Understanding Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH), sometimes known as an enlarged prostate, is a disorder that is more typical as people get older. In essence, this condition causes the prostate to expand, which then causes complications like urinary tract, bladder, or kidney problems. Your preparation for Pharmacology must cover BPH. 

The disorder known as benign prostate hyperplasia causes the prostate gland to expand and press against the urethra.As a result, the patient cannot adequately pass urine.

The leftover urine in the bladder causes the urge to urinate more frequently and urgently. Patients that are elderly are frequently affected. For people who do not want surgery, medications are administered.

Read this blog further to get a quick overview of this important topic for PSYCHIATRY to ace your NEET PG exam preparation.

Symptoms Of Benign Prostate Hyperplasia

Typical signs of BPH include:

• Urination is the term for the frequent or urgent need to urinate.
• More frequent urination during night.
• Having trouble urinating.
• Weak pee flow or intermittent urine flow.
• Dribbling after the last urinal passage.
• Bladder not being able to empty completely.

Less frequent signs include:

• Infection in the urinary system.
• Being unable to urinate.
• Urine with blood in it.

BPH symptoms typically worsen over time. But occasionally they do not change over time or even get better.

The severity of the symptoms is not always based on the prostate's size. Major symptoms can occur in some people with modestly enlarged prostates. Some men with extremely enlarged prostates may experience modest issues. Additionally, some men with enlarged prostates have none.

Causes Of Benign Prostate Hyperplasia

The prostate gland is located below the bladder. The tube that transports urine from the bladder out of the penis is known as the urethra. This tube passes through the centre of the prostate. As the prostate enlarges, urine flow is obstructed.

The prostate gland keeps on growing throughou the life.. This growth frequently causes the prostate to expand to the point that it causes pain or obstructs urine flow.

It is uncertain why the prostate enlarges specifically. It might result from changes in the ratio of sex hormones as you get older.

Risk Factors Of Benign prostate Hyperplasia

A enlarged prostate is at risk for the following:

• Aging. Before the age of 40, signs of an enlarged prostate gland are uncommon. Following that, there is a higher likelihood of developing an enlarged prostate and the symptoms that go along with it.
• History of the family. You are more susceptible to developing prostate issues if a blood relative does.
• Cardiovascular Disease and Diabetes. Diabetes may increase the risk of BPH, according to studies. Heart illness may also exist.
• Lifestyle. BPH risk is heightened by obesity. Reducing the risk through exercise can assist.

Diagnosis Of Benign Prostate Hyperplasia

Most likely, your doctor will begin by asking you about your symptoms. Additionally, you'll get a physical examination. There may be the following on this exam:

• Digital rectal examination. Your rectum is probed with a finger by the medical professional to see whether your prostate is enlarged.
• Test the urine. A lab examines a sample of your urine to determine whether you have a disease or another issue that could cause symptoms similar to those of BPH.
• Examination of the blood. If you have renal issues, the results can reveal that.
• After that, you might require more testing to assist confirm an enlarged prostate. These assessments consist of:
• Blood Test for Prostate Specific Antigen (PSA). The protein produced by is known as  PSA. When the prostate enlarges, PSA levels rise. However, recent treatments, illnesses, surgeries, or prostate cancer can also cause elevated PSA values.
• Test of Urinary Flow. You urinate into a machine-attached receptacle. The device counts the amount of pee you pass and the force of your urine flow. Test results might demonstrate if your condition is improving or deteriorating over time.
• Test of the Postvoid Residual Volume. This examination determines whether you have complete bladder control. The test can be performed utilising an ultrasonic imaging examination. Alternatively, a catheter, a tube that is inserted into your bladder after you urinate to measure how much urine is left in the bladder.
• 24-hour voiding Log. This entails keeping track of how frequently and how much you urinate. If you produce more than a third of your daily pee at night, it might be particularly beneficial.

