Obstetrics and Gynaecology Flashcards
What is fetal medicine?
Fetal medicine is the specialist care of the mother with a fetus affected by or at risk of a physical anomaly/genetic anomaly or adverse pregnancy outcome due to multiple pregnancy, preterm birth of fetal growth restriction.
What is the incidence of fetal anomalies?
1% of babies have an anomaly at birth whilst 4-5% as children.
What screening tests are available during pregnancy?
Screening tests include the Dating scan which measures the nuchal transparency, anomaly scan (20 weeks) for structural problems and plus serum screens/NIPT (combination screening to detect aneuploidy or free foetal DNA for chromosomal abnormalities). These are ultrasound-based screening tests.
What conditions are detected by anomaly scans?
Anencephaly (98%)
Open spina bifida (90%)
Cleft lip (75%)
Diaphragmatic hernia (60%)
Gastroschisis (hernia not through the umbilicus and no protective coverings)
Omphalocele (hernia through the umbilicus with protective coverings)
Exomphalos
Transposition of the great arteries
Tetralogy of Fallot
Atrioventricular septal defect
bilateral renal agenesis
renal pelvis dilatation
Skeletal dysplasia
Edwards syndrome (T18)
Patau syndrome (T13)
Who is seen by fetal medicine?
Fetal medicine sees people with a previous obstetric history, family history, current pregnancy with abnormal antibodies/anomaly/screen/complex pregnancy (growth restriction or multiple pregnancy). Occasionally patients on certain medications (anti-epileptics) or infections such as CMV, TOXO, Syphilis or VZV.
How is Down’s syndrome screened for?
- Age alone: Age related risk 1:1500 at age 20 to 1:100 at age 40
- Quad test (14-20wks) with serum biomarkers (AFP, hCG, Oestriol or Inhibin A)
- Combined test (10-13.6wks) which measures nuchal thickness and serum biomarkers
- Non-invasive prenatal testing (NIPT) can be done from 9 weeks. Small fragments of fetal cells within the maternal blood, unique to this pregnancy. This is an expensive test but non-invasive and has a sensitivity of over 99%. Anyone with a combined test chance of more than 150 will qualify for NIPT. This can test for Trisomy 21, 13 and 18.
If someone has a high chance of a genetic problem due to screening or anomaly scan then what confirmatory diagnostic tests can be done?
- Chorionic villus sample (CVS) can be done up to 15 weeks (11-14). Cells are taken from the placenta known as placental villous fragments. The miscarriage risk is less than 200. This is a sensitive test but there is a risk of confined placental monsaicism where there are abnormalities in the placenta and not in the baby.
- Amniocentesis can be performed after 16 weeks where a needle is inserted and amniotic fluid samples are taken. This contains squamous cells. The miscarriage risk is less than 1:200
- NIPT cannot be used as it as an accurate screening test but not an accurate diagnostic test. It is also not appropriate if an structural abnormality can be seen.
Who is involved in the fetal medicine MDT?
The fetal medicine MDT include the fetal medicine specialists, midwives, sonographer, neonatologist, paediatric surgeon, neurosurgeon, cardiologist, palliative/bereavement and specialists from other specialities as required. The MDT offers examinations, counselling, diagnostic and therapeutic procedures, and pre-pregnancy debriefing/counselling.
How is endometrial cancer classified?
This can be categorised histologically as endometroid (grade 1-3) or non-endometroid such as uterine serous, carcinosarcoma (mixed Mullerian) or clear cell.
What are the risk factors for endometrial cancer?
Risk factors include age (peri and post-menopausal) but younger patients with high oestrogen levels are also at risk such as those with anovulation as a result of PCOS. Others include obesity (over 42 increases risk 10x), iatrogenic (oestrogen only HRT/tamoxifen) and genetic (lynch syndrome increases the risk by 3%).
What are the red flags for endometrial cancer?
Red flag symptoms include post-menopausal bleeding, irregular perimenopausal bleeding or menorrhagia which is unresponsive to hormonal treatment.
What are the investigations for endometrial cancer?
