Pharmacology - Vasoconstrictors/dialators Flashcards Preview

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Flashcards in Pharmacology - Vasoconstrictors/dialators Deck (12)
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1
Q

An increase in Total Peripharal Resistance (TPR) will occur due to what?

A

Vasoconstriction

2
Q

In the contraction of blood vessels, how are GPCRs involved?

A

Ga(q) –> Stimulates PLC, which causes an increase in Ca2+ release from the SR

This causes MLCK to phosphorylate MLC –> causing contraction

Ga(i) –> Inhibits PLC

3
Q

How do Calcium Channel Blockers (CCBs) work?

A

They block L-type Voltage-Activated Ca2+ channels (L-VACCs)

There are 2 different forms of these…

Cav1.2a –> Cardiac Muscle

Cav1.2b –> Smooth Muscle

This allows for a degree of selectivity

4
Q

What is ‘Calcium Sensitisation’?

A

Where intracellular process causes inhibitory responses on MLCP (which itself causes relaxation), and so less calcium is needed to be present to causes contraction of muscles and blood vessels

5
Q

What is Endothelin-1 (ET-1)?

And how is it made?

A

A molecule that increases BP when bound to specific receptors (ET A/B) on smooth muscle

So ET A antagonists can be used to treat hypertension

Stimulates vasodialation factors (eg, NO) when bound to ET B receptors in endothelium

Its made via various enzymes such as Furin and Endothelin-Converting Enzyme (ECE) in endothelial cells

6
Q

What causes the relaxation of smooth muscle?

A

Opening of K+ channels –> causes hyperpolarisation, which is like a negative feedback to L-type VACCs

SERCA2 uptakes Ca2+ back into the SR

Nitric Oxide and ANPs cause more cGMP to be produced, causing Protein Kinase G to stimulate MLCP (relaxation)

The binding of agonists to Gs GPCRs will cause Protein Kinase A to inhibit MCLK (inhibiting contraction)

8
Q

How is eNOS activated?

And what are the effects?

A

An agonists binds to a GPCR in an endothelial cell, causing an increase in Ca2+. This causes calmodulin (linked with Ca2+) to activate eNOS, which stimulates the production of NO

NO then activates soluble Guanylyl Cyclase (sGC) in the smooth muscle, increasing cGMP levels…. causing Protein Kinase G to stimulate MLCP (relaxation)

9
Q

What is Asymmetric dimethylarginine (ADMA)?

A

An endogenous NOS inhibitor –> So decreases the amount of natural NO that we produce

Present in higher levels in people suffering from hypercholesterimia, hypertension, kidney faliure etc…

It is a marker of endothelial dysfunction and a risk factor for CVD

10
Q

Why do men like selective PDE5 inhibitors?

A

Because they prevent cGMP breakdown, and so less PKG…. so less relaxation occurs….

Allowing them to get erections!

Eg, sildenafil (viagra)

11
Q

Explain the synthesis of Prostnoids

A

Calcium stimulates cPLA2, which forms Arachidonic acid

COX-1 converts this to PGG2 –> PGH2

Thromboxane Synthase converts PGH2 –> TXA2 (in platelets)

PGD Synthase converts PGH2 –> PGD2 (in mast cells)

Prostacyclin Synthase converts PGH2 –> PGI2 (in endothelial cells)

12
Q

What is Endothelial-derived Hyperpolarising Factor (EDHF)?

A

An independent cellular pathway that causes vasodialation via hyperpolarisation of smooth muscle cells

Usually caused by K+ channel opening

18
Q

What are the 3 different isoforms of Nitric Oxide Synthase?

A

Endothelial (eNOS) –> Constitutively expressed and dependent on calcium

Will cause vasodialation in blood vessels and reduce aggregation of platelets

Neuronal (nNOS) –> Used in neurotransmission, gastric emptying and erections

Inducible (iNOS) –> Calcium independent

Used in host defence, often activated by LPS