The document discusses cardiac glycosides, specifically digoxin. It describes digoxin's mechanisms of action, including increasing cardiac contractility and decreasing heart rate. Therapeutic uses include heart failure and arrhythmias. Signs of digoxin toxicity are described. Treatment of digoxin toxicity may include administration of Digibind antibody fragments. Nursing care focuses on monitoring for toxicity and maintaining appropriate electrolyte levels.

1. Cardiac Glycosides
By: Muhammad Aurangzeb
Lecturer-INS/KMU

2. By the end of this unit learners, will be able to:
• Review inotropic, chronotropic and dromotropic effects of
cardiovascular drugs.
• Describe the therapeutic effects and therapeutic uses of digoxin.
• Discuss digitalization.
• Discuss the signs and symptoms of early moderate and severe
digoxin toxicity.
• Describe the nursing care related to digoxin toxicity.
• Calculate the drug dosage accurately while administering oral and
parenteral medication
Objectives

3. What is a failing Heart ???
Inability of the heart to pump sufficient blood to meet the
metabolic demands of the body
• Systolic - In IHD, Valvular incompetence, cardiomyopathy and
myocarditis etc.
• Diastolic - In Hypertension, aortic stenosis, congenital heart
disease and hypertrophic cardiomyopathy
Reduced efficiency of the heart as a pump – reduced Cardiac
Output

4. Cardioactive glycosides
Drugs having the cardiac Inotropic property – increase in force of
contraction and cardiac output in a failing (hypodynamic) heart
– They increase the myocardial contractility and improves cardiac
output without proportionate increase in Oxygen consumption -
Cardiac Tonic
– Do not increase the heart rate
• In contrast, Sympathomimetics or the cardiac stimulants
increase Heart Rate and Oxygen consumption without increase in
cardiac output
MYOCARDIAL EFFICIENCY !

5. The difference between Inotropic, Chronotropic and
Dromotropic
Basis of Comparison Inotropic Chronotropic Dromotropic
Definition
Medicines that alter the force or
energy of heart’s muscular
contraction.
Drugs or medicines that change
the heart rate and rhythm.
Drugs that affect the conduction
of electric impulses through the
heart.
Categorization
Positive Inotopic: Strengthens the
force of cardiac contraction.
Negative Inotropic: Weakens the
force of cardiac contraction.
Positive Chronotropic: Plays a role
of accelerating the heart
rate. Negative Chronotropic:
Slows down the heart rate.
Positive Dromotropic: Speeds up
conduction of electric impulse
through the heart.
Negative Dromotropic: Slows
down conduction of electric
impulse through the heart.
Examples
Positive Inotropic: Dopamine,
Epinephrine, Isoproterenol,
Amiodarone, digoxin etc.
Negative Inotropic: Labetol and
propanolol.
Positive Chronotropic: Atropine,
Milrinone and Theophylline.
Negative Chronotropic: Digoxin,
acetylcholine and metoprolol.
Positive Dromotropic:
Phenytoin.
Negative Dromotropic:
verapamil.

6. Specific Drugs
• Three different digitalis compounds (cardiac
glycosides) are listed in the table below. The
compound most commonly used in the Pakistan is
digoxin. Ouabain is used primarily as a research tool.
Drug
Oral
bioavailability*
Half-life (hours) Elimination
Digoxin 75% 40 kidneys
Digitoxin >90% 160 liver
Ouabain 0% 20 kidneys

7. What is digoxin?
Digoxin (Lanoxin) is a cardiac glycoside, C41H64O14, obtained from the leaves of the
foxglove, Digitalis lanata. Digoxin acts by blocking the Na+K+ ATPase pump.

8. Foxglove
In 1775 William Withering
demonstrated that the leaves of the
foxglove plant alleviated certain forms
of dropsy (edema), and in 1799 John
Ferriar ascribed their beneficial
effects to a primary action on the
heart.
Initially, digitalis was used to treat
dropsy, which is an old term for
edema. Subsequent investigations
found that digitalis was most useful
for edema that was caused by a
weakened heart (i.e., heart failure).