Investigations are with an USS endometrial thickness and biopsy for diagnosis. MRI pelvis +/- CT chest, abdomen and pelvis is used for staging.
What is the treatment for endometrial cancer?
Treatment is with hysterectomy for disease which is confined to the uterus, chemotherapy for high grade disease outside uterus, radiotherapy reduces the risk of local recurrence and hormones (high dose progesterones and Mirena coil) if there is a desire to preserve fertility or other treatment options are not suitable.
What are the types of ovarian cancer?
There are three subtypes of ovarian cancer
Epithelial (serous (distal end of the fallopian tube with stick lesions)/ mucinous (ovary or appendix)/endometroid/clear cell/Brenner (low grade urothelium like tumours),
Stromal/sex-cord
Germ cell (analogous with testicular tumours so grow quickly but very treatable).
What are the risk factors for ovarian cancer?
Risk factors are post-menopausal/peri-menopausal age, subfertility/endometriosis, BRCA (the BRCA homologous recombination defect is seen in 50% of high-grade ovarian tumour and can be treated with PARP inhibitors) and Lynch syndrome (10% increased risk)
What are the symptoms of ovarian cancer?
Symptoms/red flags include abdominal swelling, early satiety, nausea, vomiting, changes in bowel habit, and abdominal pain or discomfort. It is known as the silent killer because of the vague symptomatology, IBS does not usually develop in the 50s so should be suspicious. Bloating that is due to a bowel problem usually gets worse throughout the day whereas ovarian bloating will remain constant.
What are the investigations for ovarian cancer?
Investigations include Ca125 and USS. CT chest, abdomen and pelvis or MRI with contrast and diffusion weighted imaging is used to determine if the mass is likely to be malignant.
What is the treatment for ovarian cancer?
Treatment is with debulking surgery and chemotherapy. Ca125 is non-specific as it goes up with a cold, pregnancy, peritoneal cancer, renal failure, heart failure and appendicitis. 50% of women with ovarian cancer will have a normal Ca125 so a high level of suspicion should have a USS. HIPEC chemotherapy can be started at the end of the surgery and is known as hot chemotherapy which is delivered through the peritoneum.
Describe the etiology of cervical cancer
HPV related cancer types include squamous cell carcinomas, glandular (adenocarcinomas) and neuroendocrine tumours. Non-HPV related cancers are very rare adenocarcinomas such as adenoma malignum and clear cell cancers. Cancer which arise from non-cervical cells include lymphomas and sarcomas. Squamous cell carcinoma is the most common and is associated with HPV. The vaccination covers 16 and 18 but there are other HPV variants which are carcinogenic. HPV associated adenocarcinomas (glandular) are likely caused by HPV 16.
Due to the smear programme the squamous cell carcinomas are becoming less common as CINs are easily detected whereas the premalignant lesion of the adenocarcinomas (CGIN) are less easily picked up with a smear. Therefore, the squamous cell carcinoma incidence has decreased more than the adenocarcinoma incidence.
What are the risk factors for cervical cancer?
Risk factors include HPV, smoking, and non-participation in cervical smear programme. Whether COCP and early intercourse increases the risk is debated as this may just be increased likelihood of coming into contact with HPV. Symptoms/red flags include detection in the smear program, post-coital bleeding, malodourous discharge, pelvic pain, and renal failure.
What are the investigations for cervical cancer?
Examination, biopsy, MRI and PET CT
What is the treatment for cervical cancer?
Local excision (loop or knife cone), radical trachelectomy/hysterectomy with pelvic node dissection, radical chemoradiotherapy (tumours larger than 4 cm but confined to the pelvis) or palliative chemotherapy and/or radiotherapy.
Squamous cell cancers very rarely spread to the ovaries, but adenocarcinomas do so the ovaries may be removed in the hysterectomy. Radical chemotherapy is curative treatment, but the morbidity is higher than the surgery. The aim is not to give all three treatments (surgery, chemotherapy, and radiotherapy) because the morbidity becomes almost intolerable.
What are the types of vulval cancer?
