Block 5: BPH, ED, UI Med Chem Flashcards
Drugs used for BPH?
Reversal of urethral constriction via smooth muscle action: a1a-Adrenergic antagonist (sx tx)
Inhibitors of conversion of testosterone to DHT: 5a-reductase inhibitors (dx tx)
What drugs are for ED?
PDE-5 Inhibitors
Prostaglandin E1 (PGE1)
What drugs are used for urinary incontinence?
- Anticholinergics
* Darifenacin (Enablex)
* Oxybutynin (Ditropan)
* Tolterodine (Detrol) - b3-Adrenergic agonists
* Mirabegron (Myrbetriq) - Anti-diuretic hormone (ADH)
* Desmopressin (DDAVP)
MOA of selective a1 adrenergic antagonists?
Decrease smooth muscle contraction in prostate (a1a) and vasculature (a1b)
What are the selective a1 adrenergic antagonists?
- Prazosin
- Terazosin
- Doxazosin
- Tamsulosin
- Alfuzosin
- Silodosin (Rapaflo): exclusive for BPH
MOA of Inhibitors of 5a-reductase?
What are the isoforms of 5a reductase?
Type 1: skin and liver
Type 2: Reproductive tissues
What cause BPH?
DHT is a potent androgen that can cause prostate enlargement
How do the 5a reductase inhibitors differ from one another?
Finasteride (Proscar): 30X>selective for Type 2 5a-reductase
Dutasteride (Avodart): 10X> inhibitor of Type 2 5a-reductase
Both finasteride and dutasteride inhibit only Type 2 – thus DHT synthesis may continues to occur elsewhere and potential for continued prostate enlargement exists
What is the benefits of combo therapy for BPH?
Synergistic effect and lowering of dx progression
Describe the MOA of smooth muscle constration/relaxation?
cAMP and cGMP and relax muscle
What isoform is the focus in ED tx?
PDE5 inhibition
What was modified from Zaprinast to produce Sildenafil?
- Reduce lipophilicity and incr H2O solubility
- Add sulfonamide
- Mimic cGMP structure with the guanine structure
What is the endogenous substrate of PDE5?
cGMP
What is the first PO anti-impotence drug?
Sildenafil (Viagra)
What are the ADRs of Sildenafil?
Only >10-fold for PDE5 vs PDE6:
* PDE6 is in the retina altering color vision: bluish vision, making green and blue indistinguishable or vision loss
* Potentiates the action of nitrates used for angina -> hypotension, MI
What are the PDE5 inhibitors indicated for ED?
- Sildenafil (Viagra)
- Tadalafil (Cialis)
- Vardenafil (Levitra)
Advantages of vardenafill and tadalafil than sildenafil?
Vardenafil (Levitra):
* 30X more selective for PDE5 than sildenafil
* 10X more potent at PDE5 than sildenafil/tadalafil
Tadalafil (Cialis):
* 85X more selective for PDE5 than sildenafil
* Equipotent at PDE5 with sildenafil
Overall lower dosing = lower risk of ADRs
What does a lower IC50 number mean?
More potent, requiring less drug to reach action
What is the difference between selectivity and potency?
Selectivity: 1 drug, 2 targets
Potency: 2 drugs, 1 target
What is the function of PGE1?
Endogenous vasodilator: Used mainly in maintaining patent ductus arteriosis in peds until surgical fix can occur
Forms of PGE1 products?
CaverJet: injectable in corpus cavernosum of the penis
Muse: urethral suppositpory
PGE1 topical cream: Vitaros
What drug class is this?
Anti-muscarinic: acetylcholine and bulk
Selectivity of Oxybutynin?
M1-M3
Selectvity of Tolterodine?
M2-M3
Darifenacin
Brand
Enablex
Solifenacin
Brand
Vesicare
Oxybutynin
Brand
Ditropan
Tolterodine
Brand
Detrol
Mirabegron
Brand, Structure
Myrbetriq
b3-receptor: mimics epinephrine
Identify
Epinephrine
Identify
Ach
Identify
guanine
Where are Vasopressin receptors found? MOA?
V1 (peripheral)
V2 (renal)
Indications for vasopressin?
- central diabetes insipidus (desmopressin)
- vWb dx due to its ability to increase factor
What is DDAVP?
Analogue of vasopressin by altering Arg and deaminated Cys to form a more acidic and stable product (more PO F)
ADR of vasopressin?
HTN, fluid retention
5a reductase inhibitors mimics what endogenous substrate?
Testosterone
Anti muscarinics must mimic what endogenous substrate?
Ach
