculation or reaching orgasm.
Alpha-2 Blood Vessels Vasodilation (inconsequential in - The alpha-2 receptors are on the presynaptic (before the synapse) neuron. They work on a negative feedback system. When enough
periphery) neurotransmitter collects in the synaptic space, it stimulates the alpha-2 receptor which signals the neuron to stop releasing additional
norepinephrine. This results in a decrease in adrenergic response resulting in vasodilation.

- How do alpha1 blockers decrease blood pressure? Alpha-1 blockers decrease the strength of contraction and cause vasodilation
- In consideration of this effect, what nursing action is important? These effects can cause first-dose syncope, so first doses should be taken at night.
- Alpha-1 blockers are prescribed for older men w prostate problems in addition to HTN. Why would this be a good choice? To help w benign prostatic hyperplasia (BPH)
- What adverse effect, unrelated to BP control or urination, could cause problems for patients taking alpha-blockers? They have troublesome sexual side effects

Central Alpha2 Agonists (Selective for the alpha-2 receptors)

- Cross the blood-brain barrier where they access and stimulate the presynaptic alpha-2 adrenergic receptors. This decreases the release of NE, causes vessel dilation, and
thus decreases BP.
Can you name two examples of centrally-acting alpha-2 adrenergic agonists? Methyldopa* and clonidine. Both have roles as antihypertensives.
*Methyldopa is recommended as one of the drugs of choice for pregnant women w HTN. (The other are labetalol, a beta blocker, and nifedipine, a CCB)

Beta-Adrenergic Antagonists - Review Effects of Beta-Adrenergic Agonists/Antagonists

This table illustrates the effect of beta-adrenergic stimulation.

TYPE ORGAN TISSUE RESPONSE TO RECEPTOR BLOCKADE

Beta-1 Heart Increase Contraction, Increase Heart rate
Beta-2 Lungs Bronchodilation
Uterus Relaxation
Urinary Bladder Relaxation of detrusor (bladder wall) muscle

EFFECTS OF BETA-ADRENERGIC BLOCKADE - This is what happens when beta-adrenergic receptors are blocked.

TYPE ORGAN TISSUE RESPONSE TO BETA BLOCKERS

Beta-1 Heart Decrease Contraction, decrease HR
Beta-2 Lungs Bronchoconstriction
Uterus Contraction
Urinary Bladder Contraction of detrusor muscle

Examples of beta antagonists (beta blockers): atenolol, metoprolol, propranolol, and others ending in -olol
Beta antagonists (beta-blockers)—may be either: Cardioselective (block beta-1 receptors)-metoprolol or Nonselective (block both beta-1 and beta-2 receptors)-propranolol
What are other cardiac uses for beta blockers?
- Because they decrease the cardiac workload, they decrease myocardial oxygen demands, so beta blockers are also indicated to prevent angina.
- Because they slow conduction, they are also prescribed for both supraventricular and ventricular tachydysrhythmias, so beta blockers are also classified as
antidysrhythmic (AKA antiarrhythmics).
How can β blockers compromise perfusion & oxygenation?
- Exercise intolerance can be a problem when the heart doesn’t increase the strength of contraction and HR to compensate for increased demands of activity.
 - Bronchoconstriction can worsen asthma and other respiratory illnesses.
What are noncardiac adverse effects of β blockers?
- Uterus contraction is a potential risk in pregnancy
- Contraction of the detrusor (bladder wall) muscle can worsen tendencies toward urinary incontinence.
- Beta-blockers can also cause erectile dysfunction.
Other Notes about Beta Blockers
- Beta-blockers prescribed for stage fright and test anxiety because they decrease the adrenergic surge that causes sxs assoc w anxiety.
- Beta-blockers can cause hypoglycemia because they block glucose production mediated by adrenergic activity.
- Beta-blockers can mask hypoglycemia because they prevent some s/s of hypoglycemia such as tachycardia, tremors, and anxiety.
- Beta-blockers should be tapered off when discontinued. If stopped suddenly, rebound HTN can occur.
Combined alpha and beta Blockers - Some adrenergic antagonists have both alpha and beta-blocker activity. - Examples: labetalol and carvedilol