9. Mechanisms of action
• Digitalis compounds are potent inhibitors of cellular
Na+/K+-ATPase. This ion transport system moves
sodium ions out of the cell and brings potassium ions
into the cell.
• The Na+/K+-ATPase also plays an active role in the
membrane potential.
• This pump is electrogenic because it transports 3
sodium ions out of the cell for every 2 potassium ions
that enter the cell.
• This can add several negative millivolts to the
membrane potential depending on the activity of the
pump.

10. Cont…
• By inhibiting the Na+/K+-ATPase, cardiac glycosides cause
intracellular sodium concentration to increase. This then leads to an
accumulation of intracellular calcium via the Na+-Ca++ exchange
system. In the heart, increased intracellular calcium causes more
calcium to be released by the sarcoplasmic reticulum, thereby
making more calcium available to bind to troponin-C, which
increases contractility (inotropy). Inhibition of the Na+/K+-ATPase in
vascular smooth muscle causes depolarization, which causes
smooth muscle contraction and vasoconstriction.
• By mechanisms that are not fully understood, digitalis compounds
also increase vagal efferent activity to the heart.
• This parasympathomimetic action of digitalis reduces sinoatrial
firing rate (decreases heart rate; negative chronotropy) and
reduces conduction velocity of electrical impulses through the
atrioventricular node (negative dromotropy).

12. Na+
K+
K+
Na+
Na+ Ca2+
Ca2+
Na+/K+ ATPase Na+/Ca2+ Exchange
Myofilaments
CONTRACTILITY
Digitalis
K+
K+
K+ K+
Inside cell
Outside cell (blood)
Na+
Na+Na+
Na+

13. Na+
K+
K+
Na+
Na+ Ca2+
Ca2+
Na+/K+ ATPase Na+/Ca2+ Exchange
Myofilaments
CONTRACTILITY
Digitalis
K+
K+
K+ K+
Inside cell
Outside cell (blood)
Na+
Na+
Na+
Na+
Ca2+
Ca2+
Ca2+
What would happen if Ca2+ was given?
What would happen if K+ was low?

14. Digoxin
Properties of digoxin
• Increases inotropy (contractility) of the heart
• Decreases chronotropy (heart rate)
• Natriuresis (sodium loss)  minor effect
• Neurohormonal effects
- Plasma Norepinephrine
- Peripheral nervous system activity
- RAAS activity
- Vagal tone

15. Digoxin
• Properties of digoxin
• Giving calcium would greatly increase intracellular
calcium levels when high digoxin levels are present.
This can cause severe arrhythmias.
• Low potassium levels also potentiates the actions of
digoxin since both potassium and digoxin compete for
the same binding site on the Na+/K+ ATPase pump.
Thus if there was only a little potassium present,
digoxin will be able to bind easier and inhibit the
pump.

16. Pharmacokinetics
• The total loading dose of parenteral digoxin is 500 to
1000 micrograms (0.5 to 1.0 mg) depending on age,
lean body weight and renal function.
• Absorption: 60–80% absorbed after oral
administration of tablets; 70–85% absorbed after
administration of elixir; 80% absorbed from IM sites
(IM route not recommended due to pain/irritation).
• Distribution: Widely distributed; crosses placenta and
enters breast milk.
• Metabolism and Excretion: Excreted almost entirely
unchanged by the kidneys.
• Half-life: 36–48 hr (↑ in renal impairment).

