Digoxin is a drug derived from foxglove that increases the strength of heart contractions and regulates heart rhythm. It is used to treat heart failure and abnormal heart rhythms. Digoxin works by increasing the amount of calcium available to heart muscles to improve contraction. Common side effects include nausea, vomiting, and heart palpitations. In cases of toxicity, treatment includes administering digoxin immune fab to remove digoxin from the bloodstream.
Nitroglycerin is a vasodilator that relaxes blood vessels. It is used to treat angina by dilating coronary arteries and reducing the workload on the heart. Nitroglycerin is administered sublingually as a tablet or spray for
2. Digoxin
‘it has a power over the motion of the heart to a degree yet unobserved in any
other medicine…’
Withering, 1775
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3. Introduction
• Digoxin is a naturally occurring drug
and
comes from the foxglove plant
(Digitalis spp.)
• Classified as a
Cardiac Glycoside
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4. Pharmacology
• Digoxin exert
positive inotropic effects
through improved availability of
calcium to myocardial contractile elements,
thereby
increasing cardiac output in CHF.
• Antiarrhythmic actions of digoxin are caused primarily
by
an increase in AV nodal refractory period.
Sanaullah Aslam (Product Manager)
6. Therapeutic Indications
Most useful in the treatment of
supraventricular tachycardias,
especially
in persistent atrial fibrillation
Sanaullah Aslam (Product Manager)
7. Therapeutic Indications
Digoxin is given to patients with
atrial fibrillation
and also in
sinus rhythm
who remain symptomatic
despite treatment with
an ACE inhibitor, a diuretic, and beta-blocker.
Sanaullah Aslam (Product Manager)
8. Administration and Adult Dosage
• IV loading dosage
10–15 micro g/kg in divided doses over 12–24 hr at
intervals of 6–8 hr.
• PO loading dosage
Usually, 0.5–0.75 mg is given and then
0.125–0.375 mg q 6–8 hr until the desired effect or total
digitalizing dosage is achieved.
• Maintenance dosage
Usual maintenance dosage ranges from 0.125–0.5 mg/day
Sanaullah Aslam (Product Manager)
9. Administration and Adult Dosage
• IM not recommended.
• Decrease loading and maintenance dosages with
renal impairment.
• Base dosage on ideal body weight in obese
individuals.
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10. Administration and Adult Dosage
For intravenous infusion,
dilute with
• sodium chloride 0.9% intravenous infusion or
• glucose 5%
to a max. concentration of
62.5 micrograms/mL.
Sanaullah Aslam (Product Manager)
12. Toxicity……….
• It may sometimes be difficult to distinguish between
toxic effects and clinical deterioration
because
symptoms of both are similar.
• Digoxin should be used with special care
in the elderly
who may be particularly susceptible
to digitalis toxicity.
Sanaullah Aslam (Product Manager)
14. Digoxin Toxicity: Treatment
• Treatment of severe or life-threatening digoxin toxicity
should include
IV digoxin immune Fab.
• About 40 mg (one vial) of digoxin-specific Fab
• Exact dosage can be calculated based on
estimated total body stores.
Sanaullah Aslam (Product Manager)
15. Digoxin immune fab:
Mechanism of Action
• Binds to digoxin molecules, reducing free digoxin
levels.
• Results in a shift in the equilibrium away from
receptor binding.
• Fab-digoxin complexes are cleared by the kidney and
mononuclear phagocyte system.
Sanaullah Aslam (Product Manager)
19. MECHANISM OF ACTION
Interaction with sulfhydryl (SH-) groups (nitrate
receptors) inside cells of vascular smooth muscles
Stimulation of formation of endothelial factor of
relaxation of vessels (ЕRF) – nitrogen oxide (NO)
Decreasing of ionized Са2+ contents
Relaxation, dilation of vessels, including coronary
vessels
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20. Pharmacokinetics
• Rapidly absorbed from the oral mucosa
• Well absorbed from the gastrointestinal tract and
through the skin
• Extensive first-pass metabolism
• Therapeutic effect is apparent within 1 to 3 minutes of
use of sublingual tablets, sublingual spray, or buccal
tablets
• within 30 to 60 minutes of applying an ointment or
transdermal patch; and
• within 1 to 2 minutes after intravenous doses
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21. • in the management of angina pectoris
• heart failure
• myocardial infarction
Effects
• Relaxes blood vessel walls
• Dilates coronary arteries
• Reduces workload of heart
Uses
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22. Administration
• In the management of acute angina, nitroglycerine is
given as sublingual tablets, a sublingual aerosol
spray, or buccal tablets.
