Pharmacology ADME (IC15) Flashcards
Describe the absorption profile of Ethinyl Estradiol (EE)
Well absorbed orally, onset 30-60min, F~0.45
May be administered in transdermal patch, vaginal ring as well
Describe the distribution profile of Ethinyl Estradiol (EE)
Highly plasma protein bound, ~98%
Describe the metabolism of Ethinyl Estradiol (EE)
Metabolised in liver
Phase 1: hydroxylation by CYP3A4 (think DDI, FDI)
Phase 2: conjugation with glucuronide and sulfation into hormonally inert ethinylestradiol glucuronides and ethinylestradiol sulfate
*Enterohapatic recirculation of ethinylestradioll sulfate can enhance effect of EE
(liver => bile => SI => absorption by enterocyte and transport back to liver)
Describe the excretion profile of Ethinyl Estradiol (EE)
Excreted in feces and urine
What are some adverse effects of EE?
*Relate back to IC16, CI in IC16
- Breast tenderness
- Headache
- Fluid retention (bloating)
- Nausea
- Dizziness
- Weight gain
More severe:
- Breast cancer
- VTE
- MI/Stroke
- Liver damage
Describe the absorption profile of Norethindrone
Well absorbed orally, once a day
F~64%
Describe the distribution profile of Norethindrone
Highly plasma protein bound (e.g., albumin)
Describe the metabolism of Norethindrone
Metabolised in liver
Phase 1: Reduction
Phase 2: Glucuronidation and Sulfation
Some evidence suggest that norethindrone can be metabolised in the liver to EE - potential cardiovascular complications (VTE)
Describe the excretion of Norethindrone
Excreted in urine and feces
What are some adverse effects of Norethindrone?
*Relate back to IC16
- Headache
- Dizziness
- Bloating (more due to E)
- Weight gain
- Episodes of unpredictable spotting and bleeding (initially)
- Amenorrhea
Why is Norethindrone not recommended for women planning a pregnancy soon?
Ovulation suppression can persist for as long as 1.5y
Describe the in depth MOA of Tamsulosin (BPH)
Tamsulosin - reversible alpha-1 receptor antagonist
- Inhibits vasoconstriction induced by endogenous catecholamines (noradrenaline)
- Blocks alpha receptor on smooth muscle of prostate, prostatic urethra, bladder neck, lead to decrease muscle tone, relaxation of prostate smooth muscle and reduction in bladder obstruction, and improvement in urinary flow
Explain the selectivity of Tamsulosin
Selective for urinary a1A receptors predominantly found in prostate and LUT
Does not favour a1B receptors on blood vessels and heart
Describe the absorption profile of Tamsulosin
Well absorbed orally, 0.4mg once a day
Describe the distribution profile of Tamsulosin
Highly bound to plasma protein (90-99%)
Small Vd (0.2L/kg)
Describe the metabolism of Tamsulosin
Metabolized in liver by CYP3A4, CYP2D6
- watch out DDI, FDI
Describe the excretion of Tamsulosin
Excreted in urine
What drugs are contraindicated with Tamsulosin?
Other alpha-1 adrenergic antagonists
E.g.,
- Prazosin
- Epinephrine
=> Hypotension
Apart from decreasing prostate size (use in BPH), Finasteride (5ARI) can also cause _____
Increase hair growth (on scalp)
- may use 1mg daily for male pattern baldness or in hirsutism in women
*Thus, use in BPH, use in androgenic alopecia
*Dose in hair problems is 20% of that in BPH (1mg vs 5mg)
By reducing prostate size, Finasteride reduces _____
Finasteride reduces:
- progression of BPH
- the need for surgical procedure (TURP, prostatectomy)
Describe the absorption profile of Finasteride (5ARI)
Well absorbed orally 5mg daily
No dose adjustment required in renal insufficiency, liver failure, elderly patients
Describe the distribution profile of Finasteride (5ARI)
Highly plasma protein bound ~90%
Describe the metabolism of Finasteride (5ARI)
Metabolized by liver (e.g., CYP3A4)
Describe the excretion of Finasteride (5ARI)
50% unchanged drug excreted in feces
Metabolites excreted in urine and feces
Where is PDE5 enzyme highly expressed?
Highly expressed in the corpora cavernosa of the penis and its vasculature
Poorly expressed in the myocardium
Thus, has tissue specificity
Describe the absorption profile of Sildenafil (PDE5i)
Well absorbed orally 50mg daily
*Lower initial starting dose required for pt with renal failure, elderly >= 65yo, those taking alpha blockers, and those taking CYP3A4 inhibitors
Describe the distribution profile of Sildenafil (PDE5i)
Widely distributed, but can concentrate highly in penis
Describe the metabolism of Sildenafil (PDE5i)
CYP3A4 - major (*require lower dose with concurrent CYP3A4 inhibitor)
CYP2C9 - minor
Describe the excretion of Sildenafil (PDE5i)
Metabolites excreted in feces
