IC16 PK of male endocrine drugs Flashcards
tamsulosin drug type
Reversible α-1 receptor antagonist
tamsulosin MOA
- Reduces vasoconstriction induced by endogenous catecholamines
- Blocking of α-adrenoreceptors on smooth muscle of prostate, prostatic urethra & bladder neck → Relaxation of SM → increases max urinary flow rate ⇒ relieving obstruction
- Improves symptoms related to bladder instability & tension of SM of lower urinary tract
tamsulosin MOA
selectivity
Greater for α1A; better blockade for α1A (prostate & BV) than α1B (BV & heart) receptors
* Hence lesser effect of tamsulosin on BP & better for BPH
tamsulosin effects
benefits; time for improvement
- Effects on urinary stage & voiding symptoms maintained during long term therapy
Can hold & pass urine better ⇒ reduces pain - Delays need for surgery/ catheterisation
- Improvement in urinary flow rate after a few hours/ days after administration
tamsulosin PK
absorption
Well absorbed orally (take 0.4 mg OD)
tamsulosin PK
distribution
Highly bound to plasma protein (> 90%)
Not readily distributed to tissues ⇒ Small Vd (0.2L/ kg)
tamsulosin PK
metabolism
enzymes involved, t1/2
- By CYPs (ie: CYP3A4, CYP2D6)
Take note: do not take drug with grapefruit juice → affects liver enzymes - t1/2 ~ 20-25 hour ⇒ hence OD dosing
tamsulosin PK
excretion
~10% excreted unchanged in urine
* Requires dose adjustment for renal impairment
Metabolites more soluble in urine (~90%)
tamsulosin AE
Abnormal ejaculation
Back pain
tamsulosin c/i
Concurrent use of another α1 adrenoceptor antagonist (CVS patients)
finasteride drug type
5α-reductase inhibitor
finasteride MOA
- Competitive inhibition of 5α-reductase
No conversion of testosterone to DHT, esp in male genitalia - Hence decreases prostate size (with higher dose, 5mg)
Also increases hair growth (with lower dose, 1mg)
finasteride clinical effects
improved urine flow, reduces frequency of acute retention of urine & the need to surgical procedures
finasteride clinical treatment
time for effects, serum prostate-specific Ag
May take up to 6 months to see clinical effects after initiating treatment
Serum prostate-specific Ag levels decreases with finasteride
finasteride PK
absorption
F
Well absorbed orally (5 mg OD)
F ~ 0.65
finasteride PK
distribution
Vd
High plasma protein bound (~90%) ⇒ Small Vd
finasteride PK
metabolism
t1/2
By liver (CYP3A4)
t1/2 ~ 6 hr
finasteride PK
excretion
50% unchanged in faeces
metabolites in urine & faces
finasteride dose adjustments
Not required for liver failure, renal insufficiency & elderly patients
finasteride AE
Loss of libido & sexual potency
Gynaecomastia (rare)
finasteride c/i
Women & children; pregnancy
sildenafil: drug type
PDE5 inhibitor
sildenafil: MOA
- Inhibits phosphodiesterase type-5 (PDE5) in penis
- No conversion of cGMP to 5’GMP
Outcomes
(4) Increases cGMP levels in response to NO-release by sexual stimulation
(5) causes SM relaxation
(6) increased BF to corpora cavernosa
(7) erection
sildenafil: MOA
specificity of drug
expression of PDE5
PDE5 highly expressed in Corpora cavernosa of penis & vasculature; poorly in myocardium ⇒ tissue specificity to compound
sildenafil: initiation of dose
Ideally lowest recommended dose possible, especially for >65 years old
sildenafil: PK
distribution
Widely distributed ⇒ large Vd
sildenafil: PK
absorption
onset, F, duration of action
- well absorbed orally (5mg OD)
- Onset: 30-60 mins
- F ~0.4
- Duration of action (max): ~12 hours
sildenafil: PK
metabolism
t1/2
By liver: CYP3A4 (major), CYP2C9 (minor)
t1/2 ~4 hours
sildenafil: PK
excretion
Metabolites largely excreted in faeces (80%) & lesser in urine (13%)
Remaining unchanged in urine
sildenafil: dose adjustment requirments
Not required for liver failure, renal insufficiency & elderly patients
sildenafil: AE
- Headache, dizziness, flushing, dyspepsia
- Blur vision → blue-green tinting of vision (due to blockage of retinal PDE6)
- Priapism (similar feeling to BPH)
sildenafil: c/i
Cardiac patients on GTN (generates NO; accumulates cGMP)
* Potentiates vasodilation effect on GTN due to increased cGMP; due to concomitant blockade of cGMP degradation by sildenafil
* Have potential marked vasodilation & hypotension