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Physiology and Pharmacology > Smooth muscle pharmacology > Flashcards

Smooth muscle pharmacology Flashcards

1
Q

What are the two channels that mediate regulation of smooth muscle tone

A

L-type Ca2+ channel (opened by numerous depolarising mechanisms)

GPCR coupled to Gq/11

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2
Q

What does Protein kinase G (PKG) do?

A
  • Stimulates MLCP
  • Stimulates PMCA
  • Stimulates SERCA
  • Activates K+ channels that cause hyperpolarisation and inactivate Ca2+ channels
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3
Q

Angina is a condition managed by pharmacological manipulation of smooth muscle contraction. What is angina?

A

Inadequate myocardial oxygen supply

  • Fixed vessel narrowing
  • Endothelial dysfunction
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4
Q

What is stable and unstable angina?

A

Stable
-Episodic, brought on by exertion, relieved by rest

Unstable
-Symptomatic even at rest

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5
Q

Describe the pharmacological management of angina

A
  • Organic nitrates act directly on the smooth muscle cell to increase nitric oxide production
  • The release leads to smooth muscle relaxation, vasodilation
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6
Q

What does the pharmacological management of angina primarily target?
Whats the secondary target?

A

Veins to reduce preload and oxygen demand in the myocardium

Secondary action on the coronary collaterals to improve oxygen delivery to the ischaemic myocardium

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7
Q

What are the effects of organic nitrates on venodilation?

A
  • Induce venodilation
  • Reduces venous pressure and the venous return to the heart
  • Reduces work of the heart (Starlings Law)
  • Reduces oxygen demand
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8
Q

When coronary artery disease (CAD) is left untreated, what happens to the blood flow in the ischaemic myocardium compared to normal one?

A

Artery is blocked by Atheromatous plaque and arterioles are fully dilated. Blood flow isnt as strong

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9
Q

What does the nitrate dilate when treating CAD. What does this cause?

A

Nitrate dilates collateral

Blood flow to ischaemic myocardium increased

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10
Q

Name the organic nitrates that would be used for treating CAD

A
  • Glyceryl trinitrate (GTN)

- Isosorbide dinitrate/isosorbide mononitrate

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11
Q

What are the characteristics of glyceryl trinitrate?

A
  • Dont directly release NO
  • GTN-NO2-NO-Guanylate cyclase
  • Biologically inactive
  • Half life ~40mins
  • Low bioavailability if given orally
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12
Q

What are the characteristics of isosorbide dinitrate?

A
  • Do not directly release NO
  • Isosorbide dinitrate/mononitrate-NO2-NO-Guanylate cyclase
  • Biologically inactive
  • Half life ~2-4 hours
  • Bioavailability varies
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13
Q

Nitric oxide reduced in the mouth can also affect blood pressure. How can this affect be altered?

A

With the use of mouthwash

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14
Q

Hypertension is a condition managed by pharmacological manipulation of smooth muscle contraction. What are the consequences of hypertension?

A
  • Left ventricular hypertrophy
  • Renal failure
  • Stroke
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15
Q

What is a systolic and diastolic blood pressure in mmHg?

A

Diastolic- 90mmHg

Systolic- 140mmHg

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16
Q

What is the pharmacological management of hypertension?

A

Calcium channel blockers act at I-type calcium channels on vascular smooth muscle but also at I-type calcium channels in cardiac myocytes

17
Q

What are the three main classes of calcium channel blockers? Give examples of each of them

A
  • Dihydropyridines (Nifedipine and amlodipine)
  • Benzothiazepines (Diltiazem)
  • Phenylalkylamines (Verapamil)
18
Q

How are calcium channel blockers usually administered, what’s their bioavailability and their half life?

A

Orally
Bioavailability 10-30%
Half life 2-4 hours

19
Q

In severe cases of hypertension, what can KATP channel openers be taken with?

A

Beta blocker and diuretics

20
Q

What do K-ATP channel openers do and give 2 examples of them?

A

Open K-ATP channels in the smooth muscle cell membrane and hyperpolarise the smooth muscle cell

Minoxidil and Nicorandil

21
Q

a1 adrenoreceptors are the first part of the signalling cascade that ultimately leads to smooth muscle contraction following activation of the sympathetic nervous system. What do alpha 1 blockers do?

Give an example of one

A

a1 antagonists (blockers) prevent this signalling cascade and therefore lead to vasodilation

Prazozin

22
Q

Summarise how hypertension can be managed

A

By preventing the rise in intracellular calcium needed to initiate cross-bridge formation by:

  • Blocking calcium channels
  • Opening potassium channels
  • Blocking a adrenoreceptors
23
Q

Summarise how angina can be managed

A

By exploiting smooth muscle tone through NO-mediated vasodilation

Physiology and Pharmacology (22 decks)

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