Anti-Anginal

Question 1

Classical angina

Answer 1

1. occurs if the coronary artery is narrowed
2. the reduced blood flow through narrowed arteries can’t meet the increased O2 demand–>
3. Symptoms occur with increased emotional or physical exertion.

Question 2

Variant Angina aka Prinzmetal’s angina

Answer 2

1. results from a reversible spasm of large coronary arteries, usually at the site of atherosclerotic plaque
2. can occur at rest or irrespective of the amount of physical or emotional exertion

Question 3

acute coronary syndrome aka unstable angina

Answer 3

1. characterized by increased frequency and severity as a result of combo of atherosclerotic plaques and vasospasm
2. symptoms occur even at rest
3. might signal an impending MI–>treat as medical emergency

Question 4

2 strategies for treatment of angina

Answer 4

1. increase O2 delivery: Nitrates & Ca Channel Blockers
2. Reduce O2 requirement: beta blockers
3. anti platelet drugs (i.e. low dose aspirin, abciximab) are also used

Question 5

Which anti anginal meds work to increase Oxygen delivery to tissues?

Answer 5

Nitrates & Calcium Channel Blockers (CCB)

Question 6

Which anti anginal meds work to reduce the oxygen requirement?

Answer 6

beta adrenergic blockers

Question 7

Ranolazine

Answer 7

a newer drug that works to increase the efficiency of oxygen utilization by partial fatty acid oxidation inhibitors (pFOX inhibitors)

1. a pFOX inhibitor (partial fatty acid oxidation inhibitor) in myocardium
2. primary mechanism of action involves reduced contractility
3. action results from blockade of a late sodium current that facilitates calcium entry via the sodium-calcium exchanger

Question 8

Examples of Nitrates

Answer 8

1. Nitroglycerine (GTN)
2. Isosorbide dinitrate
3. Isosorbide mononitrate

Question 9

Nitrates

Answer 9

1. powerful vasodilators
2. act by releasing NO
3. NO–> smooth muscle relaxation
4. effectiveness due to action on capacitance vessels to reduce cardiac pre-load: Dilation of collateral coronary vessels

Question 10

Nitrates MOA

Answer 10

1. NO formation is triggered by Ach, Bradykinin, histamine & serotonin
2. NO activates Guanylyl Cyclase (GC) to form cGMP–> smooth muscle relaxation
3. Contraction of vascular smooth muscle is triggered by influx of calcium
4. . Ca combines with calmodulin & converts enzyme myosin light chain kinase to its active form (MLCK)
5. MLCK phosphorylates the myosin light chains–>initiates interaction btw myosin & actin
6. Nitrates dephosphorylate Myosin light chains to prevent their interaction with actin
7. phosphodiesterase breaks down cGMP. a phosphodiesterase inhibitor (i.e. Sildenafil) results in an increase in the amount of cGMP–>more dephospho rylation of MLC–>more muscle relaxation

Combining nitrates with sildenafil–>sudden severe hypotension

Question 11

Sildenafil

Answer 11

phosphodiesterase inhibitor

phosphodiesterase breaks down cGMP. a phosphodiesterase inhibitor (i.e. Sildenafil) results in an increase in the amount of cGMP–>more dephospho rylation of MLC–>more muscle relaxation

Question 12

Glyceryl trinitrate (GTN)

delivery?

Answer 12

aka nitroglycerine

1. given sublingually to avoid 1st pass metab; also rapidly absorbed
2. also available in transdermal patch & via IV

Question 13

How do nitrates work?

Any other uses?

Answer 13

they decrease the cardiac preload by preferentially dilating veins

Other uses: cyanide poisoning (sodium nitrite, amyl nitrite with sodium thiosulfate)
NITRITE used in cyanide bc converts Hb to MetHb, which has higher affinity for cyanide.

Question 14

Adverse effects of nitrates

Answer 14

1. severe headache (from vasodilation of extracerebral bv)
2. Tolerance occurs with long term use (need higher doses)
3. Postural hypotension & reflex tachycardia
4. Methemoglobinemia caused by NITRITES, not nitrates

“monday disease” in production of substances involving nitrates is an example of the tolerance (build it up over the week) & the symptoms (headache)

Question 15

Nitrates have an interaction with? How?

Answer 15

Sildenafil (viagra)

1. these agents inhibit a phosphodiesterase isoform (PDE5) that metabolizes cGMP in smooth muscle
2. the increased cGMP in erectile smooth muscle relaxes it, allowing for greater inflow of blood & more effective & prolonged erection
3. this effect also occurs in vascular sm. as a result the combo of nitrates (via increase in cGMP production) & a PDE5 inhibitor (through decreased breakdown of cGMP) –> synergistic relaxation of vascular sm with potentially dangerous HYPOTENSION & inadequate perfusion of critical organs

Question 16

Calcium Channel Blockers block what type of channel? where is it located?

