B.6

Question 1

Drugs acting on RAAS

Answer 1

1. ACE-I: Enalapril, Perindopril, Captopril, Ramipril
2. ARBs: Losartan, Valsartan, Valsartan+sacubitril, Irbesartan
3. Inhibitors of Aldosterone dependent Na/K ATPase formation: Spironolactone, Eplerenone

Question 2

Primary hyperaldosteronism

Answer 2

Conn’s syndrome

Question 3

Secondary hyperaldosteronism

Answer 3

Congestive HF, liver cirrhosis, Nephrosis

Question 4

Enalapril

Answer 4

Kinetics: metabolized in the liver, fast acting (good abs.), T1/2= 11h, dose adj. in kidney failure

Question 5

Perindopril

Answer 5

Kinetics: prodrug, T1/2=9h, dose adjustment in renal failure

Question 6

Ramipril

Answer 6

Kinetics: fast acting (good abs.), hepatic metabolism, T1/2=15h, dose adj. in kidney failure

Question 7

Captopril

Answer 7

Kinetics: T1/2=2h, fast acting (good abs.), dose adj. in kidney failure

Question 8

Captopril, Enalapril, Perindopril, Ramipril

Answer 8

MOA: ACE-I (inhibits conversion of ANG-I→ANG-II, Inhibits conversion of Bradykinin to its inactive metabolite), increased diuresis and natriuresis, reduced vasoconstriction, reduced Aldosterone and ADH secretion (→K+ retention), inhibition of cardiac remodeling and diabetic nephropathy, increased insulin sensitivity & reduced insulin resistance;
SEs: dry painful cough (due to bradykinin effect in the lungs, switch to ARBs), Hyperkalemia (always take into account renal function and other agents affecting kindey function/ion balance), angioneurotic edema (bradykinin effect), proteinuria (agranulocytosis /neutropenia with captopril), Pregnancy (developmental abnormalities, fetal damage in pregnant women- fetal anuria, renal dysplasia), renal failure (mainly in case of bilateral renal artery stenosis, mainly in combination with diuretics/NSAID);
Contra-IND: pregnancy, lactation, C1-esterase inhibitor deficiency (increase kalikrein activation→ angioedema) or other conditions that predispose to angioedema, aortic stenosis, bilateral renal artery stenosis (can increase risk of azotemia, b/c they reduce the pressure of the efferent arterioles and reduce glomerular filtration pressure);
IND: Hypertonia (especially in HTN of diabetic and renal origin / for acute BP surges - captopril), HFrEF (post-MI HF → first line agent in combination with BBL / reduce remodeling, reduce mortality), Diabetic nephropathy (and other renal diseases-associated with proteinuria)

Question 9

Losartan, Valsartan, Irbesartan

Answer 9

MOA: selective AT1-R antagonists (→ inhibit the classical vasoconstrictive pathway);
IND: ACE-I intolerance → hypertonia, HFrEF, Diabetic nephropathy;
Contra-IND: should NOT be combined with ACE-I, pregnancy, lactation, bilateral renal artery stenosis (can increase risk of azotemia, b/c they reduce the pressure of the efferent arterioles and reduce glomerular filtration pressure);
SEs: Hyperkalemia (always take into account renal function and other agents affecting kindey function/ion balance), Pregnancy (developmental abnormalities, fetal damage in pregnant women- fetal anuria, renal dysplasia), renal failure (mainly in case of bilateral renal artery stenosis, mainly in combination with diuretics/NSAID)

Question 10

Valsartan+Sacubitril

Answer 10

Sacubitril: neprilysin inhibitor (neprylisin is relevant in the metabolism of ANP/BNP) - increases the natriuretic and vasodilating effects of these peptides;
IND: mainly in resistant HFrEF therapy (if the patient tolerates RAAS inihibitors)

Question 11

Eplerenon

Answer 11

IND: In addition to β-blockers, to reduce risk of cardiovascular mortality and morbidity in stable patients with LV dysfunction and clinical evidence of HF after recent MI; In addition to standart tehrapy, to reduce the CV morbidity and mortality in adult patients with New York heart association (NYHA) class II (chronic) HF and LV systolic dysfunction

Question 12

Spironolactone, Eplerenon

Answer 12

MOA: K+-sparing diuretics in the distal collecting ducts (inhibit the expression of Aldosterone-dependent Na+/K+-ATPase and the luminar Na+ transporters), leads to Na+/Cl-, H2O secretion increases, K+/H+ secretion decreases;
Extra: effects depend on endogenous aldosterone levels;
SEs: hyperkalemia & metabolic acidosis, CNS & GI SEs, spironolacton has high affinity to estrogen and progesterone receptors (→gynecomastia), epleronone SARA (selective aldosterone R antagonist);
Kinetics: adm. p.o (X1-2/day), active metabolite → prolonged effect; Contra-IND: GFR<10 ml/min or in HF GFR<30ml/min;
IND: HTN auxiliary treatment (in drug resistant cases, mostly eplerenone), resistant HFrEF, hyperaldosteronism (primary and secondary), resistant edema

Question 13

The only water soluble ACE-I

Answer 13

Lisinopril
note: excreted by the kidneys

Question 14

First line antihypertensive pharmacotherapy

Answer 14

5 drug groups (AABCD):
ACE-I: Angiotensin converting enzyme inhibitors
ARB: angiotensin receptor blocker
BBL: beta blockers
CCB: Ca2+ channel blockers
DIU: Diuretics
ABL: alpha blockers
MRA: mineralocorticoid receptor antagonist

Question 15

AABCD that can also be used for resistant hypertantion

Answer 15

ABL
MRA
Centrally acting drugs

Question 16

Physiological functions of L-type Ca2+ channels

Answer 16

Endocrine cells:
β-cells: Ca2+ channels subtypes (Cav1.3 and Cav1.2) affect insulin secretion
note: Clinical relevance:
High dose of LTCCB reduce insulin secretion and cause hyperglycemia

Question 17

coronary steal syndrome

Answer 17

Vasodilator induced coronary blood flow disturbance in the distal segment of an atherosclerotic occlusion. e.g. short-acting DHPs