DRUGS THAT INHIBIT ACTIVITY OF THE RENIN-ANGIOTENSIN SYSTEM

Angiotensin Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, & Direct Renin Inhibitors
ACE Inhibitors - ACEIs decrease conversion of angiotensin I to angiotensin II; BP is controlled because there is less angiotensin II to cause vasoconstriction and fluid retention.
- Examples (end in –pril)

- captopril (Capoten) - lisinopril (Zestril)

- enalapril (Vasotec) - quinapril (Accupril)

- ACEIs have a renal-protective effect which makes it a drug of choice for patients with diabetes mellitus
- Cough is a common SE (ACE normally breaks down inflammatory mediator bradykinin in lungs. ACE is inhibited, there is an increase of bradykinin in lungs.)
- Angioedema with ACEIs is rare but can be life-threatening
ARBs - ARBs block angiotensin II receptors; By blocking receptors, they prevent the vasoconstriction and fluid retention that contributes to elevated BP
- Examples (end in –sartan): losartan (Cozaar) - valsartan (Diovan) - eprosartan (Teveten) - irbesartan (Avapro)

Direct Renin Inhibitors (DRIs) - aliskiren (Tekturna) - Renin is necessary for the conversion of angiotensinogen to angiotensin I.
- By preventing this conversion, DRIs have the same outcome (i.e. decreased production of angiotensin II) as ACEIs.
Important Lifespan Considerations
Boxed Warning: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. D/C asap once pregnancy is detected.
Which antihypertensives act on the renin-angiotensin system? ACEIs – ARBs – DRIs
More about ACEIs, ARBs, and DRIs
- ACEIs are drug of choice for HF. ARBs drug of choice after ACEIs. DRIs are a drug of choice for HF if pt cant take ACEIs or ARBs.
- Combining ACEIs, ARBs, and DRIs in any combination may increase mortality risk.
- ACEIs, ARBs, and DRIs may contribute to hyperkalemia, Knowing this, because diuretics are often combined with other drugs to treat hypertension…
Which diuretics are likely to increase the risk for hyperkalemia? Potassium-sparing diuretics increase the risk for hyperkalemia.
Which diuretics may be given with ACEIs, ARBs, and DRIs to decrease the risk for hyperkalemia?
- Thiazide or loop diuretics increase the risk for hypokalemia, so giving these w ACEIs, ARBs, and DRIs, balances the tendencies of these drugs to cause hyperkalemia.

DRUGS THAT BLOCK CALCIUM RECEPTORS TO PROMOTE VASODILATION TO DECREASE SYSTEMIC VASCULAR RESISTANCE (SVR)
Calcium Channel Blockers (CCBs): Calcium has a role in muscle contraction - By blocking calcium receptors, CCBs promote muscle relaxation in vessels increase vasodilation
and decreases SVR. Two primary categories: Dihydropyridines & Non-dihydropyridine
CCB Distinctions
 Dihydropyridines - prominently vasodilators / Uses: Management of HTN or chronic stable angina / Ex: Nifedipine, felodipine, nicardipine, amlodipine,
Non-dihydropyridines - have less vasodilator effect, but they have a greater depressive effect on cardiac conduction and contractility.
- Uses: Management of HTN, chronic stable angina, and cardiac dysrhythmias / Ex: verapamil and diltiazem.
MOA for Cardiovascular Indications for CCBs
- Management of hypertension: Vasodilation of peripheral vessels decreases SVR
- Management of angina: Decreasing cardiac workload decreases O2 demand
- Management of selected dysrhythmias (e.g. SVT, PSVT, afib, aflutter) by non-dihydropyridines Calcium channels blocked in the SA and AV
Common Adverse Effects of CCBs
- Peripheral edema (pedal edema) – more common w dihydropyridines
- Constipation – more common with non-dihydropyridines
- Bradycardia and decreased cardiac output – non dihydropyridines
- Gingival hyperplasia – both classes of CCBs
Significant interactions - Ingestion of grapefruit juice and the dihydropyridine calcium channel blockers can elevate the plasma concentration of the CCB. It may also
elevate the non-dihydropyridines (diltiazem, verapamil) but to a lesser degree.

