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Semester 2: Physiology > pharmacology of CVS > Flashcards

pharmacology of CVS Flashcards

1
Q

What is angina?

A

Angina is chest pain or pressure, usually due to not enough blood flow to the heart muscle. Imbalance between demand and supply of oxygen to the heart

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2
Q

What are some symptoms of angina?

A
  • crushing chest pain, also in the jaw, shoulders, arms, etc.
  • shortness of breath
  • sweating
  • nausea
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3
Q

What increases the risk of an angina attack?

A
  • INCREASED SYSTOLIC BLOOD PRESSURE (AFTERLOAD): the heart has to work harder to eject blood and so requires more oxygen
  • INCREASED SYMPATHETIC NERVE ACTIVITY: this increases heart rate, increases contractility and increases vasoconstriction
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4
Q

What are the different types of angina pectoris?

A
  • STABLE ANGINA (MOST COMMON): exercise-induced - predictable, relieved by rest and medications
  • UNSTABLE ANGINA (ACUTE CORONARY SYNDROME, MORE SERIOUS): exercise-induced - unpredictable, may indicate thrombosis or plaque rupture
  • VARIANT (PRINZMETAL) ANGINA: symptoms present at rest
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5
Q

Describe how an atheroma can lead to an angina during exercise.

A

In a normal heart, the resistance is low in the large coronary artery, and high in the arterioles. During exercise, metabolic vasodilation of the arterioles reduces the total resistance. This means that there is increased blood flow to meet the increased O2 demands.

In a heart with an atheroma, there is stenosis in the large coronary artery, increasing the resistance. This means that metabolic hyperaemia occurs at rest, so that the blood flow meets the O2 needs.
During exercise, arterioles will further dilate to reduce resistance, but the total resistance is still too high to dominate the stenosis.
This means that the O2 demand cannot be met, and angina develops.

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6
Q

What are the aims of the treatment for an atheroma?

A

IMPROVE THE PROGNOSIS:

  • prevent MI and death
  • reduce plaque progression
  • stabilise plaque
  • prevent thrombosis

MINIMISE SYMPTOMS:
- improve quality of life

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7
Q

What drugs can be used to treat angina?

A
  • nitrates
  • calcium-blockers
  • β-blockers
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8
Q

How do β-blockers work in treating angina?

A

They reduce the actions of sympathetic activity (noradrenaline and adrenaline) on β1 adrenoreceptors in the heart.

  • they slow the heart rate and AV conduction; this increases diastolic time, which increases coronary artery perfusion
  • they reduce the force of contractility; this reduces myocardial work and oxygen consumption
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9
Q

How do calcium-blockers work in treating angina?

A

They reduce the Ca2+ entry into cardiac myocytes/ vascular smooth muscle cells; this reduced contractility.

  • they can cause direct coronary vasodilation so there is more coronary blood flow
  • they reduce TPR/ BP/ afterload, so the heart works less to eject blood
  • they reduce the force of contraction, so there is less O2 consumption
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10
Q

What are the three subtypes of calcium-blockers (with examples of each)?

A
  • dihydropyridines (vascular): Amplodipine, Nifedipine
  • benzothiazepines (cardiac): Verapamil
  • diphenylalkyamines (both): Diltiazem
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11
Q

What are some side effects of DHP’s?

A
  • lower limb oedemas (because of the increased capillary pressure in the lower limbs)
  • flushing and headache (caused by excess vasodilatation)
  • reflex tachycardia (increased vasodilation causes increased baroreflex, so increased sympathetic activity)
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12
Q

Describe how nitric oxide is made in the body, and how it affects it.

A

Stimulated by shear stress, acetylcholine, histamine, bradykinin, etc., an enzyme called endothelium NO synthase (eNOS) converts L-Arginine to NO.
This NO diffuses from the endothelial cell to the vascular smooth muscle cell, where it will stimulate Guanylyl Cyclase to make more cGMP from GTP. cGMP activates Protein Kinase G.

Protein Kinase G reduces smooth muscle tone by:

  • myosin light chain dephosphorylation
  • increasing uptake of Ca2+ by the SR, causing a decrease in cytoplasmic levels
  • activating K+ channels, causing hyperpolarisation and closing of the VGCCs
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13
Q

Where does vasodilation occur?

A

1) coronary artery dilatation: increases collateral arteriole dilation to shunt blood from areas of good perfusion to poor perfusion (between functional end-arteries)
2) venodilatation: decreases venous return and preload
3) arteriole dilatation: decreases TPR and afterload

Decreased preload and afterload reduces the myocardial O2 demand, so will relieve symptoms.

