Pharmacology Flashcards
What do strong opioids act as?
Mu receptors agonists
What do weak opioids act as?
Mu, delta or kappa receptor agonists
What are the features of warfarin embryopathy?
Hypoplasia of nasal bridge Congenital heart defects Ventriculomegaly Agenesis of the corpus callosum Stippled epiphyses
What proportion of exposed fetuses develop warfarin embryopathy?
5%
At what gestation may warfarin embryopathy occur?
6-12 weeks
How does warfarin work?
Inhibits vitamin K dependent clotting factors - 10,9,7,2
Is warfarin safe to use in breastfeeding?
Yes
What should warfarin be switched for during pregnancy?
LMWH
What are the 2 most common dihydrofolate reductase (DHFR) inhibitors?
1) Methotrexate
2) Trimethoprim
What is the max dose of lidocaine?
3mg/kg (7mg/kg with adrenaline)
What is the lidocaine conversion?
1% lidocaine =1g/100mL or 10mg/mL
What is the half-life of lidocaine?
2 hours
What is the mechanism of action of lidocaine?
Blocks fast voltage gated sodium channels
What are the 2 different antenatal steroid courses available?
Betamethasone 12 mg IM x 2 doses or
Dexamethasone 6 mg IM x 4 doses
How many x more potent is fentanyl than morphine?
x80-100
What are the adverse effects of ACEi/ARBs on a fetus?
1) Congenital Malformations
2) Renal dysgenesis
3) Oligohydramnios as a result of fetal oliguria
4) Pulmonary hypoplasia
5) IUGR
6) Neonatal anuric renal failure
What are the adverse effects of carbimazole on a fetus?
1) Choanal atresia
2) GIT defects
3) Omphalocoele
4) Aplasia cutis
What is the mode of action of cyclizine?
Histamine H1-receptor antagonist
What is the mode of action of promethazine?
Histamine H1-receptor antagonist
What is the mode of action of ondansetron?
Serotonin 5-HT3 receptor antagonist
What is the mode of action of prochlorperazine?
Dopamine D2 receptor antagonist
What is the mode of action of metoclopramide?
Dopamine D2 receptor antagonist
5-HT3 receptor antagonist
5-HT4 receptor agonist
In whom would you not consider metoclopramide in pregnancy and why?
In those <20 years old due to the risk of oculogyric crisis
When may warfarin be restarted after delivery?
5-7 days after - although it is safe in breastfeeding the delay is due to to the risk of PPH
What are the phase 1 reactions of drug metabolism?
Oxidation, reduction or hydrolysis —> leading to products being more reactive
What are the phase 2 reactions of drug metabolism?
Conjugation —> leading to inactivation of a drug
In those at risk of VTE, when should LMWH be started?
In the first trimester
How does heparin prevent coagulation?
Inactivation of antithrombin III
What are the S/Es of heparin?
1) Bleeding
2) Thombocytopenia
3) Hypoaldosteronism
4) Osteoporosis
What is the most common inherited haemostatic disorder?
Von Willebrand’s
What blood test profile represents Von Willebrand’s
PT = unaffected
APTT = prolonged
Bleeding time = prolonged
Plt count = unaffected
Which Abx damage the 8th cranial nerve in the fetus and are ototoxic?
The aminoglycosides - e.g. gentamicin and streptomicin
Which Abx can cause neonatal haemolysis?
Both sulphonamides and trimethoprim (an co-trimoxazole which is a combination of the two)
Which local anaesthetic(s) are amide?
Lidocaine
Which local anaesthetic(s) are ester?
Benzocaine; procaine; tetracaine
Which anti-hypertensive is an alpha-2-agonist?
Methyldopa
What is the half life of warfarin?
40 hours
How long does it take for warfarin to reach its full effect?
3 days
How does tranexamic acid work?
Inhibits the activation of plasminogen
Maternal use of metronidazole during breastfeeding is associated with what in the infant?