• These dosage forms may also be used before an
activity or stress which might provoke an attack.
• One sublingual tablet (usual strength 300 to 600
micrograms) is placed under the tongue.
Sanaullah Aslam (Product Manager)
23. Administration
• In case of aerosol spray
one or two sprays of 400 micrograms each
are directed onto or under the tongue,
then the mouth is closed;
three sprays may be used if necessary.
Sanaullah Aslam (Product Manager)
24. TREATMENT OF HEART FAILURE
• Given intravenously
in an initial dose of 5 to 25 micrograms/minute.
• Buccal tablets
in doses of 5 mg repeated as needed until symptoms
are controlled.
• In chronic heart failure
buccal tablets may be given
in doses of 5 to 10 mg three times daily.
Sanaullah Aslam (Product Manager)
25. TREATMENT OF M.I.
• Used intravenously,
and to induce hypotension
or
control hypertension during surgery.
The initial dose is 5 to 25 micrograms/minute,
adjusted according to response.
Sanaullah Aslam (Product Manager)
26. USE IN OBSTETRICS & GYNAECOLOGY
• The intravenous injection of Nitroglycerine
50 to 100 micrograms
repeated to a total dose of 200 micrograms
if necessary has produced
sufficient uterine relaxation in postpartum women
for the manual extraction of retained placentas
Sanaullah Aslam (Product Manager)
27. Tolerance:
• Tolerance tends to develop
in the majority of patients on continuous nitrate therapy
and
nitrate-free intervals are often employed
to avoid this problem
Sanaullah Aslam (Product Manager)
28. ADVERSE EFFECTS:
• flushing of the face,
• dizziness,
• tachycardia, and
• throbbing headache.
• Large doses cause vomiting,
• restlessness,
• blurred vision,
• hypotension,
• syncope,
• and rarely cyanosis,
• and methaemoglobinaemia;
• impairment of respiration and bradycardia may ensueSanaullah Aslam (Product Manager)
29. Treatment of Adverse Effects:
• Oxygen, with assisted respiration, may be needed in severe
poisoning and
• Infusion of plasma expanders or suitable electrolyte
solutions may be required to maintain the circulation
• If methaemoglobinaemia occurs methylthioninium chloride
may be given intravenously. In the case of severe poisoning
with tablets the stomach may be emptied by lavage.
• If large amounts have been ingested within 1 hour, activated
charcoal may be considered.
Sanaullah Aslam (Product Manager)
30. References:
• Martindale: The complete drug reference (36th Edition)
• BNF 2009
• DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.
• http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330
s026lbl.pdf, FDA Package Insert for Digoxin
• Hack JB. Chapter 64. Cardioactive steroids. In: Hack JB, ed.
Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill;
2011.
• Schaeffer TH, Mlynarchek SL, Stanford CF. JAOA 2010; 110: 587-592
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Positive inotropic drugs increase the force of contraction of the myocardium. (BNF 2009). reduce conductivity within the atrioventricular (AV) node
Refractory period: a period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation.
For management of atrial fibrillation the maintenance dose of the cardiac glycoside can usually be determined by the ventricular rate at rest, which should not be allowed to fall below 60 beats per minute
Supraventricular tachycardia is a rapid heart rate (tachycardia, or a heart rate above 100 beats per minute) that is caused by electrical impulses that originate above the heart's ventricles
Atrial fibrillation (AF or A-fib) is the most common abnormal heart rhythm. It may cause no symptoms, but is often associated with palpitations, fainting, chest pain, or congestive heart failure.(atrial fibrillation is the progressive fibrosis of the atria)
Sinus rhythm means a normal heart beat, both with respect to the heart rate and rhythm.
