David asked
I had been taking hydrochlorothiazide and amlodipine to control my blood pressure. My potassium levels were frequently below normal and resulted in visits to the ER, one hospital admissions and visit to my doctor. Neither my family physician nor my oncologist pointed out that the hydrochlorothiazide depletes potassium, although both now say they knew it did. My family physician did not answer my question about why he did not consider hydrochlorothiazide a factor in my chronic low potassium. I was admitted to the hospital for an infection and difficulty staying awake, lab tests again showed a too-low potassium level, the admitting physician told me to immediately stop taking the hydrochlorothiazide; he substituted Lisinopril. My potassium level has been in the normal range ever since and my blood pressure is much better control than it has been for years, when it was quite erratic. Here's the problem: I seem to suffer the three top-listed side effects for Lisinopril: dizziness, blurred vision and tiredness. I have to lay down for an hour or two or three before these problems subside. I currently take Lisinopril 5 mg and Amlodipine 5 mg every morning with breakfast. If I took these medications just before I went to bed at night, would they have the same effect on my blood pressure, now under control, and continue to produce potassium as advertised? Many thanks for your help. David
Answer
Generally speaking, there is no significant therapeutic difference in regard to the time of day you take your blood pressure medication, lisinopril in this case. The main factors in deciding administration time are:
- Drug efficacy
- Consideration of potential side effects
- Convenience
Morning Or Evening?
There is some controversy as to whether or not time of day (in regard to taking your medication) has a significant effect on blood pressure or likelihood of cardiovascular events (e.g. heart attack and stroke). Some studies suggest that taking blood pressure medication in the evening could potentially lower your overall blood pressure and even lower the risk of heart attack. However, this is more theoretical and no studies have firmly concluded evening dosing is better than morning dosing.
Evening dosing has its supporters for a variety of reasons. It is fairly well concluded that cardiovascular events occur much more frequently in the morning versus other times of the day. Most individuals have a rise in blood pressure in the morning due to a variety of factors (e.g. circadian rhythm, physical stress etc...). The theory is that if you take your blood pressure medication in the morning, it will have a significant loss in effect by the time bedtime (and early morning) arrives. Night time dosing is thought to exert a more positive effect on blood pressure control and a reduction in cardiovascular events as drug levels will be higher throughout the evening and early morning.
The problem with many of the studies that evaluate time of day in regard to blood pressure medication administration is that they are generally looking at all blood pressure medications. Many of the older medications do not last 24 hours like many current ones due. In addition, many of the older blood pressure medications exert their effects directly (e.g. alpha antagonists) on the on the blood vessels, relaxing them to lower blood pressure. The effect of these medications is more immediate and tend to wear off over time.
Newer blood pressure medications inhibit an enzyme (e.g. ACE-Inhibitors), or block a receptor (e.g. ARBs) in the body. These effects are generally longer lasting. Although the aforementioned alpha antagonists do block a receptor as well, it is generally for much shorter periods of time.
The drug you are taking, lisinopril, is an ACE-Inhibitor. ACE-Inhibitors inhibit an enzyme known as 'angiotensin converting enzyme'. Enzyme inhibition can last for much longer than 24 hours with consistent dosing. As long as you take your lisinopril consistently, time of day does not have a significant difference in effect. At the very least, studies are not conclusive.
Side Effect Consideration
The main reason why you would want to switch to night time, or before bed dosing, is for side effect avoidance. It is well known that blood pressure medications can cause dizziness, sedation or even orthostatic hypotension (a significant drop in blood pressure when you go from a lying position to a standing position). Often times, night time dosing can alleviate these problems.
Not all blood pressure medications are recommended for night time use however. Diuretics, such as hydrochlorothiazine, may make you need to go to the bathroom more often, interrupting sleep. ACE-Inhibitors, such as lisinopril are fine to dose in the evening however and night time dosing is even recommended if you are experiencing side effects.
In addition, it is important that you pick a time of day that works best for you to take your medication consistently. Taking your medication at the same time of day, every day, is typically associated with better blood pressure control and cardiovascular outcomes. It allows the drug to reach consistent (i.e. 'steady state') levels in the body for optimal effect.
Night time administration of lisinopril should not affect your potassium levels. It is well known that ACE-Inhibitors increase potassium levels and can cause hyperkalemia if you have pre-existing conditions that put you at risk or you are taking additional medications that can cause it. The time of day you take your lisinopril however, makes no difference in that regard.
Lastly, amlodipine is recommended to be dosed in the morning or evening and can be taken at the same time as lisinopril.
