Amlodipine is one of the most commonly prescribed drugs in the UK and the most prescribed high blood pressure medication. When patients are diagnosed with high blood pressure and medication is recommended amlodipine may be the first choice, but not always. Taking any drugs comes with a risk of side effects with amlodipine associated with few common side effects. Ultimately, patients may be prescribed an amlodipine alternative drug. Today, I will discuss amlodipine alternative drugs according to recommended treatment for blood pressure.
Table of Contents
Amlodipine is classified as a calcium channel blocker (CCB). As the name suggests, amlodipine stops the movement of calcium into the heart and blood vessels. Calcium is responsible for smooth muscle contractions. Consequently, amlodipine causes the muscles to relax and blood vessels to dilate, which helps to decrease blood pressure.
Is amlodipine a beta blocker?
Many patients ask if amlodipine is a beta-blocker. The answer is: no. Calcium channel blockers have a distinct mechanism of action from beta blockers.
Why amlodipine is the most popular blood pressure drug in the UK?
High blood pressure is managed with different drugs in a stepwise manner. Three main patient factors that determine the choice of blood pressure medication are:
- the age
- diabetes status
Calcium channel blockers like amlodipine are recommended as the first-line treatment in no-diabetic patients who are over 55 years of age or patients who are of Caribbean or African origin (any age).
The prevalence of high blood pressure increases with age. In England, 58% of men and women aged 65 to 74 have high blood pressure (GOV.UK, 2017), which explains the popularity of amlodipine.
High blood pressure medication is changed, or an additional drug is prescribed if treatment does not produce satisfactory results, or patients experience side effects.
Amlodipine – common side effects
The use of amlodipine and other calcium channel blockers is associated with several common side effects, including (BNF, 2021):
- tachycardia (fast heart rate)
- oedema (swellings)
- muscle cramps
Ankle swelling (oedema) is one of the common side effects associated with amlodipine use. Ankle swelling caused by amlodipine is probably the most troublesome side effect and usually requires changing amlodipine to an alternative treatment. Relaxation of blood vessels caused by amlodipine can also lead to fluid accumulation in the tissues, particularly in the lower extremities such as the ankles. Oedema happens when blood vessels relax, and the pressure inside the vessels decreases, which can cause fluid to leak out into the surrounding tissues.
Do all calcium channel blockers cause ankle swelling (oedema)?
Sometimes in practice, patients get switched from amlodipine to an alternative calcium channel blocker. It would be reasonable to ask whether all calcium channel blockers have the potential to cause ankle swelling. The simple answer is: yes.
Related post: Amlodipine vs Felodipine.
Available information suggests that lercanidipine may be associated with a lower frequency of oedema when compared to first-generation calcium channel blockers (for example nifedipine, verapamil, and diltiazem) as confirmed by meta-analysis (review of a large number of clinical studies), but not when compared to a second generation CCB (amlodipine). In the UK, verapamil, and diltiazem are mainly used for the management of angina, rather than high blood pressure. Other side effects (headache and flushing) were found to be of a similar frequency among calcium channel blockers.
The same review concluded that investigated calcium channel blockers are equally effective in terms of blood pressure reduction.
Can you replace amlodipine with lifestyle changes to control blood pressure?
This post mainly focuses on drugs alternative to amlodipine. Patients are usually given advice by their doctor about lifestyle which may contribute to high blood pressure. The area of lifestyle and its impact on blood pressure deserves a separate discussion, however, the importance of the topic should not be ignored.
Lifestyle changes, diet and exercise have a significant impact on blood pressure. The key aspect of lifestyle changes is physical exercise. There is an overwhelming amount of evidence to show the beneficial effects of exercise on the prevention as well as treatment of hypertension. Exercise reduces both systolic and diastolic blood pressure. Additionally, the reduction of blood pressure has immediate effects, with a lowering effect lasting for more than 24 hours. Regular exercise contributes to a sustained reduction in blood pressure (Hegde et al., 2015).
Amlodipine alternative drugs: ACE inhibitors
ACE inhibitors are another popular class of antihypertensive drugs. ACE inhibitors would be offered as first-line treatment of high BP, to all diabetic patients (regardless of their ethnicity) and patients under 55 years of age without diabetes.