Emergency loading dose, by intravenous infusion (but rarely necessary), 0.75–1 mg over at least 2 hours then maintenance dose by mouth on the following day
If 60kg man needs 10microgram/kg IV dose then 60*10=600microgram digoxin is required………dilution will be as follows
62.5microgram(is present in)=1ml
1 microgram=1/62.5
600 microgram=1/62.5*600=9.6ml
Pharmacokinetics: For plasma-digoxin concentration assay, blood should ideally be taken at least 6 hours after a dose; plasma-digoxin concentration should be maintained in the range 0.8 – 2 micrograms/ litre.
The likelihood of toxicity increases progressively through the range 1.5 to 3 micrograms/litre for digoxin.
Digoxin toxicity causes hyperkalemia (high potassium). The sodium/potassium ATPase pump normally causes sodium to leave cells and potassium to enter cells. Blocking this mechanism results in higher serum potassium levels.
Digoxin toxicity is worsened in states of hypokalemia (low potassium) since digoxin normally binds to the ATPase pump on the same site as potassium. When potassium levels are low, digoxin can more easily bind to the ATPase pump exerting the inhibitory effects.
Toxicity can often be managed by discontinuing digoxin; serious manifestations require urgent specialist management. Digoxin-specific antibody fragments are available for reversal of life-threatening overdosage.
Ocular manifestations include xanthopsia (seeing yellow).
plasma concentration of digoxin increased by alprazolam (increased risk of toxicity)
plasma concentration of digoxin increased by alprazolam (increased risk of toxicity)
Glyceryl trinitrate is widely distributed with a large apparent volume of distribution. It is taken up by smooth muscle cells of blood vessels and the nitrate group is cleaved to inorganic nitrite and then to nitric oxide. This reaction requires the presence of cysteine or another thiol. Glyceryl trinitrate also undergoes hydrolysis in plasma and is rapidly metabolised in the liver by glutathione-organic nitrate reductase to dinitrates and mononitrates. The dinitrates are less potent vasodilators than glyceryl trinitrate; the mononitrates may have some vasodilator activity.
b. Nitroglycerin
i. Nitroglycerin works in most patients within 5 minutes.
ii. Patients take one dose under the tongue if they have angina that does not go away with rest.
iii. If the pain is still present after 5 minutes, patients are typically instructed by their doctors to take a second dose.
iv. If second dose does not work, most patients are told to take a third dose and then call for EMS.
v. If the patient has not taken all three doses, EMT-Bs can help to administer the medication, if allowed by local protocol.
vi. Nitroglycerin comes in several forms.
(a) Small white pill, placed sublingually
(b) Spray, taken sublingually
(c) Skin patch, applied to the chest
vii. It has several effects on the circulatory system.
(a) Relaxes the muscle of blood vessel walls
(b) Dilates coronary arteries
(c) Increases blood flow and the supply of oxygen to the heart muscle
(d) Decreases the workload of the heart
(e) Dilates blood vessels in other parts of the body
(f) Sometimes causes low blood pressure and/or a severe headache
(g) Can increase or decrease pulse rate
viii. Take the patient’s blood pressure within 5 minutes after each dose.
Other indications include inducing
hypotension and controlling hypertension during surgery.
which all produce a rapid onset of therapeutic effect and provide rapid relief of anginal pain.
The dose may be repeated as required but patients should be advised to seek medical care if pain persists after a total of 3 doses within 15 minutes
Slow - or long-acting nitroglycerin can be used as a preventative treatment for angina but not until beta blockers are tried first.
The usual range is 10 to 200 micrograms/minute but some surgical patients may require up to 400 micrograms/minute.
The usual range is 10 to 200 micrograms/minute but some surgical patients may require up to 400 micrograms/minute.
Migraine. Although use of glyceryl trinitrate may precipitate or exacerbate migraine. Inhalation of glyceryl trinitrate at the onset of a migraine aura aborted attacks in a patient at risk of permanent neurological damage from migraine. Standard prophylactic therapy had previously been unsuccessful.
Repeated doses of a nitrate exhaust tissue stores of sulfhydryl groups and this is one mechanism that may account for the development of tolerance
An increase in free-radical production during nitrate therapy has also been suggested, and may inhibit bioactivation of the nitrate