Cardiac Drugs Flashcards
Why do we need to be able to modulate HR?
HR needs to be lowered for those with a high HR since it can increase the risk of arrhythmias.
↑Myocardial O2 consumption – heart must work harder. ↓Diastolic time = ↓Coronary perfusion as it only occurs during diastole
How do Calcium Channel Blockers (CCB) modulate HR?
Why do the VGGCs need to be selectively targeted?
What are the 3 subtypes of CCBs and give an example?
What are some concerns with CCB usage?
- They block VGCCs to prevent Ca2+ entering SAN cells; reduce HR.
- There are VGGCs in other places, like cardiac myocytes and vascular smooth muscle - can lead to unwanted effects.
- Vascular selective - Amlodipine
- Cardiac selective - Verapamil
- Vascular AND Cardiac selective - Diltiazem
- Vascular selective - Amlodipine
- It affects contractility - can make heart failure worse (cause heart block)
How do Funny channel (If) blockers modulate HR? Give example
What’s it used to treat?
e.g. Ivabradine
They are selective inhibitors of Funny channels in SAN = ↓Pacemaker potential frequency = ↓HR
- Heart failure and Angina
How do parasympathetic nerves decrease HR?
Release ACh at M2 receptors = inhibit Adenyl cyclase = ↓cAMP = ↓HR
How do β1-receptor blockers modulate HR? Give example
What’s it used to treat?
What are some concerns with these blockers?
e.g. Atenolol
Act as antagonists to reduce sympathetic action on SAN cells - NA/Adr can’t bind.
They prevent HR from increasing too much, therefore reducing how hard the heart is working.
- Angina
- • Can’t be used in asthmatic patients
• Not used with CCBs - can ↓Contractility too much = Bradycardia
• Fatigue.
How do Muscarinic receptor blockers modulate HR? Give example
When can it be used?
What’s a concern of using this drug?
e.g. Atropine
Act as antagonists to reduce parasympathetic action on SAN - ACh can’t bind.
They remove the inhibitory influence on HR = ↑HR and create a more stable CO.
- After an MI: HR can drop too much = ↓CO even more in a heart that’s already poorly functioning. However, these blockers are used to treat COPD, over-active bladder, IBS.
- Can cause tachycardia, which will increase O2 demand on the heart - dangerous in those with co-morbidities e.g. COPD, Angina
Why do we need to be able to modulate Contractility?
Increase contractility to maintain CO during heart failure - maintains organ perfusion.
What are the type of Ionotropic drugs that increase contractility and how?
LOOK AT DIAGRAM!
Gs-coupled receptor agonists, PDE inhibitors, Other Ca2+ rising processes.
The ionotropic effect is where the β1-adrenoceptors or glucagon receptors on cardiac myocytes increase cAMP levels. This will then increase PKA - some is converted into AMP using PDE3.
Increase in PKA leads to phosphorylation of VGCCs = Ca influx = CICR. The increase in [Ca2+] in the cell increases the number of actin-myosin interactions to increase contractility.
What are the types of Gs-coupled receptor agonists? How do they work? What are they used to treat? Give examples
- β1-adrenoceptor agonists e.g. adrenaline, dopamine - used to treat acute heart failure
- Other Gs-coupled agonists, e.g. glucagon - used in those with acute heart failure who aren’t taking any β-blockers.
Gs agonists aren’t used in chronic heart failure as they will ↑HR and myocardial work.
• PDE inhibitors e.g. amrinone, inhibits PDE3, which is used to convert cAMP into AMP. This will cause a build up of cAMP, so more PKA is activated to ↑↑VGCCs/Ca influx - only used in severe and chronic cases, like those waiting for heart transplants.
What are the 2 types of Ca2+ rising processes? How do they work? What are they used for? Give examples
LOOK AT DIAGRAM!
- Cardiac Glycosides e.g. digoxin, ↑Contractility by ↓Ca2+ extrusion from the cell - but they’re very toxic.
Digoxin inhibits Na/K ATPase on membrane = Na+ builds up in cell. The Na gradient will decrease = ↓Ca2+ moved out via Na/Ca exchanger (NCX) = ↑Ca2+ taken up into stores. This will lead to ↑CICR = stronger contraction.
- Ca2+ sensitisers e.g. Levosimedan, don’t affect [Ca2+]. They ↑Contractile apparatus sensitivity to Ca2+, so contraction works better at lower [Ca2+].
These drugs are used in decompensated heart failure (sudden worsening of symptoms of heart failure).
Why are β-blockers used in heart failure?
Chronic heart failure has a poor CO and needs better contractility, so we expect β1-adrenoceptor activity to be increased, but it isn’t.
β-blockers are used instead as the main treatment option. This is because they:
• Prevent a failing heart from working too hard by ↓Contractility
• Prevent a failing heart from working too hard by ↓HR to ↑Diastolic time = ↑Coronary perfusion.
• Prevent down-regulation of β1-adrenoceptors caused by excess compensatory sympathetic activity during heart failure.
• Prevent β-adrenoreceptor-associated arrhythmias.
What drugs are used to modulate Afterload?
- Diuretics cause more fluid excretion to ↓BV, CVP and SV. This will then ↓CO = ↓BP.
- ACEi and ARBs ↓Ang II-induced vasoconstriction = ↓TPR, and they ↓Ang II-induced Aldosterone secretion = ↓BV = CO.
What’s the clinical need for modulating coronary blood flow?
What drugs are used to modulate coronary blood flow?
- In angina, the heart pain is because of the poor blood flow to the heart, which is due to the blockage of coronary arteries, so the coronary arteries need to be dilated more to ↑Blood flow and relieve the symptoms.
- Nitrate donors e.g. GTN spray. There’s a process that releases NO into the vascular smooth muscle cells, causing vasodilation. GTN mimics this process to release more NO = even more vasodilation of coronary arteries.