You Might Require Tests Such as:

• Ultrasonography of the Transrectal Area. The rectum is implanted with a device that generates images using sound waves. It measures and examines the prostate.
• Biopsy of the Prostate. Transrectal ultrasonography is used to direct needles used to collect prostate tissue samples. Your doctor can determine if you have prostate cancer by examining the tissue.
• Investigations of Pressure flow and Urodynamics. The bladder is reached by inserting a catheter through the urethra.
• To test bladder pressure and assess how well the bladder muscles function, water or, less frequently, air is progressively injected into the bladder.
• Cystoscopy. One inserts a flexible, lit instrument into the urethra. A doctor can use it to see within the bladder and urethra. You will receive a painkiller before this exam to help you relax.

Treatment Of Benign Prostate Hyperplasia

Drugs used in Benign Prostatic Hyperplasia (BPH)

• Fast acting component: α-Blockers. These further include the α1 selective blockers and α1A selective blocker (for bladder).
  • The α1 selective blockers are useful for both BPH and hypertension (HTN) e.g., Prazosin, Terazosin, and Doxazosin. Terazosin and Doxazosin have a quinazoline moiety, which is effective in prostate smooth muscle apoptosis. Alfuzosin is useful only in the management of BPH alone. The disadvantage of α1 blockers is that the patient may develop hypotension repeatedly.
  • α1A selective blockers are only useful for BPH and have no effect on HTN or BP, e.g., Tamsulosin and Silodosin. An important complication (adverse effect) of Tamsulosin is floppy iris syndrome, which is an intraoperative complication. Tamsulosin and silodosin are the drugs of choice for BPH. They don't affect the BP.
• Slow-acting component: These take months to show their effect. They are called 5α-reductase inhibitors.

5α Reductase Inhibitors

• Testosterone is converted into dihydrotestosterone (DTH).
• This conversion is done by an enzyme called 5α reductase inhibitor. Increased DTH can lead to BHP, androgenic alopecia, and hirsutism.  These can be treated with 5α reductase inhibitors, e.g., Finasteride. Thus, the mechanism of action of finasteride is type 2 5α reductase inhibition. Dutasteride inhibits both type 1 and type 2 5α reductases. It is approved only for BPH treatment. These drugs have shown to decrease the size of the prostate in prolonged use.

Drugs used in the Management of Erectile Dysfunction

Oral Drugs

• Oral drugs are phosphodiesterase (PDE) V inhibitors, e.g., Avanafil, Sildenafil, Vardenafil, and Tadalafil (ASVT). Avanafil is a short-acting drug, while tadalafil is a longer-acting drug.
• Mechanism of action of sildenafil:
  • Penile nerve stimulation can release nitrous oxide (NO). This stimulates an enzyme called soluble guanylyl cyclase (SGC), which in turn converts the guanosine triphosphate (GTP) to guanosine 3',5'-cyclic monophosphate (cGMP). 
  • The cGMP activates protein kinase G (PKG), which causes vasodilation (VD). This is responsible for penile erection.
  • In erectile dysfunction, the cGMP is broken down into 5'-GMP. The enzyme responsible for this breakdown is PDE V.
  • Thus, to increase the penile erection duration, the cGMP level should be increased. This is done by inhibiting the PDE V enzyme. This increases the vasodilation period and the duration of the erection. This is the mechanism of action of sildenafil.

Q. Can sildenafil and nitrates be combined?

Ans: Both drugs increase cGMP. This leads to a severe fall in BP, resulting in severe hypotension. Thus, any PDE V inhibitor given with nitrate has a risk of severe hypotension.

• Pharmacokinetics of PDE V inhibitors:
  • These are not aphrodisiacs. They only prolong the duration of the erection. These should be given 1-2 hours before sexual intercourse. Any PDE V inhibitor given with nitrate has a risk of severe hypotension.
• Adverse effects of PDE V inhibitors: 
  • Decrease in BP
  • Increased heart rate (HR)
  • Blue or green tinted vision (due to PDE 6 inhibition in the retina). 
  • Sometimes there is a prolonged erection.