DRUGS THAT DILATE PERIPHERAL VESSELS TO DECREASE SYSTEMIC VASCULAR RESISTANCE (SVR)
Vasodilator: Dilate peripheral arteries and/or veins to decrease SVR
- Examples
- diazoxide (Hyperstat): Most often used in hypertensive emergencies
- hydralazine HCl (Apresoline): Most often used in hypertensive emergencies
- sodium nitroprusside (Nipride): Most often used in hypertensive emergencies
- minoxidil (Loniten)- What is another indication (purpose) of this drug? - minoxidil (Rogaine) for male-pattern baldness

DRUGS THAT DECREASE CIRCULATORY VOLUME AND PRELOAD

Diuretics: Three diuretics are a mainstay of antihypertensive therapy.
- Thiazides: The most used antihypertensive
- High-ceiling or loop diuretics: Reserved for pts requiring greater diuresis or those w low glomerular filtration rate (GFR)
- Potassium-sparing diuretics: The least effective for HTN. The primary use is to balance K+ loss that occurs w thiazides and loop diuretics.
Diuretics: Common Adverse Effects
- Thiazides: Potential problems: hypokalemia, dehydration, hyperglycemia, hyperuricemia
- High-ceiling or loop diuretics: Potential problems: hypokalemia, dehydration, hyperglycemia, hyperuricemia, hearing loss
- Potassium-sparing diuretics: Potential problem: hyperkalemia
For each diuretic class listed, there a risk of hypokalemia or hyperkalemia. Can you identify which?
- Thiazides, e.g. hydrochlorothiazide (HCTZ): Risk of hypokalemia
- Loop diuretics, e.g furosemide (Lasix): Risk of hypokalemia
- Potassium-sparing diuretics, e.g. spironolactone (Aldactone) or triamterene (Dyrenium): Risk of hyperkalemia
Differentiating Potassium-Sparing Diuretics: There are two types of potassium-sparing diuretics. Each has different adverse effects.
— Aldosterone antagonists – blocks aldosterone to retain potassium and excrete sodium in distal nephron. Example: spironolactone (Aldactone)
¡ Causes endocrine adverse effects, e.g. gynecomastia, menstrual irregularities, impotence, hirsutism, and deepening of the voice.
— Nonaldosterone antagonists – directly disrupts sodium-potassium exchange in distal nephron. Example: triamterene (Dyrenium)
¡ No endocrine adverse effects
Diuretic Sites of Action
— Loop diuretics act on the loop of Henle: +20% of Na+ (thus H2O) is reabsorbed by the body site; therefore, loop diuretics can decrease more volume
— Thiazide diuretics act on the distal tubule: +10% of Na+ (thus H2O) is reabsorbed by the body site; therefore, thiazide diuretics are less effective than loop diuretics
— Potassium-sparing diuretics act on the collecting duct: +3-5% of Na+ (thus H2O) is reabsorbed by the body at this site; therefore, these diuretics are not very effective
Why would a potassium-sparing diuretic be prescribed? - It can balance the potassium-wasting effect of thiazide & loop diuretics
Special Note
— Thiazides: Ability to promote diuresis depends on renal fxn / Ineffective if renal function decreased
— Loop diuretics: Effective when renal fxn is compromised / Risk of ototoxicity manifested by tinnitus, vertigo, decreased hearing
— Thiazide and loop diuretics: Can cause hyperuricemia lead to gout (or gout exacerbation) / Can cause hyperglycemia lead to monitor closely in ps w DM.

DRUGS FOR ANGINA

Cardiovascular Drug Review
What purpose do antianginal drugs serve?