The whole list of ACE inhibitors includes over 10 drugs which are licensed for high blood pressure treatment.
How do ACE inhibitors reduce blood pressure?
ACE inhibitors work by blocking the action of the ACE enzyme, which is responsible for converting angiotensin I to angiotensin II.
Angiotensin II is a hormone that causes blood vessels to constrict, which increases blood pressure. By blocking the production of angiotensin II, ACE inhibitors cause blood vessels to dilate, which leads to a reduction in blood pressure.
ACE inhibitors also reduce the release of aldosterone, a hormone that promotes the retention of salt and water in the body. By decreasing aldosterone levels, ACE inhibitors can cause a decrease in blood volume, which also helps to reduce blood pressure.
What are the common side effects associated with ACE inhibitors?
Common side effects associated with ACE inhibitor use include;
- Headaches, dizziness
- Tickling, dry cough which does not go away
- Abdominal discomfort, dyspepsia, diarrhoea, nausea, vomiting
ACE inhibitors are usually started at a low dose and titrated up according to the response, hence the availability of different tablets and capsule strengths.
Ramipril as amlodipine alternative
Ramipril is the most popular ACE inhibitor prescribed for blood pressure in the UK and the second most popular high blood pressure medication. There are no specific recommendations to prescribe ramipril as a first-line treatment for BP. Ramipril, lisinopril and perindopril may be preferred for people who had a heart attack or patients with heart failure (NICE, 2020).
Ramipril comes in form of capsules and tablets. The strength of ramipril varies from 1.25mg of ramipril to 10mg.
Lisinopril is the second most prescribed ACE inhibitor in the UK for the treatment of blood pressure. Lisinopril comes only in form of tablets, ranging from 2.5mg to 20mg of lisinopril per tablet.
There is a significant gap in the number of prescriptions issued for enalapril and the second most popular ACE inhibitor, lisinopril. With over 1.5 mln prescriptions issued in the last 12 months (OpenPrescribing.net, 2021), enalapril is still a popular drug for the management of high BP.
Enalapril’s strength ranges from 2.5mg to 20mg per tablet.
Angiotensin II receptor antagonists
Angiotensin II receptor antagonists (blockers) are used in the treatment of the same conditions as ACE inhibitors including high blood pressure.
The mechanism of action of angiotensin II receptor blockers is different to calcium channel blockers (amlodipine) or ACE inhibitors. As the name suggests angiotensin II receptor antagonists, block angiotensin II (a ‘compound’) and consequently relax the smooth muscle and decrease the blood pressure.
Unlike ACE inhibitors, angiotensin II receptor blockers do not cause cough or oedema.
The most common angiotensin II receptor blockers used in the UK are:
Angiotensin II receptor blockers: common side effects:
- Hyperkalaemia (low level of potassium)
- Abdominal pain, nausea, and vomiting
- Postural hypotension (drop in blood pressure when standing up)
Can angiotensin II receptor antagonists be alternatives for amlodipine?
Looking at the guidelines for the management of high blood pressure, angiotensin II receptor antagonists can be offered instead of ACE inhibitors (ramipril) when initiating the treatment, in particular to patients who:
- Have diabetes of any age or family origin.
- Are under 55 years of age but not black African or African–Caribbean family origin.
Losartan is the most commonly prescribed angiotensin II receptor blocker with over 10mln prescriptions issued in the last 12 months (OpenPrescribing.net, 2021).
The second most prescribed angiotensin II receptor blocker does not differ in terms of effectiveness from losartan.
Current evidence is insufficient to show that one particular angiotensin II receptor blocker is more effective than others in reducing blood pressure (Tsoi et al., 2018).
Amlodipine alternative drugs: diuretics
Thiazide-type diuretics would be offered instead of amlodipine when amlodipine is not tolerated for example due to oedema in patients over 55 or patients who are of Caribbean or African origin (no diabetes).
Diuretics, commonly known as ‘water tablets’, increase the amount of urine produced by the kidneys, which helps to reduce the amount of fluid in the body, consequently reducing blood pressure.
