1. Critical illnesses are often associated with circulatory, respiratory, hepatic and/or renal dys­function that may alter the pharmacokinetics and/or pharmacodynamics of drugs.
2. Decisions about routes of administration and doses of drugs used during medical emergen­cies must consider the physiological status of the patient, the pharmacokinetic and pharmacodynamic characteristics of the particular drug, and how the two interact.
3. Adverse drug reactions and interactions are more likely in critically ill patients due to the effect of the disease on drug kinetics, the decreased toxic-therapeutic ratio due to severe under­lying illness, and the large number of medications that such patients receive. Adverse reactions to drugs should be considered when unexplained deterioration or failure to respond to therapy are encountered.
4. Preservation of function of vital organs is a fundamental concept of critical care therapeutics. Preservation of cardiovascular functions requires attention to fluid and electrolyte status, prompt correction of arrhythmias and shock, and measures to preserve the myocardium against ischaemic injury.
5. Preservation of respiratory function requires protection of the airway, cautious use of fluids and oxygen, and prompt recognition and management of infection.
6. Preservation of cerebral function requires maintaining cerebral blood flow with adequate oxygen and glucose sufficient to meet the metabolic demands of the brain. This entails main­taining adequate systemic circulation, control of intracranial hypertension, and prompt control of seizures and hyperthermia.



7. Critically ill patients are particularly susceptible to infections, gastric stress erosions and ulcers, adult respiratory distress syndrome, pulmonary emboli, and haemostatic disorders. The risks of such complications may be reduced by meticulous care of catheters, pulmonary toilet, cautious use of fluids, prompt treatment of infection when it occurs, and selective prophylactic drug therapies.
8. Shock can be produced by many different processes including myocardial infarction, hypovolaemia, sepsis, drug overdose, burns, hypothermia, spinal cord transsection and anaphylaxis. Optimum treatment of shock depends on knowledge of the pathophysiology of the shock state and the pharmacology of the drugs.
9. Features of acute drug intoxication include coma, agitated delirium, seizures, hypo- and hyperthermia, shock, arrhythmias, aspiration and pulmonary oedema. Successful therapy of acute drug intoxication depends on the integration and application of knowledge of the pharmacology of both the intoxicating drug and the drugs used in therapy, as well as the principles of supportive critical care.

• Hypertension ( high blood pressure ),
• heart failure,
• diabetic kidney disease,
• and heart attack treatment ( when the function of the left ventricle has been affected),
• kidney failure,
• kidney hypertension,
• managing people with a high risk of heart disease,
• chronic kidney disease,
• preventing a second stroke.

General Information of the drug

• Enalapril begins working about 1 hour after you take it and continues to work for 24 hours.
• Enalapril maleate and other ACE inhibitors work by preventing the conversion of a hormone called ‘Angiotensin I‘ to another hormone called ‘Angiotensin II‘ , a potent blood-vessel constrictor. Preventing this conversion relaxes blood vessels, thus reducing blood pressure and relieving symptoms of heart failure.
• Enalapril also affects the production of other hormones and enzymes that participate in the regulation of blood-vessel dilation.

Cautions

• Enalapril occasionally causes very low blood pressure.
• Do not take enalapril if you are allergic or sensitive to any of its ingredients. Severe sensitivity reactions can occur in hemodialysis patients taking enalapril or those undergoing venom immunization.
• Swelling of the face, extremities, or throat has been known to occur with enalapril, which can be dangerous (see below section on “Important Notes” ).
• Enalapril may affect your kidney function, especially if you have congestive heart failure. Your doctor should check your urine for protein content during the first few months of treatment. Dosage adjustment of enalapril is necessary if you have reduced kidney function.
• Enalapril can affect white-blood-cell counts, possibly increasing your susceptibility to infection. Your doctor should monitor your blood counts periodically.
• Enalapril may cause serious injury or death to the fetus if taken during pregnancy. Pregnant women should not take enalapril.
• ACE inhibitors may be less effective in some black patients with high blood pressure, especially when dietary salt intake is high. Nevertheless, they should still be considered useful blood pressure treatments. Swelling beneath the skin to form welts is more common among black patients.

How the Drug works ?

• Antacids and enalapril should be taken at least 2 hours apart.
• The blood-pressure-lowering effect of enalapril is additive with diuretic drugs and beta blockers. Any other drug that causes a rapid drop in blood pressure should be used with caution if you are taking enalapril.
• Enalapril may increase the effects of lithium; this combination should be used with caution.
• Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the blood-pressure-lowering effects of enalapril and other ACE inhibitors. The combination may cause reductions in kidney function.
• Enalapril may increase blood-potassium levels, especially when taken with dyazide or other potassium-sparing diuretics.
• Capsaicin may trigger or aggravate the cough associated with enalapril therapy.
• Rifampin may reduce the effects of enalapril.
• The combination of allopurinol and enalapril increases the chance of side effects. Avoid this combination as severe sensitivity reactions can occur in those taking allopurinol.
• Enalapril affects blood levels of digoxin. More digoxin in the blood increases the chance of digoxin-related side effects, while less digoxin in the blood can compromise its effectiveness.
• Indomethacin may reduce the blood-pressure-lowering effects of enalapril.
• Phenothiazine sedatives and antiemetics may increase the effects of enalapril.