Diarrhoea
Over what period after administration are corticosteroids most effective in reducing respiratory distress if delivery occurs?
24 hours - 7 days
Through which mechanism of action and which receptor does cabergonline suppress lactation?
Agonist at D2 receptor
What is the mechanism of action of clomifene?
Blocks oestrogen receptors in the hypothalamus, increasing FSH pulse frequency
What is the mechanism of action of mifepristone?
Progesterone antagonist
What type of drug is misoprostal?
Synthetic prostaglandin
What is the main estrogenic component of the combined oral contraceptive pill?
Ethinylestradiol
What class of drug is ulipristal acetate?
Selective progesterone receptor modulator
What is the mechanism of action of hydralazine?
Direct smooth muscle relaxant
Which enzyme is blocked by acetazolamide?
Carbonic anhydrase
What is the total extra iron requirement in pregnancy?
1000mg
What is the major constituent of pulmonary surfactant?
Dipalmitoylphosphatidylcholine
What are the S/Es of labetolol?
IUGR, with prolonged use
What are the S/Es of methyldopa?
1) Rebound HTN
2) Depressed mood
3) Flattened CTG variability
4) Hepatitis
What type of drug is nifedipine?
Dihydropyridine - it blocks inwards flux of calcium through voltage gated channels
What are the S/Es of nifedipine?
1) Acute hypotension
2) Peripheral oedema
3) Headache and flushing
What are the affects of ACEi’s in pregnancy?
1) Congential malformations, esp. to CVS
2) Skull defect
3) Oligohydramnios
What is the first line tocolytic?
Nifedipine
What is the 2nd line tocolytic?
Atosiban
What type of drug is atosiban?
Oxytocin antagonist
What drug may be given prior to ECV?
Terbutaline can increase procedural success in primips. It is a one-off dose and can cause S/Es of transient maternal tachycardia and tremor
Women at risk of pre-eclampsia and should be offered aspirin 75mg are:
- HTN disease during pregnancy
- CKD
- Autoimmune disease e.g. SLE
- T1DM or T2DM
- Chronic HTN
What are the S/E of nitrous oxide?
Nausea
What are the S/Es of IM pethidine?
N+V
Narcosis
Respiratory depression in the neonate if given within 2 hours of delivery
In whom should carboprost be avoided?
Caution in HTN, avoided in asthma
In whom should ergometrine be avoided?
HTN
What are the potential side effects of epidural?
1) Hypotension
2) Loss of mobility
3) Higher chance of assisted delivery
4) Complications associated with insertion, e.g. dural tap, haematoma, high blockade
What may be used as an anti-emetic in resistant cases of HG where everything else have been tried?
Corticosteroids
Why is heartburn more common in pregnancy?
The action of progesterone on the lower oesophageal sphincter causes it to have reduced tone.
What is the mechanism of action of mefenamic acid?
Prostaglandin production inhibitor
By how much may mefenamic acid reduce bleeding?
30%
What is the mechanism of action of tranexamic acid?
Anti-fibrinolytic - blocks conversion of plasminogen to plasmin, reducing fibrinolysis
By how much may tranexamic acid reduced blood loss?
40-50%
What drugs may be used to reduce detrusor over-activity (urge incontinence)?
Tolterodine and oxybutynin - both are muscarinic antagonists on M3
What drug might be used in stress incontinence?
Duloxetine - it increases urinary sphincter tone, SNRI action
What are the different classes of cytotoxic agents?
1) Antimetabolites
2) Alkylating agents
3) Intercalating agents
4) Anti-tumour antibiotics
5) Drugs directed against spindle microtubules, inhibiting mitosis
What are examples of antimetabolites?
5-FU, methotrexate
What is an example of alkylating agents?
Cyclophosphamide
What are examples of intercalating agents?
Cisplatin, carboplatin
What are examples of anti-tumour antibiotics?
