Pharmacology Flashcards
what does SERMs stand for, can you name three SERMS
SERMS = selective oestrogen receptor modulators
e.g. tamoxifen, raloxifene, clomiphene
in general how do SERMs work
SERMS work to target oestrogen receptors - they can have agonist or antagonist effects on the oestrogen receptors
what is the primary licence for tamoxifen
Treatment of breast cancer
what is another secondary indication for tamoxifen other than Rx of breast cancer
anovulatory induction
describe tamoxifen MOA in breast tissue
Tamoxifen is an ER antagonist in breast tissue however it is an agonist in the endometrial ER receptors, bone and lipids
what are the risks associated with tamoxifen
increase VTE risk, increase thickness of endometrial lining (agonist here) - increased risk of endometrial cancer
are any SERMs in the UK licences for Rx of postmenopausal symptoms
no
what is raloxifene liscenced indication
treatment of osteoporosis in PMW but not considered first line
How does raloxifene work to treat osteoporosis
ER agonist in bone - prevents bone resorption by osteoclasts
what is the liscenced indication for clomiphene
Induction of ovulation
where does clomiphene work to increase gonadotrophin release
directly on the hypothalamus
what are the known risks associated with using clomiphene for treatment of infertility
multiple gestations
after 12 cycles or more increases risk of ovarian cancer
ovarian cysts
hot flushes
Clomiphene, raloxifene and tamoxifen all increase the risk of VTE
True or false
False - clomiphene is not a/s with any increased risk of VTE
Tamoxifen and raloxifene both increase risk of VTE
SERMs work to improve postmenopausal symptoms
true or false
false - can actually worsen them
specifically tamoxifen and clomiphene commonly worsen hot flushes, not sure about raloxifene
what effect does tamoxifen and raloxifene have on cholesterol
decreases total cholesterol and LDL, no effect on HDL
what class of medication should be avoided in women on SERM
SSRIs - specifically avoid paroexteine with tamoxifen
SSRIs can reduce the effectiveness of SERMs
can you list the classes of antibiotics that are bactericidal
Penicillins & cephalosporins are very cidal for real microbes
Penicillins
cephalopsporins
Aminoglycosides
Vancomycin
Cephalosporins
Fluroquinolones
Rifampicin
Metronidazole
can you name the antibiotics which are bacteriostatic (i.e. halt the growth of the bacteria but don’t kill them)
trimethoprim
macrolides
chloramphenicol
tetracyclines
clindamycin
linezolid
what is the best choice antidepressant in postpartum women BF
sertraline
(but ultimately choice of anti-depressant PP will be determined by which drug they have been on during pregnancy)
which class of anti-depressants is best to avoid during pregnancy and pp period and why?
TCA due to risk associated with OD
is warfarin considered safe when breastfeeding
yes - switch to warfarin usually around day 5 PP purely to reduce risk of PMH
which anticoagulants out of the following list are considered safe when BF
- warfarin
LMWH
DOACs
LMWH and warfarin are considered safe whilst BF
not enough evidence on DOACs so advised to avoid/ not use first line
which antihypertensives are safe to use in BF women
enalapril
labetalol
nifedipine (and other CCB e.g amlodipine)
which classes of antihypertensive drugs are best avoided in breastfeeding women
diuretics and ARBs (angiotensin receptor blockers) other ace-inhibitors except for enalapril
what dosing schedule is preferred for women using antihypertensives when BF
OD
BD
TDS
QDS
OD
out of the following anti-hypertensives which are considered safe when breastfeeding?
