Pharmacology Notes

Owner: Samantha Anne Nicole S. Sanchez

DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
○​ Lungs → pulmonary edema
CHAPTER 22: Treatment of Heart Failure ○​ Systemic veins → peripheral
edema

📌 Key Concept: CONGESTION

●​ Accumulation of blood in:
○​ Heart

TY
○​ Lungs
○​ Peripheral tissues
●​ Hallmark of chronic heart failure (CHF)

📌 Structural & Fluid Effects

R
PE
●​ Cardiac dilation (enlarged heart)
●​ Pulmonary edema → fluid in lungs
●​ Peripheral edema → especially lower
extremities

🫀 HEART FAILURE (CHF) O

📌 Clinical Manifestations (VERY
PR
📌 Definition HIGH-YIELD)

●​ Fatigue / tiredness → ↓ perfusion

●​ Heart failure (HF) = inability of the heart ●​ Shortness of breath (dyspnea) →
to pump enough blood to meet tissue pulmonary congestion
'S

demands ●​ Rapid heartbeat (tachycardia) →

●​ Leads to ↓ cardiac output (CO) → ↓ compensatory
oxygen delivery ●​ Pulmonary edema
LE

●​ Peripheral edema (legs, ankles)

📌 Major Causes
●​ Untreated hypertension → ↑ afterload
📌 Key Hemodynamic Change
O

→ cardiac strain ●​ ↓ Cardiac Output (CO)​

●​ Myocardial infarction (MI) → loss of → cannot meet body’s oxygen demand
IC

functional myocardium
●​ Valvular defects → impaired forward
flow
📌 Nature of Disease
N

●​ Other conditions → ↓ contractility ●​ Chronic condition → requires lifelong

📌 Core Pathophysiology
management
●​ Often referred to as Chronic Heart
Failure (CHF)
1.​ ↓ Contractile force
2.​
3.​
→ ↓ Cardiac Output (CO)
→ ↓ Blood pressure
💊 Treatment (MULTI-DRUG
4.​
5.​
→ Blood accumulates in heart
→ Backflow (congestion):
⚠️ Usually requires 2 or more drugs
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
1. Diuretics ●​ The key problem is reduced cardiac
output (CO)
●​ ↓ fluid volume → ↓ edema & congestion ●​ This leads to impaired tissue
perfusion
2. Vasodilators ●​ CHF is a progressive and chronic
disease
●​ ↓ preload & afterload → easier pumping

3. Beta Blockers
📌 Core Pathophysiology

TY
When the heart’s pumping ability decreases:
●​ ↓ heart workload
●​ Improve survival 1.​ ↓ Cardiac Output (CO)

R
2.​ → ↓ Blood pressure
4. Digoxin (Cardiac Glycoside) 3.​ → ↓ Tissue perfusion

PE
4.​ → Body activates compensatory
●​ ↑ contractility (positive inotrope) mechanisms
●​ Helps improve CO
⚠️ These mechanisms are initially helpful but
become maladaptive over time

O
⚠️ COMPENSATORY MECHANISMS (VERY
PR
IMPORTANT — ALWAYS TESTED)

1.🧠 Sympathetic Nervous System (SNS)

Activation
'S

When CO drops, the body activates the SNS to

maintain perfusion.
LE

Mechanism:

●​ Release of:
O

○​ Norepinephrine (NE)
○​ Epinephrine (Epi)
IC

Effects:

🫀 CHRONIC HEART FAILURE (CHF)

N

●​ α₁ receptors (vascular smooth

muscle)​

📌 Definition → Vasoconstriction → ↑ Blood pressure

●​ β₁ receptors (heart)​
→ ↑ Heart rate (tachycardia)​
Chronic heart failure (CHF) is a condition in → ↑ Myocardial contractility
which the heart cannot adequately pump
enough blood to supply the tissues and organs Purpose:
with oxygen and essential nutrients.
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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👉 Compensate by increasing CO and BP ●​ ↑ Water reabsorption in kidney tubules
●​ Stimulates thirst (hypothalamus)
Long-term effect:
👉 Result:
●​ ↑ Cardiac workload
●​ ↑ Oxygen demand ●​ Further ↑ blood volume
●​ Contributes to cardiac damage and ●​ Contributes to fluid overload
progression of HF

