Lisinopril Not Working? Reasons Your Blood Pressure Medication Might Not Be Working

Is Lisinopril not working? Explore alternatives and solutions when blood pressure medications like Losartan or Valsartan stop working. Find out more.

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Reviewed by Alex Evans, PharmD, MBA

Published 20 December 2023

There are various drugs, such as lisinopril, that can be prescribed to treat high blood pressure. Over time you may notice that the medication becomes less effective, or perhaps it was never effective to begin with. This is a dilemma for many people across the world and can be caused by a number of reasons.

In this article, we will focus on why a drug such as lisinopril might not work to help treat a person’s blood pressure, discussing the alternative and the possible side effects of taking blood pressure medication.

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Understanding high blood pressure

High blood pressure, also known as hypertension, is a common but potentially very serious health condition. It is caused by the force of blood against the walls of the arteries being too high as a result of blood vessels becoming too narrow or stiffening. Because of this, the heart needs to work harder to pump blood around the body.

Sometimes referred to as the ‘silent killer’ because a person can suffer from the condition without any obvious symptoms. High blood pressure is not to be taken lightly and if left unmanaged, very serious health conditions can develop, such as heart disease or a stroke.

Resistant Hypertension

One form of high blood pressure is resistant hypertension, which is blood pressure that is still high even after using at least 3 blood pressure medications. If a person is suffering from a resistant form of hypertension then it is likely there is a secondary cause involved, meaning additional types of treatment may be required to fully tackle the issue. In addition, older age and obesity make people more likely to develop resistant hypertension.

As hypertension does not cause any noticeable symptoms, people suffering from the condition may underestimate its potential impact and lack the motivation to take blood pressure medication on a daily basis. This can result in long-term damage to the heart and other vital organs, resulting in life-threatening conditions.

Possible causes of resistant hypertension

There are several conditions that could cause resistant hypertension that need to be addressed to increase the success rate of blood pressure medication.

  • Plaque can accumulate in blood vessels carrying blood to your kidneys. This is referred to as renal artery stenosis and can lead to a number of complications, including chronic kidney disease and stroke.
  • Changes to natural hormones in your body that control blood pressure can also lead to resistant hypertension.
  • Sleep-related issues, such as obstructive sleep apnea can also cause changes to blood pressure. This is a potentially serious condition that involves a person stopping breathing for short periods at a time when sleeping. A clear sign of this is when a person snores loudly and still feels tired in the morning after a full night’s sleep.

What happens when you hit a high blood pressure plateau?

Another cause for concern is when an individual hits a blood pressure plateau, meaning their blood pressure remains consistently high despite taking medication on a daily basis. If a person is seeing no change to their blood pressure then they should consult with their healthcare provider to discuss an alternative medication or an adjustment in the dosage.

One issue that may impact the effectiveness of drugs such as lisinopril or losartan is obesity, smoking, high alcohol consumption, or recreational drug use, as these substances can interfere with the flow of blood.

Common blood pressure medications

There are a range of medications that can help to control blood pressure and bring it back down to healthy levels. These medications include:

  • ARBs (Angiotensin II Receptor Blockers) help to relax and widen blood vessels by blocking the effects of specific hormones.
  • Diuretics help kidneys remove excess water and salt to reduce the amount of fluid that flows through blood vessels.
  • ACE Inhibitors (Angiotensin-converting-enzyme) work slightly differently to ARBs but also relax blood vessels by blocking the effects of hormones.
  • Beta-Blockers control adrenaline, reducing the heart rate and output of blood.
  • Alpha-Blockers make it easier for blood to flow through your blood vessels by reducing the nerve signals that tighten blood vessels.
  • Alpha-2 Receptor Agonists work in a similar way to alpha-blockers by also helping decrease the nerve signals that can tighten your blood vessels.
  • Direct Vasodilators relax the muscles in blood vessel walls to help them widen.

What is Lisinopril and what does it do?

Lisinopril is an ACE Inhibitor used to treat high blood pressure (hypertension) and other conditions, including heart failure. It may also be prescribed after a heart attack.

How quickly does Lisinopril lower blood pressure?

Lisinopril can start to work within a few hours of being taken, helping to lower a person’s blood pressure. However, in some cases, it may take up to a few months before the medication can do what it is supposed to.

If a person has been prescribed lisinopril then it is important that they continue to take it for as long as they are directed. Even if a person feels fit and healthy, the fact that high blood pressure shows no symptoms means the drug may still be required. If a person suddenly stops taking lisinopril, their blood pressure could spike dramatically.

Always consult with your healthcare provider if you are considering stopping taking a medication such as lisinopril.

Common side effects and risks of taking Lisinopril

Although generally well tolerated, lisinopril can have side effects, just like any other type of medication. Every person is different and some people may not notice any side effects at all, or they may ease over time as their body adjusts.