Bleomycin, doxorubicin
What are examples of drugs directed against spindle microtubules, inhibiting mitosis?
Vincristine
What is the mechanism of action of antimetabolites?
Interfere with DNA and RNA synthesis
What is the mechanism of action of alkylating agents?
Form covalent bonds in DNA
What is the mechanism of action of intercalating agents?
Bind to DNA and so inhibit replication
What is the mechanism of action of anti-tumour antibiotics?
Lead to inhibition of DNA synthesis
What are the side effects of chemo?
- Bone marrow suppression - cellular nadir tends to occur at approx. 7-14 days
- N&V
- Mucositis - ulcers to mucous membranes, particularly oral, esp. with methotrexate
- Diarrhoea - usually transient
- Alopecia
- Tinnitus - associated with cisplatin
- Peripheral neuropathy
- Lethargy
- Anorexia
What chemo regimes are used in ovarian cancer?
Platinum-based regimes - carboplatin +/- paclitaxel
What chemo regimes are used in endometrial cancer?
More limited role, usually reserved for metastatic disease
Caroplatin +/- paclitaxel, or doxorubicin and cisplatin
What chemo regimes are used in cervical cancer?
Cisplatin + radiotherapy
What chemo regime is used in vulval cancer?
%-FU +/- cisplatin in combination with radiotherapy for those unfit for surgery/symptoms control in metastatic disease
What is the most potent oestrogen in the reproductive years?
Estradiol, followed by estrone
What is the most potent oestrogen in the menopause?
Estrone
What are the two types of oestrogen receptor?
Alpha and beta
Where are alpha oestrogen receptors found?
Endometrium; bone; breast cancer cells; ovarian stroma cells; hypothalamus
Where are beta oestrogen receptors found?
Kidney; brain; bone; heart; lungs; intestinal mucosa; prostate; endothelial cells
Which receptor is the chief mediator of oestrogen on bone?
Alpha
How is oestrogen metabolised?
Primarily in the liver, by conjugation and hydroxylation
Conjugation = catalysed by glucuronyl transferases and sulphontransferases
Hydroxylation = catalysed by cytochrome P450
What will suppress hepatic SHBG production?
Androgens Insulin Corticoids Progestogens GH
What type of drug is clomifene?
Selective oestrogen receptor modulator
What is an alternative to NSAIDs/progesterone’s/COCP/anti-fibrinolytic in reducing menstrual blood loss?
Danazol - isoxazole derivative of ethinyl testosterone - however androgen-like effects tend to be unacceptable to pts.
What is tibolone?
A synthetic steroid that has estrogenic, progestogenic and androgenic properties - it causes endometrial atrophy and so no withdrawal bleed, therefore an alternative to combined continuous HRT, can relieve menopausal symptoms and prevent bone loss
What is meant by bioavailability?
The proportion of drug that reaches the circulation unchanged - IV drugs therefore have 100% bioavailability
What is meant by volume of distribution?
Theoretical volume of water in which the amount of drug would need to be uniformly distributed to produce an observed blood concentration
What molecular weight must a drug be in order to be excreted by bile (and into faeces)?
> /= 300 Da
What are the effects of enzyme inducers?
Result in increased activity of cytochrome p450 enzyme, and therefore lower levels of the drug
What are some examples of enzyme inducers?
‘CRAPS’
Carbemazepine Rifampicin A - bArbiturates Phenytoin St John's Wort
What are the effects of enzyme inhibitors?
Inhibit hepatic metabolisms resulting in increased plasma levels of the drug, increasing the risk of toxicity and side effects
What are some examples of enzyme inhibitors?
'Some Certain Silly Compounds Annoyingly Inhibit Enzymes, Grrrr' Sodium valproate Cimetidine Sulphonamides Ciprofloxacin Antifungals/amiodarone Isoniazid Erythromycin/clary Grapefruit juice
Which drugs do not cross the placenta?