❗ OVERALL EFFECT OF COMPENSATION

TY
2. 🧪
Renin-Angiotensin-Aldosterone System
(RAAS) Although these mechanisms aim to restore
circulation:

R
Activated due to reduced renal perfusion
Long-term consequences:

PE
Step-by-Step Pathway:
●​ Cardiac hypertrophy
1.​ Kidneys release RENIN ○​ Thickening of heart muscle
2.​ Renin converts: ●​ Cardiac remodeling
○​ Angiotensinogen (from liver)
→ Angiotensin I
3.​ ACE (from lungs) converts: O ○​ Structural changes in heart
shape
●​ Heart enlargement (dilation)
PR
○​ Angiotensin I → Angiotensin II ●​ Decreased efficiency of contraction

🔥 Effects of Angiotensin II (VERY 👉 Ultimately:

HIGH-YIELD)
●​ Heart becomes weaker
'S

●​ Potent vasoconstrictor​ ●​ CHF progressively worsens

→ ↑ Blood pressure

💊 TREATMENT OF CHF (DETAILED +

●​ Stimulates release of:
LE

○​ Aldosterone (adrenal cortex)

○​ ADH (posterior pituitary) HIGH-YIELD)

💧 Aldosterone Effects 🎯 MAIN GOAL:

O

3.

●​ Acts on kidneys: ●​ Improve cardiac output

IC

○​ ↑ Sodium (Na⁺) reabsorption ●​ Reduce workload of the heart

○​ Water follows sodium ●​ Prevent harmful compensatory effects

👉 Result: ●​ Reduce symptoms (especially

N

congestion)

●​ ↑ Blood volume
●​ ↑ Venous return (preload)
1. 🧴 Vasodilators (CORE THERAPY)
4. 💦 ADH (Antidiuretic Hormone) Mechanism:

●​ Relax vascular smooth muscle → dilate

Actions: blood vessels
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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Effects on Hemodynamics: ●​ Block β₁ receptors

A. ↓ Preload Effects:

●​ Caused by venous dilation ●​ ↓ Heart rate

●​ Preload = amount of blood returning to ●​ ↓ Contractility (initially)
the heart ●​ ↓ SNS overactivation

👉 ↓ venous return → ↓ volume the heart must

TY
Long-term benefit:
pump
●​ Protects heart from chronic
B. ↓ Afterload sympathetic damage

R
●​ Improves survival
●​ Caused by arterial dilation
●​ Afterload = resistance the heart must

PE
overcome to eject blood

👉 ↓ resistance → easier ejection of blood 4. 💊 Digoxin (Cardiac Glycoside)

Overall Effect:

●​ ↓ Cardiac workload
O
Mechanism:

●​ Positive inotrope → ↑ myocardial

PR
●​ ↑ Cardiac output contractility

👉 This is the primary benefit of vasodilators Current role:

in CHF
●​ Second-line drug

💧 Diuretics
'S

●​ Used when:
2.
○​ Symptoms persist despite other
therapy
LE

Mechanism:

●​ Promote excretion of: 5. 🧬

SGLT2 Inhibitors (NEW + VERY
○​ Sodium IMPORTANT)
O

○​ Water
Examples:
IC

Effects:
●​ Dapagliflozin
●​ ↓ Blood volume ●​ Empagliflozin
●​ ↓ Edema (pulmonary + peripheral)
N

●​ ↓ Congestion Mechanism:

👉 Very important for symptom control ●​ ↓ Sodium reabsorption in kidneys

●​ ↑ Sodium delivery to distal tubule
3. ❤️ Beta Blockers
Effects:
Mechanism:
●​ ↓ Preload
●​ ↓ Afterload
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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●​ ↓ Sympathetic activity → further helps improve circulation and
reduce cardiac workload
Clinical Benefits:

●​ ↓ Hospitalization rates ⚠️ TYPES OF DIURETICS IN CHF (VERY

●​ ↓ Cardiovascular mortality HIGH-YIELD)

👉 Now included in CHF treatment guidelines There are 3 major classes:

TY
1.​ Thiazide diuretics
2.​ Loop diuretics (organic acids)
3.​ Aldosterone antagonists
(potassium-sparing)

R
💧 DIURETIC THERAPY OF CHF 🧂 THIAZIDE DIURETICS

PE
1.