• Decrease frequency of anginal attacks • Prevent or delays a myocardial infarction

• Decrease duration and intensity of anginal pain • Improve cardiac functional capacity*

* Functional capacity is an estimate of what the patient's heart will allow the patient to do. For example, a patient may be accustomed to walking rather than driving
places, but if angina causes pain with walking, it limits this activity; thus, it limits functional capacity.
What would decrease O2 supply? Any mechanism that decreases coronary artery circulation - Plaque accumulation in coronary arteries & Spasm of coronary artery decreases
• What would increase O2 demand? Increased HR, cardiac contractility, Increased preload, Increased afterload
• Increased preload
▫ Left ventricular end-diastolic volume (how full the ventricle is just before contraction)
▫ The heart must work harder to eject greater volumes
• Increased afterload
▫ Afterload = systemic vascular resistance (SVR is increased w narrowed arterial vessels)
▫ The heart must work harder to eject blood into constricted or narrow blood vessels
How do antianginals work? Antianginal drugs either increase oxygen supply, decrease oxygen demand, or both.
• They may increase oxygen supply to Increase blood flow and Decrease coronary artery spasm
• They may decrease oxygen demand to decrease the heart rate, cardiac contractility, preload, afterload
Nitrates
How do nitrates work? They increase oxygen supply by dilating coronary arteries
• They decrease oxygen demand by relaxing smooth muscle cells in arteries and veins leads to dilates blood vessels so the heart doesn’t have to work so hard
▫ Decreases preload (venous dilation reduces venous return)
▫ Decreases afterload (relaxed arteriolar vessels decrease systemic vascular resistance)
Rapid and Long-Acting Nitrates
• Rapid-acting nitrates: Used to abort an anginal attack/ Taken b4 activity to prevent an anginal attack / Forms: sublingual, translingual spray, IV
• Long-acting nitrates: Used to prevent an anginal attack / Forms: tablets, patches, ointment
What major side effect of nitrates would you anticipate based on decreased preload and decreased afterload? Decreased BP!
Hypotension may be dramatic and can cause syncope, so what will you advise when teaching? Pt should sit or lie down when taking rapid-acting nitro!
Because nitroglycerin decreases BP, what should you assess before giving it in a hospital setting? Check BP before giving and every 5 minutes afterward
▫ BP decreases from SL administration are transient and are not a reason to hold subsequent doses.
▫ Contact prescriber if SBP <90 mm Hg systolic and/or HR <60 beats/min or greater than 100 beats/min. (NOTE: Most resources say to check BP & HR twice
before notifying prescriber because it often rebounds quickly (i.e. by the time the prescriber would be notified, it would be okay)
Other than decreased BP, what are some other common side effects or problems associated with nitrates such as nitroglycerin?
• Headache (thought to be d/t vasodilation of vessels in the brain): Acetaminophen used to manage HA & Decreases over time w daily preventive therapy
• Reflex tachycardia (body’s attempt to maintain a stable cardiac output) - Usually transient
Nitrate Tolerance
What can be done to help decrease nitrate tolerance?
• Nitrate-free zone
 ▫ Instead of trying to maintain a steady-state in the blood, nitrate-free scheduling allows for a drop in serum drug levels
▫ It is common practice to remove a nitrate patch at night and replace it in the morning.
Nitrate Cautions and Contraindications
• Additive hypotensive effects when given with other drugs that decrease BP
• Dangerous if given with phosphodiesterase 5 (PD5) inhibitors erectile-dysfunction drugs such as sildenafil (Viagra) or tadalafil (Cialis).
Special Nitroglycerin Teaching
• Teaching for sublingual tablets
▫ Store in the original container (protects from light and moisture).
▫ Drugs lose potency quickly once opened; opened bottles should be replaced within 6 months. (Some resources say 3-6 months)
▫ Take one at the start of chest pain and repeat every 5 minutes until pain is relieved or until 3 doses are taken.
▫ Place under tongue and do not swallow.
▫ The dissolving tablet should burn or tingle; if it does not, it may have lost its potency.
Beta Blockers (AKA Beta Adrenergic Antagonists)
How do beta blockers manage angina? These actions decrease oxygen demand.