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14
Q

Describe stable angina (classic)

A

• Follows a set pattern/predictable (recurrent episodes have similar onset, pattern, duration and intensity)
• Short duration radiation to left arm, neck, jaw or back (lasts max 5 mins)
• Precipitated by exertion; increased cardiac oxygen demand
• Not life threatening but can be a warning of a stroke
• Relieved by rest and medication
Symptoms attributes to MI

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15
Q

Describe how stable angina arises

A

Narrowing of coronary artery caused by stenosis = restricted blood flow to area of myocardium it supplies. The oxygen it receives when the heart has to work harder is insufficient meaning anaerobic respiration is used causing pain

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16
Q

Describe unstable angina

A 
• Unpredictable 
	• Pain symptoms more severe and can last longer 
	• Happens with little exertion 
	• May not have a trigger 
	• Not relieved by rest/meds
	• Progresses from stable angina 
Regarded as emergency
17
Q

Describe how unstable angina arises (due to plaque rupture)

A

Clot formation occludes coronary artery = critical reduction in blood flow meaning oxygen supply is inadequate even at rest (this is transient)

18
Q

Describe variant angina (prinzmetal angina)

A

• Occurs in early hours or late hours (morning or night)
• Episodes lasting 15 mins
• RARE
• Present in younger patients
• Painful attacks that spread from chest to head, shoulders or arms
• Symptoms are heart burn, nausea, sweating, dizziness and palpitation migraines and Raynaud’s phenomenon
• Usually due to a spasm in the coronary arteries (happens in cycles)
Can be relieved by taking medication

19
Q

Describe how variant angina arises

A

Coronary spasm (can be causes by cocaine) = critical reduction in blood flow so that oxygen supply is inadequate

20
Q

Describe the angina treatment strategy

A
  1. To improve perfusion
    Increase oxygen delivery by improving coronary arteries blood flow using coronary vasodilator
    1. To reduce metabolic demand
      Reduce oxygen demand by decreasing cardiac work using vasodilator sand cardiac depressants
      Vasodilator: reduces afterload and preload
      Cardiac depressants: reduces heart rate and contractility
    2. Prevention
      Prophylactic to reduce the risk of subsequent episodes
      Lipid lowering drugs
      Anti coagulants
      Fibrinolytic
      Anti platelets
21
Q

What are examples of nitrates that can work as an anti angina drug?

A

Glyceryl trinitrate

Isosorbide mononitrate

22
Q

What are the effects of anti anginal nitrates?

A
  • Peripheral vasodilation = decrease IV pressure = decrease cardiac preload
    • Arterial dilation = decrease TPR = reduces afterload
    • Both of these actions lower oxygen demand by decreasing the work of the heart
23
Q

What are the adverse effects of anti anginal nitrates?

A
  • Throbbing headache
    • Flushing
    • Syncope
    • Postural hypotension (venodilation)

Reflex tachycardia (sympathetic flow)

24
Q

Describe the mechanism of action of anti anginal nitrates

A

• Organic nitrates mimic the effects of endogenous NO
1. Shear stress, Ach, histamine or bradykinin activates eNOS to convert L-arginine into nitric oxide
Nitric oxide donors cause dilation of smooth muscle
2. Nitric oxide activates guanylyl cyclase to convert GTP —> cGMP
cGMP can then be converted to GMP using PDE5 (phosphodiesterase type 5)
3. cGMP is then converted to protein kinase G
4. Protein kinase K reduces smooth muscle tone:
• Myosin light chain dephosphorylation
• Increases uptake of calcium ions by SR causing a decrease in cytoplasmic level
• Activates K+ channels causing hyperpolarisation and closing VGCC
This NO diffuses from the endothelial cell to the vascular smooth muscle cell, where it will stimulate Guanylyl Cyclase to make more cGMP from GTP. cGMP activates Protein Kinase G.

25
Q

Describe the properties of NO that enable it to dilate the smooth muscle

A

Continuously produced/released

Lipophilic soluble gas

Freely diffusible out of endothelium into surrounding vascular smooth muscle cells

26
Q

Describe the mechanism of action of PKG on smooth muscle

A

Protein kinase K reduces smooth muscle tone:
• Myosin light chain dephosphorylation
• Increases uptake of calcium ions by SR causing a decrease in cytoplasmic level
Activates K+ channels causing hyperpolarisation and closing VGCC

