Hydrazine

Similar to nitroperoxide, it causes vasodilation and most arterioles by the mechanism of NO release in
endothelial cells.

It is sold in the form of tablets and injections and is one of the safe drugs during pregnancy. Of course,
this medicine is used less nowadays.

Complications:

1. Lupus-like syndrome, which is dose-dependent and is not common below 222 mg per day.
2. Headache
3. Tachycardia
4. Cardiac angina
5. Severe fluid retention

Calcium channel blockers or antagonosts:

It reduces the impulse transmission in the conduction system of the heart and also reduces the heart
rate. Amlodipine, nifedipine, verapamil and diltiazem can be mentioned among the most important
drugs of this category. CCBs are divided into two types:

1) Dihydropyridine, such as nifedipine and amlodipine

2) non-dihydropyridine, such as diltiazem and verapamil.

Mechanism of action of CCB:

CCB drugs reduce blood pressure using the following 2 mechanisms:

1. Inhibition of voltage-dependent calcium channels (L-type channels) in smooth and cardiac muscles,
which causes a decrease in heart rate and its contraction force, as well as a decrease in cardiac
output.
2. Inhibition of vascular calcium channels that cause vasodilation (reduction of PVR peripheral
resistance).

Different effects of two types of CCB:

1) Dihydropyridines have many effects on vasodilation. While they have little effects on the
contractile strength of the heart and the SA and AV nodes.
2) Non-dihydropyridines have prominent effects on the heart and have less effects on blood
vessels. Therefore, a drug like verapamil is expected to have good effects in the treatment
of arrhythmia.

Amlodipine is widely used in Iran and its Indian brand name is Amlopress. The half-life of this drug is
high (35-52 hours), so it is taken once a day.

When prescribing CCB for a patient with heart failure, we choose a drug that has vascular effects and
no cardiac effects. (Dihydropyridines).

Clinical application of CCB:

•Both types of CCB can be used in the treatment of hypertension and cardiac ischemia.

• Verapamil is stronger than diltiazem in every way. Increases heart contraction strength, affects AV
and SA nodes and Vasodilation.

• In conditions such as PVD (peripheral vascular disease) and cases where only systolic blood pressure is
high or ISH( isolated systolic hypertension) , dihydropyridines compared to Non-dihydropyridines are
preferred.

(side applications)

•Arrhythmia treatment

• Treatment of achalasia (stricture of lower esophageal sphincter)

• Using diltiazem ointment topically to relieve the contraction of the anus sphincter

• Stroke treatment

• Nifedipin relaxes the smooth muscle and leads to premature birth.

☣️ Side effects of CCB:

1) Headache
2) Flushing
3) High doses of these may cause ankle edema.
4) Constipation Especially with verapamil 2
5) If these drugs, especially non-dihydropyridines, are used in high doses, they cause severe
bradycardia and heart block.

🔈 The limiting factor in the administration of amlodipine and nifedipine is reflex tachycardia. It should
be noted that diltiazem and verapamil drugs cause bradycardia.

💢 Medicines that inhibit the renin-angiotensin system

It is very widely used and has a place in the discussion of blood pressure, heart ischemia and heart
failure.

1)🖤 ACE inhibitors:

These drugs are known as “prils”, such as captopril, enalapril, lisinopril, benzapril and fusinopril, the first
three drugs are available in Iran.

These drugs are angiotensin converting enzyme inhibitors and prevent the conversion of angiotensin I to
II.

2- ARB:

These drugs are known as sartan family and are angiotensin receptor antagonists (Angiotensin II
Receptor Blocker), such as losartan, valsartan, candesartan, ibersartan, telmisartan and saralazine
Injectable.losartan and valsartan are the most famous drugs of this family in Iran.
Mechanism of action of ACEI and ARB:

Angiotensinogen, which is produced by the liver, is converted to angiotensin I under the influence of
renin. Renin is also inhibited by Aliskiren.

Angiotensin I is converted to angiotensin II by ACE (II kininase), ACEI drugs exert their effect with this
enzyme.

ACE also inactivates bradykinin (a vasodilator). Accordingly, ACEI drugs reduce the production of
angiotensin II, which is a vasoconstrictor.
and preventing the inactivation of bradykinin (which is a vasodilator) cause severe vasodilation and as a
result decrease blood pressure.

By acting on its receptor, angiotensin II causes vasoconstriction and aldosterone secretion.

ARB drugs such as losartan with receptor blocking

Angiotensin II prevents its effects and lowers blood pressure.

Medicines such as spirolactone and eplerenone, which are aldosterone antagonists, prevent the effects
of aldosterone and cause a drop in blood pressure.
ACEI and ARB side effects:

1) mild and mild hyperkalemia (it can even be severe)

2) Severe drop in blood pressure when taking the first dose of medicine ( First hypotension dose). For
this reason, start these drugs with low doses and gradually increase them . Taking into account the
patient's tolerance, they increase the dose until the desired result is achieved.

3) ACEIs cause dry cough in 5-32% of cases, which is due to the increase in the level of bradykinin and
substance P in the body.

4) ACEIs suppress the bone marrow and cause pancytopenia in some people.

5) ACEIs can also cause angioedema.(Angioneurotic edema).

6) Disturbance in the sense of taste with Captopril

7) The simultaneous use of these two categories of drugs with thiazides can have a synergistic effect
and reduce blood pressure too much.

🔈 In Bald Kafr,( ‫( بالد کفر‬a CBC test is taken before the administration of ACEI and after the
administration
They repeat the drug test to see if it has an effect on the bone marrow or Not, but in Iran we don't have
this kind of games and because again this is ARB It doesn't have any complications.

🔷 Contraindications for ACEI and ARB:

1) During pregnancy, especially in the second and third trimesters

2) Renovascular diseases
3) Bilateral renal artery stenosis, because angiotensin II affects the efferent arteriole more than the
afferent Arteriole. By preventing the function of angiotensin II, GFR decreases and Azotemia
occurs.

⚫Applications:

1) Diabetes: drugs prevent diabetic nephropathy.

Even if the patient is normotensive, these drugs are used to prevent renal nephropathy.

2) Heart failure: the renin-angiotensin system is very active in heart failure, so using this drug is
effective in suppressing the high activity of this system.
3) Chronic kidney disease (CKD)
4) Proteinuria: Angiotensin II causes contraction of the efferent artery, so by taking these drugs and
dilating the efferent vessels, proteinuria decreases.
5) Treatment of cystine stones: Captopril, like penicillamine, has a thiol group that causes the
excretion of cysteine.
6) After MI: It improves remodeling and improves EF.

⚫Drug interference:

These two groups together with spironolactone, eplerenone and potassium salts can cause dangerous
hyperkalemia.

NSAID drugs such as ibuprofen and indomethacin reduce the effectiveness of these drugs.

Both drug classes increase the risk of lithium poisoning by increasing the blood concentration of lithium.

🔈 RI (renin inhibitor) group

Aliskiren is the newest antihypertensive drug that is a renin inhibitor. Its side effects are headache and
diarrhea (in high doses), but it does not cause cough

(It can cause cough and angioedema, but its severity will be less than ACEI). Other side effects of ACEI
are not known. The important thing about this drug is that it is metabolized by CYP 3A4 and can cause
extensive drug interactions.

3 Renin inhibitors.
((((Note: Nitrate, CCB and beta blocker reduce the heart’s need for oxygen.

Note: Nitrate, CCB and not beta blockers increase oxygenation.))))