Fundamentally this is a skin cancer and thus the majority are squamous cell carcinomas however there are other rare forms such as BCC and malignant melanoma. The adenocarcinomas are Bartholin’s gland carcinomas (usually post-menopausal) or in Paget’s disease. However, they behave differently from typically skin cancers.
What are the risk factors for vulval cancer?
Risk factors for vulval cancer include vulval dermatosis (lichen sclerosis or lichen planus) and HPV (types 16, 32 and 18). HPV related cancer presents with normal looking vulval tissue whereas lichen diseases present with white lesions
What are the symptoms of vulval cancer?
Suspicious symptoms include a vulval lump or ulcer with pain/itchiness which may make them struggle to sit down. Itchiness which is not responding to candesartan should be examined.
What investigations should be done for vulval cancer?
examination, biopsy and then a CT chest, abdomen, and pelvis
What is the treatment for vulval cancer?
Treatment is with a wide local excision (+/- skin flap reconstruction), groin node dissection (sentinel or full clearance), chemotherapy to downstage a tumour or radiotherapy and as an alternative to surgery.
Describe the natural history of chlamydia
This is caused by chlamydia trachomatis and is the most common STI in the UK. It is highly infectious spreading to 75% of the partners of an infected individual. It can affect the male/female urethra, cervix, rectum, pharynx, and conjunctiva. It is often asymptomatic and diagnosed on routine screening.
What are the symptoms of chlamydia in men?
Urethral discharge, dysuria, urethral discomfort, and testicular pain
What are the symptoms of chlamydia in women?
Vaginal discharge, dysuria, lower abdominal pain, and dyspareunia
What are the extra-genital symptoms of chlamydia?
Rectal discharge, conjunctivitis and systemic illness
What are the complications of chlamydia infection?
Complications include pelvic inflammatory disease, epididymo-orchitis, sexually acquired reactive arthritis (SARA is a triad of urethritis, conjunctivitis, and polyarthritis) and perihepatitis (Fitz-Hugh-Curtis Syndrome). There are increased rates of sub-fertility and ectopic pregnancy in women who have had complications from chlamydia.
How is chlamydia diagnosed?
Diagnosis is with vulvo-vaginal nucleic acid amplification swabs (NAAT) or a cervical NAAT, but this is less accurate and requires a physician to do it. In men, a first pass urine sample is sent for a NAAT test and extra genital sites such as the pharyngeal, rectal or conjunctival swabs can also be sent for NAAT. Chlamydia cannot be seen on a microscope, but pus cells may suggest infection (unspecific for chlamydia) therefore NAAT is the best test.
What is the treatment for chlamydia?
The management is doxycycline 100mg BD (twice a day) for 7 days. Second line is with azithromycin 1g stat followed by 500mg OD for 2 days (first line in pregnancy or breastfeeding). For under 25s repeat screening is offered at 12 weeks to check for re-infection.
Partner notification should be provided by all asymptomatic males and all females for the last 6 months but only notify partners in the last month if the patient is a male with urethral symptoms.
What is lymphogranuloma venereum?
There are three serovars of Chlamydia trachomatis:
1. A-C types cause trachoma (blindness) and usually found in tropical countries
- D-K types cause chlamydia in the genital tract
- L1-L3 cause LGV
Classical LGV is endemic in parts of Africa, India, SE Asia, Caribbean, and C/S America. A new presentation of LGV re-emerged in MSM (men who have sex with men) in early 2000s and has spread across the UK, Europe, Australia, and the US.
How does classical LGV present?
Primary: small painless papules which are ulcerated
Secondary: gross lymphadenopathy, buboes, necrosed to form abscesses
Tertiary: Scaring, fibrosis, rectal strictures, and fistulae
Primary rectal LGV presents with direct transmission to the rectal mucosa and therefore haemorrhagic proctitis which is often mistaken for IBD. Haemorrhagic proctitis is bleeding, pain, tenesmus and change in bowel habit.
How is LGV diagnosed?
