Pharmacology Flashcards
Half life of mifepristone
25-30hours
Structure of heparin
Polysaccharide (repeating disaccarides)
Amount of hormone released in LNG in 24 hours (mirena)
20 micrograms/ 24 hours
MOA Fluconazole
Inhibits synthesis of ergosterol from lanosterol, inhibiting cell wall synthesis
MOA labetalol
Competitive alpha-1 (selective) and non-selective beta-1 blocker (antagonist)
MOA warfarin
Competitively inhibits vit K epoxide reductase complex 1. Interferes with synthesis of vitamin K dependent clotting factors (X, IX, VII and II- 1972)
MOA dalteparin
Factor Xa and thrombin inhibitor
MOA raltegavir
Integrase inhibitor
Metabolism of isoniazid
N-acetylation of its hydrazine in the liver
MOA of methotrexate
Dihydrofolate reductase inhibitor
MOA of clomiphene citrate
When should it be taken? Dose?
Selective estrogen receptor modulator:
Induces LH/FSH release by occupying oestrogen receptors in hypothalamus, promoting FSH release.
Stimulates ovarian aromatase activity and up regulate of granulosa LH receptors.
Stimulates ovulation
D2-6 of cycle. 50-100mg.
Dinoprostone MOA
Prostaglandin E2- stimulates uterine contractions
Contraceptive implant MOA
Ovulation inhibition and increase in viscosity of cervical mucus.
Teratogenic effect of ACEi
Fetal renal damage
Oligohydramnios
Skull defects
Most common side effect of oxybutynin
Dry mouth (antimuscarinic)
Absolute contraindications to COCP
<21 days post partum with other risk factors for VTE
0-6 weeks post partum and breastfeeding
Age >=35 and smokes >=15 cigarettes per day
Hypertension with BP >160 systolic or >100 diastolic
Vascular disease, heart disease, stroke/ TIA
History of VTE or current VTE
Major surgery (>30 mins) with prolonged immobilisation
Known thrombogenic mutation e.g. factor V Leiden
Antiphospholipid syndrome
Complicated valvular/ congenital heart disease (e.g. pulmonary hypertension)
Cardiomyopathy with impaired cardiac function
AF
Migraine with aura
Current breast cancer
Severe (decompensated) liver cirrhosis
MOA penicillins
Beta-lactam: inhibit peptidoglycan cross-links in bacterial cell wall synthesis (bactericidal)
MOA cephalosporins & examples
Beta lactam: inhibit peptidoglycan cross-links in bacterial cell wall synthesis (bactericidal)
Cefalexin, Ceftriaxone, Cefuroxime
MOA macrolides and examples
Excretion
Peptidyltransferase inhibitor. Reversibly bind 50S ribosome, block peptide elongation (bacteriostatic)
Erythromycin, Clarithromycin, Azithromycin
Excreted by liver
MOA fluoroquinolones and examples
DNA gyrase inhibitor- required to supercoil DNA = inhibit nucleic acid synthesis
Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin
MOA Tetracyclines and examples
Bind to 30S subunit of microbial ribosomes, blocking attachment of aminoacyl-tRNA to the A site on the ribosome
Lymecycline, Oxytetracycline, Doxycycline
MOA Nitrofurantoin
Damages bacterial DNA via multiple reactive intermediaries
MOA Trimethoprim
Dihydrofolate reductase inhibitor (thus inhibiting bacterial DNA synthesis)
ACEi/ ARBs adverse effect on fetus/ neonate
Congenital Malformations
Renal dysgenesis
Oligohydramnios as a result of fetal oliguria
Pulmonary hypoplasia
IUGR
Neonatal anuric renal failure
Carbimazole adverse effect on fetus/ neonate
Choanal atresia
GIT defects
Omphalocoele
Aplasia cutis (missing section of skin)
Warfarin adverse effect on fetus/ neonate
Warfarin Embryopathy:
- Hypoplasia of nasal bridge
- Congenital heart defects
- Ventriculomegaly
- Agenesis of the corpus callosum
- Stippled epiphyses (focal bone calcification)
- Risk of intracranial haemorrhage in 3rd trimester
-Diaphragmatic hernia
Metronidazole adverse effect on fetus/ neonate
Diarrhoea
Lactose intolerance
Gentamicin/ Erythromycin adverse effect on fetus/ neonate
Ototoxicity
Tetracycline adverse effect on fetus/ neonate
Yellowing of teeth
Suggested link with cleft palate
Lithium adverse effect on fetus/ neonate
Cardiac Defects- Ebstein’s anomaly
Sodium Valporate adverse effect on fetus/ neonate
Cardiac Defects
SSRIs adverse effect on fetus/ neonate
Withdrawal syndrome in neonates
Some linked to CVS defects and Pulmonary Hypertension but evidence conflicting
Highest risk time to take warfarin?