• Slows HR (negative chronotropic effect) • Slow conduction thru V node (negative • Decreases the force of myocardial
dromotropic effect) contraction (negative inotropic effect)

What serious cardiac adverse effects will you watch for based on the following actions of beta blockers?

• Negative chronotropic effect: Bradycardia & • Negative dromotropic effect: Heart block • Negative inotropic effect: Decreased cardiac
Exercise intolerance (AV conduction block) output & Hypotension

Calcium Channel Blockers

How do calcium channel blockers manage angina?
Calcium has a role in the contraction of cardiac and skeletal muscle and of vascular smooth muscle cells.
• By decreasing calcium entry in cardiac muscle, the force of cardiac contraction is decreased.
• By decreasing calcium entry in vascular smooth muscle, vessels dilate.
They also decrease conduction through the SA and AV nodes, which slow the heart rate.
These actions decrease oxygen demand. Because they decrease vasospasm, they also increase oxygen supply in vasospastic (Prinzmetal’s) angina.
What are some common side effects of calcium channel blockers? Hypotension, Peripheral edema, Constipation
What food substance, if taken with some calcium channel blockers, can cause toxicity? Grapefruit juice!
What are the 3 classes of antianginal drugs you just reviewed? Nitrates, Beta Blockers, & Calcium Channel Blockers

ANTIDYSRHYTHMICS Jeopardy

1. What is the mechanism of action for the Class I antidysrhythmic agents and what is their primary effect?
Class I antidysrhythmics are sodium channel blockers. Their primary effect is slowed conduction through the atria, ventricles, and His-Purkinje system.

2. Class I drugs are divided into groups a, b, and c. What are common examples in each category and for what dysrhythmias are they primarily indicated?
Group Ia: quinidine, procainamide, disopyramide, tx supraventricular & ventricular dysrhythmias
Group Ib: lidocaine, tocainide, mexiletine; TX ventricular dysrhythmias
Group Ic: flecainide, moricizine, propafenone; tx WPW-related and ventricular dysrhythmias
3. What is cinchonism and what does it have to do with quinidine?
Cinchonism is a syndrome that characterizes quinidine toxicity. Signs and symptoms include tinnitus, hearing loss, vertigo, nausea and vomiting, headache, and visual
disturbances.

4. What effect does quinidine have on digoxin?

Quinidine reduces the excretion of digoxin leading to dig toxicity. It will be important to closely monitor dig levels if these are given together.

5. Quinidine, procainamide, and disopyramide (all Class Ia antidysrhythmics) can cause torsades de pointes. What is torsades de pointes?
Torsades de pointes (AKA torsade) means “twisting of points” and is a term used to characterize a type of ventricular tachycardia that, on the EKG, presents with QRS
complexes that appear to twist around the baseline. Both Class Ia and Class III anti-dysrhythmics are common causes.

6. Class Ib antidsyrhythmics are highly selective for abnormal tissue. How does this make a class Ib antidysrhythmic such as lidocaine particularly suitable for
certain ventricular dysrhythmias?
Because lidocaine acts on the abnormal region (e.g. areas that are irritated secondary to ischemia), it can be used to abolish dysrhythmias initiated by ectopic foci.

7. What is meant by the term prodysrhythmic effects and how what do they have to do with antidysrhythmic drugs?
All antidysrhythmic drugs have the potential to worsen existing dysrhythmias and to generate new dysrhythmias. Because of this potential, antidysrhythmic drugs should
only be used when dysrhythmias are clinically significant and creating problems for the patient.

8. The CAST study found that Class Ic antidysrhythmics (e.g. flecainide, moricizine, and propafenone) have extensive proarrhythmic effects. What action by these
agents would be the probable cause of this?
Class Ic hese agents can slow conduction to critical levels, particularly in the AV node where suppression is profound. This sets the stage for dangerous ventricular
dysrhythmias to develop. Reentrant dysrhythmias are particularly common.