27
Q

Name 2 anti anginal beta blockers

A
  1. Atenolol

2. Bisoprolol

28
Q

Describe the effects of anti anginal beta blockers

A

• Inhibits If pacemaker current in the SA node = decrease HR
• Reduce the force of cardiac contraction = improved exercise tolerance
• Both of these actions reduce cardiac output and lower blood pressure
Slower heart rate = lengthens diastole and gives more time for coronary perfusion, which effectively improves myocardial oxygen supply

29
Q

Describe the adverse effects of anti anginal beta blockers

A

Bronchospasm

Fatigue

Postural hypotension

30
Q

Describe the contraindication of anti anginal beta blockers

A

Asthma blocks beta-2 receptors can cause constriction and bronchospasm

Heart block where atrial ventricular conduction is poor and may block AV node

31
Q

Describe the mechanism of action of beta blockers

A

Reduces the sympathetic activity of NA and adrenaline on beta-1 adrenoreceptors in the heart
Two mechanisms
1. Sino atrial node: increased funny current increases HR
NA binds to B1 receptor bound to Gs on SA node = activates adenylate cyclase = ATP—> cAMP
cAMP increases sodium influx = increases If = increase HR
2. Ventricular myocytes: increase Ca2+ channel increased force of contraction
NA binds to B1 receptors bound to Gs on myocyte = activates adenylate cyclase = ATP—> cAMP
cAMP activates PKA = activation of VGCC = influx of calcium ions
Calcium ions activate ryanodine receptor = CICR = further increase in calcium ions (Ca2+ influx)
Increases force of contraction

32
Q

Name some examples of anti anginal calcium channel blockers

A

Dihydropyridines: amlodipine, nifedipine (vascular)
Benzothiazepines: verapamil (cardiac)
Diphenylalkyamines: diltiazem (both)

33
Q

Describe the effects of anti anginal calcium channel blockers

A
  • Reduce calcium entry into cardiac myocytes/vascular smooth muscle cells = reduce contractility
  • Direct coronary vasodilation = more coronary blood flow
  • Reduces TPR/BP/afterload = heart works less hard to eject blood

Reduce force of contraction = less oxygen consumption

34
Q

Describe the adverse effects of DHPs

A
  • Increased capillary pressure in lower limbs = lower limb oedema
  • Flushing and headaches due to excess vasodilation
  • Reflex tachycardia: vasodilation = increased sympathetic activity (baroreflex) = increase HR/contractility
35
Q

Describe a precaution that needs to be taken into account when taking anti anginal calcium channel blockers

A

Blocking calcium channels in the heart may alter electrical conductivity and contractility

36
Q

Describe the mechanism of action of anti anginal calcium channel blockers

A

Reduces calcium influx through voltage gated L type calcium channels in smooth and cardiac muscle
Two mechanisms:
1. Ventricular myocyte
• NA binds to B1 receptor bound to Gs on ventricular myocyte = activates adenylate cyclase= ATP–>cAMP
cAMP activates PKA = activation of VGCC = influx of calcium ions
Calcium ions activate ryanodine receptor = CICR = further increase in calcium ions (Ca2+ influx)
Increases force of contraction
2. Vascular smooth muscle
NA binds to A1 receptor bound to Gq/11 on vascular smooth muscle = activates PLC = PIP2—>DAG
- DAG activates PKC = activates influx of sodium = activates VGCC = influx of calcium ions
- PLC is also —-> IP3 which binds to SR = increased CICR
Both these increase the intracellular calcium = vasoconstriction
Drugs which can block VGCC and prevents calcium ion entry = reduce force of contraction in ventricular myocytes and causes vasodilation in vascular smooth muscle

37
Q

Name other anti anginals in accordance with NICE

A
  1. Nicorandil
    Potassium channel activator and hyperpolarisation = decreased VGCC and Ca2+ entry = coronary vasodilation
    Has a nitrate moiety so part of its mechanism is via NO generation
    1. Ivabradine
      Specific inhibitor of the If current in the SA node = slow sinus HR
      Decreases pacemaker potential frequency = decreases HR to reduce myocardial oxygen demand
    2. Ranolazine
      Late sodium current inhibitor = reduces calcium ions in ischaemic myocardial cells = reduce oxygen demand + reduce compression of small intramyocardial coronary vessels = improves myocardial perfusion
38
Q

Name 3 prophylactic drugs used to treat angina

A
  1. Aspirin
    Inhibits COX = decreases thromboxane A2 and platelet aggregation (GPIIb/IIIa expression)
    1. Clopidogrel
      Inhibits ADP receptor on platelets, reducing aggregation
    2. Statins
      HMG CoA reductase inhibitor = lowers cholesterol levels

Semester 2: Physiology (35 decks)

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