Tag: Erectile Dysfunction

Erectile Dysfunction

ERECTILE DYSFUNCTION

Q. 1

A 30 yr old male presents to the OPD with Erectile dysfunction. Basic screening evaluation is unremarkable. Which of the following should be the next step in the evaluation/management of this patient?

 A

Cavernosometry

 B

Neurological testing

 C

Oral Sildenafil citrate trial

 D

Penile ultrasound doppler study

Q. 1

A 30 yr old male presents to the OPD with Erectile dysfunction. Basic screening evaluation is unremarkable. Which of the following should be the next step in the evaluation/management of this patient?

 A

Cavernosometry

 B

Neurological testing

 C

Oral Sildenafil citrate trial

 D

Penile ultrasound doppler study

Ans. C

Explanation:

Specialised investigations such as Penile Doppler Ultrasound, Dynamic Infusion Cavernosography and Neurological testing are rarely necessary in the evaluation of Erectile Dysfunction.
These investigations are indicated in selected complicated cases and are not indicated for the initial evaluation of Erectile Dysfunction.
So the most appropriate next step in management in this patient would be a trial of oral phosphodiesterase type 5 inhibitor sildenafil.
 
Evaluation of a patient with sexual dysfunction involves taking thorough history and performing physical examination.
Basic laboratory investigations done includes estimation of CBC, lipid profiles, serum prolactin and testosterone.
Additional diagnostic testing is rarely necessary in the evaluation of erectile dysfunction.  
 
Specialized test involves (1) studies of nocturnal penile tumescence and rigidity, (2) vascular testing (in-office injection of vasoactive substances, penile Doppler ultrasound, penile angiography, dynamic infusion cavernosography/cavernosometry), (3) neurologic testing (biothesiometry-graded vibratory perception, somatosensory evoked potentials), and (4) psychological diagnostic tests.
 
Ref: Harrison’s Internal Medicine, 18th Edition, Chapter 48

Q. 2

Sympathomimetic drugs are used in all of the conditions, except:

 A

High blood pressure

 B

Acute uncompensated cardiac failure

 C

Low blood pressure

 D

Erectile dysfunction

Q. 2

Sympathomimetic drugs are used in all of the conditions, except:

 A

High blood pressure

 B

Acute uncompensated cardiac failure

 C

Low blood pressure

 D

Erectile dysfunction

Ans. D

Explanation:

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


Q. 3

Which of the following is an adverse effect of thiazide diuretics?

 A

Hyperkalemic metabolic acidosis

 B

Hypolipidemia

 C

Hypouricemia

 D

Erectile dysfunction

Q. 3

Which of the following is an adverse effect of thiazide diuretics?

 A

Hyperkalemic metabolic acidosis

 B

Hypolipidemia

 C

Hypouricemia

 D

Erectile dysfunction

Ans. D

Explanation:

The incidence of erectile dysfunction is greater with Na+-Cl– symport inhibitors than with several other antihypertensive agents (e.g., beta adrenergic receptor antagonists, Ca2+-       channel blockers, or angiotensin converting enzyme inhibitors).
 

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.

Quiz In Between


Q. 4

Which of the following agent is not used in erectile dysfunction?

 A

PGE2

 B

Vardenafil

 C

Phenylephrine

 D

Alprostadil

Q. 4

Which of the following agent is not used in erectile dysfunction?

 A

PGE2

 B

Vardenafil

 C

Phenylephrine

 D

Alprostadil

Ans. C

Explanation:

The agents used for erectile dysfunction are:

Hormone replacement for documented androgen deficiency on endocrinologic evaluation, using testosterone injections (300 mg intramuscularly every 3 weeks) topical 1% testosterone gel (2.5–10 g/d) or topical patches (2.5–5 mg/d), after prostate-specific antigen and digital rectal examination screening.
 
Direct injection of vasoactive prostaglandins into the penis
 
Alprostadil urethral suppository pellets (125, 250, 500, and 1000 mcg)
 
PDE-5 inhibitors: Sildenafil, 25–100 mg; vardenafil, 5–20 mg; or tadalafil, 5–20 mg used 1 h prior to anticipated sexual activity.
 