9. Class Ib antidysrhythmic agents such as lidocaine and mexiletine cross the blood-brain barrier. With this in mind, what adverse effects should be expected?
Central nervous system effects of lidocaine and mexiletine include anxiety, agitation, confusion, psychosis, and seizures.

10. Although quinidine is primarily a depressant, AV conduction is increased. What special problem does this present?
Atrial fibrillation bombards the AV node with impulses; however, the AV node cannot conduct them all, so this has a role in controlling the ventricular response rate.
When quinidine is given, the atrial rate may begin to fall but the ventricular rate may begin to rise as more impulses are transmitted through the AV node. For this reason,
digoxin is sometimes given prior to giving quinidine in order to control conduction until the atrial rate is sufficiently controlled.

11. What is the mechanism of action for the Class II antidysrhythmic agents and what is their primary effect?
Class II antidysrhythmics are beta-adrenergic blocking agents. Their primary effect is

– Reduced automaticity in SA node – Slowed conduction in AV node – Reduced myocardial contractility

12. What are the primary dysrhythmias for which beta blockers are given?
Because they slow the heart rate and conduction, beta blockers are primarily used to control the rate of supraventricular tachyarrhythmias.

13. In addition to the antidysrhythmic properties of beta blockers, what other indications do they have?
Beta blockers have many uses based on their antagonism of adrenergic stimulation. These include treatment of hypertension, angina, reduction of post-MI reinfarction,
migraine headache prevention, glaucoma, tremors, and even stage fright.
14. What are common adverse effects of beta blockers?
The adverse effects of beta blockers are primarily those expected from antagonism of adrenergic action. They include, bradycardia, heart block, hypotension, and heart
failure. They prevent bronchodilation so can be problematic for patients with asthma. They can also cause impotence (a common cause for nonadherence).

15. What is the difference between selective and nonselective beta antagonists?
Selective beta antagonists block primarily beta1 receptors. These are also known as cardioselective beta antagonists. Nonselective beta antagonists block both beta1 and
beta2 receptors. Beta2 receptor blockade leads to the pulmonary problems associated with beta antagonists. mnemonic for beta1 = 1 heart / beta2 = 2 lungs

16. What is the mechanism of action for the Class III antidysrhythmic agents and what is their primary effect?
Class III antidysrhythmics are potassium channel blockers. Their primary effect is delayed repolarization of fast potential and subsequent prolongation of the action
potential duration and the effective refactory period.

17. What is the primary dysrrhythmia for which a Class III antidysrhythmic such as amiodarone (Cordarone) would be given?
Amiodarone is given to treat and prevent recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia. It can also be used for atrial
dysrhythmias (e.g. to convert atrial fibrillation), but this is a less common use

18. What is the primary severe toxicity that limits the use of amiodarone?
The most serious adverse effect is pulmonary toxicity, which may be manifested by pneumonitis, alveolitis, and pulmonary fibrosis. This develops in 2-17% of patients
and carries a 10% mortality.

19. What are common adverse effects of amiodarone (other than pulmonary toxicity)?
Because amiodarone suppresses SA and AV node activity, it can cause bradycardia. By reducing myocardial contractility, it can precipitate heart failure.
Most patients will develop corneal microdeposits leading to photophobia and blurred vision. Optic neuropathy with blindness has occurred. From 2-5% develop a blue-
gray skin discoloration. Finally, because it crosses the blood-brain barrier, CNS effects such as ataxia, tremor, and mental status changes may occur.

20. What body or organ systems should be monitored when patients are taking amiodarone?
In addition to monitoring the cardiovascular system, it is essential to monitor respiratory system status because of the high rate of pulmonary toxicity. Also, because
amiodarone can cause hepatic and thyroid dysfunction, it is important to obtain baseline liver and thyroid function studies and to monitor these periodically.

