Asthma and COPD Medications

Erectile Dysfunction (ED)

• ED involves the inability to maintain a penile erection for successful sexual activity.
• Causes include vascular disease, diabetes, depression, hypertension (HTN), multiple sclerosis (MS), medications, and prostatic surgery.
• First-line treatment for ED is PDE-5 inhibitors.
• Other treatments include alprostadil and penile implants.

Phosphodiesterase-5 (PDE-5) Inhibitors

• Mechanism of Action (MOA): Inhibit PDE-5 degradation of cGMP, allowing cGMP-mediated arteriole smooth muscle relaxation in the corpus cavernosum, leading to increased blood flow and prolonged erection.
• First-line treatment for ED.
• Agents include sildenafil, tadalafil, vardenafil, and avanafil.

PDE-5 Inhibitors: Duration of Action (DOA) and Peak Concentration

• Avanafil: Time to peak concentration is 30-45 minutes (fastest).
• Sildenafil & Vardenafil: Take 1 hour before activity, on an empty stomach, DOA approximately 4 hours.
• Sildenafil: Time to peak concentration is 60 minutes.
• Vardenafil: Time to peak concentration is 60 minutes.
• Tadalafil: Longer time to peak (120 minutes), but has a longer DOA, allowing for once-daily dosing or PRN use.
• Avanafil: Quickest onset.

PDE-5 Inhibitors: Kinetics

• Sildenafil and Vardenafil: Take 1 hour before activity on an empty stomach; duration of action approximately 4 hours.
• Tadalafil: Longer time to peak, longer duration of action allows for once-daily dosing or PRN.
• Avanafil: Quickest onset.
• All are metabolized by CYP3A4.
• Dose adjustment is required in mild to moderate hepatic impairment.
• Avoid use in severe hepatic impairment.
• Food interaction: The absorbtion of Sildenafil and Vardenafil is reduced when taken with fatty foods.

PDE-5 Inhibitors: Adverse Drug Events (ADEs)

• Most common side effects include headache, flushing, dyspepsia, and nasal congestion.
• Disturbances of color vision (PDE-6 inhibition) may occur (blue tinted vision).
• Sudden hearing loss is a possible side effect.
• Tadalafil can cause back pain and myalgias (PDE-11 inhibition).
• Priapism is a rare, medical emergency (longer than 4 hours).

PDE-5 Inhibitors: Interactions

• Contraindicated with nitrates.
• Additive hypotensive effects with alpha-blockers (typically end in "zosin").
• Decrease the dose with potent 3A4 inhibitors.
• Do not use vardenafil with dronedarone due to QT prolongation.

Alpha-Blockers for ED

• Additive hypotensive effects with alpha-blockers.

Alprostadil

• MOA: Synthetic prostaglandin E1 that allows for relaxation of smooth muscle and arteriole dilation in the corpus cavernosum, increasing blood flow and causing prolonged erection.
• Administered as an intraurethral suppository or intrapenile injection.
• Used in patients who are not candidates for oral therapy, also in patients on nitrates.
• Kinetics: Minimal systemic absorption. Its also used in patients on Mitrates or any patient taking nitrates.
• Suppository: Onset in 5-10 minutes, duration 30-60 minutes.
• Injection: Onset in 2-25 minutes, duration 30-60 minutes.
• Adverse effects include hypotension (rare), headache (rare), local penile, urethral, and testicular pain, and priapism.

Benign Prostatic Hyperplasia (BPH)

• Characterized by benign enlargement of the prostate gland, which encroaches on the urethra, causing urinary hesitancy and frequency, weak stream, and incomplete emptying.
• Significantly impacts quality of life
• Pharmacologic therapies include alpha-1 antagonists, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors.
• Tadalafil can be used for BPH, sometimes in combination with other BPH medications.

Alpha-1 Antagonists for BPH

• MOA: Block alpha-1 receptors in the prostate, leading to smooth muscle relaxation.
• Doxazosin, terazosin, and alfuzosin affect both alpha-1a and alpha-1b receptors, greater risk of hypotension.
• Tamsulosin and silodosin are more selective for alpha-1a receptors and preferred and help to relieve BPH symptoms.
• Used to improve urine flow and provide symptomatic improvement in BPH but do not reduce prostate size or stop disease progression.
• Agents include terazosin, doxazosin, alfuzosin, tamsulosin, and silodosin.

Alpha-1 Antagonists: Kinetics

• Administered orally with food.
• Duration is 8-22 hours, with peak effect 1-4 hours after administration.
• Silodosin requires dose adjustment in renal impairment and is contraindicated if severe.
• Take at BEDTIME to reduce risk of fainting!.

Alpha-1 Antagonists: Adverse Drug Events (ADEs)

• Dizziness, headache, orthostatic hypotension, drowsiness, nasal congestion, and tachycardia, retrograde ejaculation.
• Inhibition of ejaculation, retrograde ejaculation.
• Floppy iris syndrome during eye surgery (risk for cataract surgery)
• Alfuzosin has QT prolongation.

5-alpha Reductase Inhibitors for BPH

• Used to treat BPH with testes > 40g.
• MOA: Inhibit 5-alpha reductase, blocking the conversion of testosterone to DHT, preventing DHT stimulation of the prostate, leading to prostate shrinkage and improved urine flow, SLOW Dx progression!.
• Used to decrease prostate size and improve symptoms in BPH.
• Takes 6-12 months to be effective, takes long time.
• Can be combined with alpha-1 antagonists if BPH drug didn't work alone
• Agents include finasteride and dutasteride
• Takes 6-12 months to be effective.

5-alpha Reductase Inhibitors: Adverse Drug Events (ADEs)

• Sexual dysfunction, even after discontinuation.
• Decreased ejaculate, decreased libido, ED.
• Gynecomastia.
• Oligospermia/Low sperm count.
• Teratogenic: Women who are pregnant or of childbearing age should not handle the medication, as it can be absorbed through the skin!
• Reversible! If stop the agent, Side effects may reduce.

Agent That Increases Risk of Cataracts

• Floppy iris syndrome, a side effect of alpha-1 antagonists, increases the risk for cataract surgery.

Unique Handling Requirement

• Women who are pregnant or of childbearing age should not handle finasteride or dutasteride (5-alpha reductase inhibitors) due to teratogenic effects and skin absorption.