Answer 16

CCB block voltage-gated L-type calcium channels in cardiac & smooth muscle

Question 17

Examples of CCB

Answer 17

a) Dihydropyridines (DHP):
1. nifedipine, amlodipine, nicardipine, nimodipine
b) Verapamil, diltiazem

Question 18

Examples of Dihydropyridines (DHP)

Answer 18

1. nifedipine
2. amlodipine
3. nicardipine
4. nimodipine

Question 19

Important differences in vascular selectivity between CCB

Answer 19

in general, DHPs have a greater ratio of vascular smooth muscle effects compared to cardiac effects than either diltiazem or verapamil

Question 20

Nimodipine is particularly selective for

Answer 20

cerebral blood vessels–>used to treat subarachnoid hemorrhage

Question 21

Verapamil & Diltiazem function & use

Answer 21

block calcium-dependent conduction in the AV node & are used to treat AV nodal arrhythmias

Question 22

How do CCB work to treat angina?

Answer 22

They decrease both preload and after load–> decreasing workload on the heart!

Question 23

Nifedipine

1. what is it?
2. Effects?
3. Use?
4. ADR?

Answer 23

1. mainly arteriolar vasodilator
2. minimal effect on cardiac conduction or HR–>NOT USED FOR ARRHYTHMIAS
3. useful to treat varying angina
4. ADR:
5. flushing
6. headache
7. hypotension
8. peripheral edema

All the ADR are results of the vasodilation

Question 24

ADR of Nifedipine

Answer 24

1. flushing
2. headache
3. hypotension
4. peripheral edema

All the ADR are results of the vasodilation

Question 25

Verapamil | What? Use? Interactions/toxicities?

Answer 25

More selective for cardiac calcium channels (but will also affect bv) 1. slows cardiac conduction 2. decreases HR & O2 demand 3. causes more negative inotropic effect than nifedipine 4. Weaker vasodilator than nifedipine--DIP always more powerful 5. Drug interaction: with digoxin (increases digoxin levels)

Question 26

Diltiazem

Answer 26

same as verapamil--More selective for cardiac calcium channels (but will also affect bv) 1. has specific coronary vasodilating effect relieving coronary vasospasm 2. particularly useful in variant angina 3. ADR: low

Question 27

ADR of CCB (generally)

Answer 27

1. cause hypotension due to vasodilation 2. peripheral edema 3. overdose leads to cardiac arrest (bc blocked channels--> decreased FOC), bradycardia, AV block & Heart Failure

Question 28

What condition is contraindicated against CCB?

Answer 28

Heart Failure! IN heart failure the cardiac output isn't sufficient to meet the body's demands. CCB will further decrease the heart's FOC--> further decreasing it's CO.

Question 29

How are Beta blockers used to treat angina?

Answer 29

1. work by opposing the action of adrenaline on the heart 2. block B1 receptors present in the heart--> results in unopposed alpha effects-->vasoconstriction 3. results in a decrease in HR, BP & contractility 4. this decreases the myocardial oxygen requirements at REST & DURING EXERCISE 5. they do NOT HAVE ANY EFFECT ON MYOCARDIAL O2 SUPPLY! 6. they are used in combo with other anti-anginal drugs ie beta blockers + nitrates bc nitrates -->vasodilation + reflex tachycardia but the beta blockers will help prevent the tachycardia

Question 30

When are beta blockers contraindicated in treating angina

Answer 30

in vasospastic angina, bc beta blockers will cause further vasoconstriction block B1 receptors present in the heart--> results in unopposed alpha effects-->vasoconstriction

Question 31

DOC in acute relief of symptoms in all types of angina

Answer 31

Nitrates

Question 32

What is used as prophylactic therapy in vasospastic/variant/Prinzmetal's angina?

Answer 32

Ca channel blockers they're also useful in angina of effort

Question 33

When should you use beta blockers to treat angina?

Answer 33

ONLY for prophylaxis of angina. They're effective in preventing EXERCISE-INDUCED angina

Question 34

Nitrates have a preference for?

Answer 34

veins

Question 35

How do nitrates treat angina?

Answer 35

release NO-->sm relaxation through activation of cGMP--> ultimate reduction in preload

Question 36

How do you overcome the reflex tachycardia associated with nitrates?

Answer 36

Give them in conjunction with beta blockeres

Question 37

Nifedipine has a preference for?

Answer 37

arteries

Question 38

Nimodipine has a preference for

Answer 38

cerebral blood vessels

Question 39

decreases HR, BP & contractility

Answer 39

beta blockers reducing these-->decreases myocardial oxygen requirements at rest & during exercise

Question 40

blocks AV nodal conduction

Answer 40

verapamil & diltiazem

Question 41

abciximab

Answer 41

anti platelet effect; used like aspirin in treatment of angina

Question 42

reduces contractility by blocking late sodium current that facilitates calcium entry via the sodium-calcium exchanger

Answer 42

Ranolazine