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Digoxin & Nitroglycerin by Dr. Sanaullah Aslam (Complete)
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
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Digoxin & Nitroglycerin by Dr. Sanaullah Aslam (Complete)
- 1. Digoxin & Nitroglycerin •Presented by: Sanaullah Aslam Sanaullah Aslam (Product Manager)
- 2. Digoxin ‘it has apower over the motion of the heart to a degree yet unobserved in any other medicine…’ Withering, 1775 Sanaullah Aslam (Product Manager)
- 3. Introduction • Digoxin isa naturally occurring drug and comes from the foxglove plant (Digitalis spp.) • Classified as a Cardiac Glycoside Sanaullah Aslam (Product Manager)
- 4. Pharmacology • Digoxin exert positiveinotropic 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)
- 5. Mechanism of Action SanaullahAslam (Product Manager)
- 6. Therapeutic Indications Most usefulin the treatment of supraventricular tachycardias, especially in persistent atrial fibrillation Sanaullah Aslam (Product Manager)
- 7. Therapeutic Indications Digoxin isgiven 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 AdultDosage • 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 AdultDosage • IM not recommended. • Decrease loading and maintenance dosages with renal impairment. • Base dosage on ideal body weight in obese individuals. Sanaullah Aslam (Product Manager)
- 10. Administration and AdultDosage 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)
- 11. Pharmacokinetics • Oral bioavailability:60-85% • Volume of distribution: 6-8 litres/kg • Elimination: Predominantly kidneys • Elimination half-life, t1/2: 36-40 hours • Therapeutic range: 0.8-2 g/L Sanaullah Aslam (Product Manager)
- 12. Toxicity………. • It maysometimes 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)
- 13. Toxicity………. Hypokalaemia predisposes the patientto digitalis toxicity; It is managed by giving a potassium sparing diuretic or potassium supplementation. 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: Mechanismof 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)
- 16. Vincent van Gogh SanaullahAslam (Product Manager)
- 17. Sanaullah Aslam (ProductManager)
- 18.
- 19. MECHANISM OF ACTION Interactionwith 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 Sanaullah Aslam (Product Manager)
- 20. Pharmacokinetics • Rapidly absorbedfrom 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 Sanaullah Aslam (Product Manager)
- 21. • in themanagement of angina pectoris • heart failure • myocardial infarction Effects • Relaxes blood vessel walls • Dilates coronary arteries • Reduces workload of heart Uses Sanaullah Aslam (Product Manager)
- 22. Administration • In themanagement 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 caseof 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 HEARTFAILURE • 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 tendsto 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: • flushingof 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 AdverseEffects: • 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: Thecomplete 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 Sanaullah Aslam (Product Manager)
- 31.
Editor's Notes
- #4 Purpurea,lanata
- #5 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.
- #7 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)
- #8 Sinus rhythm means a normal heart beat, both with respect to the heart rate and rhythm.
- #10 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
- #12 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
- #14 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.
- #17 The likelihood of toxicity increases progressively through the range 1.5 to 3 micrograms/litre for digoxin.
- #18 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.
- #20 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.
- #25 Ocular manifestations include xanthopsia (seeing yellow).
- #26 plasma concentration of digoxin increased by alprazolam (increased risk of toxicity)
- #27 plasma concentration of digoxin increased by alprazolam (increased risk of toxicity)
- #30 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.
- #33 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.
- #36 Other indications include inducing hypotension and controlling hypertension during surgery.
- #37 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.
- #41 The usual range is 10 to 200 micrograms/minute but some surgical patients may require up to 400 micrograms/minute.
- #42 The usual range is 10 to 200 micrograms/minute but some surgical patients may require up to 400 micrograms/minute.
- #43 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.
- #45 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
- #46 hypotension (which can be severe),