📌 General Role of Diuretics in CHF 📌 Mechanism of Action

Diuretics are widely used in the management of
chronic heart failure (CHF) and are essential for
symptom control.
O ●​ Act on distal tubules of nephron
●​ Block sodium reabsorption
PR
🎯 Main Therapeutic Effect: 📌 Effects
●​ ↑ Sodium excretion
●​ Elimination of excess sodium (Na⁺)
●​ ↑ Water excretion
and water via the kidneys
'S

●​ Also causes:

📌 Why Diuretics are Important in CHF ○​ Potassium loss →

hypokalemia
LE

In CHF:
📌 Potency
●​ There is sodium and water retention
●​ Moderate potency
O

●​ This leads to:

📌 Clinical Use
○​ Edema (peripheral swelling)
○​ Pulmonary congestion
IC

👉 Therefore: ●​ Best for:

○​ Mild to moderate CHF
N

●​ Removing sodium + water = ↓ fluid ○​ Patients with normal renal

overload function

📌 Additional Benefit 📌 Key Differences Within Class

●​ Sodium excretion also produces a ●​ Mainly differ in:
vasodilating effect​ ○​ Potency
○​ Duration of action
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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⚠️ Important Adverse Effect 📌 Duration of Action
●​ Hypokalemia (VERY HIGH-YIELD) ●​ About 4–8 hours

🔁 LOOP DIURETICS (ORGANIC ACIDS)

2.
⚠️ Important Adverse Effect
📌 Mechanism of Action ●​ Hypokalemia

TY
●​ Act on: 3. ALDOSTERONE ANTAGONISTS
○​ Thick ascending limb of loop (POTASSIUM-SPARING)
of Henle
📌 Mechanism of Action

R
📌 Effects

PE
●​ Act on:
●​ ↑ Massive excretion of: ○​ Collecting ducts of nephron
○​ Sodium
○​ Water 📌 Normal Role of Aldosterone
●​ Also causes:

📌 Potency
○​ Potassium loss
O ●​ ↑ Sodium retention
●​ ↑ Potassium excretion
PR
●​ Most potent diuretics
📌 Effects of Aldosterone Antagonists
📌 Clinical Use (VERY HIGH-YIELD)
●​ ↑ Sodium excretion
'S

●​ ↓ Potassium excretion (retain K⁺)

●​ Severe CHF 👉 Hence called: Potassium-sparing diuretics

LE

●​ Impaired renal function

●​ Acute heart failure (emergency use) 📌 Importance in CHF
●​ CHF → ↑ aldosterone activity
O

📌 Special Feature
●​ Blocking aldosterone:
○​ Improves outcomes
IC

○​ ↓ mortality (VERY
●​ Can be given intravenously (IV)​ HIGH-YIELD)
→ Rapid relief of:
📌 Drugs
N

○​ Pulmonary edema
○​ Severe congestion

📌 Common Drugs A. Aldosterone Receptor Antagonists

●​ Spironolactone
●​ Furosemide ○​ Competitive antagonist
●​ Bumetanide ○​ Works best when aldosterone is
●​ Torsemide elevated
●​ Eplerenone
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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○​ Similar to spironolactone
○​ Fewer adverse effects

B. Sodium Channel Blockers

●​ Amiloride
●​ Triamterene

👉 Mechanism:

TY
●​ Block sodium channels in collecting duct​
→ indirectly reduce aldosterone effects

R
🫀💊 VASODILATOR THERAPY OF CHRONIC
📌 Clinical Use

PE
HEART FAILURE (CHF)

●​ Often combined with: 📌 General Overview

○​ Thiazides

👉 Purpose:
○​ Loop diuretics
O
Vasodilator therapy is a major component in
the treatment of CHF. The primary action of
PR
vasodilator drugs is to relax or dilate blood
vessels, which leads to important hemodynamic
●​ Prevent potassium loss changes that improve heart function.

