10. Drugs and the heart Flashcards
Name the channels that open during an AP in the SA node and what they do
- If - Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels (opens at -60mV => Ca2+ enters cell)
- Ica - Transient T-type Ca2+ channel (propagates depolarisation)
- Ica - Long Lasting L-type Ca2+ channel (main upstroke of AP)
- Ik Potassium K+ channels (opens once above 0mV for repolarisation)
How does the sympathetic pathway affect the SA node?
- Increase cAMP
- Increased activity of If + Ica
- Promotes depolarisation
- Shorter phase 4 (triggering of AP - spontaneous depolarisation)
How does the parasympathetic pathway affect the SA node?
- Decreased cAMP
- Increased Ik
- Prolonged repolarisation (phase 3)
Describe how Ca2+ causes depolarisation/contraction in the heart?
• APs from the SAN promotes gating of Ca2+ channels
• Small amount of Ca2+ enters cytoplasm from outside
- through L-type channels (Ica)
• This Ca2+ induces release of Ca2+ from SR (Ca-induced Ca-release)
- RyR2 (ryanodine receptors)
- 75-80% of Ca2+
• Intracellular calcium allows formation of actin-myosin cross-bridges
• Beta receptors: Increased cAMP => increased PKA => promotion of contractile machinery + reduction of Ca2+ re-entry back into SR
What is the primary determinant of myocardial oxygen demand and why?
Myocyte contraction
• Higher HR - more contractions
• Higher afterload/contractility - greater force of contraction
• Higher preload - small increase in force of contraction
• Therefore the greater the contraction, the greater the demand for oxygen
How do beta blockers affect the AP in the SAN?
- Beta blockers block the effect of SNS
- Therefore, they affect If and Ica
- Start of depolarisation is prolonged
- Decreased HR
How do calcium antagonists affect the AP in the SAN?
- Blocks Ica
* Dissuades depolarisation
How does Ivabradine affect the AP in the SAN?
- Specifically targets If
- Impacts spontaneous generation of APs
- Prolongs the distance between successive APs
How do beta blockers and calcium antagonists influence contractility and how?
- Beta blockers - decreases contractility (indirectly decreases Ca2+ influx)
- Calcium antagonists - decreases contractility (directly decreases Ca2+ influx)
Which of the following do beta blockers and calcium antagonists influence:
• heart rate
• contractility
Both types of drugs affect both heart rate and contractility
Describe the 2 classes of calcium antagonists
• Rate slowing - cardiac and smooth muscle actions - more powerful on cardiac e.g. benzothiazepines • Non-rate slowing - smooth muscle actions only - more potent - no effect on the heart (profound vasodilation => reflex tachycardia) e.g. dihydropyridines
How do ‘potassium channel openers’ affect the heart?
- Potassium efflux
- Prolonged hyperpolarisation
- Inhibition of VGCCs
- Tissue relaxed for longer
- More dilated (coronary) blood vessels supplying the heart
How do organic nitrates affect the heart?
- Promote NO production in endothelial cells
- NO causes VSMC relaxation by activating guanylate cylase
- Decreased afterload (vasodilation)
- Decreased preload (venodilation)
- Short acting symptomatic treatment for angina (similar effects to potassium channel openers)
How do you treat angina?
- Beta blockers or calcium antagonists permanently
- If you get angina - intervene acutely by giving nitrate to improve myocardial oxygen sypply
- Nitrates may need to be taken before exercise
What are the unwanted effects of beta blockers?
• Worsening cardiac failure (beta blockers reduce work heart has to do - bad CO reduction as heart already has poor output)
• Bradycardia - less AVN conduction
• Bronchoconstriction - blockade of β2
• Hypoglycaemia (in diabetics on insulin) - due to decreased glycogenolysis/gluconeogenesis
• Cold extremities and worsening peripheral arterial disease (β2 blockade in skeletal muscle vessels)
• Fatigue
• Impotence
• Depression
• CNS effects e.g. nightmares
• Increased TPR - worsens HF
- pindolol and carvedilol can stop this and decrease TPR due to ISA and alpha 1 blocking respectively