Male GU Pharmacology Flashcards
Drug classes used to tx BPH
Alpha-1 adrenergic receptor antagonists
Steroid 5alpha reductase inhibitors
PDE-5 inhibitor (tadalafil)
Classes of drugs used to tx erectile dysfunction
PDE-5 inhibitors
PGE1 agonist (alprostadil)
What drugs are included in the alpha-1 adrenergic receptor antagonist class used to tx BPH?
Terazosin Doxazosin Tamsulosin Silodosin Alfuzosin
What drugs are included in the steroid 5alpha reductase inhibitors class used to tx BPH?
Finasteride
Dutasteride
What drugs are included in the PDE-5 inhibitors class used to tx ED?
Sildenafil
Vardenafil
Tadalafil
Avanafil
Describe MOA of alpha1 receptor antagonists in terms of mediating LUTS
Alpha-1A receptor + NE stimulation normally leads to muscle contraction and bladder out let obstruction
Alpha-1D receptors + NE normally lead to detrusor instability
MOA of alpha-1 antagonists is to compete with NE to reduce spasm, promote muscle relaxation and improve urine flow
Specificity, uroselectivity, and AEs associated with terazosin and doxazosin
Specificity: alpha-1»_space;> alpha-2; take 1 hour prior!
NOT uroselective
AEs: postural hypotension, dizziness, fatigue
Drug interactions associated with the alpha-1 adrenergic receptor antagonists (terazosin, doxazosin, tamsulosin, silodosin, and alfudosin)
PDE-5 inhibitors (sildenafil, vardenafil)
What drug interaction is important to keep in mind with select alpha-1 adrenergic receptor antagonists (particularly tamsulosin, silodosin, and alfuzosin)?
increase the concentration of CYP3A4 substrates
Specificity, uroselectivity, and AEs associated with tamsulosin and silodosin
Specificity: alpha-1A = alpha-1D > alpha-1B
Uroselective for alpha-1A = alpha-1D
AEs: reduced ejaculation; intraoperative floppy iris syndrome (IFIS)
Specificity, uroselectivity, and AEs associated with alfuzosin
Non-specific
Alpha-1 selective
AE: QT prolongation
Which of the alpha-1adrenergic receptor antagonists has functional uroselectivity, meaning that it distributes into the prostate more than the serum, but must be avoided in hepatic impairment?
Alfuzosin
T/F: alpha-1 adrenergic receptor antagonists are the best monotherapy for prompt relief of BPH symptoms
True
MOA of steroid 5-alpha reductase inhibitors used for BPH
Shrink prostate and Prevent further enlargement
Prevents steroid 5alpha reductase (SAR) type 1 and type 2 from converting serum T to DHT
DHT starvation causes epithelial atrophy, shrinkage, and gradual relief of LUTS (effects take ~3-6months)
What is the difference between finasteride and dunasteride in terms of selectivity?
Finasteride is specific to SAR-2
Dunasteride is a DUal inhibitor — SAR-1 and SAR-2
Which is more effective at decreasing serum DHT — finasteride or dutasteride?
Dutasteride is 20% better than finasteride at decreasing serum DHT
AEs of finasteride and dutasteride
Erectile dysfunction
Gynecomastia
Depressed libido
Ejaculation disturbances
Why must finasteride and dutasteride be used with caution in pts with liver abnormalities?
Metabolized by hepatic CYP3A
When would you use combination therapy for BPH, meaning an alpha-1 adrenergic antagonist + 5alpha-reductase inhibitor?
Severe symptoms of BPH
Known to have large prostate
No response from monotherapy
What drug is now approved by the FDA for treating patients with BOTH BPH and ED?
PDE-5 inhibitor: tadalafil
MOA of PDE-5 inhibitors like tadalafil
PDE-5 inhibitors are competitive inhibitors of the PDE-5 enzyme —> preventing the conversion of cGMP to 5’-GMP [increases availability of cGMP to propagate smooth muscle relaxation so that erection is maintained]
Clearance of all PDE-5 inhibitors
Hepatic CYP 3A4
Onset, duration of action, stomach contents, and half-life of PDE-5 inhibitor: sildenafil (viagra)
Onset: take 1 hour prior
Duration of action = 4 hours
Stomach contents: empty
Half life = 4 hrs
Onset, duration of action, stomach contents, and half-life of PDE-5 inhibitor: vardenafil (levitra)
Onset: take 1 hour prior
Duration of action = 4-5 hrs
Stomach contents: empty
Half life = 4 hrs
Onset, duration of action, stomach contents, and half-life of PDE-5 inhibitor: tadalafil (cialis)
Onset: take 1 hour prior
Duration of action = 36 hours (longest MOA!)
Stomach contents do not matter
Half life = 18 hrs
Onset, duration of action, stomach contents, and half-life of PDE-5 inhibitor: avanafil (stendra)
Onset: take 15 minutes prior (high dose) or take 30 minutes prior (nml dose) — FASTEST!
Duration of action = 4 hrs
Stomach contents do not matter
Half life = 4 hrs
Adverse effects of sildenafil, vardenafil, and avanafil
Blue vision or blurred vision due to additional inhibition of PDE-6 in the retina
PDE-5 inhibitor related side effects
Headache
Dyspepsia
Nasal congestion
PDE-6 related (sildenafil, vardenafil and avanafil) — blue/blurred vision
Specific to tadalafil: back pain, myalgia, limb pain
Contraindications to PDE-5 inhibitor use for ED
Organic nitrates!! — leads to extreme and dangerous hypotension
Specific to vardenafil: pt needs to be hemodynamically stable
Specific to tadalafil: when used for BPH, concurrent alpha-1 blockers not recommended
Specific to sildenafil: concurrent alpha-blockers initiated at lowest recommended dose
Second line ED therapies include vacuum erection devices, or penile injections with ______
Alprostadil
MOA of alprostadil for ED
prostaglandin E1 analog —Leads to increases in cAMP, decreases in iCa++, smooth muscle relaxation, and erection
AEs with alprostadil
Prolonged erection (priapism) — medical emergency; need to evacuate clogged blood because it can result in permanent corporal fibrosis and ED (can also occur with PDE-5 inhibitors but less common); tx is sympathomimmetic (phenylephrine) + aspiration
