Lecture 10: Diuretics Flashcards
What are sympathomimetics?
Drugs that mimic sympathetic activity
How can sympathomimetics be b1 selective?
Either by selectively (dopamine) or by alpha 1/beta 2 effects cancelling (dobutamine)
How must sympathomimeitcs be given?
Intravenously
Why must sympathomimetics be given IV?
As they can induce side effects inc;
- Tachycardias
- Arrhythmias
- Anginal Pain
- Hyppertension (vasoconstriction) (a1)
Describe how beta agonists work/ effects?
Beta agonist
- Increase GsGTP (also = inc HR)
- Activate Adenylate Cyclase
- Increase cAMP = Ca channel activation (inc inotropy) and PKA activation = Vasodilation
Describe the dopamine dose relationship
Dopamine at low doses activates the D1 receptors which cause vessel bed dilation. i.e coronary bed vasodilation
Whats the function of dopamine at moderate doses?
At moderate doses dopamine binds to to b1 adenoreceptors - increasing contractility and inotropy.
At high doses they bind a1 receptors and cause vasoconstriction
Describe dobutamine dose function;
Dobutamine
- Synthetic catecholamine
- Binds both B1 and B2 at a ratio of 3:1
- Potent inotrope
Drawback;
- Increases myocardial O2 consumption
Whats the function of PDE?
Converts cAMP into AMP
How do PDE inhibitors function?
They increase cAMP therefore increasing cellular Ca levels and contractility
What are transduction sympathomimetics?
Milrinone and Amrinone
How do transduction sympathomimetics work?
Increase activity of cAMP by inhibiting PDE.
Causing:
- Increased PKA activity and increase iCa
Whats the downside to transduction sympathomimetics?
Clinical trials show no real benefit with 27% increase in mortality.
Last resort drug.
What drug is given as a vasodilator?
Glycerol Nitrate
It is metabolised into NO
= vasodilation (decreased TPR, preload, afterload)
Describe how vasodilators function on a VR curve?
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
How is Glycerol nitrate given?
Sublingual injection or injection.
Can cause headaches as dilates cerebral vasculature
What drugs target the RAA system?
ACE inhibitors ANG 2 receptor blockers Aldosterone Inhibitors Renin Inhibitors Diuretics
Describe in short how diuretics work?
Decrease BV
Decreased BP = lowered pressure overload
Decreased VR = lowered preload and ventricular dilation
Describe where diuretics work?
Loop agents
DCT
Collecting Duct
Osmotic diuretics
Describe how loop diuretics work and an example;
Furosemide
- Prevent re-absoprtion of up to 30% filtered Na (powerful) thus decereased H2O diffusion
Describe a diuretic that acts on the collecting duct
Thiazide
- Prevent re-absoprtion of up to 10% filtered Na (mild) thus decereased H2O diffusion
Describe a diuretic that acts on the collecting duct;
Spirinolactone, Amilioride
K sparring
Weak diuretic
Whats an osmotic diuretic?
Not useful in heart failure because of pulmonary oedema, usually in acute poisoning for rapid diuresis
Whats the risk of all diuretics?
The potential for loss of electrolytes and hypotension
How does thiazide work and side effects?
Acts on the smooth muscle beds in the DCT. Prevents up to 10% Na reabsorption
Side effects
- K loss
- Hypotension
What are loop diuretics useful for?
Prevents up to 30% Na reabsoprtion
useful for;
- Pulmonary and refractory oedema
- Kidney failure
What are the possible side effects od loop diuretics?
- Ototoxicity
- Hypovolemia
- Hypokalemia
- Hypomagnesia
What are the properties of K sparring drugs?
- Weak diuretics that act on CD
- Very useful for controlling K loss
What are the side effects of k Sparring drugs?
- Hypokalemia
- Spirinolactone has estrogen like effects
How doe ACE inhibitors work?
- Prevents ANG 2 production thus causes vasodilation and inhibits aldosterone production consequentially
What are ACE inhibitors very useful for?
- Controlling K loss
- Hypertension
First drug choice for hypertension
What are some possible side effects of ACE inhibitors?
- Dry Cough (bradykinin shares similar receptor)
- Hypotension
- Hyperkalemia
What is an example of ANG 2 blocker?
ANG 2 receptor blocker = Losartan blocks AT1
(doesnt affect bradykinin thus no dry couch)
Reduces BP
Why is ANG 2 receptor blockers more promising?
- Better tolerated that ACE inhibitors as no dry couh
Side effets;
- Less vasodilation than ACE inhibitros
- Birth defects
