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Pharmacology Block 2 > 08 Smooth Muscle > Flashcards

08 Smooth Muscle Flashcards

1
Q

Electromechanical Coupling

A
    • operates thru changes in cell membrane potential

- - - 40 to - 70mV

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2
Q

Pharmacomechanical Coupling

A
    • operates independent of cell membrane potential

- - Receptors / Intracellular Signaling

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3
Q

Mechanism of Smooth Muscle Contraction

A
  • PLC => DG + IP3 (IP3 on SR releases Ca2+)
  • VG Ca2+ channel
  • Myosin Light Chain (MLC) Kinase: when phosphorylated, leads to contraction in actin
  • Rho Kinase: inactivates myosin phosphatase which dephosphorylates MLC

Contraction = actin + MLC(P)

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4
Q

Mechanisms of Smooth Muscle Relaxation

A

Block:

  • VG Ca2+ channel
  • Rho kinase
  • Agonist binding Receptor

Paracrine Factors:

  • NO
  • Dopamine
  • Prostacyclin
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5
Q

Pre-Load

A

Volume of blood in ventricles at end of diastole

Increased in:

  • Hypervolemia
  • Regurgitation of cardiac valves
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6
Q

Afterload

A

Resistance left ventricle must overcome to circulate blood

Increased in:

  • Hypertension
  • Vasoconstriction

An increase in afterload increases cardiac workload

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7
Q

What is decreased with Nitrates?

A

Pre-load

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8
Q

What is the mechanism of action of Nitric Oxide (NO)?

A

NO binds to guanylate cyclase which converts GTP to cGMP

cGMP leads relaxation

Arterial and venous circulation (venous dominant)

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9
Q

Nitroglycerin

A

Organic Nitrate

  • Venous (dominant)

Tx: Heart Failure
Toxicity: Hypotension

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10
Q

What organic nitrate can be used to treat heart failure?

A

Nitroglycerin

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11
Q

When using Nitroglycerin, what happens to stroke volume and Left Ventricular End-Diastolic Pressure?

A

LV End-Diastolic Pressure: Dec

SV: No change

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12
Q

Nitroprusside

A

NO Releasing

Relaxation of arterial and venous circulation

Tx: Hypertensive Emergencies
Toxicity: Hypotension

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13
Q

What organic nitrate can be used to treat hypertensive emergencies?

A

Nitroprusside

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14
Q

When using nitroprusside, what happens to stroke volume and Left Ventricular End-Diastolic Pressure?

A

LV End-Diastolic Pressure: Dec

SV: Inc

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15
Q

Hydralazine

A

Direct Vasodilator

Arterial Circulation

Tx:

  • Heart Failure
  • Severe Hypertension

Toxicity: Hypotension

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16
Q

When using hydralazine, where does it work?

A

Directly increases cGMP leading to relaxation

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17
Q

When using hydralazine, what happens to stroke volume and Left Ventricular End-Diastolic Pressure?

A

LV End-Diastolic Pressure: Dec

SV: Inc

Decreased afterload

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18
Q

What direct vasodilator can be used to treat heart failure (In combination) or severe hypertension?

A

Hydralazine

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19
Q

Minoxidil

A

Direct Vasodilator

Arterial Circulation
K+ ATP channel opener

Tx:
- severe hypertension

Toxicity: Fluid retenion

20
Q

What direct vasodilator is a K+ ATP channel opener?

A

Minoxidil

21
Q

What direct vasodilator can results in a side effect of fluid retention?

A

Minoxidil

22
Q

Diazoxide

A

Membrane Channel Dilator

K+ Channel Activator (efflux)

Tx: Hypertensive Emergencies

Toxicity: Hypoglycemia

23
Q

What drug is a K+ channel activator used to treat hypertensive emergencies?

A

Diazoxide

24
Q

What membrane channel dilator can have a side effect of hypoglycemia?

A

Diazoxide

25
Q

Ca2+ Channel Blockers

A

Membrane Channel Dilator

Non-selective
Arterial circulation

Dihydropyridine–nifedipine
Phenylalkylamine–verapamil
Benzothiazapine–diltazem

Blocks contractions in heart and smooth muscle

26
Q

What phosphodiesterases are located in cardiac muscle? smooth muscle?

A

Heart: PDE3

Smooth Muscle: PDE3 and PDE5

27
Q

What is the function of phosphodiesterase in cardiac muscle? smooth muscle?

A

Heart:
- PDE3 converts cAMP into AMP, which prevents contraction

Smooth muscle:

  • PDE5 converts cGMP into GMP, preventing relaxation
  • PDE3 converts cAMP into AMP, which prevents contraction
28
Q

Milrinone, Inamrinone, Cilostazol

A

Phosphodiesterase (PDE3) inhibitors

Located in cardiac and smooth muscle

  • prevents PDE3 from converting cAMP into AMP
  • cAMP will activate PKA which will phosphorylate proteins and lead to contraction

Tx: Heart Failure

29
Q

What drugs prevents PDE3 from converting cAMP into AMP, therefore creating more forceful contractions for the treatment of heart failure?

A

Milrinone, Inamrinone, Cilostazol

30
Q

Sildenafil, Tadalafil

A

Phosphodiesterase (PDE5) inhibitors

Located in smooth muscle

  • prevents PDE5 from converting cGMP into GMP
  • cGMP results in decreased Ca2+ leading to smooth muscle relaxation

Tx: Erectile Dysfunction

31
Q

What drug is used to treat erectile dysfunction?

A

Sildenafil, Tadalafil

PDE5 inhibitors

32
Q

What drug prevents PDE5 from converting cGMP into GMP, resulting in smooth muscle relaxation?

A

Sildenafil, Tadalafil

33
Q

Renin-Angiotensin Blockers

A

Smooth muscle dilator

  1. Angiotensin Converting Enzyme (ACE) Inhibitors
  2. Angiotensin Receptor Blockers
  3. Renin Inhibitors
  4. Arterial (dominant) and Venous Circulation
34
Q

Fenoldopam

A

Vasodilator

Dopamine 1 Receptor

Arterial and Venous Circulation

Inc RBF and Na+ Excretion

Tx: Hypertensive Crisis

35
Q

What vasodilator drug binds dopamine 1 receptor for the treatment of hypertensive crisis?

A

Fenoldopam

36
Q

What vasodilator drug increases renal blood flood and Na+ excretion?

A

Fenoldopam

37
Q

Prazosin

A

Vasodilator

Alpha-adrenergic blocker (prevents NE binding)

Arterial and Venous Circulation

38
Q

What drug is an alpha-adrenergic antagonist resulting in vasodilation?

A

Prazosin

39
Q

Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol

A

B2 agonist

Bronchodilators

inc cAMP activates PKA leading to relaxation

Toxicity: Tachycardia

40
Q

What B2 agonists can be used for bronchodilation?

A

Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol

41
Q

What AE can you get from B2 agonists?

A

Tachycardia

42
Q

Ipratropium, Tiotropium

A

Anti-cholinergic

Bronchodilators

Prevents muscarinic receptors from contracting respiratory muscles

Mucous secretion

43
Q

What anti-cholinergic drugs can be used as a bronchodilator and to increase mucous secretions?

A

Ipratropium, Tiotropium

44
Q

Theophylline, Aminophylline

A

Methylxanthine

Bronchodilators
- increased mucociliary clearance

Phosphodiesterase Inhibition
Adenosine Receptor Antagonism

45
Q

What bronchodilator drug can work as a phosphodiesterase inhibitor and/or Adenosine Receptor Antagonist?

A

Theophylline, Aminophylline

Pharmacology Block 2 (12 decks)

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