Diagnosis is with a rectal NAAT for Chlamydia which needs LGV testing added on to the form. There should be a biopsy of lymph nodes and a culture of fluid from the bubo (75-85% sensitivity).
What is the management of LGV?
Management is with Doxycycline 100mg BD for 3/52. A test is cure is done and partner notification should be done for partners 4 weeks before becoming symptomatic or 3 months if they were asymptomatic.
Describe the natural history of gonorrhoea?
This is caused by the gram-negative intracellular diplococci Neisseria Gonorrhoea. Symptoms are similar to chlamydia but the urethral and vaginal discharge teds to be more purulent. 90% of males will be symptomatic and symptoms occur within 2-5 days of infection.
Resistance is a serious problem in gonorrhoea with 9.2% of cases resistant to azithromycin. Ceftriaxone resistance is very low but increased in strains with reduced sensitivity and resistance is on the rise.
How is gonorrhoea diagnosed?
Diagnosis is with microscopy which is less than 50% sensitive in women but 95% sensitive in men. NAAT has over 95% sensitivity so should be used for women. A culture should be performed for everyone with a positive NAAT and all contacts at all sites that they have sex. All tests are doubled checked for false positives. Triple site testing is offered to women and MSM. Women who do not have anal sex can also get gonorrhoea in the rectum.
What are the complications of gonorrhea?
Complications include PID, PO, SARA and disseminated gonococcal infection which presents as a rash with a polyarthritis. It is more common in women but is very rare.
What is the management of gonorrhea?
Management is with:
1st line: Ceftriaxone 1g IM stat or ciprofloxacin 500mg PO if culture is sensitive
2nd line: Gentamicin 240mg IM stat and 2g azithromycin PO or cefixime 400mg PO and azithromycin 2g
3rd line: Spectinomycin 2g IM and azithromycin 2g PO or azithromycin 2g PO alone
All patients should have a test of cure at 2 weeks. Partners of the patient 2 weeks before symptomatic males should be notified or 3 months for asymptomatic males and all females. Partners should only be treated empirically if they have had sex in the last 14 days, everyone else should be tested and then treated.
Describe the natural history of syphilis
This is caused by Trepnonema pallidum (gram negative spirochaete). 75% of cases occur in MSM but rates are increasing in women and heterosexual men. There are also increasing rates of congenital syphilis which has a 40% mortality. The older the patient the worse the outcomes.
What is primary syphilis?
After an incubation of 21 days (range 9-80 days) there can develop a chancre (anogenital, single, painless, indurated lesion), moderate lymphadenopathy and ulcers which resolve over 3-8/52.
What is secondary syphilis?
After an incubation of 3/12 there can develop a maculopapular rash over palms, soles and widespread over the rest of the body (75%), chondylomata lata (wart lesions which need penicillin), mucocutaneous lesions (6-30%), generalised lymphadenopathy (50-86%), sore throat, malaise, weight loss, fever, MSK and multi-system involvement. Tinnitus, ocular syphilis and strokes can occur at this stage.
What is tertiary syphilis?
- Cardiovascular syphilis presents 10-30 years after infection and is symptomatic/complicated in 10%. In the ascending aorta there may be dilatation or aortic regurgitation. Rarely coronary ostial stenosis and saccular aneurysms can occur.
- Granulomatous syphilis occurs between 2-15 years and present with granulomatous lesions with a central necrosis.
- Neurological syphilis (neurosyphilis): This famously presents with the Argyle Robertson pupil which does not dilate to light but does dilate to accommodation. Argyle Robertson pupil presents in Tabes Dorsalis neurosyphilis (15-25 years) which also presents with lightening pains and sensory ataxia. General paresis neurosyphilis (10-25 years) causes progressive dementia with seizures. Finally, meningo-vascular neurosyphilis presents 2-7 years after exposure and usually affects younger patients. The MCA is affected which causes focal arteritis leading to ischaemic stroke, they may have a prodrome of headache, liable emotions and insomnia.
How is syphilis diagnosed?