⚠️ Important Adverse Effect 📌 Primary Effects of Vasodilation

'S

●​ Hyperkalemia (VERY HIGH-YIELD) When blood vessels dilate:

LE

⚠️ ADVERSE EFFECTS OF DIURETICS ●​ Peripheral resistance decreases

●​ Blood pressure decreases

📌 Thiazides & Loop Diuretics 📌 Impact on the Heart

O

●​ Nausea These changes produce several beneficial

IC

●​ Hypotension effects:
●​ Hypokalemia
●​ Hyperuricemia ●​ Decreased cardiac workload
N

●​ Hyperglycemia ●​ Decreased myocardial oxygen

consumption
📌 Potassium-Sparing Diuretics ●​ Improved efficiency of cardiac
pumping
●​ Hyperkalemia (MAIN RISK) ●​ Increased cardiac output (CO)

👉 The heart is able to pump more efficiently

with less effort, which is crucial in CHF.
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
By decreasing preload, afterload, or both:

📌 KEY HEMODYNAMIC CONCEPTS (VERY ●​ Cardiac workload is reduced

●​ Efficiency of contraction improves
IMPORTANT) ●​ Cardiac output increases

🔴 Afterload 👉 This is the main therapeutic effect of

vasodilators in CHF

TY
●​ Defined as the force the heart must
generate to overcome vascular
resistance in order to eject blood from
💊 CLASSIFICATION OF VASODILATORS
the left ventricle.
Vasodilators are classified based on their

R
primary site of action:
Effect of Vasodilators:

PE
1.​ Arterial dilators
●​ Arterial dilation → ↓ afterload
2.​ Venous dilators (venodilators)
●​ Lower blood pressure → easier ejection
3.​ Balanced dilators
of blood

👉 The heart does not need to work as hard 🔴 1. ARTERIAL DILATORS

O
🔵 Preload 📌 Example: Hydralazine
PR
●​ Defined as the amount of blood
returning to the heart (venous return) 📌 Mechanism of Action
'S

●​ Believed to act through formation of

Effect of Vasodilators:
nitric oxide (NO)
●​ Venous dilation → ↓ preload ●​ Nitric oxide is a natural vasodilator
LE

●​ Reduced blood volume entering the produced in blood vessels

📌 Effects
heart

👉 This reduces cardiac workload

O

●​ Dilates arteries
⚖️ Balanced Vasodilation ●​ Decreases systemic blood pressure
IC

●​ Reduces afterload
Some drugs dilate both arteries and veins,
producing: 📌 Result in CHF
N

●​ ↓ Afterload ●​ Reduced resistance → easier ejection of

●​ ↓ Preload blood

👉 This is referred to as “balanced ●​ Increased cardiac output

vasodilation”
⚠️ Adverse Effects
📌 Overall Hemodynamic Benefit Mostly related to excessive vasodilation:
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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●​ Nausea ⚠️ Adverse Effects
●​ Headache
●​ Postural hypotension ●​ Headache (very common)
●​ Reflex tachycardia (VERY ●​ Dizziness
IMPORTANT) ●​ Vasomotor flushing
●​ Postural hypotension

🔵 2. VENOUS DILATORS (VENODILATORS) ●​ Reflex tachycardia

⚖️ 3. BALANCED VASODILATORS (MOST

TY
📌 Examples IMPORTANT CLASS)
●​ Nitroglycerin

R
●​ Isosorbide dinitrate

📌 Major Drug Classes

PE
📌 Mechanism of Action ●​ ACE Inhibitors (ACEIs)
●​ Angiotensin Receptor Blockers
(ARBs)
●​ Primarily dilate:
○​ Large veins
○​ Vena cava
O
👉 These are the preferred drugs in CHF
PR
📌 Effects 📌 Mechanism Basis
These drugs act by inhibiting the effects of
●​ Decrease venous return to the heart
angiotensin II, which normally causes:
●​ Decrease preload
'S

📌 Importance in CHF ●​ Vasoconstriction

●​ Aldosterone release
LE

●​ ADH release
In CHF:

●​ The heart is often congested and 📌 Effects of Blocking Angiotensin II

O

overloaded with blood

●​ Vasodilation
●​ Contractile force is reduced
●​ Decreased sodium and water
👉 Venodilation:
IC

retention

●​ Reduces volume entering the heart

🧪 ACE INHIBITORS (ACEIs)
N

●​ Allows heart to pump more effectively

📌 Result 📌 Mechanisms of Action (TWO KEY

MECHANISMS)
●​ Improved cardiac output
●​ Reduced congestion 1. Inhibition of ACE Enzyme