Diuretics’ common side effects (NICE, 2021):
- dry mouth;
- erectile dysfunction;
- hyperglycaemia (increased sugar level);
- hyperuricaemia; nausea;
- postural hypotension (drop in blood pressure when standing up);
- skin reactions (rashes)
Indapamide is second-most prescribed thiazide-type diuretics. According to the guide on the management of high blood pressure, indapamide is the preferred diuretic in the treatment of hypertension, because:
- Indapamide has been shown to effectively lower blood pressure in people with hypertension, both as monotherapy (when used alone) and in combination with other blood pressure-lowering medications.
- Compared to other diuretics, such as furosemide and hydrochlorothiazides, indapamide has a lower risk of side effects such as electrolyte imbalances, including low levels of potassium, magnesium, and sodium.
- Indapamide has a longer duration of action than other diuretics, meaning that it can be taken once a day and still maintain its blood pressure-lowering effects.
- Indapamide has been shown to reduce the risk of cardiovascular events, such as heart attacks and strokes, in people with hypertension. It may also have protective effects on the heart and blood vessels, beyond its blood pressure-lowering effects.
Also classified as a diuretic, chlortalidone is not commonly prescribed in the UK for the management of high blood pressure.
Bendroflumethiazide is the most commonly prescribed diuretic in the UK. However, bendroflumethiazide is no longer recommended diuretic in the UK for the treatment of high blood pressure. Indapamide and chlorthalidone are preferred diuretics in the management of BP.
The above list was completed based on stage 1 of blood pressure management (initiating the treatment).
Further treatment of blood pressure combines the use of two or three drugs, for example at stage 2 one could be treated with:
- Calcium channel blocker (amlodipine) and ACE inhibitor (ramipril) or angiotensin II receptor blocker (losartan) or diuretic.
- At stage 3 patients are treated with a combination of three different drugs and in stage 4 with four antihypertensive drugs.
I listed the most popular antihypertensive drugs used in the UK, which are considered the first-line treatment of high blood pressure. Although the aim of this post was to list amlodipine alternative drugs, it is clear from the post that the selection of alternative drugs is based on individual patients and any other underlying conditions they may have.
BNF (2021). Amlodipine: side effects (For all calcium channel blockers). Available at: https://bnf.nice.org.uk/drug/amlodipine.html Accessed on 23/03/2023
Gov. UK (2017). Health matters: combating high blood pressure. Available at: https://www.gov.uk/government/publications/health-matters-combating-high-blood-pressure/health-matters-combating-high-blood-pressure#:~:text=In%20terms%20of%20prevalence%2C%20in,aged%2065%20to%2074%20years. Accessed on 23/03/2023
Hegde SM, Solomon SD (2015). Influence of Physical Activity on Hypertension and Cardiac Structure and Function. Curr Hypertens Rep. 2015;17(10):77. doi:10.1007/s11906-015-0588-3 Available at: https://dx.doi.org/10.1007%2Fs11906-015-0588-3 Accessed on 23/03/2023
NICE (2020). Angiotensin-converting enzyme inhibitors. Available at: https://cks.nice.org.uk/topics/hypertension-not-diabetic/prescribing-information/angiotensin-converting-enzyme-inhibitors/ Accessed on 23/03/2023
NICE (2021). Side-effects: For all THIAZIDES AND RELATED DIURETICS. Available at https://bnf.nice.org.uk/drug/bendroflumethiazide.html#sideEffects Accessed on 23/03/2023
OpenPrescribing.net (2021). Period included – last 12 months (Feb ’20—Jan ’21). Available at: https://openprescribing.net/analyse/ Accessed on 23/03/2023
Tsoi B, Akioyamen LE, Bonner A, Frankfurter C, Levine M, Pullenayegum E, Goeree R, O’Reilly D (2018). Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. Heart Lung Circ. 2018 Jun;27(6):666-682. doi: 10.1016/j.hlc.2017.06.721. Epub 2017 Jul 14. PMID: 28807582. Available at: https://doi.org/10.1016/j.hlc.2017.06.721 Accessed on 23/03/2023