Important Note

• Enalapril can cause swelling of the face, lips, hands, or feet. This swelling can also affect the larynx (throat) or tongue and interfere with breathing. If this happens, go to a hospital emergency room at once.
• Call your doctor if you develop a sore throat, mouth sores, abnormal heartbeat, chest pain, persistent rash, or loss of taste perception.
• Some people who start taking enalapril after they are already on a diuretic (an agent that increases urination) could experience a rapid drop in blood pressure after their first doses or when their dosage is increased. To prevent this from happening, inform your doctor before hand ( that you are taking diuretic ) , as your doctor may tell you to stop taking your diuretic 2 or 3 days before starting enalapril or to increase your salt intake during that time. Upon your doctor advise, you may then restart on taking diuretic gradually.
• You may get dizzy if you rise to your feet too quickly from a sitting or lying position when taking enalapril.
• Avoid strenuous exercise or very hot weather because heavy sweating or dehydration can cause a rapid drop in blood pressure.
• While taking enalapril, avoid over-the-counter diet pills, decongestants, and other stimulants that can raise blood pressure.
• Do not take potassium supplements or salt substitutes containing potassium without consulting your doctor.
• Never take a double dose. If you take enalapril once a day and forget to take a dose, take it as soon as you remember. If it is within 8 hours of your next dose, skip the one you forgot and continue with your regular schedule. If you take enalapril twice a day and miss a dose, take it right away. If it is within 4 hours of your next dose, take 1 dose immediately and another in 5 or 6 hours, then go back to your regular schedule.

Possible Side Effects

Refers to Side Effects on Lexxel Drug , as these drugs works in combination in most treatments condition. However, if you experience unusual effects, do consult your doctor for advise.

Pregnancy/Breast-feeding period :

• ACE inhibitors can cause fetal injury or death. Women who are or might become pregnant should not take ACE inhibitors.
• Sexually active women of childbearing age who must take enalapril must use an effective contraceptive method to prevent pregnancy.
• If you become pregnant, stop taking the medication and call your doctor immediately.
• Nursing mothers who must take this drug should use infant formula as small amounts of enalapril pass into breast milk.

For Seniors who needs to take this drug :-

Seniors may be more sensitive to the effects of enalapril drug due to age-related losses in kidney or liver function.

General Information

• Lexxel contains 5 mg of felodipine, a calcium channel blocker, and 5 mg of enalapril, an angiotensin-converting enzyme (ACE) inhibitor. The 2 drugs in this combination belong to widely prescribed groups of hypertension medication.
• Lexxel is not meant for the initial treatment of hypertension.
• Most people taking this product have taken 1 of the ingredients as an individual pill and need more medication to control their blood pressure.
• Felodipine works by blocking the passage of calcium into heart and smooth-muscle tissue, especially the smooth muscle found in arteries. Since calcium is an essential factor in muscle contraction, any drug that affects calcium in this way will interfere with the contraction of these muscles. This causes the veins to dilate (widen), reducing blood pressure. Also, the amount of oxygen used by these muscles is reduced.
• ACE inhibitors such as enalapril work by preventing the conversion of a hormone called angiotensin Ito another hormone called angiotensin II, a potent blood-vessel constrictor. Preventing this conversion relaxes blood vessels and helps to reduce blood pressure and relieve the symptoms of heart failure.
• Enalapril’s effect on other hormones may also help to promote blood-vessel dilation. It begins working about 1 hour after you take it and continues to work for 24 hours.

How does the drug reacts ?

