Digoxin

• also called Digitalis glycosides, naturally occurring cardiac glycosides found in number plants
(obtained from the purple and white foxglove plant, and it can be poisonous)
• one of the oldest drugs (used as early as CE 1200)
• Digitalis preparations have come to be known for their effectiveness in treating heart failure
(HF). (also known as cardiac failure (CF), and previously referred to as congestive heart failure
CHF)
• Heart failure is when the heart muscle (myocardium) weakens and enlarges (it loses its ability to
pump blood through the heart and into the systemic circulation)
• Digitalis Preparations has 3 effect:
Ø positive inotropic (action increases myocardial contraction stroke volume),
Ø negative chronotropic (action decreases heart rate)
Ø negative dromotropic (action decreases conduction of heart cells)
• The increase in myocardial contractility strengthens cardiac, peripheral, and kidney function
(enhancing cardiac output, decreasing preload, improving blood flow to the periphery and
kidneys, decreasing edema, and promoting fluid excretion) not sure pa!!
• The aim is to reduce the strain the heart is under because, over time, this can wear out the heart
muscle and lead to heart failure. DIGOXIN is

Indications:

• For the treatment of mild to moderate heart failure in adult patients.

• To increase myocardial contraction in children diagnosed with heart failure.
• To maintain control ventricular rate in adult patients diagnosed with chronic atrial
fibrillation (an irregular heart rhythm that begins in your heart's upper chambers or atria)
- For people with atrial fibrillation, where the heart beats irregularly, a different volume
of blood is pumped out each time.

Mechanism of Action:

• Has two principle mechanism of action:

1. Positive Ionotropic – inhibiting the activity of sodium-potassium pump
2. AV Node Inhibition - AV Node Inhibition

Explanation need aralin:

Digoxin exerts hemodynamic, electrophysiologic, and neurohormonal effects on the cardiovascular system. It reversibly inhibits
the Na-K ATPase enzyme, leading to various beneficial effects. The Na-K ATPase enzyme functions to maintain the intracellular
environment by regulating the entry and exit of sodium, potassium, and calcium (indirectly). Na-K ATPase is also known as the
sodium pump.

- inhibiting the sodium and potassium pump, which results in an increase in intracellular sodium and an influx of
calcium into cardiac cells, causing the cardiac muscle fibers to contract more efficiently and increase cardiac output.
Digoxin has velocimetric effects on the AV node. By stimulating the parasympathetic nervous system, it
slows electrical conduction in the atrioventricular node, therefore, decreasing the heart rate.

- cardiac vagal tone modulation (represents the contribution of the parasympathetic nervous
system to cardiac regulation)

Pharmacokinetics

• Absorption rate:
- oral tablet form is 70% to 80%.
- Liquid form is 75% to 85% in liquid form.
- The protein-binding power for digoxin is 20% to 30%.
- The half-life is 30 to 40 hours
• Due to its long half-life, drug accumulation can occur (Side effects should be closely
monitored to detect digitalis toxicity.)
• Thirty percent of digoxin is metabolized by the liver, and 70% is excreted by the kidneys
mostly unchanged
• Thyroid dysfunction alters metabolism of cardiac glycosides
• Decreased dose for hypothyroidism; increased dose in hyperthyroidism

Contraindications and Cautions

Digoxin is contraindicated in the following conditions:

• Acute myocardial infarction
• Hypersensitivity to the drug
• Ventricular fibrillation
• Myocarditis
• Hypomagnesemia
• Hypokalemia
• Wolf-Parkinson-White syndrome - a relatively common heart condition that causes the heart to
beat abnormally fast for periods of time.
Its use requires caution in cases of:
• Hypercalcemia/hypocalcemia
• Renal impairment
• Diseased SA node
• Bradycardia
• AV block
 • Restrictive cardiomyopathy
• Constrictive pericarditis
• Thyroid disease – (hypothyroidism leads to delayed drug clearance, and hyperthyroidism does
the opposite.)

Adverse Effects:

• Digoxin toxicity
- Signs and symptoms:
include anorexia, diarrhea, nausea and vomiting, bradycardia (pulse rate below 60
beats/min), premature ventricular contractions, cardiac dysrhythmias, headaches,
malaise, blurred vision, visual illusions (white, green, or yellow halos around objects),
confusion, and delirium. (Older adults are more prone to toxicity.)

• Cardiotoxicity
- serious adverse reaction to digoxin, and ventricular dysrhythmias
- Three cardiac-altered functions can contribute to digoxin-induced ventricular
dysrhythmias:

1. suppression of AV conduction,
2. increased automaticity
3. a decreased refractory period in a decreased refractory period in ventricular
muscle

- ventricular muscle. The antidysrhythmic phenytoin and lidocaine are effective in

treating digoxin induced ventricular dysrhythmias. Lidocaine should be limited to short-
term treatment

Drug to drug interactions

Ø Interactions with:

- potent diuretics, such as furosemide and hydrochlorothiazide

- hypokalemia
- Cortisone preparations
- Antacids

Nursing Responsibilities:
 • Ascertain apical pulse rate before administering digoxin. Do not administer if pulse rate is
below 60 beats/min.
• Determine signs of peripheral and pulmonary edema, which indicate HF is present.
• Monitor serum digoxin level (normal therapeutic drug range is 0.8 to 2 ng/mL). A serum
digoxin level greater than 2 ng/mL is indicative of digitalis toxicity.
• Monitor serum potassium level (normal range is 3.5 to 5.0 mEq/L), and report if
hypokalemia (<3.5 mEq/L) is present.

