Pharmacology Diuretics and Their Mechanisms

Nursing 3314: Pharmacology

• Course taught by Juan Feng, PhD, RN, CNE
• Focuses on cardiac drugs

Cardiac Review

• Covers heart anatomy, chambers, blood flow, electrical and mechanical function, layers, valves, and hemodynamics
• Depicts the major blood vessels and arteries
• Diagram highlights different parts of the heart (e.g., atria, ventricles, valves) and blood oxygenation levels in different chambers.
• Indicates oxygen rich and poor blood flow

Module 5: Diuretics and Potassium

• Reviews diuretics and their impact on potassium levels
• Discusses different types of diuretics

Types of Diuretics

• Loop Diuretics

• Thiazide

• Osmotic diuretics

• Potassium-sparing Diuretics

• Diuretics increase urine output.

• Normal urine output is typically 30 mL per hour or greater.

• Diuretics function by blocking sodium and chloride reabsorption.

Kidney Tubule/Diuretic Sites of Action

• Provides a diagram illustrating where various diuretics act within the kidney tubules.
• Shows the specific locations of diuretic action along the renal tubule system (e.g., proximal convoluted tubule)

Diuretics: Types/Prototypes

• Loop: furosemide (Lasix)
• Thiazides: hydrochlorothiazide (Hydrodiuril)
• Osmotic: Mannitol (Osmitrol)
• Potassium-sparing: Spironolactone (Aldactone)

Diuretics: Loop

• Prototype: furosemide (Lasix)
• Indications: used mainly for fluid overload in conditions like heart failure
• Mechanism: rapid acting loop diuretic, inhibiting Na and Cl reabsorption in ascending Loop of Henle
• Therapeutic Action: reduces edema and blood pressure
• Adverse Effects: postural hypotension, loss of K, Na, Mg, Cl, hypokalemia, hyponatremia, hypochloremia, nausea, vomiting, dehydration, tinnitus, and circulatory collapse.

Furosemide (continued)

• Nursing Implications: check potassium levels before administering, daily weight monitoring, frequent monitoring of blood pressure and signs of hypotension
• Dosage: varies based on route (oral, IV, IM), with IV acting rapidly and lasting for a specific period
• Drug Interactions: risk of digitalis toxicity in low potassium, combined use with aminoglycosides, lithium, and other antihypertensives can lead to hypotension.

Question: Which is a symptom of dehydration?

• Correct answer: Oliguria (low urine output)

Question: Which nursing intervention is most important before giving oral furosemide (Lasix)?

• Correct answer: Monitor the amount of urine excreted during the previous 24 hours.
• Patient's potassium levels should also be checked before giving Lasix.

Question: What time does the nurse schedule a lasix medication?

• Correct answer: 8 AM, with breakfast to avoid upsetting the stomach.

Hydrochlorothiazide (Hydrodiuril)

• Prototype drug for thiazides
• MOA: Blocks Na and Cl reabsorption in the early segment of the distal convoluted tubule
• Indication: Hypertension, sometimes as the first choice for African-Americans, mild/moderate heart failure
• Adverse effects: Hyponatremia, hypochloremia, hypokalemia, dehydration, pregnancy category B, may elevate glucose levels, and can precipitate gouty arthritis
• Drug Interactions: promotes digitalis toxicity, increases hypotensive effects if combined with other antihypertensives.

Osmotic Diuretics (Mannitol)

• Osmotic diuretic (only one currently used in the USA)
• Mechanism: Creates an osmotic force that blocks passive water reabsorption in the proximal convoluted tubule
• Indications: preventing or slowing renal failure, severe hypotension, hypovolemic shock, reducing intracranial pressure, and reduction of intraocular pressure
• Adverse Effects: headache, nausea & vomiting, electrolyte imbalance, possible edema, congestive heart failure
• Administration: solutions range from 5-25%, and should be warm and then cooled before IV administration, monitoring urine flow rate

Potassium-Sparing Diuretics

• Two categories:
  • Aldosterone antagonists (e.g., spironolactone)
  • Nonaldosterone antagonists (e.g., triamterene, amiloride)

Spironolactone (Aldactone)

• Aldosterone antagonist (prototype drug.)
• MOA: Blocks aldosterone, leading to potassium retention and sodium/water excretion
• Indications: Hypertension, edema (often used in conjunction with loop/thiazide diuretics because of low diuresis),
• Adverse Effects: Hyperkalemia (potassium levels greater than 5.0), gynecomastia, menstrual irregularities (due to chemical structure similar to steroid hormones).