●​ Prevents conversion of:

○​ Angiotensin I → Angiotensin II
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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👉 Results: ●​ Prevent actions of angiotensin II:
○​ Vasoconstriction
●​ ↓ Angiotensin II ○​ Aldosterone release
●​ ↓ Vasoconstriction ○​ ADH release

👉 Leads to:
●​ ↑ Vasodilation
●​ ↑ Sodium & water excretion

2. Increased Bradykinin Levels ●​ Vasodilation

●​ ↑ Sodium and water excretion

TY
●​ ACE normally breaks down bradykinin
●​ Inhibition → ↑ bradykinin 📌 Key Difference from ACEIs
👉 Bradykinin: ●​ ❌ Do NOT affect bradykinin

R
●​ Potent vasodilator
📌 Clinical Significance

PE
●​ Enhances therapeutic effect

📌 Net Effects ●​ Less risk of:

○​ Dry cough

●​
●​
↓ Preload
↓ Afterload O ○​ Angioedema

📌 Overall Effect
PR
●​ ↑ Cardiac output
●​ ↓ Fluid retention
●​ Balanced vasodilation

⚠️ Adverse Effects (VERY HIGH-YIELD) ●​

●​
↓ Preload
↓ Afterload
●​ ↑ Cardiac output
'S

●​ Headache
●​ Dizziness
●​ Hypotension 💊 ARNI (NEW CLASS — VERY IMPORTANT)
LE

●​ Hyperkalemia
●​
●​
Dry cough (classic side effect)
Angioedema (serious reaction)
📌 Example
👉 Caused by ↑ bradykinin
O

●​ Sacubitril + Valsartan (Entresto)

📌 Drug Class
IC

🧬 ANGIOTENSIN RECEPTOR BLOCKERS

(ARBs) ●​ Angiotensin Receptor–Neprilysin
N

Inhibitor (ARNI)

📌 Mechanism of Action 📌 Mechanism of Action

Valsartan (ARB component)
●​ Block Angiotensin II receptors (AT₁
receptors) ●​ Blocks angiotensin II receptor

📌 Effects Sacubitril (Neprilysin inhibitor)

Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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●​ Inhibits breakdown of: 👉 Due to increased bradykinin
○​ Natriuretic peptides

📌 Effects
●​ ↑ Vasodilation

TY
●​ ↑ Sodium excretion
●​ ↓ Preload
●​ ↓ Afterload

📌 Clinical Use

R
PE
●​ Indicated for:
○​ NYHA Class II–IV CHF

📌 Benefits O
PR
●​ ↓ Hospitalization
●​ ↓ Mortality

⚠️ Important Considerations
'S

●​ ❌ Contraindicated in pregnancy
●​ ⚠️ Must wait 36 hours after stopping
LE

ACE inhibitors

⚠️ ADVERSE EFFECTS OF ACEIs & ARBs

O

(SUMMARY)

📌 Common Effects
IC

●​ Headache
N

●​ Dizziness

🫀💊 USE OF ADRENERGIC
●​ Hypotension
●​ Hyperkalemia
●​ GI disturbances BETA-BLOCKERS IN CHF

📌 ACEI-Specific Effects 📌 General Overview

●​ Dry cough
●​ Angioedema
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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Adrenergic beta-blockers are an important ●​ Increased cardiac workload
component in the treatment of chronic heart ●​ Increased oxygen demand
failure (CHF). Although their direct effects may ●​ Progressive cardiac damage
initially seem counterintuitive, they play a
crucial role in improving long-term cardiac
function and survival.
📌 Therapeutic Benefit of Beta-Blockers
1. ❤️ Slowing Heart Rate
📌 Basic Mechanism of Action (Review)

TY
●​ ↓ HR → ↑ diastolic filling time
●​ Beta-blockers bind to beta-adrenergic ●​ Heart fills more completely

👉 Result:
receptors
●​ They block the effects of:

R
○​ Norepinephrine (NE)
○​ Epinephrine (Epi) ●​ Improved efficiency of pumping

💥 Reduced Cardiac Stress

PE
📌 Primary Target in CHF 2.