6-12 weeks
5% chance of Warfarin emyropathy
Can Warfarin be used during breastfeeding?
Yes.
Women converted to LMWH during pregnancy should be changed back 5-7 days after delivery
Licensed use of Tamoxifen
Contraindications
MOA
Oestrogen receptor positive breast ca & anovulatory infertility
CI: personal or FHx of VTE
MOA: Selective Estrogen Receptor Modulator
(Increases risk of endometrial ca.)
Max dose of lidocaine
3mg/kg (without adrenaline)
7mg/kg (with adrenaline)
1% lidocaine = 1g/100ml or 10mg/ml.
Max dose for 70kg patient is 210mg = 21ml of 1% lidocaine
MOA of cyclizine
Histamine H1-receptor antagonist
MOA of Promethazine
Histamine H1-receptor antagonist
MOA Ondansetron
Serotonin 5-HT3 receptor antagonist
Prochlorperazine MOA
Dopamine D2 receptor antagonist
Metoclopramide MOA
Dopamine D2 receptor antagonist
5-HT3 receptor antagonist
5-HT4 receptor agonist
MOA Lincosamide Abx and example
Interfere with synthesis of proteins via binding 50S ribosomal subunit, inhibiting peptide bond formation
Clindamycin
MOA Terbinafine and amorolfine (anti-fungals)
Inhibit squalene epoxidase- enzyme that catalyses conversion of squalene to lanosterol.
Lanosterol is a precursor to Ergosgterol- a vital component of fungal cell walls.
How does clomiphene trigger ovulation?
It inhibits oestrogen receptors in the hypothalamus, inhibiting the negative feedback effect of oestrogen.
This results in more GnRH release, therefore more LH/ FSH release from the anterior pituitary, driving ovarian follicular activity
Risk of using metoclopramide in young people
Can cause oculogyric crisis (spasmodic movements of eyeballs into a fixed position, usually upwards) and is not licensed for people under 20 years old.
Should be limited to 5 days use.
How many times stronger than morphine is fentanyl?
80 to 100 times stronger
Codeine/ tramadol MOA
Agonists of the Mu receptor, but also agonists at the Delta and Kappa receptors
Morphine’s primary MOA
Mu receptor agonist
As is fentanyl and methadone
Benefits of antenatal steroids vs risks
Who is offered them
Benefits: Associated with significant reduction in rates of neonatal death, RDS and intraventicular haemorrhage & safe for mother
Risks: may cause low blood sugars in baby after birth. Less information on long term implications for babies, may affect brain development leading to delay in reaching developmental milestones, but evidence is limited.
Offered to women due to have planned CS between 37 and 39 weeks, probably reducing the chance the baby will need admission to neonatal unit for breathing problems
Also offered to those at risk of spontaneous vaginal birth 24+0 to 34+6 weeks gestation
Regimens of antenatal corticosteroids
Who should receive them?
When are they most effective?
Dexamethasone IM 6mg x4 doses
Betamethasone 12mg IM x 2 doses 12h apart
Single course is recommended in women between 24+0 and 34+6 at risk of preterm delivery
Recommended for women having ELCS before 38+6
Most effective 24h- 7 days after administration
MOA lidocaine
Lidocaine half life
Blocks fast voltage gated sodium channels
Half life 2h
MOA metronidazole
Nitroimidazole class- inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells
Cabergoline and Bromocriptine are agonists of which receptor?
D2 –> reduce dopamine levels and milk production
Half life of oxytocin
How long to respond following IV/ IM dose and when it subsides
5 minutes
Following intravenous administration, uterine response occurs almost immediately and subsides within 1 hour
Following intramuscular injection, uterine response occurs within 3 to 5 minutes and persists for 2 to 3 hours
Following iv infusion, steady state and maximal uterine activity is reached after 20-40 minutes hence oxytocin infusion is increased every 30 minutes
Half life of Misoprostal
20-40 minutes
Half life of ergometrine
30-120 minutes
MOA of TXA
Plasminogen-activator inhibitor (Inhibits plasmin formation)
It inhibits the dissolution of thrombosis (and fibrin) that leads to menstrual flow.
It can reduce flow by up to 50%.
MOA mefanamic acid
Works by inhibiting prostaglandin synthesis.
