HF Pharmacology Flashcards
List some medications that cause or exacerbate chronic HF
NSAIDS, centrally acting Ca2+ channel blockers, TCA’s, corticosteroids (anti-chol + alpha block), anthracycline chemotherapeutic agents, clozapine, recreational stimulants (amphetamines or cocaine)
What hormone system counters RAAS upregulation in HFrEF?
Natriuretic peptide system
- inhibit secretion of arginine vasopressin
- modulates autonomic nervous system activity ---> endothelin-1 or phenylephrine ---> relax arterial and venous tissue
What effect does b-type natriuretic peptide (BNP) have?
cleaved from pre-pro B-type natriuretic peptide –> BNP —> inc natriuresis (urinary sodium excretion) and vasodilation
What is the mechanism of A-type natriuretic peptide (ANP)?
Atrial stretch —> production of pre-pro atrial/a-type natriuretic peptide —> ANP —> dilate renal afferent arterioles and constrict efferent arterioles —> inc GFR
Also vasodilates
Why is vasodilation important in heart failure?
Reduce system vascular resistance, reducing the work of the heart and delivering more blood around the body
What is urodilatin and what does it do?
Related to ANP and derived from same precursor in the kidney
MOA = inc blood vol and arterial pressure —> secretion of urodilatin from DCT and collecting duct —> diuresis, natriuresis, vasodilation
Which metallopeptidase is responsible for natriuretic peptide clearance? How does it do this?
Neprolysin –> nonspecific cleaver of ANP, BNP, CNP, and urodilatin
MOA = Cleaves natriuretic peptides causing inactivation and breaks down ATII
Also targets = endothelin, vasopressin, bradykinin
Name the neprolysin inhibitor used in HF
Sacubitril (pro drug)
What is the MOA of sacubitril?
Sacubitril is converted to active metabolite by plasma esterase –> active metabolite inhibits neprolysin —> dec degradation of NPs
Secondary inc in ATII –> thus requires combination with valsartan
Effects = dec sympathetic tone and aldosterone, inc GFR, inc bradykinin levels
Give an example of an ARNI and why it is relevant to HF treatment
ARNI = angiotensin receptor/neprolysin inhibitor
e.g. valsartan + sacubitril
Sacubitril (neprolysin inhibitor) must be used in combination with a ARB due to its tendency to inc ATII concentrations. This will prevent activation of RAAS which would otherwise inc H20/Na retention and vasoconstriction
Put simply, what do cardiac glycosides do?
Stimulate vagal tone in a dose dependent manner
Name the relevant cardiac glycosides used in HF
Digoxin
What effect does digoxin have on the heart?
Positive Ionotropic = increases the force of contraction
Negative chronotropic = slows the rate of contraction
Negative dromotropic = decreases conduction velocity
What is the MOA of digoxin?
Inhibition of Na+K+ATPase pump on myocyte membranes > inc Intracellular Na2+ > promotes Na+/Ca2+ exchange > influx of Ca2+ > inc Ca2+ storage in sarcoplasmic reticulum > inc myocardial contractility
What effect does digoxin have in myocardial ischaemia?
Ischaemia also causes inhibition Na+K+ATPase pump
This will cause inc sensitivity of Digoxin
