treatment of cardiovascular disease 3 and 4

Question 1

what is ischaemic heart disease

Answer 1

imbalance in myocardial oxygen demand (work rater and load) and myocardial oxygen supply (thrombus, atheroma and vasoconstriction)

Question 2

what are the aims of treating IHD

Answer 2

Increase oxygen supply to heart tissue or reduce work done by heart
Nitrates inc both, main is reducing work
Beta blockers and ca channel blockers also mostly reduce work

Question 3

How is coronary blood flow regulated

Answer 3

Endothelium-derived relaxing factor (nitric oxide)

Nitrates>NO + GC >cGMP to convert Myosin L-C-PO4 to Myosin L-C = relaxation

Question 4

how is cardiac work load regulated

Answer 4

End diastolic volume (preload) regulated by sympathetic system, RAAS, (contractility of venules, Na and H20 retention)
Heart rate reg by sympathetic system/Ca2+
Contractility (sympathetic system/Ca2+)
Total peripheral resistance (sympathetic system/RAAS)

Question 5

what is stable angina

Answer 5

Stable Angina – predictable pattern of pain during exercise, that is relieved by rest (02 supply and demand rebalanced)
Treatment – decrease work done by heart and/or increase blood supply and treat risk factors

Question 6

how to nitrates aid treatment of heart disease

Answer 6

inc NO > inc cGMP > dec preload > dec workload

or inc NO > dilate some coronary arteries to increase O2 supply

Question 7

what are the side affects of nitrates

Answer 7

Postural hypotension – due to peripheral dilation and reduced heart rate
Headache – peripheral dilation
Dizziness
Eg GTN

Question 8

what is reflex tachycardia

Answer 8

due to activation of sympathetic nervous system, release noradrenaline in response to nitrates dropping blood pressure. Use beta blockers to prevent increase in heart rate.

Question 9

what do beta blockers do

Answer 9

Dec frequency and force contraction
Decrease cardiac output
Beta blockers also inhibit renin release from kidney so inhibit RAAS

Question 10

what are side effects of beta blockers

Answer 10

Bronchoconstriction – contraindicated asthma
Fatigue
Contraindicated in patients with peripheral vascular disease
Eg bisoprolol

Question 11

what are Ca2+ channel antagonists (CCBs)

Answer 11

Dec frequency and force of contraction (phenylalkamines/benzothiazepines)
Increase dilation of arterioles (dihydropyridines)
Decrease cardiac workload
Mixing with beta blockers can cause severe bradycardia and even heart block

Question 12

how do CCBs affect frequency and force of contraction

Answer 12

CCBs can reduced heart beat by blocking L-type channels in the SA and AV nodes. Slow rate of depolarisation and reduced action potential generation. Decrease force of contraction in ventricles by reducing calcium entry through L-type channels.

Question 13

what does ivabradine do

Answer 13

Blocks pacemaker current (Ih/f) in the nodal tissue of the heart
Reduce Na+ entry through if channels. So slow the rate of depolarisation of the SA node cells and reduce firing frequency and the heart rate. Doesn’t directly alter force of contraction.

Question 14

what are the side effects of ivabradine

Answer 14

Luminous phenomena (Ih) in retina
Blurred vision
Dizziness

Question 15

what are alternative treatments of IHD

Answer 15

Long-acting nitrates (isosorbide mononitrate) to decrease preload 
eg Nicorandil (nitrate like action and K+ ATP channel opener)

Question 16

what is ranolazine

Answer 16

more sodium ions enter in ischaemia
Partially removed via exchanger (Na+ enter via conc gradient and remove Ca2+ against its conc gradient to shorten contraction)
Late sodium channel overexpressed so doesn’t work so less sodium removed = more work for the heart
Blocks the late sodium channel so less sodium can enter

Question 17

where does cholesterol come from

Answer 17

Cholesterol comes from 2 main sources
Diet va GI tract or produced in liver
Drugs designed to inhibit this uptake or reduce production
Frontline treatment are STATINS eg simvastatin or atorvastatin

Question 18

how do statins work

Answer 18

Statins decrease the production of liver by inhibiting the CoA enzyme. This stimulates the liver cells to express LDL receptors so the liver cells scavenge LDL cholesterol from plasma. Reduces plasma LDL cholesterol levels

Question 19

what are other secondary preventers of IHD

Answer 19

Aspirin
Antiplatelet agents (aspirin/clopidogrel)
Ace inhibitors (eg ramipril) and ARBs (losartan)
Decrease workload of the heart

Question 20

How is unstable angina treated

Answer 20

Unstable angina as for stable angina + antiplatelet (plaque more likely to rupture)
Aspirin, aspirin + clopidogrel (prasugrel, ticagrelor)

Question 21

how do anti platelet agents work

Answer 21

Platelet activation occurs when the endothelial cells become damaged. Releases ADP, acts on P2Y12 receptors to stimulate the platelet to stick to GPIIb/IIIa receptors. Fibrinogen binds to these receptors to cross link platelets. Activation of COX helps platelet activation through production of thromboxane A2. Aspirin inhibits COX irreversibly. Clopidogrel, prasugrel and ticagrelor are ADP antagonists and block P2Y12 receptors.

Question 22

how does clopidogrel work

Answer 22

Has to be activated CYP2C19 so reduces activity in bloodstream in polymorphisms and stops platelet activation
Prasugrel requires hydrolysis by esterase to work, not CY2C19 (useful for those with polymorphism)
Irreversible so bad when bleeding
Ticagrelor – orally active as absorbed in active form, reversible

Question 23

how is MI diagnosed

Answer 23

Pain, sweating, tachycardia, cold clammy skin

Question 24

how is MI treated

Answer 24

Pain relief – diamorphine u-opioid receptors
Decreases pain, anxiety, sympathetic drive, vasodilates
Oxygen
Aspirin/GTN
Clot busting drugs
Eg tenectaplase – breaks down tPA

Question 25

how can beta blockers, rivaroxaban and ACE inhibitors treat MI

Answer 25

Beta blockers – decrease cardiac workload, prevents arrythmias eg metaprolol- short acting and bioprolol – longer acting
ACE inhibitors – decrease cardiac workload, prevents remodelling development of heart failure eg ramipril
Anti-coagulant – in long term bed rest prevents thrombus formation eg warfarin/apixaban/rivaroxaban/dabigatran/LMWH

Question 26

how does digitoxin work to treat HF

Answer 26

Binds to Na/K ATPase and inhibits its action. This increase levels of Na ions inside heart muscle cells. This inhibits Na/Ca exchanger which leads to build up of Ca inside muscle cell and stronger contraction

Question 27

How is HF treated

Answer 27

Amiodarone

K channel blocker that increase the refractory period of ventricular myocytes and can terminate arrythmias.