●​ ↓ SNS overstimulation
●​ β₁ receptors (heart)
●​ ↓ myocardial oxygen demand

📌 Direct Cardiac Effects O

👉 Protects the heart from long-term damage
PR
Blocking β₁ receptors leads to: 3. 🧪 Effect on Kidneys (VERY HIGH-YIELD)

●​ ↓ Heart rate (negative chronotropic ●​ β₁ receptors are also present on:

effect) ○​ Juxtaglomerular (JG) cells of
'S

●​ ↓ Force of contraction (negative the kidneys

inotropic effect)

⚠️ IMPORTANT CONCEPT (VERY 📌 Role of JG Cells

LE

HIGH-YIELD) ●​ Release renin

👉 These effects appear opposite of what is 📌 Effect of Beta-Blockade

O

needed in CHF​
(because CHF already has ↓ contractility)
●​ ↓ Renin release​
IC

📌 Why Beta-Blockers Are Beneficial in CHF → ↓ activation of

Renin-Angiotensin-Aldosterone

🔥 Key Idea: System (RAAS)

N

CHF is associated with chronic overactivation

📌 Result of RAAS Suppression
of the sympathetic nervous system (SNS)
●​ ↓ Vasoconstriction

📌 Effects of Excess SNS in CHF ●​ ↓ Sodium & water retention

●​ Persistent tachycardia
👉 This reduces:
Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
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●​ Preload ●​ Bradycardia
●​ Afterload ●​ Hypotension
●​ Fatigue

💊 DRUGS USED (VERY HIGH-YIELD) ●​ Possible worsening of HF if overdosed

Preferred beta-blockers in CHF: 🔥 INTEGRATED MECHANISM SUMMARY

●​ Metoprolol
📌 In CHF:

TY
●​ Bisoprolol
●​ Nebivolol
1.​ ↓ CO → SNS activation
●​ Carvedilol
2.​ SNS → ↑ HR + ↑ contractility + ↑ renin

📌 Special Feature: Carvedilol

R
3.​ Chronic effect → cardiac damage

📌 Beta-blockers:

PE
●​ Blocks:
○​ β receptors
●​ Block β₁ receptors →
○​ α₁ receptors
○​ ↓ HR

📌 Additional Effect: O ○​ ↓ renin release

📌 Final Result:
PR
●​ Vasodilation (via α₁ blockade)

👉 Leads to: ●​
●​
↑ Filling time
↓ RAAS activation
●​ ↓ Peripheral resistance ●​ ↓ cardiac stress
●​ Improved long-term function
'S

●​ Further ↓ cardiac workload

⚠️ DOSING CONSIDERATION (VERY 🫀💊 CARDIAC GLYCOSIDES (DIGOXIN)

LE

IMPORTANT)

●​ Use LOW therapeutic doses

📌 GENERAL OVERVIEW
O

●​ Start low and titrate slowly Cardiac glycosides are a class of drugs

📌 Why?
originally derived from the plant species:
IC

●​ Digitalis purpurea
Excessive beta blockade can cause: ●​ Digitalis lanata
N

●​ ↓ Contractility too much Because of this origin, the term “digitalis” is

●​ ↓ Cardiac output often used to refer to this group of drugs.

👉 Can worsen heart failure 👉 In current clinical practice:

⚠️ ADVERSE EFFECTS (IMPLIED +
●​ Digoxin is the only cardiac glycoside
still widely used
HIGH-YIELD)
Pharmacology Notes
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📌 PRIMARY THERAPEUTIC ROLE ●​ ↑ Excretion of sodium and water
●​ ↓ Edema and fluid overload
The most important effect of digoxin is:

👉 Increase in myocardial contractility 2. 🧠 PARASYMPATHETIC (VAGAL) EFFECT

(positive inotropic effect)
Digoxin also enhances parasympathetic
(vagal) tone.
This is particularly useful in chronic heart
failure (CHF) where the heart’s pumping ability
📌 Mechanism:

TY
is impaired.

●​ Stimulates the vagus nerve

🧪 PHARMACOLOGIC EFFECTS (VERY 📌 Effects on Heart:

R
HIGH-YIELD — DO NOT SKIP)

❤️

PE
●​ ↓ SA node activity → ↓ heart rate
1. POSITIVE INOTROPIC EFFECT (MAIN ●​ ↓ AV node conduction
EFFECT)

Digoxin increases the force of contraction of

📌 Clinical Terms:
the myocardium.