• The blood-pressure-lowering effect of Lexxel adds to that of diuretic (agent that increases urination) drugs or beta blockers.
• Any other drug that causes a rapid blood-pressure drop should be used with caution if you are taking Lexxel.
• When taken with Dyazide or other potassium-sparing diuretics, Lexxel may raise blood-potassium levels.
• Lexxel may increase the effects of lithium; this combination should be used with caution.
• Capsaicin may cause or aggravate the cough associated with Lexxel therapy.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the blood-pressure-lowering effect of Lexxel.
• Phenothiazine sedatives and antiemetics may increase the effects of Lexxel.
• Rifampin may reduce the effects of Lexxel.
• Combining allopurinol with Lexxel increases the risk of an adverse drug reaction.
• Cimetidine, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, nefazodone, ketoconazole, itraconazole, erythromycin, telithromycin, aprepitant, fluconazole, and verapamil increase the amount of felodipine in the blood, causing a slight increase in the drug’s effect and possible side effects.
• Phenytoin and other hydantoin anti-seizure drugs, carbamazepine, and barbiturate sleeping pills and sedatives may decrease the amount of felodipine in the blood, reducing its effect.
• Felodipine may increase the effects of theophylline (a drug used to treat asthma and other respiratory problems) and oral anticoagulant (blood-thinning) drugs.
• Felodipine may increase blood levels of tacrolimus. Tacrolimus dose adjustment may be needed.
• Felodipine may interact with quinidine (an antiarrhythmic) to produce low blood pressure, very slow heart rate, abnormal heart rhythms, and swelling in the arms or legs.

Cautions

• Do not take Lexxel if you are allergic or sensitive to any of its ingredients. It could causes very low blood pressure, although rarely occurs.
• Lexxel should be used with caution by people with kidney disease, as it may also affect your kidneys, especially if you have congestive heart failure (CHF). Your doctor should check your urine for protein content during the first few months of treatment.
• Enalapril may affect white-blood-cell counts, possibly increasing your susceptibility to infection. Your doctor should monitor your blood counts periodically.
• ACE inhibitors can cause injury or death to a developing fetus in the last 2 trimesters. Pregnant women should not take Lexxel or any ACE inhibitor.
• People taking a beta-blocking drug who begin taking felodipine may develop heart failure or increased angina pain. Angina pain may also increase if your felodipine dosage is increased.
• People with severe liver disease break down felodipine much more slowly than those with less severe disease or normal livers.
• While taking any ACE inhibitor, sudden and painless swelling in the hands, face, feet, lips, tongue, or throat may develop. If this happens,  stop taking the medication at once , and contact your doctor. This condition usually goes away on its own, though antihistamines may also prove helpful.

Usual Dose and Intakes

• This drug is for adult only.
• 1 tablet a day. ( May be increased to 2 tablets if further blood pressure reduction is necessary after 1-2 weeks of treatment. )
• Overdose may cause low blood pressure. ( In case of overdose, contact your doctor or go to a hospital for emergency attention. ALWAYS bring the prescription bottle or container. )
• Lexxel may be taken without regard to food or meals ( you may take it with food if it upsets your stomach. )
• Avoid grapefruit juice while you are on Lexxel.
• Do not break, crush, or chew Lexxel tablets.
• Maintain good dental hygiene while taking Lexxel and use extra care when brushing or flossing teeth because of the increased risk of oral infection associated with Lexxel.
• Avoid over-the-counter diet pills, decongestants. and stimulants while taking Lexxel; they may raise blood pressure.

Possible Side Effects and Notes

*Side effects are more common with higher dosages and increasing age.
Most common side effects includes :-

• swelling in the ankles, feet, and legs;
• dizziness;
• lightheadedness;
• muscle weakness or cramps;
• facial flushing;
• headache;
• fatigue;
• nausea;
• chronic- (long-term) cough.  ( The cough usually goes away a few days after you stop taking the medication. )

Rare and Less common side effects ( Contact Your Doctor for advise )  :-

• respiratory infection,
• cough,
• tingling in the hands or feet,
• upset stomach,
• abdominal pain,
• chest pain,
• constipation,
• diarrhea,
• heart palpitations,
• sore throat,
• runny nose,
• back pain, rash,
• angina (condition characterized by brief attacks of chest pain),
• vomiting,
• bronchitis,
• urinary tract infection,
• breathing difficulties,
• Unusual condition affecting your heart, muscles and joints, stomach and intestines, sexual function, kidney or liver, and other body parts.

Hypertension may be present without symptoms, thus continue taking your medication and follow any instructions for diet restriction or other treatments to help maintain lower blood pressure, even if you feel well.

Do not take a double dose.

- If you forget a dose, take it as soon as you remember. If it is almost time for your next dose, skip the dose you forgot and continue with your regular schedule.

For those under Pregnancy/Breast-feeding period

Women who are or might be pregnant should not take Lexxel. ACE inhibitors have caused low blood pressure, kidney failure, slow skull formation, and death in the fetus when taken during the last 6 months of pregnancy.

Women of childbearing age who must take Lexxel must use an effective contraceptive method.

If you become pregnant, stop taking the medication and call your doctor immediately.
Nursing mothers who must take Lexxel should use infant formula, as small amounts of enalapril + felodipine are known to pass into breast milk.

Seniors citizen :-

• Especially those with liver disease, may be more sensitive to the drug’s effects. Take it with care., it is best to consult doctor before taking it.