Pharmacodynamics of Drugs for Heart Failure
Session 33: Pharmacodynamics of Drugs for Heart Failure
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe mechanism of action of drugs for heart failure
Describe drug interactions associated with drugs for heart failure
Describe side effects of drugs for heart failure
Describe contraindications of drugs for heart failure
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD projector
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
45 minutes
45 minutes
Presentation/
Mechanism of Action of Drugs for Heart
Mechanism of Action of Drugs for Heart
2
2
45 minutes
45 minutes
Buzzing
Failure
Failure
Buzzing
Failure
Failure
3
3
20 minutes
20 minutes
Presentation/
Drug Interactions Associated Drugs for Heart
Drug Interactions Associated Drugs for Heart
3
3
20 minutes
20 minutes
brainstorming
Failure
Failure
brainstorming
Failure
Failure
4
4
20 minutes
20 minutes
Presentation
Side Effects of Drugs for Heart Failure
Side Effects of Drugs for Heart Failure
5
5
20 minutes
20 minutes
Presentation/
Contraindications of Drugs for Heart Failure
Contraindications of Drugs for Heart Failure
5
5
20 minutes
20 minutes
Brainstorming
Contraindications of Drugs for Heart Failure
Contraindications of Drugs for Heart Failure
Brainstorming
6
6
05 minutes
05 minutes
Presentation
Key Points
Key Points
7
7
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 261 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Mechanism of Action of Drugs for Heart Failure (45 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
How do Drugs for Heart Failure produce their pharmacological effects?
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
Drugs for Heart Failure
Diuretics
o In Chronic heart failure: a diuretic is used to control symptomatic oedema and dyspnoea in patients with heart failure.
o For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of drugs acting on urinal genital system
o Spironolactone improves survival in patients with cardiac failure and counters diuretic-induced hypokalaemia.
o Diuretic-induced hypokalaemia increases the toxicity of digoxin. Conversely, spironolactone and other K+-retaining diuretics (e.g. amiloride, triamterene) can cause severe hyperkalaemia, especially if given with ACEI or sartans to patients with renal impairment.
o It is therefore important to monitor plasma K+ during treatment with all diuretic therapy.
Angiotensin-Converting Enzyme Inhibitors
For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of drugs acting on urinal genital
system (session ) and Pharmacodynamics of Antihypertensive drugs(session )
When symptoms are mild, diuretics can be temporarily discontinued a day or two before starting an ACEI, reducing the likelihood of first-dose hypotension.
PST 05104 Pharmacology & Therapeutics 262 NTA Level 5 Semester 1 Facilitator Guide
Angiotensin Receptor Antagonists, Sartans
o For more information on adverse effects, interactions, contraindications and mechanism refer a session on Pharmacodynamics of Pharmacodynamics of Antihypertensive drugs (session).
o As in hypertension, the pharmacodynamics of sartans are similar to those of ACEI apart from a lower incidence of some adverse effects, including, particularly, dry Inotropic action: Through the action of Na/K/ATP ion pump blockade, the following sequence of ionic events occurs:
o ↓ Na exits the cell o ↑ Intracellular Na
o ↓ Na electrochemical gradient for Na-Ca exchanger o ↓ Ca exits the cell
o ↑ Intracellular Ca
o The increase in intracellular calcium results in increased contractility, SV, and CO.
o In heart failure, sympathetic tone is increased as a compensatory mechanism to increase CO.
o Digoxin increases contractility and hence SV and CO, therefore reducing the need for sympathetic compensation cough. Thus digoxin reduces the sympathetic tone in heart failure
Beta blockers
o For more information on adverse effects, interactions , contraindications and mechanism refer a session on Pharmacodynamics of Antihypertensives
o Beta-blockers are negative inotropes and so intuitively would be expected to worsen heart failure.
o There is, however, a rationale for their use in terms of antagonizing counter regulatory sympathetic activation and several randomized controlled trials have demonstrated improved survival when a β-adrenoceptor antagonist is added to other drugs, including an ACEI.
Beta1-Adrenergic Agonists: Dobutamine ,Dopamine, Amrinone and Milrinone
o Improves cardiac performance by their positive inotropic effects and vasodilatation ((β-2), minimum effects on HR by dobutamine)
Increase in intracellular cAMP → results in the entry of Ca2+ into the myocardial
cells increases, thus enhancing contraction
Diminished effects after long-time infusions and possible worsening upon withdrawal o Ibopamine which is a pro-drug and has actions at β-1, β-2, D1 and D2 is not preferred
because of the non-selectivity hence increased toxicity.
Glucagon
o Glucagon increases cyclic AMP thus increasing myocardial contraction hence used in acute cardiac dysfunction due to overdose of β-blockers
Inhibitors of Phosphodiesterase III
o Inhibitors of phosphodiesterase III which is specific to the heart and responsible for degradation of cyclic AMP thus increases myocardial contractility are also used.