17. Pharmacokinetics
• The long half-life of digitalis compounds necessitates special
considerations when dosing. With a half-life of 40 hours, digoxin
would require several days of constant dosing to reach steady-state,
therapeutic plasma levels. Therefore, when initiating treatment, a
special dosing regimen involving "loading doses" is used to rapidly
increase digoxin plasma levels. This process is termed
"digitalization."
• For digoxin, the therapeutic plasma concentration range is 0.5 - 1.5
ng/ml. It is very important that therapeutic plasma levels are not
exceeded because digitalis compounds have a relatively narrow
therapeutic safety window. Plasma concentrations above 2.0 ng/ml
can lead to digitalis toxicity.
• If toxicity occurs with digoxin, it may take several days for the
plasma concentrations to fall to safe levels because of the long half-
life.

18. Digitalization
• Administration of digitalis in a dosage schedule
designed to produce and then maintain optimal therapeutic
concentrations of its cardiotonic glycosides.

19. Cont…
Digoxin has low therapeutic window and margin of safety is very low.
Therapeutic level of digoxin is 0.5 – 1.5 ng/ml. It is administered in such a way
that patient gets maximum benefits with minimal adverse effects. Previously
rapid digitalization was done but obsolete now
• Rapid IV: Seldom used now: As extreme measure in CHF and atrial
fibrillation - 0.25 mg slow IV stat followed by 0.1 mg every Hourly
• Slow digitalization:
• Digoxin 0.25 mg (or even 0.125mg) daily in the evening – full response in
5-7 days
• If no improvement administer 0.375 for 1 week
• If no, administer 0.5 mg in next week
• Monitor patient for blood levels, If bradycardia, stop the drug
• Rapid digitalization (oral): 0.5 to 1 mg stat then 0.25 mg every 6 Hourly
• - Monitor for toxicity - Patient is digitalized within 24 Hours

20. Drug Interactions
• Many commonly used drugs interact with digitalis compounds. The
Class IA antiarrhythmic, quinidine, competes with digoxin for
binding sites and depresses renal clearance of digoxin. These effects
increase digoxin levels and can produce toxicity. Similar interactions
occur with calcium-channel blockers and nonsteroidal anti-
inflammatory drugs. Other drugs that interact with digitalis
compounds are amiodarone (Class III antiarrhythmic) and beta-
blockers. Diuretics can indirectly interact with digoxin because of
their potential for decreasing plasma potassium levels (i.e.,
producing hypokalemia). Hypokalemia results in increased digoxin
binding to the Na+/K+-ATPase and thereby enhances
digoxin's therapeutic and toxic effects. Hypercalcemia enhances
digitalis-induced increases in intracellular calcium, which can lead to
calcium overload and increased susceptibility to digitalis-induced
arrhythmias.

21. Therapeutic Uses of Digitalis Compounds
• Heart Failure
• ↑ inotropy
• ↑ ejection fraction
• ↓ preload
• ↓ pulmonary congestion/edema
• Arrhythmias
• ↓ AV nodal conduction
(parasympathomimetic effect)
• ↓ ventricular rate in atrial flutter
and fibrillation

22. Digoxin
• Digoxin and exercise
• Digoxin has been shown to increase exercise performance in
patients with mild to moderate heart failure
• Digoxin does not increase exercise capacity in normal subjects
• Digoxin is very dangerous in athletes (especially marathon
runners) due to the increased risk of kidney failure from
dehydration which results in the accumulation of digoxin
(since the kidneys normally help eliminate digoxin from the
blood)

23. Adverse Reactions/Side Effects
• CNS: fatigue, headache, weakness.
• EENT: blurred vision, yellow or green vision
• CV: ARRHYTHMIAS, bradycardia, ECG changes, AV block, SA
block
• GI: anorexia, nausea, vomiting, diarrhea
• Hemat: thrombocytopenia
• Metabolic: electrolyte imbalances with acute digoxin
toxicity
• Note: Underline indicate most frequent.

24. Contraindication/Precautions
• Contraindicated in:
• Hypersensitivity;
• Uncontrolled ventricular arrhythmias;
• AV block (in absence of pacemaker);
• Constrictive pericarditis;
• Known alcohol intolerance (elixir only).