Ref: Papadakis MA, McPhee SJ, “Erectile Dysfunction.” Quick Medical Diagnosis & Treatment

Q. 5

Most accurate treatment of erectile dysfunction:

 A

Sildenafil

 B

Master and johnson technique

 C

B-blockers

 D

Papaverine

Q. 5

Most accurate treatment of erectile dysfunction:

 A

Sildenafil

 B

Master and johnson technique

 C

B-blockers

 D

Papaverine

Ans. A

Explanation:

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


Q. 6

Side effect of thiazide diuretics are all except ?

 A

Hyponatremia

 B

Hypokalemia

 C

Erectile dysfunction

 D

Hypocalcemia

Q. 6

Side effect of thiazide diuretics are all except ?

 A

Hyponatremia

 B

Hypokalemia

 C

Erectile dysfunction

 D

Hypocalcemia

Ans. A

Explanation:

Ans. is ‘A’ i.e., Hypocalcemia

Thiazides cause hypercalcemia (see above explanation).

Quiz In Between


Q. 7

Alprostadil is not used for –

 A

Erectile dysfunction

 B

Pulmonary hypertension

 C

Patent ductus arteriosus

 D

Critical limb ischemia

Q. 7

Alprostadil is not used for –

 A

Erectile dysfunction

 B

Pulmonary hypertension

 C

Patent ductus arteriosus

 D

Critical limb ischemia

Ans. C

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.


Q. 8

Prostaglandins are used in all except

 A

Cervical ripening

 B

PPH

 C

Erectile dysfunction

 D

Palliative treatment of PDA

Q. 8

Prostaglandins are used in all except

 A

Cervical ripening

 B

PPH

 C

Erectile dysfunction

 D

Palliative treatment of PDA

Ans. D

Explanation:

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


Q. 9

The following may be used in erectile dysfunction except –

 A

Phenylephrine

 B

Apomorphine

 C

Alprostidil

 D

All

Q. 9

The following may be used in erectile dysfunction except –

 A

Phenylephrine

 B

Apomorphine

 C

Alprostidil

 D

All

Ans. A

Explanation:

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

Quiz In Between


Q. 10

Sildenafil acts by inhibiting –

 A

Phosphodiesterase – 2

 B

Phosphodiesterase-5

 C

Adenyl cyclase

 D

Guanyl cyclase

Q. 10

Sildenafil acts by inhibiting –

 A

Phosphodiesterase – 2

 B

Phosphodiesterase-5

 C

Adenyl cyclase

 D

Guanyl cyclase

Ans. B

Explanation:

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

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


Q. 11

Result of interaction of Sildenafil with NO is ?

 A

Hypotension

 B

Urticaria

 C

Flushing

 D

Headache

Q. 11

Result of interaction of Sildenafil with NO is ?

 A

Hypotension

 B

Urticaria

 C

Flushing

 D

Headache

Ans. A

Explanation:

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.


Q. 12

Not used in erectile dysfunction –

 A

PGE -2

 B

Vardalafil

 C

Phenylephrine

 D

Alprostadil

Q. 12

Not used in erectile dysfunction –

 A

PGE -2

 B

Vardalafil

 C

Phenylephrine

 D

Alprostadil

Ans. C

Explanation:

Ans. is ‘c’ i.e., Phenylephrine

Quiz In Between


Q. 13

Bremelanotide is used for –

 A

Erectile dysfunction

 B

LUTS

 C

Hormone resistant prostate cancer

 D

Metastatic RCC

Q. 13

Bremelanotide is used for –

 A

Erectile dysfunction

 B

LUTS

 C

Hormone resistant prostate cancer

 D

Metastatic RCC

Ans. A

Explanation:

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.


Q. 14

Mechanism of action of sildenafil is:           

March 2012

 A

5 alpha reductase inhibitor

 B

Antiandrogen

 C

Phosphodiesterase-5 inhibitor

 D

Androgenic

Q. 14

Mechanism of action of sildenafil is:           

March 2012

 A

5 alpha reductase inhibitor

 B

Antiandrogen

 C

Phosphodiesterase-5 inhibitor

 D

Androgenic

Ans. C

Explanation:

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.

Q. 15

Organic cause for erectile dysfunction is most commonly:     

March 2009

 A

Psychological

 B

Vascular

 C

Neuronal

 D

Hormonal

Q. 15

Organic cause for erectile dysfunction is most commonly:     

March 2009

 A

Psychological

 B

Vascular

 C

Neuronal

 D

Hormonal

Ans. B

Explanation:

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.