If a Chancre is present (primary or some secondary) then a dark ground microscopy (usually genital lesions only as other sites less accurate) or PCR swab-from the chancre and rash could be taken. Blood tests should always be repeated if negative and high suspicion. The serology is not particularly sensitive. Once there has been a positive syphilis test it will be positive for life.
What is the management of syphilis?
Management should always be done by the GUM clinic because of the reaction called Jarisch Herxheimer reaction, partner notification and health advice. Prep and Pep may need to be considered.
Primary/secondary/early latent: 2.4MU benzathine penicillin IM stat
Late latent: 2.4MU benzathine IM stat weekly for 3 weeks
Neurosyphilis: 1.8-2.4 MU procaine penicillin IM OD for 14 days with 500 mg QDS probenecid orally, and 40-60 mg Prednisolone given for 72 hours.
Partner notification for primary is last 3 months, secondary is 2 years and tertiary is guided by previous serology and try and notify as many as possible. Serology should be repeated in 12 months to monitor.
What is the natural history of mycoplasma genitalium?
This is the smallest known self-replicating bacteria. Lots of people carry it without symptoms. Symptoms are similar to chlamydia, and it is responsible for 30% of cases of non-specific urethritis. This is seen in men with clinical urethritis and pus cells (neutrophils) under the microscope. Once Chlamydia and Gonorrhoea are excluded, 30% of those remaining cases will be caused by mycoplasma genitalium.
Indications for testing are NSU, PID, muco-purulent cervicitis, Epididymo-orchitis, sexually acquired proctitis or a current sexual partner has a positive case. Testing is with a NAAT test in the area the patient has sex in and rectal in needed. They should be tested for macrolide resistance genes (parC and 23s rRNA).
How is mycoplasma genitalium managed?
Uncomplicated: Doxycycline 100mg BD for 7 days followed by Azithromycin 1g stat and then 500mg OD for 2/7. This is in macrolide sensitive samples.
Complicated infections are those which fail first line, presented with PID or epididymo orchitis. They should be treated with Moxifloxacin 400mg OD for 14/7 and test of cure at 5 weeks. Only current partners should be notified.
What is the natural history of Herpes Simplex?
Type 1 is the most common cause of genital herpes whereas type 2 is more likely to cause recurrent symptoms.
Initial episodes can be primary or non-primary. In primary cases there are no antibodies to either HSV1 or 2 whereas non-primary has prior antibodies to HSV1 or 2. Recurrent episodes are reactivations of a latent infection.
What are the symptoms of HSV?
Symptoms include painful ulceration, dysuria, vaginal or urethral discharge (deep ulceration), prodrome of flu like illness, lymphadenopathy, mild fever, some are asymptomatic or have minor symptoms such as itching. Signs can include vesicles, ulcers (shallow based ulcers) and local lymphadenopathy. The first herpes episodes tends to be bilateral whereas recurrent episodes tend to be unilateral.
What are the causes of genital ulcers?
Causes of genital ulcers can include HSV, Behcet’s, drug reaction, VIN (Vulval intraepithelial metaplasia) carcinoma, lichen planus, lichen sclerosis, Steven Johnson’s syndrome, candidiasis, LGV, chancroid, syphilis and donovanosis.
What are the extra genital manifestations of HSV?
Extra genital manifestations of herpes include meningitis, encephalitis, herpetic eye disease (dendritic ulcers) and skin lesions such as herpetic whitlow on the finger.
What are the complications of HSV?
Complications of HSV include urinary retention, auto-inoculation, secondary bacterial infection of lesions, aseptic meningitis, herpes proctitis and neonatal herpes.
How is HSV diagnosed?
Diagnosis is with a viral PCR swab from skin lesions such as open ulcers or by popping a vesicle. Serology of type specific IgG and a culture may be required. IgG will be negative in early infection and there is often cross reactivity. IgG does not distinguish between oral or genital HSV and there is a poor predictive value in low prevalence populations.
What are the management options for HSV?
Supportive: Salt bathing, local anaesthetic gels, urinate in warm water such as a shower or bath and take regular analgesia. Vaseline may be used as a barrier to protect the skin. Avoid sex when ulcers are present and counsel them on asymptomatic shedding.
