Hypertension

Renin inhibitors
Angiotensinogen analogues, peptide-like drugs
enalkiren, remikiren, ciprokiren, zenkiren,
aliskiren
Aliskiren: non-peptide – per os
50-80% PRA
Ind:Essential hypertension, mono, Comb (ACEI,
ARBs, HCTZ)
Ci:Renal and liver failure, elderly, DM2 patients
 Renin inhibitors
• Aliskiren: non-peptide – per os
Phk: BA: ~2,5% , t1/2: 20-40 h, css: 5-8 day excretion: unchanged
– feces; kidney (25%)
Se: hyperkalemia, angioedema, rash; diarrhea (↑D),
abdominal pain, reflux;
Ci: under 18 years, angioedema, 1st trimester of
pregnancy,
breast-feeding
Drug interaction
CYP: no
furosemide absorption↓ (50%)
irbesartan: aliskiren cmax↓ (50%)
P-gp inh: ketoconazol, cyclosporine, atorvastatin: C alisk↑
 ACE-Inhibitors
General:
ATII, bradykinin
Prodrugs (except: captopril, lisinopril)
No reflex tachycardia and rebound effect
Ci:
Angioneurotic edema, Renal and Hepatic ins.
children, pregnancy, nursing
Side eff.
Dry cough, Hypotension, angioneurotic edema,
renal fail. , xerostomia, impotence, appetite
 ACE-Inhibitors
Drug interactions:
NSAIDs, K+ sparing diuretics, oral anti diabetics
Insuline(hypoglycemia)
 ACE-Inhibitors
Captopril
Non peptide, competitive ACE-inh. Antagonist
Non prodrug
Ind: Hypertension, cardiac failure, After MI
treatment(left ventricular disf.)
General side effects!
 ACE-Inhibitors
Enalapril
Prodrug(Enalapril Enalaprilate)
No tachycardia, pre and after load
Excreted by kidney
Ind:Hypertension,Cardiac failure(Digoxin, Diuretics)
No rebound effect
 ACE-Inhibitors
Lisinopril (non prodrug)
Ind: Hypertension
Adjuvant therapy of cardiac decompensation
Rare side effects
Quinapril
Ind: Essential hypertension, cardiac failure
Benazepril
Ind: Hypertension, progressive chronic renal failure
 ACE-Inhibitors
Perindopril
Ind: Hypertension, cardiac failure
Cilazapril
Ind: Essential and renal hypertension,
chronic heart failure
Ramipril
Hypertension, MI, Stroke
 ACE-Inhibitors
Trandolapril
peripheral resistance, afterload, hypertophy
of left ventricle
Ind: Essential hypertension, after MI
(disfunction of left ventricle)
Se: orthostatic hypotension (begining)
Spirapril
Ind: hypertension
Se: headache, dizziness, cough, fatigue
 ACE-Inhibitors
Fosinopril no rebound effect
Ind: hypertension, cardiac failure
Zofenopril highly lipophylic
cardioprotective, inhibits hypertrophy,
antioxidant
Ind: hypertension, AMI
Se: cough, dizziness, headache, nausea,
fatigue;
Ci: angioedema, sever hepatic failure,
pregnancy(2nd,3rd) and genaral Ci
 ACE-Inhibitors
Combinations
ACE-inh + diuretics
Enalapril and Hydrochlorotiazid
Perindopril and Indapamid
Quinapril and Hydrochlorotiazid
Benazepril and Hydrochlorotiazid
Cilazapril and Hydrochlorotiazid
ACE-inh + Ca-channel blockers
Trandolapril and Verapamil
Ramipril and Felodipin
 ARBs
Angiotensin II receptor antagonists
AT1 antagonists:
- dilatation of arterioles (cardiac output )
- aldosterone liberation 
- NA liberation 
- central sympathetic tone 
- endothelin liberation 
- no effect on bradykinin biotransformation
1. Blood pressure 
2. Remodelling (left ventricle) 
3. Remodelling of vessel walls 

Competitive antagonism except losartan and candesartan (prodrugs!)

Thiazides
K+-spearing diuretics, K+
Losartan : prodrug
cholesterol and uric acid level↓
no rebound hypertension
Ind: mild and moderate hypertension
(monotherapy also; young and elder people also)
afro-americans: moderate effect
cardiac depression
gout
Ci: pregnancy, nursing
Se: mild, temporary; dizziness, myalgia
Di: K+-level: K+-spearing diuretics, potassium supplement
Phk: good abs, first-pass effect
(14%), BA: 33%, PB: 99%
BBB: no
Candesartan-cilexethyl prodrug
better, than losartan
Phk: BA:42%, PB: 98%
Ind: essential hypertension
Ci: pregnancy, nursing, sever hepatic failure
Se: no
Di: no

Valsartan : non-prodrug
I: hypertension
Ci: pregnancy, nursing, childhood
Se: rare, mild
Di: see losartan
Irbesartan: non-prodrug
uric acid: no effect
Phk: BA: 60-80%, PB: 90%
Ind: Essential hypertension
Ci: pregnancy, nursing
Se: headache
Eprosartan : non-prodrug
no rebound hypertension
Ind: essential hypertension
Ci: pregnancy, nursing, severe hapatic failure
Se: mild, temporary
Di: see. Losartan
Phk: fast abs (meal ↓)
BA: 13%, PB: 98%
Telmisartan non-prodrug
Phk: fast abs, PB: ~100%
Ind:Essential hypertension
Ci: - pregnancy, nursing
- sever hepatic and renal insufficiency
- childhood
Se: rare; back pain, chest pain, vision problems
Di: antihypertensive drugs

Combination of AT II antagonists and other drugs

Valsartan and hydrochlorotiazid
Irbesartan and hydrochlorotiazid
Telmisartan and hydrochlorotiazid
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