📌 Key Feature:
O ●​ Negative chronotropic effect → ↓
heart rate
PR
●​ Negative dromotropic effect → ↓ AV
conduction
●​ This increase in contractility occurs
WITHOUT increasing myocardial
oxygen consumption
📌 ECG Finding:
👉 This is very important because:
'S

●​ Prolongation of PR interval

⚠️ HEART BLOCK (VERY IMPORTANT —

LE

●​ Most drugs that increase contractility

also increase oxygen demand HIGH-YIELD)
●​ Digoxin improves efficiency instead of
increasing workload
📌 Definition:
O

📌 Resulting Effects: Heart block = impaired conduction of electrical

IC

●​ ↑ Cardiac output (CO) impulses from atria → ventricles

📌 TYPES OF HEART BLOCK

●​ Improved systemic circulation
●​ Better tissue perfusion
N

📌 Secondary Renal Effect: 🟢 First-Degree AV Block

Because cardiac output improves: ●​ All impulses conducted
●​ Prolonged PR interval

👉 This is often:
●​ ↑ Renal blood flow
●​ ↑ Kidney perfusion

👉 Leads to:
Pharmacology Notes
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●​ Therapeutically desirable (in 📌 Safe Range:
AF/flutter)
●​ 60–100 beats per minute
🟡 Second-Degree AV Block
●​ Some impulses fail to conduct
📌 If:
👉 ECG: ●​ < 60 bpm (bradycardia)
●​ 100 bpm (tachycardia)​

TY
​
●​ Some P waves not followed by QRS

Examples:
👉 Consult physician before administration

R
●​ 2:1 block → every other beat blocked
●​ 3:1, 4:1 ratios also possible ⚙️ MECHANISM OF ACTION (STEP-BY-STEP

PE
🔴 Third-Degree (Complete) Heart Block — VERY HIGH-YIELD)

●​ No impulses pass through AV node

●​ Atria and ventricles beat independently
🔹 Step 1: Inhibition of Na⁺/K⁺ ATPase
O
⚠️ This is:
PR
Digoxin inhibits the Na⁺/K⁺ ATPase pump in
●​ Life-threatening cardiac cells.
●​ Requires immediate treatment
📌 Normal Function:
📌 Clinical Use of This Effect
'S

●​ Pumps:
○​ Na⁺ OUT of the cell
In:
○​ K⁺ INTO the cell
LE

●​ Atrial fibrillation
●​ Atrial flutter
📌 Effect of Inhibition:
👉 Digoxin: ●​ ↑ Intracellular Na⁺
O

●​ Slows AV conduction 🔹 Step 2: Effect on Na⁺/Ca²⁺ Exchanger

IC

●​ Reduces ventricular rate

●​ Prevents excessive ventricular Normally:
stimulation
N

●​ Na⁺ enters cell

⚠️ SPECIAL ADMINISTRATION
●​ Ca²⁺ is pumped OUT

CONSIDERATION With ↑ Na⁺ inside cell:

Before giving digoxin: ●​ Na⁺/Ca²⁺ exchanger slows down

👉 Check patient’s pulse 👉 Result:

Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
●​ ↓ Ca²⁺ removal ●​ Minimal plasma protein binding

🔹 Step 3: ↑ Intracellular Ca²⁺ 📌 Excretion

●​ Calcium accumulates inside cardiac ●​ Mostly unchanged via kidneys
cells
📌 Half-Life
🔹 Step 4: Enhanced Contractile Proteins

TY
●​ 1.5–2 days
●​ ↑ Actin–myosin interaction ●​ Longer in:
○​ Elderly patients

R
📌 FINAL RESULT: ⚠️ EFFECT OF ELECTROLYTES

PE
(EXTREMELY HIGH-YIELD)
👉 Stronger myocardial contraction → ↑
cardiac output 🔻 Hypokalemia (LOW K⁺)
👉 MOST DANGEROUS
💊 PHARMACOKINETICS O ●​ ↑ Sensitivity to digoxin
PR
📌 Administration Routes ●​ ↑ Risk of toxicity

●​ Oral (PO) 📌 Consequences:

