Direct Renin Inhibitors
Drug manufacturers had a very hard time with the creation of direct renin inhibitors. In fact, the first renin inhibitors to become approved by the FDA are technically third generation. The first generation (created in 1972) had very little effect on blood pressure. This was because of absorption issues. The second generation of renin inhibitors gained promise when creation of them started in 1982. But just like the first generation drugs, they did not lower blood pressure effectively. They did not have strong enough chemical properties, and clinical trials on them ended in the mid to late 90s. Other drugs on the market at the time which modified the angiotensin 2 output in the body were far more effective. Fast forward to 2007 and the first renin inhibitor gets FDA approval, Tekturna.
Tekturna and it’s generic aliskiren are currently the only direct renin inhibitors on the market. These drugs work by reducing renin output, which in turn lowers angiotensin ll output. Renin produces Angiotensingen, then angiotensinogen produces angiotensin l. Then angiotensin l produces an enzyme which signals receptors to produce angiotensin ll. Angiotensin ll can constrict blood vessels and raise blood pressure. The mechanism of action in both ARBs and ACE inhibitors produce the same end result, reducing angiotensin ll output. Some patients using renin inhibitors alone do see an improvement with their hypertension. However a lot of patients often take these in addition to other hypertension medication. In fact some doctors will only prescribe these along side another drug because of their weaker effect on lowering blood pressure in some patients.
Many patient testimonials are actually quite positive for the treatment of hypertension with direct renin inhibitors. There have been reports of patients who have a history of taking beta blockers, ARBs, and ACE inhibitors and saw far better results with the use of this drug. This seems promising, considering the amount of short term side effects seem to be less than most other hypertension medication which modifys angiotensin ll output. It is important to note that the effects of these drugs vary greatly. With some users reporting as much as 40 point drops in systolic pressure, and some reporting very minimal BP lowering effectiveness or even none at all. It seems the renal system manipulations for blood pressure control can be a hit or miss for lack of better term. If you are using this medication you should have record of your BP before taking it, for comparison purposes. It is important to know how well this drug is working for you.
There is one very big unknown with direct renin inhibitors. That is how it effects the brain. Medical professionals are not sure why, but renin is produced within the brain. It is thought to be produced by two different parts in the brain. This of course brings a critical question to mind, is the brain being effected by direct renin inhibitors? Scientists performed studies on mice which showed very little effect. But in this study they were looking only for blood flow changes, not renin production. Because of the fact that medical professionals are not sure why the brain needs renin, this is a huge uncertainty as to if these drugs may have some type of negative effect on the brain with long term usage.
The known side effects of direct renin inhibitors at this point are the short term ones. Because of the fact that this drug has only been on the market since 2007, there is very little long term patient review that can be studied. This should be taken into consideration when deciding whether or not to supplement with this drug.
The most common side effects reported from patients seem to be gastrointestinal and dermatological. Here is a list; dizziness (sometimes severe), rashes, stomach upset, stomach pain, indigestion, dyspepsia, diarrhea, tiredness and fatigue, cough, headache, back pain, a sore throat, difficulty breathing, fever, nasal congestion, ear congestion, excessive gas, changes in weight, and a stuffy nose. These side effects may not be life threatening but can be persistent and irritating. Only you will know how bad they are so tell your doctor everything you are experiencing.
Many doctors may prescribe ARBs and ACE inhibitors along side a direct renin inhibitor. Although this is done fairly often, it could be dangerous. Renal output inhibition with any of these three drugs alone is fairly substantial. So mixing two of them together can potentially inhibit renal output and angiotensin ll production to a level so low it may be unsafe. This seems to be even more of a concern for patients with diabetes who have impaired renal output already. This is often overlooked by cardiologists and really needs to be taken into consideration.
There is yet another possible dangerous side effect of prescribing ACE inhibitors and ARBs alongside direct renin inhibitors. Some patients mixing these can experience kidney issues. It is thought that the severe renin system inhibition is the reason for this, but more research is needed. It is important to note that individuals with diabetes are far more likely to experience kidney problems from mixing direct renin inhibitors with other angiotensin blocking drugs. However potential kidney problems can arise from any patient mixing these drugs.
Serious side effects of direct renin inhibitors are high potassium in the blood due to renin system inhibition, fainting due to very low blood pressure, uneven or slow heart beat, and modifications to urine outputs. You can also have an allergic reaction that could swell your face and throat. There also is a possibility of renal stones and gout but those have yet to be proven. Again these are the known side effects, there could be other long term harmful side effects out there that have not been discovered yet. That is important to note. Don’t ever ignore something that seems off with your body while supplementing with any kind of drug.