- Sodium Valporate
-Phenobarbital
-Lamotrogine - Keppra
-Primodone
sodium valproate (unlike in pregnancy), lamotrigine and keppra all safe
in terms of EC what would your advice be to a breast feeding woman in terms of taking UPA (ella one)
would need to discard milk for 1 week following taking UPA (express and discard)
whereas for levonorgestrel no need to do this
Cu-IUD also fine but would need to check >4 weeks pp
Which analgesia is it best to avoid in BF women
codeine due to risk of bradycardia, apnoea and cyanosis
which analgesia are considered safe for BF women
paracetamol, ibuprofen and dihydrocodeine
what enzyme metabolises codeine
CP450 - 2D6 (CYP2D6)
What condition is aspirin associated with causing in children
Reye’s syndrome
For how long in the neonatal period should nitrofurantoin be avoided for and why
avoid using in the first 8 days of life due to risk of haemolysis, avoid altogether in people with G6PD deficiency
mifepristone works in termination of pregnancy by:
A) prostaglandin e1 receptor agonist
B) inhibin receptors agonist on the smooth muscle to cause urterine contractions
C) progesterone receptor agonist
D)progesterone receptor antagonist
D - mifepristone works by blocking progesterone receptors i.e. it is an antagonist
This decreases progesterone. Progesterone is responsible for maintaining the lining of the endometrium for pregnancy and also desensitises the body to prostaglandin. without progesterone there is increased prostaglandin that causes disruption of the endometrium and uterine bleeding
mifepristone would be contra-indicated in patients with which medical conditions
long term steroids, adrenal insufficiency
severe asthma on steroids
mifepristone belongs to what class of medications
A) alpha blocker
B) glucorticoid receptor antagonist
C) prostaglandin E1 receptor agonist
D) progesterone receptor agonist
b
mifepristone is a progesterone and glucocorticoid receptor antagonist
misoprostol belongs to what class of medications
A) alpha blocker
B) glucorticoid receptor antagonist
C) prostaglandin E1 receptor agonist
D) progesterone receptor agonist
C - prostaglandin E1 receptor agonist
(misoPROSTol = PROSTaglandin)
can you explain how misoprostol works to cause termination of pregnancy or expulsion of RPOC/incomplete miscarriage
misoprostol is a prostglandin E1 receptor agonist. It binds to prostaglandin receptors on the smooth muscle of the uterus and this leads to uterine contractions.
In the cervix it helps to prime the cervix by decreasing the collagen in the cervical stroma and decreased cervical tone from increased amplitude and frequency of contractions
how does misoprostol work to cause cervical ripening
In the cervix it helps to prime the cervix by decreasing the collagen in the cervical stroma and decreased cervical tone from increased amplitude and frequency of contractions
how long after a patient stops acretin should they wait before conceiving
1 month
1 year
2 years
3 years
2 years!
how long after a patient stops isotretinoin or aitretinoin should they wait before trying to conceive
1 month
1 year
2 years
3 years
1 month
how long after a patient receives methotrexate for medical management of ectopic pregnancy should they wait before trying to conceive?
1 month
3 months
6 months
1 year
3 months
what is the success rate for methotrexate in the treatment of ectopic pregnancies
80%
85%
90%
95%
95%
what class of medications does methotrexate to treat ectopic pregnancies
Folic acid agonist
folic acid antagonist
progesterone receptor agonist
progesterone receptor antagonist
folic acid antagonist
what is the main mechanism of action for methotrexate when used for treatment of ectopic pregnancies
A) inhibits meiosis
B) inhibits apoptosis
C) inhibits dna synthesis
D) inhibits RNA synthesis
C - inhibits DNA synthesis
what is the name of the enzyme that methotrexate inhibits
A) cGMP
B) dihydrofolate reductase
C) aromatase
D) dihydrofolate oxidase
B - dihydrofolate reductase
dihydrofolate reductase is an enzyme essential for purine production, DNA synthesis and cell replication. Any cell lacking this weill be effected. trophoblasts are rapidly dividing by mitosis and so this process is inhibited and leads to cell death.
