Erectile Dysfunction

Erection is mediated via parasympathetic stimuli, while ejaculation is under control of sympathomimetic agents.

Thus sympathomimetic agents will not help in erectile dysfunction.

Ref: Richard Finkel, Michelle Alexia Clark, Pamela C. Champe, Luigi X. Cubeddu (2009), Pharmacology, 4th Edition, Lippincott Williams and Wilkins Publications, United States Page 65 ; Principles of Anatomy and Physiology By Tartora 10th Edition, Page 580

Most serious adverse effects of thiazides are,
 

• Extracellular volume depletion

• Hypotension

• Hypokalemia

• Hyponatremia

• Hypochloremia

• Metabolic alkalosis

• Hypomagnesemia

• Hypercalcemia

• Hyperuricemia

• Decreases glucose tolerance

• Increases plasma levels of LDL cholesterol, total cholesterol, and total triglycerides

Ref: Reilly R.F., Jackson E.K. (2011). Chapter 25. Regulation of Renal Function and Vascular Volume. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

The agents used for erectile dysfunction are:

A i.e. Sildenafil

• Sildenafil is only approved & effective oral agent for erectile dysfunctionQ. It is useful in wide range of e.d.

including – pyschogenic, diabetogenic, vasculogenic, post radical prostatectomy (nerve sparing procedure) & spinal cord injury.

• It acts by inhibiting phosphodiesterase – 5 (PDE-5)Q & releasing NOQ from nerve endings & endothelium
• Other t/t for Erectile dysfunction are:

PIPE therapy (PapaverineQ/ Phentolamine Induced Penile Erection)

–          Androgen

Intraurethral – alprostodil (PGE1)

Penile prosthasis, vaccum constriction device

• Master Johnson technique is for premature ejaculationQ

p Blockers can cause erectile dysfunctionQ

Ans. is ‘A’ i.e., Hypocalcemia

Thiazides cause hypercalcemia (see above explanation).

Ans. is ‘c’ i.e., Patent ductus arteriosus

o Alprostadil is used to keep the ductus open and not to treat patent ductus arteriosus.

Ans. is ‘d’ i.e., Palliative treatment of PDA

Ans. is ‘a^‘ i.e., Phenylephrine

Drugs used in erectile dysfunction

1. Phosphodiesterase-5 inhibitors (Siledenafil, Todafil, Vardenafil).
2. Alprastadil (Prostaglandin El)
3. Papaverine
4. Androgens
5. Apomorphine

Ans. is ‘b’ i.e., Phosphodiesterase -5

o Sildenafil inhibits phosphodiesterase-5 and is used for erectile dysfuction.

Ans. is ‘a’ i.e., Hypotension

Pharmacology and Pharmacotherapeutics (New Revised 2P”/e) R.S. Satoskar, S.D. Bhandarkar & Nirmala N. Rege p. 968]

o Sildenafil, tadalafil, and vardenafil all have a significant and potentially dangerous interaction with organic nitrates, the therapeutic actions of which are mediated via their conversion to NO with resulting increases in cyclic GMP. In the presence of a PDE5 inhibitor, nitrates cause profound increases in cyclin GMP and can produce dramatic reductions in blood pressure.

Ans. is ‘c’ i.e., Phenylephrine

Ans is ‘a’ i.e. Erectile dysfunction

o Bremelanotide is an analogue of naturally occurring peptide alpha-melanocyte-stimulating hormone (alpha­MSH).

o It stimulates erection in men and male rats, and was in clinical trials for the treatments of erectile dysfunction in men and sexual arousal disorder in women.

Ans: C i.e. Phosphodiesterase-5 inhibitor

Drugs and mechanism of action

• Finsateride is a competitive inhibitor of the enzyme 5 alpha reductase (which converts testosterone into more active dihydrotestosterone)
• Flutamide is a non-steroidal drug having specific anti-androgenic, but no other hormonal activity
• Sildenafil acts by selectively inhibiting PDE-5 and enhancing nitric oxide action in corpus cavernosum
• Danazol is an orally active ethisterone derivative having weak androgenic, anabolic and progestational activities.

Ans. B: Vascular

ED is essentially a vascular disease.

It is often associated with other vascular diseases and conditions such as diabetes, hypertension, and coronary artery disease.

Other conditions associated with ED include neurologic disorders, endocrinopathies, benign prostatic hyperplasia, and depression.

Conditions associated with reduced nerve and endothelium function, such as aging, hypertension, smoking, hypercholesterolemia, and diabetes, alter the balance between contraction and relaxation factors.

These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation.

In some patients, sexual dysfunction may be the presenting symptom of these disorders.

Additionally, ED is often an adverse effect of many commonly prescribed medications.

Some psychotropic drugs and antihypertensive agents are associated with ED.

Ans. Psychological

Ans. is ‘b’ i.e., It cannot be used for the treatment of PAH

1. Tadalafil is the longest acting phosphodiesterase inhibitor used for erectile dysfunction.
2. Its half life is 17^.5 hours.
3. It can be used as once-daily phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH).

Ans. is ‘b’ i.e., cGMP

Ans. c. Phenylephrine

Ans. is ‘a’ i.e., n-blockers

Drugs used for erectile dysfunction

1. Phosphodiesterase-5 inhibitors (Siledenafil, Todafil, Vardenafil).

• By inhibiting PDE-5, these drugs prevent degradation of cGMP and potentiate the action of NO.
• These are the DOC for pharmacological therapy of erectile dysfunction.

2.Alprastadil (Prostaglandin El)

• It is a powerful vasodilator
• It acts by increasing arterial inflow by vasodilation and reducing outflow by contracting the carporal smooth muscle that occludes draining venules.
• It is the DOC for patients not responding to PDE-5 inhibitors.
• It is directly injected into corpora cavernosa.

3.  Papaverine

• It is a nonspecific phosphodiesterase inhibitor.
• Injection of papaverine with or without phentolamine into corpus cavernosum produces penile tumiscence to permit intercourse.
• Repeated injection can cause penile fibrosis.

4.Androgens

• Can be used when androgen deficiency is demonstrated to be responsible for the loss of libido and erectile dysfunction.

5.Apomorphine (Laurence 9th/e p. 546)

• A dopamine antagonist, is given by subcutaneous injection.

Ans. is ‘c’ i.e., Induction of puberty