Pharmacology Flashcards
(37 cards)
Why are thiazide diuretics less effective than loop diuretics?
Only ~5% of filtered sodium goes through the DCT, therefore only a small fraction left to be reabsorbed.
Where do thiazide diuretics work on?
Distal convoluted tubule
Give an examples of thiazide diuretics
Hydrochlorothiazide
What are CCD acting diuretics? And how do they work?
Acts on cortical collecting duct
Promote sodium excretion
What is drug is dobutamine?
An beta 1 adrenergic receptor agonist (selective)
What is dobutamine used for?
Used to treat acute heart failure, following myocardial infarction or cardiac surgery.
Given intravenously
What is dopamine used for, and why?
Acute heart failure
- Increases tissue adrenaline levels
- Stimulates ??? 1 adrenergic receptors?
- Increases renal perfusion by stimulating dopamine receptors in the renal vasculature.
- Given intravenously
- May be given in low doses with dobutamine in cardiogenic shock
What drugs are used for acute heart failure?
Dobutamine and dopamine
What groups of drugs are used for chronic heart failure? (4) Why are they used?
Diuretics - improve oxygenation, remove oedema from lungs
RAAS blockers - reduce blood pressure elevations (ACE inhibitors - keep sodium down
ARAs (angiotensin receptor antagonists) - similar to beta ACEis)
Beta blockers - reduce sympathetic drive
Cardiac glycosides - help inotropic action
What are the four sites of salt and water reabsorption (in relation to kidney)
- Proximal convoluted tubule
- Loop of Henle (loop diuretics)
- Early Distal convoluted tubule (thiazides)
- Cortical Collection Duct diuretics
Give an example of a loop diuretic (and where does it work?)
Furosemide (Lasix) - thick ascending limb
Na/K/2Cl Co-transporter is blocked.
What is spironolactone?
Specific competitive antagonist of aldosterone
Aldosterone can cause cardiac fibrosis so is good to treat heart failure
What is Aldactone?
It is a spironolactone that is potassium sparing
What’s a side effect of loop and thiazide diuretics? Why does it happen? What is the risk from the side effect?
Increases potassium excretion and hence hypokalemia. Sodium reabsorption is blocked, more sodium to CCD activates RAAS, hence excrete sodium.
Hypokalemia - risk of arrhythmia, increased toxicity of cardiac glycosides (slow k)
Briefly describe the RAS system
Renin converts angiogensinogen into angiotensin I. Angiotensin I converts into Angiotensin II through ACE (angiotensin converting enzyme, found in lungs). Angiotensin II reacts with ATI receptor to vasoconstrict and raise blood pressure, act on CNS and act on the aldosterone: fluid electrolyte balance, and is pro-inflammatory and pro-fibrotic. ATII receptor activation antagonises ATI effects
What is ACE? Where is it found? How does it do its action?
Angiotensin converting enzyme
Ubiquitous apparently, but famously in lungs
Converts ATI into ATII via cleaving,
What are some examples of ACE inhibitors? How do we remember?
Ramipril
Enalapril
If suffixes end with -pril
What are ACEi used for and why?
Used as hypertensives, also used for congestive heart failure!!!
Should be used when diuretics are used because diuretics increase compensatory RAAS by causing salt loss. ACEi block effects of increased RAAS.
Reduce after load, reduce sodium retention, reduce cardiac fibrosis (as aldosterone reduced)
Mechanism of ACE inhibitors
- Block angiotensin II formation; no vasoconstriction so blood level cannot rise, and bradykinin levels rise.
- Aldosterone production downstream is also reduced, promoting sodium and water loss, and potassium retention (avoiding hypokalemia)
What are some side effects of ACE inhibitors? (2) when is its use contraindicated?
- hypotension
- cough
- adverse effects on renal development and function in foetus and newborns
- don’t use to treat hypertension in pregnancy
What are the two angiotensin receptors and their main actions?
AT1-R : most biological actions of angiotensin occurs through this receptor. Pro-fibrotic
AT2-R : unknown function, inhibitory effects
What are Angiotensin receptor blocking drugs? (ARAs?) what are its actions why it’s used
Peptide analogues of angiotensin that block the AT1-R
Similar actions to ACE inhibitors but don’t have cough side effect
What are examples of ARAs? How do we remember?
Saralasin (competitive antagonist)
Lasartan, Valsartan (-sartan suffixes)
Cardiac glycosides e.g digoxin
What is it used for? Actions? Adverse effects?
Digoxin is most commonly used cardiac glycosides with a long plasma half life, excreted by kidneys. Narrow therapeutic range
Glycosides reduce AV node conduction and reduces atrial fibrillation
Adverse effects: arrhythmias at higher doses, AV block and ectopic foci