Insulin
Heparin - LMWH or unfractionated
When would a drug insult occur to cause limb reduction defects?
12-40 days
When would a drug insult occur to cause anencephaly?
24 days
When would a drug insult occur to cause transposition of the great vessels?
34 days
When would a drug insult occur to cause cleft lip?
36 days
When would a drug insult occur to cause VSD, syndactyly?
42 days
When would a drug insult occur to cause hypospadias?
84 days
Which drugs are teratogenic?
'All the A's' 1. AEDs 2, Abx 3. Anticoagulants 4. Antimetabolites 5. Antipsychotics 6. Acne drugs 7. Androgens 8. Alcohol
Which drugs are contraindicated in breastfeeding?
COCP - reduced milk Theophylline - irritability Aspirin - Reyes syndrome Sedatives Lithium Amiodarone Certain Abx - e.g. chloramphenicol can cause grey baby syndrome Cytotoxics
Which AED can cause hirsutism?
Phenytoin
What is the mechanism of action of cabergoline?
Dopamine receptor D2 agonist
What is phase 4 of the human drug trials?
Post-marketing surveillance
What are the drugs that can cause abortion - using acronym MET?
M - misoprostal
E - ergotamine
T - thrombolytics
When does neonatal narcotics abstinence syndrome usually present?
Within 48 hours of delivery
Why may neonatal narcotics abstinence syndrome present beyond 48 hours after delivery?
It may occur up to 4/52 after delivery because methadone can be stored in the neonatal liver, lung and spleen
What are the fetal affects of cocaine?
- FGR
- Fetal death
- Placental abruption
What are the features of fetal alcohol syndrome?
Growth - LBW
Craniofacial abnormalities - flat philtrum
CNS abnormalities - microcephaly, agenesis of the corpus callosum, cerebellar hypoplasia
Neurodevelopmental - epilepsy, hearing loss, cognitive deficit
What are the different groups of penicillins?
- Beta-lactams
- Beta-lactamase resistant
- Broad-spectrum penicillins
- Antipseudomonal penicillins
- Mecillinams
What type of drug is oseltamivir?
Neuraminidase inhibitor
What are the side effects of HAART?
- Lactic acidosis
- Hyperglycaemia
- Hepatitis
- Pancreatitis
- Peripheral neuropathy
What is the HIV therapy regime used if a woman is not taking antiretrovirals at time of pregnancy?
START (short-term anti-retroviral therapy) - a HAART regime starting between weeks 20 and 28 and being discontinued shortly after delivery
Which anti-malarial chemo-prophylaxis is safe to use in pregnancy?
Malarone
Mefloquine
What would be the choices for malarial treatment in pregnancy in the UK?
Quinine
Artesunate
How is oxytocin excreted?
Bile
Urine
What is the half-life of misoprostal?
40 mins
What are the side effects of misoprostal?
Uterine rupture Uterine hyperstimulation Amniotic fluid embolism Diarrhoea Vomiting Headache
Which prostaglandin is used in PPH and termination of pregnancy?
Prostaglandin E1
Which receptors do ergometrine work on?
5HT1
Dopamine
alpha-adrenergic
What are the contraindications to atosiban?
Pre-eclampsia Intrauterine death Intrauterine infection APH Premature ROM after 30 weeks
Is nifedipine licensed in pregnancy?
No
What is the dual mechanism of action of methyldopa?
- Centrally acting alpha-2-agonist
2. Competitive inhibitor of DOPA decarboxylase
Aside from IUGR, what is a side effect of labetalol?
Neonatal hypoglycaemia
What is the mechanism of action of labetalol?
Mixed alpha-1-beta blocker
What is the effect of thiazide diuretics in pregnancy?
Neonatal thrombocytopneia
What is the effect of statin in pregnancy?
CNS and limb defects
How much does AED use increase the risk of teratogenicity in pregnancy?
x3
What are the symptoms of neonatal BZD withdrawal syndrome?
