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Pharmacology and Therapeutics > 10. Drugs and the heart > Flashcards

10. Drugs and the heart Flashcards

1
Q

Name the channels that open during an AP in the SA node and what they do

A
  • 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)
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2
Q

How does the sympathetic pathway affect the SA node?

A
  • Increase cAMP
  • Increased activity of If + Ica
  • Promotes depolarisation
  • Shorter phase 4 (triggering of AP - spontaneous depolarisation)
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3
Q

How does the parasympathetic pathway affect the SA node?

A
  • Decreased cAMP
  • Increased Ik
  • Prolonged repolarisation (phase 3)
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4
Q

Describe how Ca2+ causes depolarisation/contraction in the heart?

A

• 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

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5
Q

What is the primary determinant of myocardial oxygen demand and why?

A

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

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6
Q

How do beta blockers affect the AP in the SAN?

A
  • Beta blockers block the effect of SNS
  • Therefore, they affect If and Ica
  • Start of depolarisation is prolonged
  • Decreased HR
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7
Q

How do calcium antagonists affect the AP in the SAN?

A
  • Blocks Ica

* Dissuades depolarisation

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8
Q

How does Ivabradine affect the AP in the SAN?

A
  • Specifically targets If
  • Impacts spontaneous generation of APs
  • Prolongs the distance between successive APs
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9
Q

How do beta blockers and calcium antagonists influence contractility and how?

A
  • Beta blockers - decreases contractility (indirectly decreases Ca2+ influx)
  • Calcium antagonists - decreases contractility (directly decreases Ca2+ influx)
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10
Q

Which of the following do beta blockers and calcium antagonists influence:
• heart rate
• contractility

A

Both types of drugs affect both heart rate and contractility

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11
Q

Describe the 2 classes of calcium antagonists

A 
• 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
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12
Q

How do ‘potassium channel openers’ affect the heart?

A
  • Potassium efflux
  • Prolonged hyperpolarisation
  • Inhibition of VGCCs
  • Tissue relaxed for longer
  • More dilated (coronary) blood vessels supplying the heart
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13
Q

How do organic nitrates affect the heart?

A
  • 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)
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14
Q

How do you treat angina?

A
  • 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
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15
Q

What are the unwanted effects of beta blockers?

A

• 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

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16
Q

What is Verapamil, how does it work and what are the unwanted effects?

A
  • Calcium antagonist
  • Affects HR (rate limiting) - effects predominantly heart related
  • Reduces ventricular responsiveness to atrial arrhythmias
  • Decreases depolarisation
  • Depresses SA automaticity and subsequent AV node conduction
  • Bradycardia and AV block
  • Constipation - gut Ca2+ channels affected, less gut contraction
17
Q

What are the unwanted effects of dihydropyridines (calcium antagonists)?

A
  • Non-rate limiting => concerned about vasodilation
  • Ankle oedema - vasodilation => more pressure on capillaries
  • Headache/flushing
  • Palpitations - baroreceptor reflex response
  • Reflex adrenergic activation

(any drugs that act as profound vasodilators e.g. K channel openers, will have the same effects)

18
Q

Give 3 simple classifications of arrhythmias?

A
  • Supraventricular arrhythmias
  • Ventricular arrhythmias
  • Complex (both of the above)

(based on the site of origin)

19
Q

What are the 4 Vaughan-Williams classes of the anti-arrhythmic drugs?

A
  • Class I - sodium channel blockade (depolarisation)
  • Class II - beta-adrenergic blockade
  • Class III - potassium channel blockade (prolonged repolarisation/membrane stabilisation)
  • Class IV - calcium channel blockade (prolonged plateau)
20
Q

How useful is the Vaughan-Williams classification system?

A
  • Limited clinical significance
  • Used to work well when we had limited drugs and their mechanisms weren’t understood well
  • Still the major classification
  • However, it was discovered there was too much crossover, so many drugs couldn’t be classified
21
Q

Why is adenosine a popular anti-arrhythmic?

A
  • Short-lived action (20-30s)
  • Used acutely
  • Safer than verapamil
22
Q

What is adenosine and how does it work?

A

• Used to terminate supraventricular tachyarrhythmias (SVT)
• Prescribed IV - very fast effect
• Multiple effects
• Predominantly on nodal tissues (A1):
- inhibit adenylate cyclase => decreased cAMP
- decreased Ca channel opening => prolonged K channel opening
- prolonged depolarisation, slower repolarisation, normalises tachyarrhythmia
• On vascular smooth muscle (A2):
- stimulation of adenylate cyclase
- increased cAMP
- relaxation of smooth muscle

23
Q

How does amiodarone work as an anti-arrhythmic?

A
  • Some beta-blocking and calcium/potassium channel effects
  • ‘Messy’ drug in terms of mechanism
  • Major effect - potassium blockade
  • Prolonged repolarisation
  • Reduces re-entry
  • Used for supraventricular and ventricular tachyarrhythmias
24
Q

What are the adverse effects of amiodarone?

A
  • Accumulates in the body (half life: 10-100 days) - side effects attributed to this
  • photosensitive skin rashes
  • hypo/hyperthyroidism
  • pulmonary fibrosis
25
Q

What are re-entry rhythms?

A
  • Normally, if APs cross paths and meet anywhere in the tissues, they cancel each other out
  • This ensures a unidirectional AP
  • If you get damaged bits of tissue where the AP struggles to get through downwards, it is easier for an AP to go back up through it in the opposite direction - ‘re-entry’
  • Can get cyclical depolarisation
  • This is the basis of arrhythmias
  • Prolonging repolarisation can reduce the likelihood of this, as the tissue hasn’t repolarised when the re-entry AP comes to the damaged tissue - AP dies out
26
Q

What is digoxin and how does it work?

A

• Treats arrhythmias - commonly AF
• Inhibition of Na-K-ATPase (Na/K pump)
• Increased intracellular Ca2+ - positive inotropic effects
• Central vagal stimulation:
- increased refractory period
- reduced rate of conduction through AVN
• Decreased HR - more time for heart to fill
• Improved ventricular contraction - improved CO
• Normal rhythm is restored

27
Q

How does digoxin improve contraction?

A
  • Digoxin competes with potassium (Na/K pump)
  • Less sodium-potassium exchange
  • Build up of sodium inside the cell (K stays outside)
  • Therefore, more sodium-calcium exchange
  • More calcium comes into the cell
  • Therefore, more powerful positive inotropic effect on ventricles
28
Q

What are the adverse effects of digoxin?

A
  • Dysrhythmias e.g. AV conduction block

* If you have too much vagal stimulation - conduction block

29
Q

Why is it important to know the plasma potassium levels of a patient before giving digoxin?

A
  • If hypokalaemic (e.g. from diuretics) - less competition between potassium and digoxin
  • Digoxin has a more powerful effect - toxic

Pharmacology and Therapeutics (33 decks)

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