The common side effects of lisinopril can include:

  • A dry and persistent cough
  • Dizziness
  • Headaches
  • Fatigue

More serious side effects may include:

  • Higher levels of potassium in the blood, result in a weak or irregular heartbeat
  • Kidney problems
  • Liver problems
  • A severe allergic reaction
  • A lower white blood count can make a person more susceptible to infections

Why Lisinopril might not work for some people

Lisinopril may not work for everyone as a person’s genetics or general health may have an impact on its effectiveness. Leading an unhealthy lifestyle can also keep your blood pressure high, despite taking blood pressure medication.

Drug interactions and other medical conditions, like kidney disease, are another reason lisinopril may not work. If your dosage is too low, that can also prevent it from bringing your blood pressure down enough.

As mentioned earlier, resistant hypertension is a form of high blood pressure that cannot be controlled even with lisinopril. This is usually due to a second cause of hypertension that is yet to be diagnosed.

Can Lisinopril stop working?

Lisinopril doesn’t stop working. But your body could become resistant to it, meaning the dosage needs to increase or your doctor needs to add another medication. There may also be other factors that could cause lisinopril to work less efficiently, such as a change in diet, exercise, stress levels, or even smoking, drinking alcohol, or the use of drugs.

Not taking the drug regularly can also impact its effectiveness, or taking it alongside other medications that may result in an unwanted interaction. There are also instances where a newly developed health condition may impact the drug’s efficacy.

Alternatives to Lisinopril

If lisinopril does not work, a person may consider alternative medication that works in a different way to regulate blood pressure. To determine whether a new medication might be more effective you should consult with your healthcare provider to discuss your current situation.

Alternative blood pressure medications that could be considered are:

  • Aliskiren
  • Amlodipine
  • Atenolol
  • Clonidine
  • Diltiazem
  • Doxazosin
  • Hydrochlorothiazide
  • Irbesartan
  • Losartan
  • Metoprolol
  • Valsartan

7 Reasons why high blood pressure medications may not be working

There are several factors that can contribute to blood pressure medication not working, ranging from interactions with other medications to incorrect dosages.

1. Incorrect diagnosis or underlying conditions

There may be an underlying medical condition that acts as a secondary cause of high blood pressure, if this is misdiagnosed or it is not identified at all then it creates a significant challenge in terms of providing adequate treatment. An example of this would be a person suffering from kidney disease which would likely reduce the effectiveness of lisinopril.

2. Non-adherence to medication regimen

If a person does not take the medication as directed by their doctor, the efficacy of the drug is likely to be low. Non-adherence could include taking an incorrect dose, missing doses, or if a person stops taking the medication abruptly.

3. Interaction with other medications or substances

Taking other medications and substances can interfere with blood pressure medication and make it less effective. This may include other medication that has been prescribed, over-the-counter medication, and some health supplements.

4. Drug resistance

Over time, a person can develop a resistance to blood pressure medications like lisinopril and losartan, meaning they are ineffective even if the correct dosage is being taken.

5. Lifestyle factors

Maintaining an unhealthy lifestyle can also counteract the impact of medication. This can include a poor diet, a lack of exercise, stress, and anxiety, a high alcohol or caffeine intake, or smoking.

6. Incorrect drug choice or dosage

Even medical professionals can make mistakes and the prescribed drug may not be the best choice to treat your high blood pressure, or perhaps the dosage is not strong enough for it to work effectively.

7. White Coat Syndrome

White coat syndrome relates to when a person’s blood pressure only increases in a medical setting, usually caused by anxiety. This could cause the doctor to think the medication is not working, however, in a normal, everyday setting it is working as it should.

What to do when other blood pressure medications don't work
What if Labetalol doesn't work

Labetalol is a beta blocker that is often prescribed to treat high blood pressure in pregnant women, but can sometimes prove ineffective because of the reasons listed above. If this is the case then it is recommended to speak with your doctor about alternative medications such as ARBs like Losartan, or a calcium channel blocker like Amlodipine

Losartan is not working

Losartan, one of the most commonly prescribed ARBs (angiotensin II receptor blockers) may also not work when it comes to reducing high blood pressure. As an alternative, medication such as Valsartan, Amlodipine, or Metoprolol could be considered.

Valsartan stopped working

Another ARB is Valsartan, and similarly to Losartan, it may not help to lower blood pressure in some people. Alternatives could include Amlodipine, Metoprolol, while a diuretic like Hydrochlorothiazide may also be an effective option.

Hydrochlorothiazide not working

The diuretic Hydrochlorothiazide can also be used to manage high blood pressure but may not work for everyone. If this is the case, then alternatives like Amlodipine, Metoprolol, or Valsartan could be prescribed instead.

Can Amlodipine stop working

Amlodipine is a calcium channel blocker used to control blood pressure. If amlodipine is not having the desired effects then other calcium channel blockers such as Diltiazem can be considered. If it is deemed that calcium channel blockers in general are having minimal impact then a medical professional may recommend another drug class such as an ACE Inhibitor (angiotensin-converting enzyme)


There are a number of reasons why a blood pressure medication such as lisinopril may not work. These reasons may include a negative interaction with another medication, resistant hypertension due to an underlying cause, or an incorrect dosage, among other things.

If this is the case, it is advised to pay a visit to your doctor to discuss the possibility of increasing your dosage or perhaps trying an alternative medication such as beta-blockers or ARBs.

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