PST 05104 Pharmacology & Therapeutics 263 NTA Level 5 Semester 1 Facilitator Guide
STEP 3: Drug Interactions Associated with Drugs for Heart Failure (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are drug interactions associated with drugs for heart failure?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Angiotensin-Converting Enzyme Inhibitors
o Important drug–drug interactions can occur with NSAIDs, which may cause renal failure and severe hyperkalaemia, especially in heart failure patients treated with ACEI.
Digoxin
o Certain drug interactions increase digoxin levels. These include; diuretics such as spironolactone, amiloride and triamterene, antiarrhythmics mainly quinidine and amiodarone, calcium antagonists verapamil only and HMG-CoA reductase inhibitors
Corticosteroids thiazide diuretics and loop diuretics increase digoxin toxicity because they decreased blood levels of potassium.
o Calcium channel blockers, Beta blockers and class 1A antidsyrhythmics increase cardiotoxicity caused by digoxin because these drugs also have positive ionotropic effect.
Amiodarone, Erythromycin, Quinidine, Tetracycline and Verapamil which inhibit cytochrome P450 isoenzymes may increase digoxin concentration during concurrent therapy
STEP 4: Adverse Effects of Drugs for Heart Failure (20 minutes)
Angiotensin-Converting Enzyme Inhibitors
o Not only is the blood pressure lower to start with, but concentrations of circulating renin are high and increased further by diuretics. ACEI cause ‗first-dose‘ hypotension most severely in patients with the greatest activation of the renin–angiotensin system.
PST 05104 Pharmacology & Therapeutics 264 NTA Level 5 Semester 1 Facilitator Guide
ACEI are usually well tolerated during chronic treatment, although dry cough is common and occasionally unacceptable apart from a lower incidence of some adverse effects, including, particularly, dry cough.
Beta blockers
Intolerance Fatigue and cold extremities are common and dose related.
Erectile dysfunction occurs, but is less common than with thiazide diuretics.
Central nervous system (CNS) effects (e.g. vivid dreams) can occur.
Airways obstruction β-adrenoceptor antagonists predispose to severe airways obstruction in patients with pre-existing obstructive airways disease, especially asthma.
Peripheral vascular disease and vasospasm β-adrenoceptor antagonists worsen claudication in patients with symptomatic atheromatous peripheral vascular disease and worsen Raynaud‘s phenomenon.
Hypoglycaemia β-adrenoceptor antagonists mask symptoms of hypoglycaemia, and slow the rate of recovery from it, because adrenaline stimulates gluconeogenesis via β2-adrenoceptors.
Heart block
Digoxin
The therapeutic index is very low.
Children experience less toxicity than adults and have a higher therapeutic range (2.5 to 3.5).
It is estimated that 20% of patients taking digoxin will experience toxicity. o Clearance is via the kidneys.
o Renal dysfunction increases the elimination half-time, which increases digoxin levels and increases the risk of toxicity. The dose must be reduced accordingly.
o Factors that increase digoxin sensitivity (and thus increase toxicity risk) include Hypokalemia (most common cause), Hypercalcemia (less common), Hypomagnesemia (less common), Hypothyroidism and Hypoxia or acidosis.
o Adverse effects (Toxicity) sign and symptoms include:
o GI: Nausea, vomiting, diarrhoea, abdominal pain and anorexia (loss of appetite)
o CNS: Confusion, dizziness, and agitation
o Cardiovascular: Arrhythmias and heart block
o Visual: Orange tinted vision, visual disturbances o Increased automaticity occurs.
o Atrial or ventricular dysrhythmias such as premature atrial contractions (PAC‘s), premature ventricular contractions (PVC‘s), atrial or ventricular tachycardia can occur.
PST 05104 Pharmacology & Therapeutics 265 NTA Level 5 Semester 1 Facilitator Guide
Treatment is to stop giving the drug for a short period, or, if there are severe cardiac arrhythmias, an antibody called Digibind can be given; Digibind binds digoxin and increases the rate of clearance
STEP 5: Contraindications of Drugs for Heart Failure (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the contraindications of Drugs used for treatment of Heart Failure? ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Diuretics
o Refer to the module on Pharmacodynamics of Drugs acting on Genital urinal system and Pharmacodynamics of Antihypertensive drugs
Angiotensin-Converting Enzyme Inhibitors
o Refer to module on Pharmacodynamics of Drugs acting on Genital urinal system and Pharmacodynamics of Antihypertensive drugs
Digoxin
o Care must be exercised when prescribing to patients at risk for toxicity
STEP 6: Key Points (5 minutes)
Treatment of heart failure involves also non pharmacological approaches drugs used in heart failure act through different mechanisms
Significant drug interactions occur when drugs for heart failure are used concomitantly with other drugs
STEP 7: Evaluation (5 minutes)
What are the adverse effects of digoxin?
How is digoxin toxicity treated/ controlled?
What is the mechanism of action of digoxin?
PST 05104 Pharmacology & Therapeutics 266 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 267 NTA Level 5 Semester 1 Facilitator Guide
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