21. What is the mechanism of action for the Class IV antidysrhythmic agents and what is their primary effect?
Class IV antidysrhythmics are calcium channel blockers. Their primary antidysrhythmic effects are

– Reduced automaticity in SA node – Slowed conduction in AV node – Reduced myocardial contractility

22. What is the primary dysrhythmia for which calcium channel blockers are given?
Calcium channel blockers have their greatest effect on slowing conduction through the AV node. For this reason, they are commonly given to slow the ventricular rate in
atrial fibrillation or atrial flutter and to convert supraventricular tachycardia to normal sinus rhythm.

23. In addition to the antidysrhythmic properties of calcium channel blockers, what other indications do they have?
Calcium channel blockers dilate peripheral arteries making them useful in management of hypertension. They also dilate coronary artieries and inhibit coronary
vasospasm making them useful in treatment of angina, particularly vasospastic (Prinzmetal’s) angina.

24. What are common adverse reactions of calcium channel blockers?

Because calcium channel blockers reduce automaticity and slow conduction, they can cause bradycardia and heart block. Because they cause peripheral artery dilation,
they can cause hypotension and peripheral edema. The combination of bradycardia and hypotension can lead to heart failure.
 25. Because calcium channel blockers are extensively metabolized by the CYP450 3A4 enzyme system, what might be anticipated if (a) a CYP450 3A4 inducer is
given or (b) CYP450 3A4 inhibitor is given?
A CYP450 3A4 inducer will accelerate metabolism resulting in faster inactivation thus inadequate drug levels.
A CYP450 3A4 inhibitor will slow metabolism resulting in slowed inactivation thus there will be elevated drug levels.

26. What is the Vaughan Williams classification of antidysrhythmic agents?

The Vaughan Williams classification categorizes antidysrhythmic agents according to the electrophysiologic effects on the action potential. There are four major classes:
Class I, Class II, Class III, Class IV. Class I has three subclasses Ia, Ib, and 1c.

27. What is particularly unique about the antidysrhythmic drug adenosine and when is it indicated?
Adenosine has a half-life of only 10 seconds so it must give given by rapid IV followed by rapid flush. A period of transient asystole typically follows administration. It is
given for supraventricular tachycardia.

28. What role does the cardiac glycoside digoxin have as an antidysrhythmic agent?
Digoxin depresses AV note condctin so can be used to control supraventricular tachydysrhythmias, particularly atrial fib or flutter with rapid ventricular response.

29. What particular concerns regarding toxicity must be considered related to cardiac glycosides such as digoxin?
Cardiac glycosides are highly toxic secondary to a low therapeutic index. (i.e. There is only a small difference between a therapeutic level and a toxic level.) For digoxin,
a half-life of 36 hours makes this particularly problematic.

30. Magnesium is considered a miscellaneous antidysrhythmic agent. What unusual dysrhythmia is it used to tx? Drug choice for suppressing Torsades de pointes.