Potassium-Sparing Diuretics (Non-Aldosterone antagonists)

• Prototype Drug: Triamterene (Dyrenium)
• MOA: Disrupts sodium-potassium exchange in the distal nephron.
• Indications: hypertension, edema (primarily to counteract potassium loss caused by other diuretics)
• Adverse Effects: nausea, vomiting, leg cramps, dizziness, and potentially hyperkalemia. Should be combined with other antihypertensive medications with caution

Potassium Supplementation

• Prototype: Potassium chloride
• Mechanism: Replacement of lost potassium
• Concerns: severe hypokalemia or hyperkalemia
• Nursing Implications:
  • IV administration guidelines (e.g., rate limits)
  • Monitoring potassium levels
  • Oral administration guidelines (e.g, with meals)
• Adverse Effects: Possible GI tract irritation, nausea, vomiting, diarrhea, severe intestinal ulcers, bleeding, perforation, and hyperkalemia.

Removal of Excess Potassium

• Steps for managing hyperkalemia
• Withholding foods/medications high in potassium;
• Drugs/infusions to reduce potassium levels
• Monitoring for complications such as heart problems
• Includes peritoneal or hemodialysis

The effect of calcium gluconate

• Demonstrates how calcium reverses some effects of hyperkalemia on heart function.

Module 6: Cardiovascular Medications

• Covers Cardiovascular Medications

2017 Hypertension Guidelines

• Provides blood pressure classifications (normal, elevated, high blood pressure, stages 1 & 2, crisis.)

Cholinergic Drugs: Atropine (AtroPen)

• Atropine (Prototype) is the only drug in this category used for cardiovascular purposes
• Muscarinic antagonists: Selectively block effects of acetylcholine at muscarinic receptors
• Indications: Bradycardia (ICU) because it increases heart rate
• Adverse Effects: tachycardia, dry mouth, blurred vision, photophobia, elevated intraocular pressure, urinary retention anhidrosis
• Interactions: with antihistamines, phenothiazine antipsychotics, tricyclic antidepressants

Actions of Adrenergic Receptors (heart related only)

• Describes the effects of adrenergic receptors on the heart, blood vessels, and kidneys
• Includes the heart-specific actions of alpha and beta receptors (ex: Beta 1 : heart and kidney)

Alpha Adrenergic Antagonists (Sympatholytics)

• Prototype: Prazosin (Minipress)
• Mechanism: Inhibits alpha 1 receptors to dilate blood vessels, decreasing blood pressure
• Indications: Essential hypertension, benign prostatic hyperplasia (BPH), Raynaud's phenomenon
• Adverse Effects: Dizziness, headaches, drowsiness, impotence, reflex tachycardia, nasal congestion, edema, postural hypotension (particularly with the first dose)

Beta Blockers

• Therapeutic Effects: reduced heart rate, reduced peripheral vascular resistance (with long-term use), reduced force of contraction, and reduced AV conduction speed
• Multiple Indications: angina, hypertension, various cardiac dysrhythmias, and heart failure
• Adverse Effects: Bradycardia, reduced cardiac output, AV heart block, heart failure, angina if rapidly withdrawn.

Beta Adrenergic Antagonists (Beta Blockers)

• Prototype : Propranolol, generic only
• Mechanism: Blocks both beta 1 and 2 adrenergic receptors.
• Therapeutic Action: Antihypertensive, reduces HR, CO
• Adverse Effects: Hypotension, bradycardia, bronchoconstriction
• Nursing Implications: Contraindicated in asthma, COPD, and check BP and HR before administration

Metoprolol (Lopressor, Toprol XL)

• Prototype 2nd-generation selective beta-1 blocker
• Mechanism: Blocks beta-1 receptors
• Action: Reduce heart rate, force of contraction, conduction velocity through AV node
• Indications: Hypertension, angina, MI, and heart failure
• Adverse Effects: Bradycardia, reduced cardiac output, AV heart block; can cause heart failure

Central Acting Alpha 2 Agonists

• Prototype: Clonidine (Catapres)
• Mechanism of action: activates alpha 2 receptors in the brainstem, reduces sympathetic outflow to blood vessels and heart, decreases blood pressure
• Indications: Hypertension, pain
• Adverse Effects: Drowsiness, sedation, xerostomia, constipation, impotence, rebound hypertension, fetal harm, euphoria, hallucinations (if abused).

Drugs Working on Renin-Angiotensin System

• Diagram illustrating the renin-angiotensin-aldosterone system (RAAS) and the effects of drugs that target it

ACE (Angiotensin-Converting Enzyme) Inhibitors

• Prototype: captopril (generic only)
• MOA: Inhibits ACE, disrupting the conversion of angiotensin I to angiotensin II to lower blood pressure
• Indications: Hypertension, heart failure, MI, also is a choice for those with diabetes
• Adverse Effects: First-dose hypotension, cough, angioedema, neutropenia, agranulocytosis, fetal injury, and hyperkalemia
• Nursing Implications: monitoring of BP before administration, and reporting of unusual symptoms (fever).

