Pharmacology Flashcards
Warfarin inhibits which clotting factors?
10, 9, 7, 2
(1972) - it inhibits vitamin k dependent clotting factors.
Warfarin and Pregnancy
- People on warfarin should be converted to LMWH during pregnancy.
- Exception - Mechanical heart valve.
Effects of warfarin on foetus
Warfarin embryopathy in 5% of foetuses exposed to warfarin between 6 and 12 weeks gestation
Warfarin is safe to use when breastfeeding T/F?
True
When should warfarin be restarted post pregnancy
Women converted to LMWH from warfarin during pregnancy should be changed back 5-7 days after delivery.
What is Warfarin Embryopathy
- Hypoplasia of nasal bridge
- Congenital heart defects
- Ventriculomegaly
*Agenesis of the corpus callosum - Stippled epiphyses
Adverse effects on fetus/neonates of ACEi and ARBs
- Congenital malformations
-Renal dysgenesis - Oligohydramnios as a result of fetal oliguria
- Pulmonary hypoplasia
- IUGR
- Neonatal anuric renal failure
Adverse effects on fetus/neonates of Carbimazole
- Choanal atresia
- GIT defects
- Omphalocoele
- Aplasia cutis
Adverse effects on fetus/neonates of Warfarin
Warfarin Embryopathy
- Hypoplasia of nasal bridge
- Congenital heart defects
- Ventriculomegaly
- Agenesis of the corpus callosum
- Stippled epiphyses
Adverse effects on fetus/neonates of Metronidazole
- Diarrhoea
- Lactose intolerance
Adverse effects on fetus/neonates of Gentamicin/Erythromycin
Ototoxicity
Adverse effects on fetus/neonates of Tetracycline
- Yellowing of teeth
- Suggested link with cleft palate
Adverse effects on fetus/neonates of Litium
Cardiac defects
Adverse effects on fetus/neonates of Sodium valporate
Cardiac defects
Adverse effects on fetus/neonates of SSRIs
- Withdrawal syndrome in neonates
- Some linked to CVS defects and pulmonary hypertension but evidence conflicting
Dihydrofolate reductase (DHFR) inhibitors
The 2 most commonly used DHFR inhibitors are:
* Methotrexate
* Trimethoprim
Tamoxifen MOA?
Selective Estrogen Receptor Modulator
When is tamoxifen contraindicated?
Contraindicated in patients with personal or family history of VTE
What type of cancer does tamoxifen increase the risk of?
Endometrial cancer
Is Tamoxifen safe to use in pregnancy?
Should be avoided in pregnancy
What is tamoxifen licensed for?
Licensed for use in oestrogen receptor positive breast cancer & anovulatory infertility
Penicillins MOA?
Beta-lactam inhibit peptidoglycan cross-links in bacterial cell wall.
Examples of penicillins?
Amoxicillin, Phenoxymethylpenicillin, Flucloxacillin
Cephalosporins MOA?
Beta-lactam inhibit peptidoglycan cross-links in bacterial cell wall.
Macrolides MOA?
Peptidyltransferase inhibitor
Examples of cephalosporins
Cefalexin, Ceftriaxone, Cefuroxime
Examples of macrolides
Erythromycin, Clarithromycin, Azithromycin.
Quinolones MOA?
DNA Gyrase inhibitor
Quinolones examples
Ciprofloxacin, Levofloxacin, Moxifloxacin
Tetracycline MOA?
Bind to 30S subunit of microbial ribosomes blocking attachment of aminoacyl-tRNA to the A site on the ribosome
Nitrofurantoin MOA?
Damages bacterial DNA via multiple reactive intermediates
Tetracycline examples
Lymecycline
Oxytetracycline
Doxycycline
Nitrofurantoin MOA?
Damages DNA via multiple reactive intermediates
Trimethoprim MOA?
Dihydrofolate reductase inhibitor
Clomiphene MOA?
Estrogen agonist and antagonist. Selective estrogen receptor modulator (SERM)
Clomiphene effects on the body.
It binds to estrogen receptors throughout the body. It is the inhibition of estrogen receptors in the hypothalamus that is thought to account for its effect on ovulation induction. Here, by inhibiting the negative feedback effect of estrogen on gonadotropin release there is up-regulation of the hypothalamic-pituitary-gonadal axis.
Lidocaine key points
- Blocks fast voltage gated sodium channels
- Anti-arrhythmic
- Half life 2 hours
- Safe to use in pregnancy
- Hepatic metabolism
- Max dose is 3mg/kg (7mg/kg with adrenaline)
Fentanyl is approximately how many times more potent than morphine?
80-100 times.
Opioids
Can act at Mu, kappa or delta receptors.
Strong opioids (morphine, fentanyl, methadone) are strong agonists of the mu receptor.
Weak opioids (codeine and tramadol) are agonists of the mu receptor but also act as agonists at the delta and kappa receptors
What are 1st line antiemetic treatments for N+V according to NICE?
Promethazine or cyclizine. Prochlorperazine is also appropriate 1st line.
