MK - Cardiac Pharmacology

Question 1

What ions are involved in the cardiac action potential? (3)

Answer 1

• Na+ influx
• Ca2+ influx (plateu)
• K+ efflux

Question 2

What allows the spread of excitation between cardiac cells?

Answer 2

Gap junctions

Question 3

What channel does Ivabradine block in its open state?

Answer 3

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel

Question 4

What are the components of the cardiac conduction and non-conduction system?

Answer 4

Conductive system: SA, AV, Bundle of His

Non-conductive: Depolarising myocytes

Question 5

What happens when the SA node has an issue?

Answer 5

Other nodes can overcome its dysfunction

Question 6

What are the 10 steps involved in excitation/contraction coupling?

Answer 6

1. Action potential from adjacent cell
2. Voltage-gated Ca2+ channels open. Ca2+ influx
3. Ca2+ induces Ca2+ release throught ryanodine receptor-channels (RyR)
4. Local release causes Ca2+ spark
5. Summed Ca2+ sparks create a Ca2+ signal
6. Ca2+ ions bind to troponin to initiate contraction
7. Relaxation occurs when Ca2+ unbinds from troponin
8. Ca2+ is pumped back into the SR for storage
9. Ca2+ is unchanged with Na+
10. Na+ gradient is maintained by the Na+-K+-ATPase

Question 7

What is an antagonist of HVA L-type Calcium Channel Agents?

Answer 7

Nifedipine-DHP (ANTAGONIST)

Question 8

What are agonists and antagonists of Ryanodine Receptors?

Answer 8

Ryanodine (AGONIST)

• At high concentrations it acts as an antagonist

Dantrolene (ANTAGONIST)

Question 9

What do sympatheic neurons cause? (5)

Answer 9

→ B1 receptors of autorhythmic cells

→ Increased Na+
→ Increased Ca++ influx

→ Increased rate of depolarisation

→ Increased Heart rate

Question 10

What do Parasympathetic neurones cause? (5)

Answer 10

Muscarinic receptors of autorhythmic cells

→ Increased K+ efflux
→ Decreased Ca++ influx

→ Hyperpolarised & Decreased rate of depolarisation

→ Decreased Heart rate

Question 11

What is the structure of β1 Adrenoreceptor structure (cardiac)?

Answer 11

Seven transmembrane (7TM) helices, which have a cylindrical structure and span the membrane

Question 12

What are 5 examples of adrenergic drugs?

Answer 12

• Noradrenaline
• Propanolol (beta non-specific antag)
• Phenylephrine (alpha1 specific agonist)
• Atenolol (beta1 specific antag)
• Prazosin (alpha1 specific antagonist, inverse agonist)

Question 13

How do secondary messengers work in GPCR activation and what does it lead to?

Answer 13

GPCR Activation → Gs →Adenylate cyclase → cAMP → PKA

Leads to:

• PKA phosphorylation of CaV1.2 increases ICa influx
• PKA phosphorylation of phospholamban produces more Ca++ATPase activity of SR so more Ca++ loading
• HCN increased the pacemaker’s current

Question 14

What are the main cholinergic drugs? (5)

Answer 14

1) Acetylcholine

2) Muscarine (Non-selective M1-5 agonist)

3) Pilocarpine (Non-selective agonist)

• increase secretion (for dry mouth)
• reverse iris dilation
• reduce intra-ocular pressure

4) Bethanecol (selective M2/3 agonist)

• treat urine retention

5) Atropine (Non-selective M1-5 antagonist)

• reduces secretions + gut motility
• dilates iris
• counteracts organophosphate actions

Question 15

What does M2 receptor activation result in?

Answer 15

Its activation results in a decrease in heart rate and a reduction in heart contraction force