1. NEWER ACE INHIBITORS AND ITS
COMBINATION THERAPY AND THEIR ROLE
IN TREATMENT OF HYPERTENSION
Presented by: ARUNAV BARMAN

2. FACTORS RESPONSIBLE FOR HIGH BLOOD
PRESSURE:
=> Family history of hypertension.
=> Over weight.
=> Alcohol consumption.
=> Physical activity.
=> Stress
=> Increased intake of salts

3. IT IS A HORMONE SYSTEM THAT REGULATES
BLOOD PRESSURE & WATER (FLUID) BALANCE.
WHEN BLOOD VOLUME IS LOW, KIDNEY
SECRETE RENIN DIRECTLY INTO THE
CIRCULATION.

4. Angiotensinogen (released by liver)
(plasma renin)
ANGIOTENSIN I
(ACE Enzyme)
ANGIOTENSIN II
STIMULATION OF
ALDOSTERONE SECRETION CONSTRICTION OF BLOOD VESSEL
INCREASE REABSORPTION OF INCREASE BLOOD
SODIUM & WATER INTO BLOOD PRESSURE

5. ACE INHIBITORS REDUCE THE ACTIVITY OF
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM.
ACE INHIBITORS BLOCK THE CONVERSION OF
ANGIOTENSIN I TO ANGIOTENSIN II

6. (1) IMIDAPRIL
IUPAC NAME:
(4S)-3-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2
yl]amino}propanoyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid
CHEMICAL DATA
Formula: C20H27N3O6
Mol. mass: 405.444 g/mol
Melting point: 214-2160
Self Life: 3 years
Half Life: 24 hours

7. ABSORPTION:
ABSORPTION OF IMIDAPRIL IS ABOUT 70%
DISTRIBUTION:
PROTEIN-BINDING: 85% (IMIDAPRIL); 53%
(IMIDAPRILAT).
METABOLISM:
IMIDAPRIL IS HYDROLYSED TO IMIDAPRILAT IN THE
LIVER.EXCRETION: 40% OF AN ORAL DOSE IS
EXCRETED RENALLY,THE REMAINING DOSE IN THE
FAECES.

8. (2) TRANDOLAPRIL:
IUPAC NAME:
(2S,3aR,7aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-
2-yl]amino}propanoyl]-octahydro-1H-indole-2-carboxylic acid
CHEMICAL DATA
Formula: C24H34N2O5
Mol. Mass: 430.537 g/mol
Melting Point = 125°C
PHARMACOKINETIC DATA
Metabolism: Hepatic
Half-life:
6 hours (trandolapril)
10 hours (trandolaprilat)
Excretion: Through urine, bile

9. BIOAVAILABILITY:
ABSOLUTE BIOAVAILABILITY AFTER ORAL
ADMINISTRATION OF TRANDOLAPRIL IS ABOUT 10%
AS TRANDOLAPRIL AND 70% AS TRANDOLAPRILAT.
DRUG INTERACTIONS:
OHA, LITHIUM
SALTS, NSAID, CIMETIDINE, DIGOXIN.
SIDE EFFECTS:
DRY COUGH, VOMITING, HYPOTENSION.

10. ADR:
DIZZINESS, HEADACHE, HYPERKALAEMIA, HYP
ONATRAEMIA.
DRUG INTERACTIONS:
POTASSIUM-SPARING
DIURETICS, POTASSIUM
SUPPLEMENTS, NSAIDS, ANTACIDS, RIFAMPI
CIN.
ADVANTAGES:
INCIDENCE OF COUGH IS LESS WITH
IMIDAPRIL THAN WITH ENALAPRIL.

11. (3) FOSINOPRIL
IUPAC NAME:
(2S,4S)-4-cyclohexyl-1-(2-{[2-methyl-1-(propanoyloxy)propoxy](4-
phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylic acid
CHEMICAL DATA
Formula C30H46NO7P
Melting point: 149-1530C
Mol. Mass: 563.663 g/mol
PHARMACOKINETIC DATA
Protein binding 87% (fosinoprilat)
Metabolism hepatic GIT mucosa (to
fosinoprilat)
Half-life 12 hours (fosinoprilat)
Excretion: renal

12. BENEFITS:
SAFER CHOICE FOR HEART FAILURE PATIENTS WITH
IMPAIRED KIDNEY FUNCTION.
DRUG INTERACTION:
LITHIUM, ANTACIDS, DIURETICS
SIDE EFFECTS:
COUGH, NAUSEA, WEIGHT GAIN, DEPRESSION
DOSE:
10 mg/day

13. (4) QUINAPRIL
IUPAC NAME:
(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-
yl]amino}propanoyl]-1,2,3,4-tetrahydroisoquinoline-3-
carboxylic acid.
Quinapril is a prodrug. It is converted to its active
metabolite, quinaprilat, in the liver.
CHEMICAL DATA
Formula: C25H30N2O5
Mol. mass : 438.516 g/mol
Melting point: 120-130OC
Solubility: Freely soluble in water
PHARMACOKINETIC DATA
Protein binding: 97%
Half-life: 2 hours

14. SIDE EFFECT:
COUGH, VOMITING, UPSET STOMACH
DOSE:
5 mg TWICE DAILY
DRUGINTERACTION:
POTASSIUM
SUPPLEMENTS, DIURETICS, TETRACYCLINE, AND
LITHIUM.

15. (4) VERAPAMIL + TRANDOLAPRIL (Tarka®)
BENEFITS: The medicine is a combination of two
different drugs; their combined effects cause a
greater drop in blood pressure than when either
medication is used alone.
(5) TRANDOLAPRIL + PARICALCITOL:
Paricalcitol may enhance the renoprotective effects
of RAS inhibitors.
Combination therapy with paricalcitol and
trandolapril has been found to reduce fibrosis in
obstructive uropathy. paricalcitol may slow the
progression of chronic kidney disease.

16. THANKS