MOA of cyclizine?
Histamine H1 receptor antagonist
MOA of Promethazine?
Histamine H1 receptor antagonist
MOA of Ondansetron?
Serotonin 5-HT3 receptor antagonist
MOA of Prochlorperazine?
Dopamine D2 receptor antagonist
MOA of Metoclopramide?
Dopamine D2 receptor antagonist
5-HT3 receptor antagonist
5-HT4 receptor agonist.
Target INR for mechanical mitral valve?
2.5-3.5
Target INR for DVT, PE & Tissue valve replacement?
2.0-3.0
Target INR for mechanical valve replacement where PE has occured despite anticoagulation at lower range?
3.0-4.0
Most common drug class cause of hyponatraemia?
Loop diuretics e.g. Furosemide
ACEi Side effects
E.g. Ramipril:
Dry cough, joint aches, postural hypotension (infrequent), renal impairment (rare), angio-oedema (rare).
Should ACEi be avoided in pregnancy?
Yes
Side effects of use of ACEi in pregnancy?
Skull defects, oligohydramnios and altered neonatal BP and renal blood flow reported.
Loop diuretics side effects?
E.g. Furosemide:
- Postural hypotension, hyponatraemia, hypokalaemia, hypocalcaemia and hypomagnesaemia, gastrointestinal upset.
Calcium channel blocker side effects?
E.g. Amlodipine:
- Peripheral oedema, abdominal pain, nausea, fatigue.
Should calcium channel blockers be avoided in pregnancy?
BNF advises most CC blockers be avoided in pregnancy as they may inhibit labour and some have shown toxicity in animal studies.
Side effects of beta blockers?
E.g. Labetalol
- Bronchospasm, cold extremities, alteration in glycaemic control, bradycardia.
NOTE: Labetalol has not been shown to be harmful except possibly in the 1st trimester. Other beta blockers may cause IUGR.
What are the maternal benefits of corticostroids use?
No known maternal benefits.
Why are antenatal corticosteroids used?
Antenatal steroids are associated with a significant reduction in rates of neonatal death, RDS and intraventricular haemorrhage and are safer for the mother.
What is a “course” of corticosteroids used in pregnancy?
Betamethasone 12mg IM x 2 doses or dexamthasone 6mg IM x 4 doses are the steroids of choice to enhance lung maturation.
Who should be offered antenatal corticosteroids?
- All women at risk of iatrogenic or spontaneous preterm birth up to 34+6 weeks gestation.
- All women for whom an elective c-section is planned prior to 38+weeks gestation.
When should antenatal steroids be given?
*A single course should be offered to women between 24+0 and 34+6 weeks gestation who are at risk of preterm birth.
When are antenatal steroids most effective?
Risk of neonatal death reduces if steroids given within first 24hrs and therefore should still be given even if delivery is expected within this time.
Most effective in reducing RDS in pregnancies that deliver 24hrs after and up to 7 days after administration of the second dose of antenatal corticosteroids.
Treatment for opioid overdose?
Naloxone
Treatment for benzodiazepine overdose?
Flumazenil
Treatment for paracetamol overdose?
Parvolex (N-acetyl cysteine)
Treatment for heparin reversal?
Protamine
Treatment for warfarin reversal?
Octiplex
Mechanism of action of imidazole antifungal group?
Binds to fungal cell membrane phospholipids and subsequent inhibition of ergosterol and other steroids biosynthesis. Change in cell permeability leads to cell death.
Examples of imidazole antifungals?
CLotrimazole, ketoconazole, miconazole and fluconazole.
MOA of nystatin and amphotericin B?
Antifungals - polyenes class.
Work by inhibition of Ergosterol.
LMWH treatment in individual <50kg?
Enoxaparin - 20mg
Dalteparin 2500u
Tinzaparin 3500u
LMWH is safe in breastfeeding T/F?
True
LMWH treatment in individual 50-90kg?
Enoxaparin - 40mg
Dalteparin - 5000u
Tinzaparin
4500u
LMWH treatment in individual 91-130kg?
Enoxaparin - 60mg
Dalteparin - 7500u
Tinzaparin - 7000u
LMWH treatment in individual 131-170kg?
Enoxaparin - 80mg
Dalteparin 10,000u
Tinzaparin 9000u
LMWH treatment in individual >170kg?
Enoxaparin 0.6mg/kg
Dalteparin 75u/kg
Tinzaparin 75u/kg
MOA of Terbinafine?
(and amorolfine) act by inhibiting squalene epoxidase - an enzyme that catalyses the conversion of squalene to lanosterol (precursor for ergosterol - a vital component in fungal cell wall).
What is the max dose of lidocaine with adrenaline?
7mg/kg
MOA of metronidazole?
Inhibits nucleic acid synthesis via nitroso radical formation which damage microbial cell DNA.
When is metoclopramide not licensed for used?
Not licensed for people under 20yrs and is known to cause oculogyric crisis in young adults.
If using - use should be limited to 5 days.
Ranitidine MOA?
Blocks H2 receptors