●​ Intravenous (IV)
●​ Arrhythmias
'S

📌 Digitalization Process ●​ Ventricular fibrillation

●​ Sudden death
LE

Phase 1: Digitalization
🔺 Hyperkalemia (HIGH K⁺)
●​ Rapid loading doses
●​ Achieve therapeutic levels quickly ●​ ↓ Effectiveness of digoxin
O

Phase 2: Maintenance 🔺 Hypercalcemia (HIGH Ca²⁺)

IC

●​ Lower doses ●​ ↑ Digoxin effect

●​ Maintain steady blood levels ●​ ↑ Risk of arrhythmias
N

📌 Absorption 📌 Important Clinical Link

●​ Food may delay absorption Patients with CHF often take:
●​ Does NOT reduce total absorption
significantly ●​ Loop or thiazide diuretics

📌 Distribution 👉 These cause:

Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
●​ Potassium loss → hypokalemia 📌 Drug:
●​ Digoxin Immune Fab (Digibind)

📌 Management: 📌 Mechanism:
●​ Encourage potassium intake: ●​ Antibodies bind digoxin → inactivate it
○​ Bananas
○​ Vegetables
📌 Effect:

TY
○​ Fruit juices
●​ Potassium supplements:
●​ ↓ Toxicity within 30–60 minutes
○​ K-Lyte
○​ Slow-K
📌 Indication:

R
⚠️ ADVERSE AND TOXIC EFFECTS

PE
●​ Life-threatening digoxin toxicity

📌 Mild Toxicity ⚠️ Contraindication

●​
●​
Nausea
Vomiting O ●​ Ventricular fibrillation
PR
●​
●​
Headache
Visual disturbances (e.g., yellow vision) 💊 CLINICAL INDICATIONS
●​ Skin rash

👉 Managed by: 📌 1. Chronic Heart Failure (CHF)

'S

●​ ↑ Contractility
●​ Reducing dose ●​ Improves CO

📌 Severe Toxicity (VERY DANGEROUS) 📌 2. Atrial Fibrillation / Atrial Flutter

LE

●​ Cardiac arrhythmias: ●​ ↓ AV conduction

○​ Premature ventricular
O

●​ ↓ Ventricular rate
contractions (PVCs)
○​ Ventricular tachycardia
🔄 DRUG INTERACTIONS (VERY
IC

○​ Ventricular fibrillation
○​ Cardiac arrest HIGH-YIELD)

📌 Management of Toxicity 📌 ↓ Digoxin Absorption

N

●​ Stop digoxin ●​ Antacids

●​ Administer: ●​ Laxatives
○​ Potassium ●​ Kaolin-pectin
○​ Antiarrhythmic drugs ●​ Cholestyramine

🧬 ANTIDOTE (VERY HIGH-YIELD) 📌 ↑ Digoxin Levels

Pharmacology Notes
Owner: Samantha Anne Nicole S. Sanchez
DO NOT DISTRIBUTE WITHOUT MY CONSENT!!
●​ Quinidine 🫀 ROLE OF DIGOXIN IN CHF THERAPY
👉 Requires:
●​ Dose reduction
📌 Mild CHF
📌 Additive Cardiac Effects ●​ Sodium restriction
●​ Diuretics

TY
●​ Verapamil
●​ Diltiazem
●​ Beta-blockers
📌 Moderate–Severe CHF
👉 May: ●​ Add:

R
○​ ACEIs / ARBs
●​ ↓ HR too much
📌 With Tachycardia

PE
●​ ↓ contractility

📌 Diuretics (VERY IMPORTANT) ●​ Add:

○​ Beta-blockers
●​ Cause hypokalemia

👉 ↑ Digoxin toxicity
O
📌 Additional Therapy
PR
●​ SGLT2 inhibitors

💉 OTHER INOTROPIC DRUGS (ACUTE HF) 📌 When Digoxin is Used

📌 Adrenergic Drugs 👉 Used when:
'S

●​ Dopamine ●​ Symptoms persist despite therapy

LE

●​ Dobutamine ●​ Contractility is insufficient

👉 β₁ stimulation → ↑ contractility ●​ Need additional support

O

📌 PDE Inhibitors
IC

●​ Amrinone
●​ Milrinone

👉 ↑ Ca²⁺ + vasodilation
N

📌 Use:
●​ Short-term
●​ Hospital setting
●​ Acute HF stabilization