Lecture 10: Diuretics

Question 1

What are sympathomimetics?

Answer 1

Drugs that mimic sympathetic activity

Question 2

How can sympathomimetics be b1 selective?

Answer 2

Either by selectively (dopamine) or by alpha 1/beta 2 effects cancelling (dobutamine)

Question 3

How must sympathomimeitcs be given?

Answer 3

Intravenously

Question 4

Why must sympathomimetics be given IV?

Answer 4

As they can induce side effects inc;

• Tachycardias
• Arrhythmias
• Anginal Pain
• Hyppertension (vasoconstriction) (a1)

Question 5

Describe how beta agonists work/ effects?

Answer 5

Beta agonist

• Increase GsGTP (also = inc HR)
• Activate Adenylate Cyclase
• Increase cAMP = Ca channel activation (inc inotropy) and PKA activation = Vasodilation

Question 6

Describe the dopamine dose relationship

Answer 6

Dopamine at low doses activates the D1 receptors which cause vessel bed dilation. i.e coronary bed vasodilation

Question 7

Whats the function of dopamine at moderate doses?

Answer 7

At moderate doses dopamine binds to to b1 adenoreceptors - increasing contractility and inotropy.

At high doses they bind a1 receptors and cause vasoconstriction

Question 8

Describe dobutamine dose function;

Answer 8

Dobutamine

• Synthetic catecholamine
• Binds both B1 and B2 at a ratio of 3:1
• Potent inotrope

Drawback;
- Increases myocardial O2 consumption

Question 9

Whats the function of PDE?

Answer 9

Converts cAMP into AMP

Question 10

How do PDE inhibitors function?

Answer 10

They increase cAMP therefore increasing cellular Ca levels and contractility

Question 11

What are transduction sympathomimetics?

Answer 11

Milrinone and Amrinone

Question 12

How do transduction sympathomimetics work?

Answer 12

Increase activity of cAMP by inhibiting PDE.
Causing:
- Increased PKA activity and increase iCa

Question 13

Whats the downside to transduction sympathomimetics?

Answer 13

Clinical trials show no real benefit with 27% increase in mortality.

Last resort drug.

Question 14

What drug is given as a vasodilator?

Answer 14

Glycerol Nitrate

It is metabolised into NO

= vasodilation (decreased TPR, preload, afterload)

Question 15

Describe how vasodilators function on a VR curve?

Answer 15

Vasodilators shift the venous return curve down so that the CO remains constant (comp vs decompensated)

i.e less VR for the same CO (improved efficiency) = less dilation of ventricles

Question 16

How is Glycerol nitrate given?

Answer 16

Sublingual injection or injection.

Can cause headaches as dilates cerebral vasculature

Question 17

What drugs target the RAA system?

Answer 17

ACE inhibitors
ANG 2 receptor blockers
Aldosterone Inhibitors
Renin Inhibitors
Diuretics

Question 18

Describe in short how diuretics work?

Answer 18

Decrease BV
Decreased BP = lowered pressure overload
Decreased VR = lowered preload and ventricular dilation

Question 19

Describe where diuretics work?

Answer 19

Loop agents
DCT
Collecting Duct
Osmotic diuretics

Question 20

Describe how loop diuretics work and an example;

Answer 20

Furosemide

• Prevent re-absoprtion of up to 30% filtered Na (powerful) thus decereased H2O diffusion

Question 21

Describe a diuretic that acts on the collecting duct

Answer 21

Thiazide

• Prevent re-absoprtion of up to 10% filtered Na (mild) thus decereased H2O diffusion

Question 22

Describe a diuretic that acts on the collecting duct;

Answer 22

Spirinolactone, Amilioride

K sparring

Weak diuretic

Question 23

Whats an osmotic diuretic?

Answer 23

Not useful in heart failure because of pulmonary oedema, usually in acute poisoning for rapid diuresis

Question 24

Whats the risk of all diuretics?

Answer 24

The potential for loss of electrolytes and hypotension

Question 25

How does thiazide work and side effects?

Answer 25

Acts on the smooth muscle beds in the DCT. Prevents up to 10% Na reabsorption

Side effects

• K loss
• Hypotension

Question 26

What are loop diuretics useful for?

Answer 26

Prevents up to 30% Na reabsoprtion

useful for;

• Pulmonary and refractory oedema
• Kidney failure

Question 27

What are the possible side effects od loop diuretics?

Answer 27

• Ototoxicity
• Hypovolemia
• Hypokalemia
• Hypomagnesia

Question 28

What are the properties of K sparring drugs?

Answer 28

• Weak diuretics that act on CD

- Very useful for controlling K loss

Question 29

What are the side effects of k Sparring drugs?

Answer 29

• Hypokalemia

- Spirinolactone has estrogen like effects

Question 30

How doe ACE inhibitors work?

Answer 30

• Prevents ANG 2 production thus causes vasodilation and inhibits aldosterone production consequentially

Question 31

What are ACE inhibitors very useful for?

Answer 31

• Controlling K loss
• Hypertension

First drug choice for hypertension

Question 32

What are some possible side effects of ACE inhibitors?

Answer 32

• Dry Cough (bradykinin shares similar receptor)
• Hypotension
• Hyperkalemia

Question 33

What is an example of ANG 2 blocker?

Answer 33

ANG 2 receptor blocker = Losartan blocks AT1

(doesnt affect bradykinin thus no dry couch)

Reduces BP

Question 34

Why is ANG 2 receptor blockers more promising?

Answer 34

• Better tolerated that ACE inhibitors as no dry couh

Side effets;

• Less vasodilation than ACE inhibitros
• Birth defects