Wednesday, March 29, 2023

Terazosin: An Altenative for High Blood Pressure Mangement

 

A patient approached me two days ago to ask me if his doctor who gave him Terazosin was the right medication for his prostate enlargement (benign prostate hypertrophy - BPH)? He told me he has high PSA, and if this meant he had cancer of the prostate?

 I explained and assured him this drug is popularly used by doctors for managing BPH. But also told him Terazosin is hardly used for treating hypertension as its action is more marked in bringing down blood pressure quite rapidly than its effects on urodynamics.

Since I have almost forgotten my pharmacology, I decided to carry out a medical experiment only on myself to demonstrate the hypotensive effects of this agent (Terazosin). But first allow me to very, very briefly explain the chemistry and action of this drug.     

Chemical name: 

1-(4-amino-6,7 -dimethoxy-2-quinazolinl)-4-(tetrahydro-2-furanyl) carbonyl -Piperazine monohydrochloride dihydrate with the empirical formula C19H25N5O4.HCl.2H2O

Generic name: Hytrin

Terazosin is presented at 1 mg, 2 mg, 5 mg.  Initial starting dose is 1 mg, titrated to higher doses as per necessary.

Pharmacology: 

Its pharmacodynamic (mode of action) is, it is a blocker of alpha-1—adrenoceptor and is indicated for hypertension that can rapidly induce hypotensive effects even after a small initial dose. This can be used as the first line treatment. It also improves urodynamic on the smooth muscle tone of the bladder as second line action. This it does by antagonizing the phenylephrine induced contractions of the bladder regulated by alpha-1-adrenergic receptors.

It is actually a marked hypotensive agent, but mainly prescribed for benign prostate enlargement (BPH) in males instead.

Since now I have briefly explained its pharmacodynamics as a very effective antihypertensive drug it is used instead for managing benign prostate hypertrophy.

I then decided to conduct a personal medical experiment on myself to evaluate how effective it is as an anti-hypertensive agent.

Study Design: 

First of all, straight away and at once I need to mention what I conducted on myself is NOT a properly designed study. I did not use large populations or small randomized samples to statistically represent large true populations with controlled / placebo groups to compare, groups on the medication and groups not on the medication.

The data collected should then be statistically analysed to look for ‘statistical significance’ to see if there is a REAL difference, and not a difference due to chance between the test group (on medication) and the controlled group (not on medication).  We, as former medical researchers, would normally follow very strict experimental and statistical protocols in our study designs and how we select our samples.

We then use sophisticated mathematical (statistical) procedures to analyse the data before we interpret the data and results.

This is the first thing I need to explain right here at the very beginning. Once again, I am only using myself as the only subject that would not be representative of any population. Besides, there was no control group, not even another one person to compare, let alone the experiment carried over and over again for consistency.  It was only a few measurements over a 12-hour period.

Finally, normally we do not give the date or the clock’s time on the watch as I did here. Normally we may record the time taken as 10 minute, 15 minutes, 30 minutes …2 hours…20 hours intervals, but not the date or actual time on the clock as I informally do here unless we want to show nocturnal and daytime variations.

Here are the very few data not worth any statistical analysis. Once again, I want to emphasize we need large samples, as large as possible to represent a true population, and the sampling we take must be randomized to prevent bias.   Bear in mind these are some of these research criteria required and must follow before I start. Are we ready?

However, despite these flaws here with only myself on this experiment, it already gives us a hint as a pilot pointer that Terazosin do have antihypertensive action on blood pressure and can be indicated for the management of high blood pressure instead of prescribing it only for BPH as doctors do. 

We may use these small initial results as a springboard for much larger, and properly designed study

Results:

Blood Pressure with 2.5 mg Terazosin (Hytrin)

Tuesday – Wednesday: 28 – 29 March 2023

Time and blood pressure

Prior to dosing at 10:15 pm: 116/ 67, 119/66, 126/71 mm Hg (Normotensive)

10:25 pm after oral dosing with 2.5 mg Hytrin: 119/72, 99/61, 107/ 65 mm Hg

10:36 pm: 97 /67, 110/73. 116/69 mm Hg (initial stage of hypotensive)

10:45 pm: 105 / 64, 108/60, 116/69 mm Hg (mild hypotension)

11:00 pm: 112 / 64, 115 /72, 102/ 59 mm Hg

Midnight, 29 March 29, 2023: 89 / 56, 82 / 50, 87 / 53 mm Hg. (Marked hypotension)

1:05 am: 83 /58, 82 / 52, 94 / 65 mm Hg (hypotensive stage)

3:13 am: 110 / 69, 106 /65, 117 / 74 mm Hg (drug effect showing false signs of wearing off)?

4:02 am: 80 /56, 94 /62, 96 / 64 mm Hg (hypotensive stage maintained)

10:39 am: 135 /71, 124 /72, 118 /80 mm Hg (hypotensive action weaning off after 12 hours)

Far too small a sample for statistical analysis. But we can see a quick rapid drop in blood pressure within just 15 minutes after an initial 2.5 mg. dose was maintained for 12 hours.

But I am unsure why is Terazosin seldom used to treat hypertension instead of other antihypertensive agents such as valsartan or valsartan with a diuretic such as valsartan + hydrochlorothiazide (Co-Diovan)? There is no indication in the literature to show the adverse effects of using Terazosin alone or concomitantly with other drugs for treating hypertension.  

Prostate-specific Antigen (PSA)

As far as his high total prostate-specific antigen (PSA) is concerned, this needs to be investigated further. A high PSA level does not necessarily mean prostate cancer, and neither a low PSA level means the absence of prostate cancer. One of the best ways to detect prostate cancer is to look at how high and fast the PSA levels rise over a period of time (PSA velocity).

If it rises far above the normal of 4.0 ng/mL within a month or so, this requires further investigations using urine tests, such as a urinalysis for blood, TRUS (trans rectal ultrasound) biopsies, x-rays, cystoscopy. TRUS biopsies are very invasive that also carries the risk of infections as the needle has to go through the distal end of the colon where there are faeces, and risk of bleeding as multiple sites, some 10 to 12 areas around the prostate gland needs to be punched out (biopsied).

One better non-invasive approach is not just taking blood to determine level of free PSA, but to look for combined PSA with protein. But this method is very time consuming and very expensive to carry out. I have not heard of this free and combined PSA being done in any of the government hospitals in this country, but I have no idea if this is available in private hospitals? Since it is expensive and time-consuming, free and combined PSA is not routinely done in most government hospitals, not even in major ones.  They may also need lab facilities and trained staff to do this

Patients with low free to total PSA in blood may be at risk of prostate cancer. PSA ratios of less than 10% free PSA, and more than 90% bound PSA is more likely to have prostate cancer. Men with constantly elevated PSA concentrations should have the free to total PSA ratio estimated. The only problem with this test is that free PSA is short-lived not only in vivo but also in vitro, so it must be measured within 24 hours of collecting the blood sample. Delay will falsely lower free to total PSA ratios which could be misinterpreted as an increased risk of cancer.

 Jb lim

 


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