25. Use Cautiously in:
• Hypokalemia (↑ risk of digoxin toxicity);
• Hypercalcemia (↑ risk of toxicity, especially with mild hypokalemia);
• Hypomagnesemia (↑ risk of digoxin toxicity);
• Diuretic use (may cause electrolyte abnormalities including hypokalemia);
• Myocardial infarction;
• Renal impairment (dose ↓ required);
• Obesity (base dose on ideal body weight);
• Geriatrics: Very sensitive to toxic effects; dose adjustments required for
age-related ↓ in renal function and body weight;
• OB: Although safety has not been established, has been used without
adverse effects on the fetus;
• Lactation: Similar concentrations in serum and breast milk result in
subtherapeutic levels in infant, use with caution.

26. Digoxin Toxicity
 Much less common in modern medicine
 Causes:
- 50% of patients are on chronic therapy
- 10% took accidental large dose
- 40% as suicide attempts
- Rarely due to ingestion of certain plants

27. Digoxin Toxicity
 Normal blood digoxin level is 0.5 – 1.5 ng/ml
 > 2.0 ng/ml leads to digoxin toxicity; exacerbated by:
- Hypokalemia (low potassium)
- Hypercalcemia (high calcium)
 The presence of hyperkalemia (> 5.0) is a bad prognostic
sign:
- If K+ < 5.0 - mortality 0%
- If K+ 5.0 – 5.5 - mortality 50%
- If K+ > 5.5 - mortality 100%

28. Digoxin Toxicity
 Any arrhythmia can occur due to digoxin toxicity!
 Brady or tachyarrhythmias occur.
 One pathognomonic rhythm is bidirectional ventricular tachycardia:

29. Signs and Symptoms
 Bradycardia or tachycardia
 Fatigue
 Nausea, vomiting, abdominal pain
 Headache
 Dizziness
 Confusion, delirium, or hallucinations
 Yellow vision (xanthopsia)

30. Treatment

31. Treatment – Digibind
Digibind is an antibody created to attack/bind digoxin

32. Nursing care related to digoxin
• Monitor apical pulse for 1 full minute before administering.
Withhold dose and notify health care professional if pulse rate
is <60 bpm in an adult, <70 bpm in a child, or <90 bpm in an
infant.
• Monitor BP periodically in patients receiving IV digoxin.
• Monitor ECG throughout IV administration and 6 hr after each
dose. Notify health care professional if bradycardia or new
arrhythmias occur.
• Teach patient to take pulse and to contact health care
professional before taking medication if pulse rate is <60 or
>100.

33. Cont…
• Observe for signs and symptoms of toxicity. In adults and
older children, the first signs of toxicity usually include
abdominal pain, anorexia, nausea, vomiting, visual
disturbances, bradycardia, and other arrhythmias.
• If signs of toxicity occur and are not severe, discontinuation of
digoxin may be all that is required.
• Correct electrolyte abnormalities.
• Administer potassium so that serum potassium is maintained
between 4.0 and 5.5 mmol/L.

34. Cont…
• Monitor ECG for evidence of potassium toxicity (peaking of T
waves).
• Treatment of life-threatening arrhythmias may include
administration of digoxin immune Fab (Digibind), which binds
to the digitalis glycoside molecule in the blood and is excreted
by the kidneys.
• Review signs and symptoms of digitalis toxicity with patient
and family.
• Advise patient to notify health care professional immediately
if these or symptoms of HF occur.

35. References
• Karch, A. M., & Karch. (2011). Focus on nursing pharmacology.
Wolters Kluwer Health/Lippincott Williams & Wilkins. [Link]
• Katzung, B. G. (2017). Basic and clinical pharmacology.
McGraw-Hill Education.
• Lehne, R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B.
(2004). Pharmacology for nursing care.
• Smeltzer, S. C., & Bare, B. G. (1992). Brunner & Suddarth’s
textbook of medical-surgical nursing. Philadelphia: JB
Lippincott