It is a member of the Angiotensin II receptor (type AT1) antagonist family of drugs used to lower BP in people with hypertension.
> Therapeutic indication:
1. Essential Hypertension.
2. May be also used to treat CHF or to prevent diabetic kidney problems.
> Pharmacology:
>> Mechanism of Action:
~> Blocks the physiologic action of Angiotensin II, including vasoconstricto and aldosteron-secreting effects by selectively inhibiting access of Angiotensin II to AT1 Rc within many tissues including; Vascular smooth muscle, adrenal gland, kidney and the heart.
~> [Angiotensin II is a potent vasoconstrictor, active hormone of the renin-angiotensin system, stimulate smooth muscle cell proliferation and a major determinant in the pathophysiology of hypertension].
As a result:
1. Reduces the development of heart vessel disease.
2. Relaxes blood vessels and prevents atherosclerosis.
** Researchers also believe Losartan's effect was caused by the drug's ability to protect low-density Lipoproteins from oxidation.
[oxidation increases toxic effect of cholesterol on arteries]
> Pharmacological properties:
1. It's a pro-drug requires activation in the liver to exert its pharmacological activity.
2. Effective, synthetic, orally active angiotensin II Rc antagonist.
3. Losartan does not block AT2 receptors.
4. Because Losartan unlike ACE inhibitors doesn't inhibit ACE, the effect doesn't interfere with response to bradykinins and Substance B.
5. Beneficial consequence is the absence of certain ACE inhibitor-induced adverse effects.
6. Both Losartan and the pharmacologically active metabolite bind selectively to the AT1 receptor.
7. They have no agonistic effect.
8. Losartan doesn't bind to or block other hormone receptor or ion channels important in cardiovascular regulation.
>> Clinical base line:
Reduce sudden death and mortality in patients with heart failure with a trend toward fewer adverse reactions compared to Captopril.
> Contra-indications:
Do not take Losartan if you:
1. Are pregnant or planning a pregnancy.
It's FDA pregnancy category D, i.e. using Losartan during pregnancy especially during the 2nd and 3rd trimesters can cause low BP, severe kidney failure, injury, and even death to the developing fetus.
2. Do have:
a. Kidney disease, renal artery stenosis.
-> could cause elevation of plasma urea and creatinine in these patients.
b. Liver disease, hepatic impairment.
-> increase plasma concentration of Losartan in cirrhotic patients.
** previous effects may be increased because of the slower clearance of Losartan from the body.
c. CHF.
d. Diabetes or allergies especially drug allergies.
e. Symptomatic hypotension
-> patients who are intravascularly volume-depleted symptomatic hypotension may occur. In general, intravascular volume depletion should be corrected prior to administration of Losartan.
f. Surgery/anesthesia
Losartan blocks the action of Angiotensin II after compensatory renin secretion.
g. Patients under hemodialysis
-> Plasma concentration of Losartan is highly variable in this patient group.
3. Are on salt-restricted diet or have high levels of potassium in your blood.
4. Are taking potassium supplements or potassium sparing diuretics such as Amiloride, Trimetrene (Dyazide) or Spironolactone.
> Pharmakodynamics:
1. Patients with mild to moderate essential HT produced statistically significant reductions in systolic and diastolic BP.
2. Losartan had no clinically significant effect on heart rate.
3. Effective in males and females, and in younger (<65 yrs) and older (> or = 65 yrs) hypertensives.
4. No evidence of the occurrence of cough in patient given Losartan.
5. Significant reduction of proteinurea occurs in non-diabetic hypertensives with proteinurea.
6. Causes a slight decrease in serum uric acid, which was persistence in chronic therapy.
7. Noeffect on autonomic reflexes, no sustained effect on plasma norepnephrine.
> Side Effects:
Along with its needed it may cause some unwanted effects although not all may occur.
Can be divided into:
I- Serious side effects:
1. Allergic reaction:
a. Hoarseness,
b. Swelling of (face, lips, mouth, hands or feet),
c. Difficulty in breathing or swallowing (sudden),
d. Closing of the throat and
e. Hives.