Chapter 43 - Antidysrhythmic Drugs

Classified into four Vaughan Williams classes:
Class I: Sodium Channel Blockers: Effective for ventricular and some supraventricular arrhythmias.
- Mechanism: Sodium channel blockers
- Primary Effect: Slow conduction through atria, ventricles, and His-Purkinje system.
- IA: Moderate sodium channel blockade, moderate delay in repolarization - Examples: Quinidine, Procainamide, Disopyramide.
- Quinidine:
- Effects on Heart: Slows impulse conduction and delays repolarization in the atria, ventricles, and His-Purkinje system - ECG: Wide QRS, Prolong QT.
- Adverse Effects: Cinchonism (ototoxicity) & cardiotoxicity. - Cinchonism Sxs: Tinnitus, hearing loss, vertigo, N/V, HA, visual disturbances.
- Black Box Warnings: Increased mortality risk in atrial flutter and fibrillation.
- Quinidine and Digoxin - Effect: Reduces digoxin excretion, leading to dig toxicity - Action: Monitor digoxin levels closely if given together.
- Risk of Torsades de Pointes: Characterized by twisting QRS complexes on EKG. Common with Class Ia and Class III antidysrhythmics. TX: Magnesium
- Increases AV Conduction: Risking higher ventricular rates. Often digoxin is given first to control ventricular rate.
- IB: Fast sodium channel blockade, minimal effect on repolarization - Examples: Lidocaine, Tocainide, Mexiletine.
- Selectivity: Highly selective for abnormal tissue, especially areas affected by ischemia.
- CNS Effects: Anxiety, agitation, confusion, psychosis, seizures (due to blood-brain barrier crossing).
- IC: Marked sodium channel blockade, minimal effect on repolarization - Examples: Flecainide, Moricizine, Propafenone.
 - CAST Study Findings: Extensive proarrhythmic effects. Slows conduction to critical levels, especially in AV node, increasing risk of reentrant dysrhythmias.
Class II: β-Adrenergic Blockers: Treat supraventricular arrhythmias and control heart rate in atrial fibrillation.
- Mechanism: Beta-adrenergic blocking agents, reducing calcium entry.
- Primary Effects: Reduced SA node automaticity, slowed AV node conduction, reduced myocardial contractility.
- Examples: Atenolol, Metoprolol, Propranolol.
- Primary Uses: Control rate of supraventricular tachyarrhythmias.
- Other Indications: Hypertension, angina, reduction of post-MI reinfarction, migraine prevention, glaucoma, tremors, stage fright.
- Adverse Effects: Bradycardia, heart block, hypotension, heart failure, asthma issues, impotence.
- Selective vs. Nonselective Beta Antagonists:
- Selective: Block beta1 receptors (cardioselective).
- Nonselective: Block both beta1 and beta2 receptors, leading to pulmonary problems.
Class III: Potassium Channel Blockers: Effective in both supraventricular and ventricular arrhythmias.
- Mechanism: Block potassium channels, prolonging action potential duration and effective refractory period.
- Primary Effect: Delayed repolarization and prolonged action potential duration.
- Examples: Amiodarone, Sotalol, Dofetilide, Ibutilide.
- Amiodarone: Treat and prevent ventricular fibrillation and unstable ventricular tachycardia.
- Unique Feature: Half-life of 10 seconds, requires rapid IV administration.
- Amiodarone Toxicity: Pulmonary toxicity (pneumonitis, alveolitis, pulmonary fibrosis).
- Adverse Effects: Bradycardia, heart failure, corneal microdeposits, optic neuropathy, blue-gray skin discoloration, CNS effects.
- Monitoring: Cardiovascular, respiratory, hepatic, and thyroid function.
- Black Box Warnings for Amiodarone: Risk of pulmonary and liver toxicity; requires regular monitoring.
Class IV: Calcium Channel Blockers: Slowing of SA nodal automaticity, delay of AV nodal conduction, reduction of myocardial contractility.
- Mechanism: Block L-type calcium channels, reducing calcium entry.
- Examples: Verapamil, Diltiazem.
- Primary Use: Slow ventricular rate in atrial fibrillation or flutter, convert supraventricular tachycardia.
- Other Indications: Hypertension management, treatment of angina (especially vasospastic angina).
- Adverse Effects: Bradycardia, heart block, hypotension, peripheral edema, heart failure.
- CYP450 3A4 Interactions:
- Inducer Effect: Faster metabolism, inadequate drug levels.
- Inhibitor Effect: Slower metabolism, elevated drug levels.
- Avoid Grape juice! Increases CCB
Other Antidysrhythmic Drugs
- Digoxin:
- Mechanism: Inhibits Na+/K+ ATPase, increasing intracellular calcium.
- Use Control supraventricular tachydysrhythmias, particularly atrial fibrillation and flutter.
- Toxicity Concerns: Low therapeutic index, risk of toxicity- Half-Life: 36 hours, making toxicity management challenging.
- Magnesium: Treating Torsades de Pointes.