It reduces menstrual loss by around 25% in three quarters of women
MOA heparin
Activation of Antithrombin III and inactivation of factor Xa
MOA Mifepristone
Anti-progestogen: competes for progesterone receptors, acting as an antagonist
Ulipristal (EllaOne) MOA
Selective anti-progesterone modulator
30mg single dose
Effective up to 5 days post SI
Inhibits ovulation
If vomiting within 3h repeat dose can be given
Levenogestrel (Levonelle) MOA
Synthetic progesterone
1.5mg single dose ASAP after SI, licensed up to 72h post SI
If vomiting within 2h, repeat dose can be given
Drug causes of hyperprolactinaemia
Atypical antipsychotics eg risperidone
Phenothiazines eg chlorpromazine
Butyrophenones eg haloperidol
Thioxanthenes
Metoclopramide
Dopamine synthesis inhibitors eg -Methyldopa
Catecholamine depletors eg Reserpine
Opiates eg Codeine
H2 antagonists eg Cimetidine, Ranitidine
Amitriptyline
SSRI’s eg Fluoxetine
Calcium channel blockers eg Verapamil
Oestrogens
Thyrotropin-releasing hormone (TRH)
MOA Atosiban
Oxytocin receptor antagonist
MOA traditional POP vs desogestrel only & brand names
Traditional POP: thickening of cervical mucus
- Norgeston
- Micronor & Noriday
- Femulen
Desogestrel POP: inhibits ovulation
- Cerezette
- Aizea
- Cerelle
- Nacrez
Which local anaesthetic is an amide and which are esters?
Lidocaine = amide
Benzocaine/ Cocaine/ Procaine/ Tetracaine = esters
Which neurotransmitter is used by the sympathetic/PS preganglionic neuron?
ACh
MOA Methyldopa
Centrally acts as alpha 2 receptor agonist
MOA Cyclizine
H1 antagonist
Why is Vit D recommended in pregnancy?
Prevent rickets in neonate
Which COCP is beneficial in PCOS?
Yasmin (ethinylestradiol/ drosperinone)- beneficial for acne and hirsutism
Dianette (cyproterone acetate, ethinylestradiol)- not if high BMI- high risk of VTE
Both are anti-androgenic
Medication for stress UI
Duloxetine
5HT and NA reuptake inhibitor- increases urinary sphincter tone
Medication for urge UI/OAB, MOA & contraindications
Tolterodine (M1-4) (1st line)
Oxybutynin (M1-4) (1st line)
Darifenacin (1st line)
Solifenacin (Vesicare) (M2/3 receptors) (2nd line)
MOA: Both muscarinic receptor antagonists- inhibit detrusor contractions
CI: Closed angle glaucoma (pilocarpine eye drops are muscarinic receptor agonists), Myasthenia graves, paralytic ileus
Mirabegron can be used if anti-muscarinic is CI (selective beta3 adrenorecptor agonist)
MOA anti-thyroids
Propylthiourcil and carbimazole
Prevent the peroxidase oxidation of iodide to iodine in the thyroid gland
Propylthiouracil also has a peripheral action (prevents deionisation of thyroxine)
LMWH MOA
Inhibits factor Xa by binding to anti-thrombin, thereby inhibiting the conversion of prothrombin to thrombin
Progestogens in contraception and their risk of VTE
COCs containing levonorgestrel, norethisterone and norgestimate carry the lowest risk of VTE.
Etonogestrel and norelgestromin are slightly higher
Highest risk: estrogen and drospirenone, gestodene, desogestrel, and co-cyprindiol (cyproterone/ethinylestradiol).
Why can’t clomifene be used >6 months
Increased risk of ovarian cancer
MOA glycopeptides and examples
G neg or positive bacteria?
Inhibit bacterial cell wall synthesis by binding to d-alanyl-d-alanine, preventing incorporation of new subunits
Vancomycin & teicoplanin
(associated with red man syndrome)
Only active agains gram positive bacteria
Not absorbed in GIT
Aminoglycosides MOA and examples
G neg or positive bacteria?
Excretion
MOA: inhibit bacterial protein synthesis. Irreversibly bind to 30S ribosomal proteins (bactericidal)
Gentamicin, Tobramycin, Netilmicin, Streptomycin
Active against G negative bacteria
Excreted via kidneys
Sulfonamides MOA and examples
Metabolism
MOA: inhibit bacterial synthesis of tetrahydrofolic acid= antimetabolite
Sulfasalazine, Sulfamethazine, sulfamethoxazole (in co-trimoxazole with trimethoprim)
Active orally, metabolised by liver, excreted by kidneys
Recognised cause of SJS
Anti-retroviral medications
Classes, examples and MOA
- Nucleotide reverse transcriptase inhibitors (NRTIs)
e.g. Zidovudine, Tenofovir, Lamivudine
MOA: Target HIV reverse transcriptase, disrupting creation of proviral DNA, halting HIV replication.
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
e.g. Doravirine, Efavirenz, Etravirine, Nevirapine, Rilpivirine
MOA: bind directly to reverse transcriptase, blocking its action
- Integrase inhibitors
e.g. Raltegravir, Elvitegravir
MOA: target HIV integrase, which is needed for viral replication. Integrase inserts viral genomic DNA into host chromosome.