2. Oligourea or Anurea.
II- Less serious side effects:
A. Incidence more frequent:
** Headache
B. Incidence less frequent:
1. Upper respiratory infection ( Nasal congestion, sinus problems)
2. Back pain
3. Dizziness
4. Leg pain
5. Insomnia
6. Diarrhea
7. Stomach upset
** Most of these side effects occur in the 1st several days as your body adjusts to the medication. if continuing you should check with the doctor.
> Precautions:
1. Use caution when performing tasks requiring alertness (driving, operating machinery or performing hazardous activities) because it may cause dizziness or drowsiness.
2. Use caution when rising from sitting or lying position.
3. If alcohol is used, it should be used cautiously because alcohol may further lower blood pressure, increase dowsiness and dizziness while taking the drug.
4. If you are breast feeding a baby, you should consult your doctor.
5. Caution is advised when the drug is used in the elderly.
6. Don't take other medications unless they have been discussed with the doctor especially OTC medications for appetite, asthma, cold, cough, and hay fever or sinus problems since they may tend to increase BP.
7. Diuretics should be avoided with Losartan.
> Interactions:
I- Drug- Disease:
presence of other medical problems may affect the use of Losartan:
A. Most significant -> Actions to reduce the risk of adverse interactions are required.
1. Pregnancy.
2. Lactating mother.
B. Significant -> Assess risk to patient and take actions as needed.
1. Dehydration/hypovolemia.
2. Liver disorders: (Liver cirrhosis, hepatic impairment, chronic hepatic disease, hepatic failure, hepatic necrosis, hepatitis).
3. Renal artery stenosis.
C. Possibly significant -> Conservative measures are recommended till more is known.
Renal impairment (mild-moderate).
II- Drug- Drug:
1. Diuretics: make the increase in potassium blood levels caused by Losartan even greater, specifically K-sparing diuretics.
2. K- supplements.
3. Salt substitute.
4. Other antihypertensive agents or drug for heart conditions.
5. OTC drugs.
6. Aspirin or Aspirin- like pain or fever medications and other drugs that can cause kidney problems such as Amphotericin, Gentamicin.
III- Drug- Diet:
a. Minerals: single oral dose of Losartan increases urinary excretion of Ca, Mg, K, Na, Cl and P. But it decreases Lithium excretion.
b. Food: slows its rate of absorption but has little impacting effect on the total amount of the dose absorbed.
> Dosage and asministration:
Adults: 25-100mg/day to be taken once or divided into 2 doses.
Children: must be determined by the doctor.
>> Notes:
1. Should be taken exactly as directed.
2. Take each dose with a full glass of water.
3. Can be taken with or without food.
4. Never increase your dose, skip any dose or stop taking it unless your doctor approves even if you don't feel sick.
5. Take the missed dose as soon as possible however, if it's almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
6. Do not double up the dose to catch up.
> Over Dose:
1. Manifisted byhypotension and tachycardia, bradycardia could occur from parasympathetic stimulation, dizziness, weakness, fatigue and fainting.
2. Seek for emergency medical attention.
> Storage:
- Should be stored at room temperature between 15-30 C away from heat, light and moisture.
- Do not store in the bathroom, near the kitchen sink or in other damp places.
- Keep it from freezing and do not refrigerate.
> Preparations:
Losartan Potassium COZAAR (Manufacture: Merk)
Available as Oral Tablets or film coated tablets of the strengthes (25, 50 and 100 mg)
Losartan Potassium Combinations HYZAAR (Manufacture Merk)
Available as Oral Tablets or film coated tablets of the strengthes (50mg with Hydrochlorothiazide 12.5mg and 100mg with Hydrochlorothiazide 25mg).
Refrences:
- Lippincott's Pharmacology
- Rang Dale Pharmacology
- Remington The Science & Practice of Pharmacy
- Middle East Drug Compendium 1999
- Internet