Angiotensin II Receptor Blockers (ARBs)

• Prototype: Losartan (Cozaar)
• MOA: Blocks angiotensin II receptors, causing dilation of blood vessels and lowering BP.
• Indications: Hypertension, diabetic retinopathy
• Adverse Effects: lower risk of cough than ACE inhibitors, but can cause angioedema

Calcium Channel Blockers

• Prototype: Verapamil (Calan)
• Mechanism: Inhibits calcium ion influx blocking the calcium ion channels.
• Therapeutic Action: Antihypertensive, reduces heart rate, anti-arrhythmic (especially for SVT (IV), anti-anginal, decreases force of contraction.)
• Adverse Effects: Dizziness, headache, fatigue, sleep disturbances, hypotension, bradycardia, constipation, nausea, edema
• Interactions: Grapefruit juice can increase drug levels, this also means other antihypertensive drugs amplify effects.

CCBs

• Diltiazem (Cardizem): similar to verapamil
• Nifedipine (Procardia): Primarily works on arteries/blood vessels not heart itself
• Indications: hypertension and angina
• Adverse Effects: edema, flushing, headache, dizziness, reflex tachycardia; some side effects are rare (e.g., maternal tachycardia)
• Drug cards should be made for all calcium channel blockers.

Vasodilators

• Prototype: Hydralazine (Apresoline)
• MOA : Selectively dilates arterioles, not veins (HR may increase)
• Indications: Essential hypertension, hypertensive crisis (IV), and heart failure
• Adverse Effects: Reflex tachycardia, increased blood volume, lupus-like syndrome, and hypotension if combined with other antihypertensives

Vasodilators (Anti-anginal)

• Prototype: Nitroglycerine (Nitrol)
• Mechanism: Relaxes vascular smooth muscle reducing preload/afterload/myocardial oxygen demand.
• Therapeutic Action: Decreases BP, relieves chest pain
• Indications: Chest pain (angina)

Nitroglycerine

• Administration routes: Sublingual tablets (give one q5 minutes up to three), sublingual spray, nitrocream (topical), transdermal patch, and capsule SR (taken for preventing chest pain); IV (Tridil) titration according to blood pressure in ICU only.
• Side effects: Headache, postural hypotension, flushing

Cardiac Glycosides (Digoxin)

• Prototype: Digoxin (digitalis)
• Mechanism: Increases force of myocardial contraction (positive inotropic effect ), increases diuresis.
• Therapeutic Action: Used in atrial fibrillation and congestive heart failure.
• Nursing Implications: Apical pulse should be taken before administration
• Indications: Heart failure (now 2nd-line drug.)
• Adverse effects: Bradycardia, heart blocks, other dysrhythmias, visual disturbances, N&V, agitation

New York Heart Association (NYHA) Class

• Classifies heart failure severity based on symptoms.
  • Class I: No symptoms
  • Class II: Mild symptoms during activity
  • Class III: Moderate symptoms during minimal activity
  • Class IV: Symptoms at rest

ACC/AHA Heart Failure Class

• Stages of heart failure: classifying patients at risk or with varying degrees of heart failure

Medications for Heart Failure

• Diuretics (e.g., furosemide)
• Beta blockers (e.g., metoprolol)
• RAAS inhibitors (e.g., ACE inhibitors: captopril, angiotensin II receptor blockers: losartan; aldosterone antagonists: spironolactone)
• Inotropics (e.g., digoxin, dopamine (Dopastat), dobutamine (Dobutrex)

Dopamine

• Catecholamine used for heart failure
• Different dosages have different effects - Low dose: primarily vasodilation - Moderate dose: increase HR, contractility, CO - High dose: primarily vasoconstriction, used to raise low blood pressure

Dobutamine

• Catecholamine
• Primary Action: Increase myocardial contractility.
• Doesn't activate alpha-1 receptors.
• Preferred over dopamine in many cases. Given via IV infusion.

Anti-Arrhythmics (Dysrhythmics)

• Used for various heart rhythms
• Classes: I, II, III, and IV
• Prototype-specific medications to control dysrhythmia (ex: Adenosine, Amiodarone, Calcium Gluconate )

Calcium Gluconate/Calcium Chloride

• Calcium chloride is more potent than calcium gluconate and should be administered undiluted.
• Use: treating hypocalcemia, magnesium toxicity, or hyperkalemia
• Administration: titrate dosage accordingly to patient EKG changes
• Contraindications: hypercalcemia, digoxin, and ventricular fibrillation

Lipid-Lowering Medications

• HMG-CoA reductase inhibitors (statins)
• Prototype: Atorvastatin (Lipitor), Lovastatin (Mevacor)
• Ezetimibe (Zetia): Cholesterol blocker
• Fibric acid derivatives (fibrates)
• Prototype: Gemfibrozil (Lopid), fenofibrate (or fenofibric acid)

Prototype drug information included for each medication class

This quiz covers key concepts related to diuretics, including mannitol, spironolactone, and furosemide. It explores their mechanisms of action, side effects, and clinical applications. Test your understanding of how these medications function and their implications in patient care.