what enzyme converts aciclovir into aciclovir monophosphate
A) granulate kinase
B) thymidine kinase
C) CK
D) Adenosine kinase
B - thymidine kinase
in patients with aciclovir resistance where are mutations commonly found
A) granulate kinase
B) thymidine kinase
C) CK
D) Adenosine kinase
B - thymidine kinase
what is the end metabolite of aciclovir that works to inhibit DNA synthesis
A) aciclovir monophosphate
B) aciclovir triphosphate
C) aciclovir diphosphate
B - aciclovir triphosphate
what class of drug is aciclovir
nucleotide analogue
when performing a pudenal nerve block what anatomical bony landmark should you first identify when performing PV examination
ischial spine
what ligament runs 1cm medial and posterior to the ischial spine that you want to try and identify when performing a pudenal nerve block
sacrospinous ligament
once you puncture the sacrospinous ligament and continue to advance your needle you will feel resistance. This is the point where you should aspirate and inject your LA when performing a pudendal nerve block. What artery could you infiltrate if you fail to aspirate
pudendal artery
What is the location of the pudendal vessels in relation to the pudendal nerve at the point when you are injecting LA if you have punctured the sacrospinous ligament advanced your needle and felt resistance?
artery lies medial to the pudendal vein
you are consenting a patient during second stage of labour for a pudendal block. can you name three complications you should inform her about
haematoma
puncture of the rectum
LA toxicity/anaphylaxis
trauma to the sciatic nerve
where does phase 1 metabolism of first pass metabolism occur?
A) smooth endoplasmic reticulum of the liver
B) smooth endoplasmic reticulum of the intestines
C) cytoplasm of the liver hepatocytes
D) cytoplasm of the intestines
A - smooth endoplasmic reticulum of the liver hepatocytes
what reactions occur in phase 1 of first pass metabolism
A) oxidation
B) conjugation
C) reduction
phase 1 involves oxidation and reduction
what reactions occur in phase 2 of first pass metabolism
A) oxidation
B) conjugation
C) reduction
B - conjugation
what is the aim of first pass metabolism
to change a lipophilic drug into a hydrophilic drug that is more easily excreted
Which of the following drug routes undergoes first pass metabolism
A) IV drugs
B) oral drugs
C) transdermal drugs
D) rectal drugs
B and D - both undergoe first pass metabolism
Which of the following drug routes do not undergoe first pass metabolism
A) IV drugs
B) oral drugs
C) transdermal drugs
D) rectal drugs
C - transdermal and and A - IV route
what are the names of the three forms of oestrogen a female body can produce
- 17 beta estradiol
- Estrone
- Estriol
which type of oestrogen do we make during reproductive years
- 17B estradiol
- Estrone
- Estriol
- 17 beta estradiol
which type of oestrogen do we produce when pregnant?
- 17B estradiol
- Estrone
- Estriol
- Estriol (E3) - produced by the placenta
which type of oestrogen do we produce once we are post-menopausal
- 17B estradiol
- Estrone
- Estriol
- Estrone (e1)
can you list the oestrogens in order of their strength, starting with most potent to the least potent
Estrone
17B estradiol
Estriol
- 17 b estradiol (most potent)
- Estrone (10 times less potent than estradiol)
- Estriol ( 100 times less potent than estradiol)
what type of oestrogen is most commonly used in HRT
1.estradiol
2. Estrone
3. Estriol
4. ethinyl estradiol
- estradiol ( as it resembles the closest form of natural oestrogen)
synthetic estradiol used in HRT is converted into what type of oestrogen by the liver
estrone
why is the risk of VTE higher with oral estrogens compared to oestrogens delivered transdermally
oral oestrogens have to undergo first pass metabolism. When they pass through the liver it activates the clotting cascade, whereas transdermal preparations avoid first pass metabolism and so won’t activate clotting cascade
what type of oestrogen does the human fetal liver produce
- 17B estradiol
- Estrone
- Estriol
- estetrol
- Estetrol
if concerned about anti-cholinergic effects in someone diagnosed with OAB which of the following drugs should you choose as treatment?