Agents that dilate blood vessels (Vasodilators)

- occurs when the muscles in your blood vessel walls relax or widens.

Type of Vasodilators:

Angiotensin-converting enzyme (ACE) inhibitors

- medications that lower your blood pressure. Direct vasodilators (directly affect the
muscle cells that line your blood vessel)
- such as benazepril (Lotensin®) or lisinopril (Prinivil®, Zestril®).

THERAPEUTIC ACTIONS AND INDICATIONS

• relax the veins and arteries to lower blood pressure

- (ACE inhibitors prevent an enzyme in the body from making angiotensin 2, a
substance that narrows blood vessels. This narrowing can cause high blood
pressure and forces the heart to work harder. Angiotensin 2 also releases
hormones that raise blood pressure.)

PHARMACOKINETICS

• Excretion via the kidneys

CONTRAINDICATIONS AND CAUTIONS

• Pregnant woman and breastfeeding

• Severe kidney disease

ADVERSE EFFECTS

• Dry cough. This is possible with all ACE inhibitors. For some people, it may go away. If it doesn’t,
you can ask your healthcare provider about ways to remedy it.
 • Dizziness. This is common with all blood pressure medications. You shouldn’t stand up too
quickly after you start taking an ACE inhibitor. Standing up too quickly can make you feel dizzy or
pass out.
• Headache.
• Drowsiness.
• Feeling fatigued.
• Weakness
• Jaundice
• Allergic reactions

DRUG – DRUG INTERACTIONS

• ACE inhibitors should not be combined with ARBs because such combinations increase the risk
of hypotension, hyperkalemia, and renal impairment (ACE inhibitors and ARBs should not be
taken together. The combination may lead to dangerously low blood pressure, high blood
potassium levels, and kidney problems.)

Angiotensin receptor blockers (ARBs)

- keep angiotensin from attaching to your blood vessel walls. Preventing this attachment
opens your blood vessels.
- Ex: losartan

THERAPEUTIC ACTIONS AND INDICATIONS

- Works by blocking receptors that the hormone acts on, specifically AT1 receptors (which
are found in the heart, blood vessels and kidneys. Blocking the action of angiotensin II
helps to lower blood pressure and prevent damage to the heart and kidneys.)
- ARBs block the action of angiotensin II, allowing the blood vessels to widen, thus making
it easier for the heart to pump blood.

PHARMACOKINETICS

- relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume,
and decreasing cellular hypertrophy.

Contraindications:

- may lead to hyperkalemia in patients with renal disease or patients taking agents likely
to cause hyperkalemia
- pregnant woman
ADVERSE EFFECTS

- headache.
- fainting.
- dizziness.
- fatigue.
- respiratory symptoms.
- vomiting and diarrhea.
- back pain.
- leg swelling.

Drug interactions

- Avoid prescribing an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin

receptor blocker (ARB) for patients at high risk of vascular events or renal dysfunction

Calcium channel blockers (CCBs)

- prevent calcium from going into your artery walls (Your arteries use calcium for
constriction, so blocking calcium leads to artery opening. CCBs are systemic vasodilators,
not direct vasodilators)

THERAPEUTIC ACTIONS AND INDICATIONS

- used to lower blood pressure.

- They stop calcium from entering the cells of the heart and arteries. (Calcium causes the
heart and arteries to squeeze more strongly. By blocking calcium, calcium channel
blockers allow blood vessels to relax and open.)

Pharmacokinetics

- low and variable oral bioavailability (because of extensive first-pass metabolism)

- Half-life is relatively short (< 12 hours).
- The exception is amlodipine which, although extensively metabolized, has a
substantially longer half-life (> 40 hours)

Contraindications

- Non-dihydropyridines are contraindicated in those with heart failure with reduced

ejection fraction
 - sick sinus syndrome (because of the possibility of causing bradycardia and worsening
cardiac output)

Adverse effect

- Constipation.
- Dizziness.
- Fast heartbeat you can feel.
- Extreme tiredness.
- Flushing.
- Headache.
- Nausea.
- Swelling in the feet and lower legs.

Drug interaction

- Several calcium channel blockers [for example, diltiazem (Cardizem LA, Tiazac), felodipine
(Plendil)] increase the level of cyclosporine (Sandimmune, Neoral, Restasis) and similarly lead to
toxicity of cyclosporine.

References:

Calcium channel blockers - statpearls - NCBI bookshelf. Available at:

https://www.ncbi.nlm.nih.gov/books/NBK482473/

Digoxin (no date) Uses, Interactions, Mechanism of Action | DrugBank Online. Available at:
https://go.drugbank.com/drugs/

Digoxin (no date)- StatPearls - NCBI Bookshelf - National Center for ... Available at:
https://www.ncbi.nlm.nih.gov/books/NBK556025

NurseStudyNet (2022) Vasodilators nursing considerations, NurseStudy.Net. Available at:

https://nursestudy.net/vasodilators-nursing-
considerations/#:~:text=Nursing%20Assessment%20%20%20Vasodilators%20Nursing%2
0Interventions%20,problems%20with%20...%20%202%20more%20rows%20

professional, C.C. medical (no date a) Angiotensin-converting enzyme (ACE) inhibitors,

Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/treatments/21934-ace-
inhibitors

professional, C.C. medical (no date) Vasodilators: Types and side effects, Cleveland Clinic.
Available at: https://my.clevelandclinic.org/health/drugs/23207-vasodilators
What to know about angiotensin 2 receptor blockers (2023) Mayo Clinic. Available at:
https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/angiotensin-
ii-receptor-blockers/art-20045009