Other Drugs in the Treatment of Erectile Dysfunction

• Androgen replacement: In cases of libido loss due to low testosterone, these can be used.
• Injectables: These are given into the penis before the intercourse. The issue with injectables is that they cause pain. Examples of injectables are Phentolamine, Papaverine, and Alprostadil.

Drugs Used in the Management of Premature Ejaculation

• Premature ejaculation is a condition where the person ejaculates early. 
• Selective serotonin reuptake inhibitors (SSRIs): Which delay the ejaculation process, e.g., Dapoxetine (FDA-approved drug) and Paroxetine (off-label use).
• Tricyclic antidepressants (TCAs): These are another class of drugs to treat premature ejaculation, e.g., Clomipramine (serotonergic property).

Hormonal Therapy of Prostate Cancer

• Prostate cancer is usually treated by surgery, but it might not always be feasible.
• Prostate cancer is a testosterone dependent cancer.
• The drugs used in its treatment include the following:
  • Androgen receptor blockers- Flutamide, Bicalutamide, Enzalutamide, and Nilutamide. All of these are approved for prostate cancer. Flutamide is also approved for acne and hirsutism.
  • Gonadotropin-releasing hormone (GnRH) agonists- Leuprolide and Goserelin. These are given as a continuous treatment.
  • GnRH antagonist- Abarelix and Degarelix.
  • Abiraterone: It acts by inhibiting the 17 α hydroxylase enzyme.
• The continuous use of GnRH agonists will increase the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH). This in turn will increase the testosterone levels. This can lead to a cancer flare-up. Later, the receptors are desensitized, which decreases FSH, LH, and testosterone. To prevent the cancer flare-up, flutamide is given three days before GnRH agonists. This is called combined androgen blockade.

Q. Can flutamide be given alone?

Ans: Whenever testosterone levels increase, it causes a negative feedback mechanism in the hypothalamus. Flutamide blocks the testosterone receptors in the hypothalamus and the pituitary gland. In the absence of negative feedback, there's an increase in testosterone production. 

This will replace the flutamide from the prostate, causing prostate cancer flare-up. Thus, flutamide cannot be given alone. GnRH agonists are continuously given along with flutamide. This desensitizes the testosterone receptors in the pituitary gland. Thus, testosterone won't be released.

What Drugs can Cause Gynecomastia?

• The drugs causing gynecomastia are: (Mnemonic- "In moving a dashing car SKODA")
  • In- Isoniazid (INH).
  • Moving- Methyldopa and Metoclopramide.
  • Dashing- Domperidone.
  • Car- Cimetidine.
  • S- Spironolactone.
  • K- Ketoconazole.
  • O- Oestrogen.
  • D- Digoxin.
  • A- Anti-androgens.

Summary

• Two important drugs used in the treatment of BPH:  α blockers (faster acting). Tamsulosin and Silodosin are the drugs of choice in the treatment of BPH, as they don't produce hypotension. The slower-acting drugs are α reductase inhibitors. They inhibit the conversion of testosterone to DTH. They decrease the size of the prostate.
• Drugs to treat erectile dysfunction are PDE V inhibitors. They increase the cGMP and cause vasodilation and increase of penile erection. They are to be avoided with nitrates as they can cause a severe drop in blood pressure. The injections include Phentolamine, Papaverine, and Alprostadil. Androgen replacement therapy can also be done.
• The SSRI of choice for premature ejaculation is Dapoxetine.
• Prostate cancer is treated with androgen receptor blockers like flutamide. It is also used to treat acne and hirsutism. The GnRH agonists are used continuously, but flutamide is added to avoid flare-ups. Flutamide isn't given alone to avoid blocking the negative feedback of testosterone. Other drugs used in the treatment of prostate cancer include GnRH antagonists (Abarelix and Degarelix) and Abiraterone (17 α hydroxylase enzyme inhibitor).

And that is everything you need to know about benign prostatic hyperplasia (BPH) for Pharmacology paper and ace your NEET PG preparation. For more informative and engaging posts like these, download the PrepLadder App and keep following our blog!