- Entry inhibitors
e.g. Maraviroc, enfuviritide
MOA: stop HIV from entering human cells. HIV must bind CD4 receptor and a co-receptor (CCR5 or CXCR4), entry inhibitors block one of these co-receptors.
- Protease inhibitors
e.g. Atazanavir, Darunavir, Lopinavir
MOA: block activity of protease enzyme, which HIV uses to break up large poly proteins into smaller pieces to make new viral particles from.
- Post attachment inhibitors e.g. Ibalizumab
MOA: bind CD4 receptor, preventing HIV GP120 protein from changing shape to engage with co-receptors.
- Booster drugs
e.g. Ritonavir, Cobicistat
MOA: boost effects of protease inhibitors- make the liver breakdown the PI more slowly, reducing clearance and increasing plasma levels.
Chloramphenicol effect on fetus
Neonatal gray syndrome
Carbamazepine effect on fetus
Diminished growth and hypospadias
Sodium valproate effect on fétus
Neural tube defects
Vitamin A/ retinoids effect on fetus
How long should be discontinued before conception
Skeletal deformity
Accumulates in skin/ fat therefore avoid conception for 2 years after treatment
Diuretic effect on fetus
Neonatal thrombocytopenia
Atenolol effect on fetus
IUGR
Neonatal hypohlycaemia
Bradycardia
Prostin
Gemeprost
Carboprost
Misoprostol
What type of PG?
Prostin = PGE2
Gemeprost = PGE1 analogue (PV)
Carboprost = 15methyl PGF2alpha (IM)
Misoprostol = PGE1
How many amino acids in Oxytocin?
Where is it synthesised?
What receptors does it work on?
How can it cause hyponatraemia?
9
Paraventricular nuclei
Acts through G protein couples receptor and allium-calmodulin complex
Has ADH like effects and can cause hyponatraemia, reflex hypotension and tachycardia
Tocolytics & MOA
When should they be used?
Nifedipine or Atosiban to allow time for steroids to work +/- in utero transfer if needed 24w-33w gestation
Atosiban = oxytocin receptor antagonist (IV infusion)
Nifedipine (CCB)- PO & cheaper than above
20mg PO, then 10-20mg TDS/ DQS according to uterine activity for 48h
Terbutaline 250mcg SC (emergency) = beta 2 adrenergic receptor agonist
Dose of MgSO4 for PET
4g loading dose
1g/h maintenance dose
Prevention/ management of PPH
Drugs & doses
Active management of third stage:
- IM oxytocin (5u, 10u) OR 1ml syntometrine (500mcg ergo and 5u oxytocin- IM)
- IV oxytocin (5u at CS or f/u dose)
- Ergometrine 250-500mcg IM or slow IV
- IV infusion 40units oxytocin in 40ml saline at 10ml/h
- Carboprost 250mcg IM, repeated every 15min as needed. Total dose shouldn’t exceed 2mg (8 doses)
- Misoprostol 1000mcg PR
Pethidine
- Dose
- Side effects
- When is it at its highest concentration in the foetus
- How does it cross the placenta
- Dose: 50-100mg every 4h IM
- Delays gastric emptying, resp depression and hypoventilation
- Highest fetal concentration 2-3h post IM injection. Fetal concentrations are higher than maternal because its a weak base and more ionised in the acidic environment of the fetal circulation
- Binds to alpha1 acid glycoprotein and readily crosses placenta by passive diffusion
Drugs that suppress lactation
Bromocriptine (D2 agonist)
Cabergoline (D2 agonist)
Aspirin
Tetracyclines
Ciprofloxacin
Litium
DIazepam
Carbimazole
Caffeine
Nicotine
Safe in breastfeeding
NSAIDs, codeine (check baby not drowsy), morphine, methadone
Penicilins, cephalosporins, macrolides
Labetalol, nifedipine, captopril, enalapril, metoprolol, atenolol, amlodipine
Phenytoin, carbemazepine, sodium valproate
SSRIs, TCAs
Warfarin
Heparin
Insulin
Drugs that increase prolactin
Metoclopramide, Domperidone
Amisulpride & most other antipsychotics
Verapamil, Methyldopa
Estrogen and COC
When is a Cu-IUCD appropriate for emergency contraception?
May be inserted within 5 days UPSI or not more than 5 days after known ovulation
Use instead of levonelle or Ellaone if patient also on Liver enzyme inducing medication, as this may affect their efficacy
Examples of alkylating agents and how they work
Cylophosphamide
Chlorambucil
Form covalent bonds with DNA side chains, causing deprivation, strong breaks and cross linking
How does diazepam cross placenta?
Can cross readily due to lipid solubility
Anti-metabolite that is the pro-drug for 6-mercaptourine & MOA
Azathioprine
MOA: Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins.
Drug associated with haemorrhage cystitis
Cyclophosphamide
Which SSRI should be avoided in first trimester and why?
Paroxetine- causes fetal heart defects