Quiz In Between


Q. 16

Most common cause of erectile dysfunction:

FMGE 10

 A

Psychological

 B

Drug induced

 C

Alcohol

 D

Diabetes

Q. 16

Most common cause of erectile dysfunction:

FMGE 10

 A

Psychological

 B

Drug induced

 C

Alcohol

 D

Diabetes

Ans. A

Explanation:

Ans. Psychological


Q. 17

TADALAFIL false is ‑

 A

It is longest acting phosphodiesterase inhibitor

 B

It cannot be used for the treatment of PAH

 C

It is used in erectile dysfunction

 D

Its half life is 17-5 hours

Q. 17

TADALAFIL false is ‑

 A

It is longest acting phosphodiesterase inhibitor

 B

It cannot be used for the treatment of PAH

 C

It is used in erectile dysfunction

 D

Its half life is 17-5 hours

Ans. B

Explanation:

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).

Q. 18

Tadalafil acts on Phosphodiesterase 5 and causes accumulation of‑

 A

cAMP

 B

cGMP

 C

PAF

 D

IL 10

Q. 18

Tadalafil acts on Phosphodiesterase 5 and causes accumulation of‑

 A

cAMP

 B

cGMP

 C

PAF

 D

IL 10

Ans. B

Explanation:

Ans. is ‘b’ i.e., cGMP

Quiz In Between


Q. 19

Which of the following agent is not used in erectile dysfunction

 A

PGE2

 B

Vardenafil

 C

Phenylephrine

 D

Alprostadil

Q. 19

Which of the following agent is not used in erectile dysfunction

 A

PGE2

 B

Vardenafil

 C

Phenylephrine

 D

Alprostadil

Ans. C

Explanation:

Ans. c. Phenylephrine


Q. 20

Not used for erectile dysfunction ‑

 A

Beta blockers

 B

Siledenafil

 C

PG-E,

 D

Papaverine

Q. 20

Not used for erectile dysfunction ‑

 A

Beta blockers

 B

Siledenafil

 C

PG-E,

 D

Papaverine

Ans. A

Explanation:

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.

Q. 21

All the following are the uses of PGElexcept –

 A

Erectile dysfunction 

 B

Induction of labor

 C

Induction of puberty 

 D

PDA

Q. 21

All the following are the uses of PGElexcept –

 A

Erectile dysfunction 

 B

Induction of labor

 C

Induction of puberty 

 D

PDA

Ans. C

Explanation:

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

Quiz In Between



Erectile Dysfunction

ERECTILE DYSFUNCTION


ERECTILE DYSFUNCTION (ED)

  • Condition in which there is an inability for a male to attain & maintain penile erection for sufficient duration that allows satisfactory intercourse.

Physiology of penile erection:

  • Normal penis erection requires parasympathetic system (S2-4), nitric oxide (NO) synthesis & normal release process.
  • NO increases cGMP levels (Most important step is metabolized by phosphodiesterase) –> smooth muscles relaxation of corpora cavernosa –> Penile erection.
  • Penis erection requires increased blood supply by vasodilatation.

Pharmacological basis:

  • Drugs producing these effects & enhancing penile erection are,
    • Phosphodiesterase inhibitors
    • α-blockers
    • PGE-2 & PGI-2 – By increasing sperm motility.

Etiology:

1. Primary causes:

  • Psychological – Most common
  • Vascular
  • Neurological
  • Hormonal

2. Secondary causes:

  • Arteriosclerosis
  • Hypertension
  • Diabetes
  • Smoking
  • Alcohol consumption
  • Drugs:
    • Maximum – Diuretics (Thiazide)
    • Others risky drugs – Alpha agonists (Phenylephrine), Beta blockers, CCB’s etc.,

MANAGEMENT:

I) MAIN ORAL THERAPY:

1. Phosphodiesterase inhibitors:

  • MOA – 
    • Normally, cGMP formed by NO action is metabolized by phosphodiesterase
  • Drugs included – 
    • Sildenafil, vardenafil, udenafil, avanafil, tadalafil & papaverine.
  • Disadvantages – 
    • Not to be prescribed for patients on nitrates, due to severe hypotension risk.

