Heart Failure Drugs Flashcards
Hydrochlorothiazide Class- Type- Target- Activity- Physiology 1 (WHERE?),2,3 and extra (3)
Class- Thiazide Diuretic Type- small mol Target- Na+/ Cl- symporter Activity- Inhibitor Physiology 1) Decrease in Na+ reabsorption IN DCT 2) Increase Na+ in DCT and CD 3) Increase natriuresis and micturition
Extra:
some HCO3- loss -> metabolic acidosis
Increase K+ loss -> hypokalaemia
Risk of gout as increase in uric acid in blood
Sacubatril (given with Valsartan) Class- Type- pro drug? Target- Activity- Physiology
Class- Nepralysin Inhibitor
Type- small mol (sacubitrilat)
Target- Nepralysin
Activity- competitive Inhibitor
Physiology
1) Nepralysin naturally cleaves/ degrades ANP and BNP which both cause micturition
2) degrading Nepralysin inc. ANP/ BNP levels… inc. micturition/ diuresis
Digoxin Class Type Target Activity Physiology 1,2,3,4 (what does it ALSO help with?)
Class- cardiac glycoside
Type- natural small mol
Target - Na+/ K+ ATPase
Activity- Competitive binding site (K+ binding site)
Physiology
1) Na+/ Ca2+ exchanger removes Ca2+ from inside cardiac myocyte after contraction
2) Inc. [Na+] inside cardiac myocyte dec. driving force to push Ca2+ -> Ca2+ remains inside
3) +ve inotropic effect and inc. force of contraction
4) decrease oedema -> symptomatic relief
Clinical- ALSO dec. AV conduction and is an anti-arrhythmic
Mannitol Class- Type- Target- Activity- Physiology 1,2,3 Clinical
VERY potent and substantial K+ loss -> hypokalaemia Class- Osmotic Diuretic Type- small mol Target- None Activity- None Physiology 1) doesn’t cross membrane 2) inc. osmotic pressure in tubular lumen (draws in fluid) 3) effect doesn’t SATURATE! Clinical- IV injected and used acutely
ANP and BNP Where are they produced? Target (where is this expressed?) Activity Physiology (hint: think ATII and Aldos) 1,2,3
Where are they produced? A= Atria B= Ventricles
Target (where is this expressed?)- NPR1 in kidney
Activity- agonist
Physiology
1)Guanylyly cycles converts GTP -> cGMP -> PkG activity
2) inhibit ENaC AND Na+/ K+/ Cl- ATPase in CD
3) Inc. GFR, dec, renin, dec ECF!
PBL Drugs: *Sacubitril/ Valsartan -> what does it do? why given with sacubitril? *Digibatran Ramapril -> what? Why is it given? Bisoprolol -> what? Why is it given?
Valsartan: AT2 blocker -> dec RAAS -> dec. aldosterone production
Valsartan
Why? nepralysin also breaks down AT2, if nepralysin is blocked (via sacubitril) then this will inc. AT2, RAAS etc. But we don’t want that as it will increase blood vol. ( from inc Na+ reabsorption) and further increase hypertension/ cardiac work. So Valsartan given to block effect of excess AT2.
Ramapril- ACE inhibitor
Prevents cleavage of AT1 -> AT2, prevent RAAS and aldosterone production, Dec. Na+ and water reabsorption, dec. blood vol
Given to decrease odeama and raised JVP
Bisoprolol - B1 adrenergic antagonis
Why?
- dec. HR and force of contraction
- dec. CO
- dec. systolic blood pressure
Slowing HR allows for more diastolic filling, increases blood flow to coronary arteries but overall decrease in cardiac work.
Acetazolamide Class- Type- Target- Activity- Physiology 1,2,3 ALSO... 4,5,6,7
Class- Carbonic Anhydrase Inhibitor
Type- small mol
Target- Carbonic Anhydrase
Activity- Inhibitor
Physiology
1) inhibits carbonic Anhydrase
2) H2CO3 not converted to H2O and CO2 as reaction not catalysed
3) increase in bicarbonate loss within urine -> more alkaline urine -> metabolic acidosis
Also…
4) less H2CO3 in tubular epithelium
5) less H+ inside tubular epithelium
6) Na+ not reabsorbed via Na+/H+ anti-porter
7) Na+ and water remain in tubule -> DIURETIC
Amiloride- Weak or potent? Class- Type- Target- Activity- Physiology
WEAK as acts on DCT where majority of Na+ already reabsorbed. Class- K+ sparing diuretic Type- small mol. Target- ENaCs Activity- Channel Blocker Physiology 1)ENaCs blocked in DCT 2) dec. Na+ reabsorption 3) inc. natriuresis and micturition 4) also K+ retention -> Hyperkalemia
Dapagliflozin Class- Type- Target- Where? Activity- Physiology
Class- SGLT2 Inhibitor Type- small mol. Target- SGLT2 -> Na+/ Glucose co-transporter Activity- competitive inhibitor Physiology 1)dec. Glucose reabsorption in PCT 2) Glycosuria -> osmotic diuresis 3) dec. Na+ reabsorption in PCT-> inc. natriuresis and dec. blood glucose
Furosemide- is it potent and why? Class- Type- Target- aka? Activity- Physiology 1,2 (WHERE?) Also 3,4
It’s potent as it acts on the loop where 15-25% of filter load is reabsorbed.
Class- Loop Diuretic
Type- Small mol
Target- Na+/K+/Cl- symporter or NKCC2 co- transporter
Activity- Inhibitor
Physiology
1) Na+ reabsorption in THICK ASCENDING LIMB
2) Inc. micturition and natriuresis
Also
3) Inc. K+ loss -> hypokalaemia
4) Inc. gout risk as dec. in uric acid secretion
Hydralazine Class Type Target Activity Physiology 1,2
Class- vasodilator Type- small mol Target - unknown Activity unknown Physiology 1) block IP3 pathway and Ca2+ release from sarcoplasmic reticulum 2) vasodilator -> hypotensive
Sprinonolactone- Weak or potent and why? Class- Type- Target- Activity- Physiology 1 (WHERE?) ,2,3
It’s WEAK as it acts on LATE DCT/ CD where majority of Na+ already reabsorbed.
Class- K+ sparing Diuretic
Type- small mol.
Target- Mineral corticosteroid receptor
Activity- Competitive antagonist
Physiology
1) Antagonises aldosterone action LATE DCT/ CD
2) Dec. expression of ENaCs and Na+/ K+ ATPase
3) K+ RETAINED -> Hyperkalemia
Ivabridine Class ? Type Target Activity Physiology 1,2,3 Clinical
Class ? Type- small mol Target- HCN (funny channel) Activity- Inhibitor Physiology 1) inhibit current -> prolongs diastolic depolarization 2) Dec. HR 3) Dec. Cardiac work
Clinical- last ditch!