- Hypotonia
- Reluctance to suckle
- Cyanosis
- Impaired metabolic response to cold stress
Is warfarin embryopathy dose-dependant?
Yes
What is the antidote to unfractionated heparin?
Protamine sulphate
What can PPIs cause in pregnancy?
Anencepahly
What can antacids in pregnancy cause?
Milk-alkali syndrome
Where dose loperamide act?
Opioid receptors of the large bowel
What is the affect of NSAIDs?
Inhibits prostaglandin synthesis by inhibiting COX1 and COX2
What are the side effects if 5-ASAs used in pregnancy in mother’s with UC/Crohn’s
Agranulocytosis
Hypospermia
Why is PTU preferred over carbimazole in pregnancy?
Lower placental transfer and excretion in breast milk
What are the uses of mifepristone?
- EC - delays ovulation and prevents implantation
2. TOP (600mg) - up to 9/40
What are the contraindications of mifepristone?
- Severe asthma
- Chronic renal failure
- Ectopic
- Acute porphyria
- Hepatic impairment
What is the most effective form of contraception, and its pearl index?
Implanon at PI <0.1
When can a COCP be used in breastfeeding vs. non-breastfeeding women?
Breastfeeding = >6 weeks post-partum ( but can reduce breast milk output) Non-breastfeeding = >3 weeks post-partum
What are the differences in dosing between high, standard and low strength oestrogen with regard to COCP?
Low = 20 micrograms Standard = 30-35 grams High = 50 micrograms
Describe first generation COCPs:
High strength oestrogen 50 micrograms
Describe second generation COCPs:
Standard strength oestrogen 30-35 micrograms
Describe third generation COCPs:
Contain new-type progesterones
What are the risks of new-type progesterones used in third generation COCPs?
Increased VTE risk
What are the advantages of new-type progesterones used in third generation COCPs?
Reduced acne, weight gain, breast symptoms, headache and breakthrough bleeding
What are the first and second generation progesterones?
Levonorgestrel
Norethisterone
What are the third generation progesterones?
Desoegestrel
Gestodene
What are the missed pill rules in COCP?
If missed <3 (2 in low-strength oestrogen COCP) - take missed pill, no need for extra precautions
If missed >3 pills (2 in low-strength oestrogen COCP) - take missed pill, extra-precautions for 7 days, if in 3rd week, omit pill-free week, if in 1st week, use EC
By how much is the risk of endometrial and ovarian cancer risk reduced by COCP?
Endometrial - 50% reduced risk, and remains reduced for >20 years after stopping COCP
Ovarian - 40-80% reduced risk in a >10 year user
Which cancers do COCP increase the risk of?
Breast and cervical cancer
What are the missed pill rules with POP?
Take missed or late pill (>3 hours with all POPs except cerazette when only late if >12hours delay), extra pre-caution for 48 hours
What are the bleeding patterns seen in POP?
Amenorrhoea - 20%
Regular bleeding - 40%
Erratic bleeding - 40%
When may women not breastfeeding have Depo-provera injection for contraception?
5 days post-partum
What are the side effects of Depo?
- Weight gain - 2kg/year in 70%
- Osteoporosis - should not be used for >2 years
- Delay in return of fertility for 6-18 months
When are peak progesterone levels after insertion of the implanon?
1-13 days
When are ovulation-inhibiting levels of progesterone reached on insertion of the implanon?
Within 24 hours
What proportion of women ovulate within 3 weeks of implanon removal?
90%
When is the copper coil effective after insertion?
Effective immediately
When is the Mirena coil effective after insertion?
If on day 1 cycle, immediately, otherwise, requires 7 days of precautions
What are the complications of IUDs?
- 5% risk of expulsion, esp. in first 3/12
- Uterine perf - 1/1000
- Pelvic infection - risk greatest in first 20 days