PR3152 IC16 Flashcards
what is the mechanism of action of tamsulosin
block alpha adrenal receptors on smooth muscle of prostate, prostatic urethra, bladder neck
alpha adrenoreceptor antagonist
inhibits vasoconstriction induced by endogenous catecholamines
decrease muscle tone = relaxation of prostate smooth muscle / reduced tension
=
improvement in urodynamics: increases maximum urinary for rate from the decreased smooth muscle tension = decreased urinary obstruction
ULTIMATELY
= improve symptoms related to bladder instability e.g., urinary storage and voiding
selectivity of tamsulosin
affects a1A receptors (blood vessels and prostate) more than a1B (blood vessels and heart) receptors
absorption of tamsulosin (include dosing)
PO 0.4mg OD
well absorbed orally
distribution of tamsulosin?
protein binding and Vd?
highly protein bound >90%
small vd 0.2L/kg
metabolism of tamsulosin
enzyme and t1/2
cyp3a4 2d6
t1/2 - 10-15h
excretion of tamsulosin
~10% really excreted unchanged in urine
ADR of tamsulosin
abnormal ejaculation
backpain
contraindication of tamsulosin
concurrent admin with another a1 receptor antagonist like non selective prazosin
= may drastically decrease bp esp in patients w cvs issues
MOA of finasteride
5 alpha reductase inhibitor
bind to the 5 alpha reductase which is used to convert testosterone to DHT
= reducing the prostate size = improve flow and frequency of urinary retention.
counselling for finasteride
may take up to 6 months for clinical effects
test for PSA, should decrease with finasteride; ideally 1.5-1.
absorption of finasteride (include dose and F
PO 5mg OD
F = 0.65
no dose adjustment in renal or hepatic impairment
distribution of finasteride (protein binding and vd)
90% protein bound
poor apparent Vd
metabolism of finasteride (t1/2)
liver
e.g. 3a4.
t1/2 6hours
ADR of finasteride
gynaecomastia (raRE)
decreased libido/sexual potency
contraindications of finasteride
special population
women children and pregnancy
additional indication of finasteride (include dose)
1mg OD
also used in male pattern baldness and hirsutism in women
excretion of finasteride
50% excreted unchanged in faeces
metabolites = faeces and urine
MOA of sildenafil
during sexual stimulation, NO released that causes increase in cGMP. cGMP is converted to 5-GMP via PDE5
sildenafil is a PDE5 inhibitor that prevents conversion to 5GMP = increase cGMP = increase smooth muscle relaxation and blood flow to the corpora cavernosa = erection
special properties of PDE5
it is highly expressed by the corpora cavernosa in the penis compared to myocardium, allowing for tissue specificity
absorption of sildenafil
including dosing, ONSET, F, DOA
pO 5mg OD
onset: 30-60MIN
F = 0.4
duration of action max 12h
no dosage adjustment
metabolism of sildenafil include enzymes and t1/2
major 3a4
minor 2c9
t1/2 = 4 hours
distribution of sildenafil
widely distributed
excretion of sildenafil
metabolites: 80% by faces, 13% urine
unchanged: remaining via urine
adr of sildenafil
flushing
back pain
headache, dizzy
blur vision (blue green tinting from inhibition of retinal PDE5)
priapism
dyspepsia
contraindication of sildenafil
X admin with GTN = potentiate vasodilation effect of GTN via increased cGMP from concomitant blockade of degradation
= vasodilation and hypotension
special dosage instruction for sildenafil
for special populations
start lowest dose esp elderly >65
MOA of ethinyl estradiol
estrogen receptor agonist
synthetic estrogen
= decrease FSH release from anterior pituitary = decrease in development of follicle + make endometrium unsuitable for implantation
indication for ethinyl estradiol
menopausal symptoms
gynaecological disorders
certain hormone sensitive cancers
distribution of EE
98% protein bound (albumin)
absorption of EE (F, onset)
oral (can also be parenteral, topical, transdermal)
F = 0.4
onset 30-60min
excretion of EE
feces and urine
metabolism of EE including t1/2
liver
phase I: hydroxylation by cyp3a4
phase II: conjugation by glucuronidation and sulphation
note that EE sulphate can undergo enterohepatic recirculation
this increases t1/2 to 13-27 hours
ADR of EE
breast tenderness
VTE
MI stroke
liver damage
weight gain
fluid retention/bloating
nausea
dizziness
headache
contraindications of EE
X venous or arterial thrombosis
X breastfeeding (<21 days post partum)
X breast cancer
X advanced diabetes with vascular disease
X HTN >160/100
moa of norethindrone
synthetic progesterone
inhibit LH release = prevent ovulation and makes endometrium unsuitable for implantation
indications of norethindrone
endometriosis
menstrual disorders
absorption of norethindrone
OD
F = 0.64
distribution of norethindrone
highly plasma protein e.g., albumin bound
metabolism of norethindrone
include t1/2
Metabolized in liver by reduction follow by glucuronidation and sulfations
t1/2 = ~8h
some evidence of percentage of norethindrone metabolised in liver to EE
excretion of norethindrone
metabolites: 50% urine 40% feces
adr of norethindrone
headache
dizziness
fluid retention/bloating
weight gain
spotting episodes
amenorrhea
notes for norethindrone
ovulation suppression may be up to 1.5 years = counsel women planning pregnancy soon after cessation therapy
partial conversion to EE (risk factor for EE complications