Important phosphodiesterase inhibitors:

Sildenafil-

    • Selectively inhibits PDE-5 –> Increases cGMP levels – Hence, effective drug.
    • Orally administered.
  • Uses –
    • ED & pulmonary hypertension management.
  • Adverse effects – 
    • Visual disturbances (blue vision).
    • Color vision defect – Due to PDE-6 inhibition present in retina.
  • Other effects – Headache, nasal congestion & flushing.
Other drugs:
  • Tadalafil – Longest acting phosphodiesterase inhibitor.
  • Avanafil – New drug for ED.
  • Papaverine – Non-selective PDE inhibitor.

II). OTHER ORAL DRUGS:

1. Dopamine agonist:

  • Apomorphine – D1 agonist.
  • Used sublingually.
  • Main adverse effect – Nausea.

2. α-blocker drugs:

  • α1 and α2 blocker (Non-selective α-inhibitor) – Phentolamine.
  • α2 blocker – Yohimbine.

3. NO precursor: L-arginine

4. Antidepressants: Trazodone

5. Restoration for erectile function: Naltrexone.

6. Herbal drugs:

  • Ginseng, kava & gingko.
  • Efficacy unestablished clinically.

7. Combination drugs:

  • Trazodone (an antidepressant) & phentolamine (non-selective α blocker) combination.

II). INTRACAVERNOSAL INJECTION THERAPY:

1. PGE analogue:

  • Alprostadil (PGE1 analogue)
  • Administered directly in cavernosal tissue.
  • More useful in patients unresponsive to oral sildenafil therapy.

2. α-blocker drugs:

  • Thymoxamine & Phentolamine – As intracavernosal injections.
  • Phentolamine – Non-selective α-blocker.
  • Thymoxamine – α-blocker with vaso-dilatory property.

3. Non-selective PDE inhibitorPapaverine

4. VIP analog:

  • Aviptadil – Causes smooth muscle relaxation.
  • Also, used in combination with phentolamine.

5. Combination drugs:

  • Ketanserin (5-HT2) & alprostadil (α-receptor antagonist) combination.

Exam Important

ERECTILE DYSFUNCTION

  • Nitric oxide (NO) increases cGMP levels (This most important step is metabolized by phosphodiesterase) → smooth muscles relaxation of corpora cavernosa –> Penile erection.
  • Primary & most common cause for ED is psychological.
  • Secondary causes for ED include arteriosclerosis, hypertension, diabetes, smoking & alcohol consumption.
  • Diuretics have the maximum risk factor for causing ED.
  • Alpha agonists (Phenylephrine), Beta blockers, CCB’s also cause erectile dysfunction.
  • Phosphodiesterase (PDE) inhibitors are the mainstay for treating erectile dysfunction.
  • PDE inhibitors include drugs like Sildenafil, vardenafil, udenafil, avanafil, tadalafil & Papaverine.
  • Main mechanism behind PDE inhibitors is by blocking PDE enzyme, which metabolizes cGMP formation by NO
  • Phosphodiesterase inhibitors are not to be prescribed for patients on nitrates, due to severe hypotension risk.
  • Sildenafil selectively inhibits PDE-5 & increases cGMP levels.
  • Sildenafil causes color vision defect (blue vision), due to inhibition of PDE-6, present in retina.
  • Tadalafil is the longest acting phosphodiesterase inhibitor.
  • Avanafil is the new drug for ED.
  • Papaverine is a non-selective PDE inhibitor used for treating ED.
  • Apomorphine is a dopamine (D1) agonist, given sublingually for treating ED.
  • Phentolamine is an α1 and α2 blocker (Non-selective), used for treating erectile dysfunction.
  • Yohimbine is an α2 blocker, used for treating erectile dysfunction.
  • L-arginine is a NO precursor used for treating ED.
  • Trazodone is an anti-depressant used for treating ED.
  • Combination of Trazodone (an antidepressant) & phentolamine (non-selective α blocker) is used for treating ED.
  • Intracavernosal injection therapy includes usage of PGE analogs, α-blockers, non-selective PDE inhibitors & VIP analogs.
  • Ketanserin (5-HT2) & alprostadil (α-receptor antagonist) combination is given intracavernosal for treating ED.
  • Papaverine is a non-selective PDE inhibitor used for treating ED.
  • Thymoxamine & Phentolamine are given as intracavernosal injections, for treating ED.
  • Thymoxamine is used for treating ED, mainly by acting as α-blocker with vaso-dilatory property.
  • Alprostadil is a PGE1 analog, given directly in cavernosal tissue, for persons unresponsive to oral sildenafil therapy during ED treatment.

 

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