A) solifenacin
B) mirabegron
C) tolterodine
D) oxybutynin
b - mirabegron - is a B3 agonist (improves parasympathetic activity by increasing relaxation of the bladder and detrusor muscle)
out of the following list which is the most selective anti-cholinergic
A) solifenacin
B) mirabegron
C) tolterodine
D) oxybutynin
A - solifenacin (m3 receptor antagonist)
which is the least selective anti-cholingeric out of the following list
A) solifenacin
B) mirabegron
C) tolterodine
D) oxybutynin
c - tolterodine (non selective)
what receptors does oxybutynin exert its action on
M1 and M3 receptors in the SM
what is the purpose of the extra ethinyl group on EE
the 17 alpha ethinyl group prevents oxidation of the c17Beta position of EE by 17 Beta HSD.
therefore EE is not converted to estrone and has higher oestrogen effects at target tissues
what is estradiol metabolised into by the liver
estrone
what enzyme is responsible for metabolising estradiol to estrone
17 beta HSD (hydroxysteroid dehydrogenase)
what happens to SHBG levels in a patient on COCP
SHBG increases and therefore less free testosterone so anti-androgenic effects
what happens to LH secretions on someone on the COCP
decrease LH therefore decrease testosterone production
what dose of hormone is contained in the implant (nexplanon)
68 mg etonogestrel (metabolite of desogestrel)
what is the release rate of etonogestrel per day in the implant at week 5-6
60-70 ug (mcg)/ day in week 5-6
what is the release rate of etonogestrel per day in the implant in
A) year 1
B) year 2
c) year 3
a - year 1 - 35-45ug (mcg/day)
b) year 2- 30-40ug (mcg/day)
c) year 3 - 25-30ug (mcg/day)
what are the two hormones and their respective doses contained in the CHC patch
EE 33.9 mcg + nolgestromin 203 mcg
what are the two hormones and their respective doses contained in the CHC ring
EE 15mcg + etonogestrel 120mcg
what is the fetal mortality rate of women with mechanical heart valves
1 in 2
1in 3
1in 5
1 in 10
1 in 3
if warfarin is used during pregnancy what is the risk of the baby developing fetal warfarin syndrome
10%
20%
30%
50%
30%
what is the most critical time period for the fetus if mum is taking warfarin
6-12 weeks
what are some of the signs of fetal warfarin encephalopathy
stippled epiphyses
nasal hypoplasia
short limbs and digits
what number of units of alcohol if drunk continuously is associated with fetal alcohol syndrome
> 5 units/day chronic usage
are statins teratogenic?
yes - should be stopped 3 months prior to conception
is retinoid acid safe in pregnancy
no teratogenic - contains vitamin A - ear malformations
when should ARBs (candesartan, losartan and valsartan) and ace-inhibitors e.g. ramipril be avoided in pregnancy
avoid in second and third trimester
which drug if used for hyperthyroidism should be avoided in pregnancy
carbimazole can cause chonal atresia, GI abnormalities and abdominal wall defects
PTU is safe
MOA of penicillins and cephalosporins
inhibit pepitidoglycoan in cross links in cell walls
MOA of macrolide
inhibit pepitdylotransfer, bind to 50s ribosomal unit
MOA of tetracyclines
bind to 30s ribosomal unit
MOA of quinolones
inhibit DNA gyrase
MOA of trimethoprim and sulfonamides
Dihydrofolate reductase inhibitor
MOA nitrofurantoin
inhibits citric acid cycle , damages bacterial DNA via multiple reactive intermediaries
MOA of metronidazole and tinidazole
inhibit nucleic acid synthesis in the cell wall
MOA aminoglycosides
bind to 30s ribosomal unit
regarding COCP mechanism of action, where in the HPO axis does progestogen act
- progestogen acts on the hypothalamus to inhibit GnRH pulses
- pituitary to inhibit the oestrogen induced LH surge
where does oestrogen act on the HPO axis in COCP to prevent ovulation
oestrogen decreases the pituitary response to GnRH and in the follicular phase inhibits the FSH surge
How does the depo inhibit ovulation
slows down the GnRH pulse generator which prevents the LH surge required for ovulation
how does CHC increase risk of VTE
decreases antithrombin III and plasminogen activator therefore increased platelet activation ==> increased VTE