Pharmacological management must be started within 5 days of symptoms in order to be effective. Treatment is with acyclovir 400mg TDS (three times a day) for 5-10 days. Valciclovir or Famciclovir can be used as alternatives.
Management of recurrences: Often this is only minor symptoms so supportive treatment is needed only. For frequent recurrences (>6 episodes per year) then suppressive treatment can be considered with acyclovir 400mg BD for 3-12 months.
In pregnancy, women with HSV should inform their midwives so that they can be offered acyclovir from 36 weeks onwards to prevent neonatal herpes simplex. The risk if greatly increased with acquisition of HSV during pregnancy so these patients should be referred to the GUM clinic so that they can be offered suppression and caesarean section. Neonatal herpes has a very high mortality and morbidity.
Serodiscordant relationships are where one partner has HSV and the other doesn’t. Counselling is offered in the GUM clinic and serology, or suppression can be considered in certain cases. Immunosuppressed patients will require long term suppression.
What is the natural history of human papilloma virus?
Low risk HPV types (6 and 11) cause benign warts and are spread by skin to skin contact and fomites.
High risk types are 16, 18, 31, 33, and 35. They can cause VIN, AIN, PIN, VAIN, CIN and other malignancies. They are screened for on smears, biopsied and sent for histology
What is the management of HPV?
Management is with cryotherapy for benign warts, topical agents (imiquimod/podophyllotoxin), electro-cautery, surgery and some patients should be left alone as 30% disappear without treatment. Atypical lesions or lesions not responding to treatment should be biopsied.
How is Hepatitis A, B and C spread?
Hepatitis A is spread by the faecal oral route, B by vertical transmission/parenteral/sexual and hepatitis C is transmitted by parenteral/sexual/vertical. Patients are seen in GUM and are screened or offer vaccination or referral to hepatology.
Describe the natural history of hepatitis A
Hepatitis A is an RNA virus which can be transmitted by oral-anal sexual contact or digital rectal exposure. The incubation period is 15-45 days (28 average) and GUM screens all patients who are MSM or who have multiple partners, group sex, or having sex on premises (public places such as saunas).
What are the symptoms of hepatitis A?
50% of Hep A patients are asymptomatic. There is a prodrome of flu like illness for 3-10 days followed by an icteric stage with jaundice, itching and RUQ pain. 15% of symptomatic patients require hospital treatment and less than 1% will develop acute fulminant liver failure unless they are infected with another hepatitis or HIV.
How is hepatitis diagnosed?
Diagnosis is with IgM (positive 45-60 days) or IgG for hep A (positive lifelong or vaccination). Other tests include HIV, Hep B, C and E and Syphilis. LFTs and clotting should be checked as with all liver issues.
What is the management of Hepatitis A in the GUM clinic?
Management is supportive but consider hospitalisation if there is vomiting, dehydration or signs of decompensated liver disease. In GUM patients are screened and IVDU are screened. Vaccination is offered to HIV or other Hep infection patients. Patients will be monitored for infection and partner notification for partners 2 weeks before and one week after jaundice who should then be vaccinated.
All acute hepatitis are notifiable diseases
Describe the natural history of hepatitis B
Hepatitis B is a DNA virus which is transmitted in blood, sexual fluids and vertically. The incubation period is 40-160 days with a prevalence of 1% in the UK. GUM screens sex workers, IVDU, MSM, HIV, high endemic areas, sexual assault victims, needlestick injuries, partners of positive people, and children born to infected mothers.
What are the symptoms of hepatitis B?
10-50% of adults are asymptomatic. There are prodromal and icteric phases, but these may be prolonged. 1% will develop acute liver failure which may be more severe than seen in hep A. Chronic carriers may suffer from fatigue and develop signs of chronic liver disease.
How is hepatitis B diagnosed?
Diagnosis is with:
1. HbsAg + (surface antigen) in hepatitis B infection
- HbsAb + is either in naturally cleared infection or vaccination
- HbeAg + (envelope antigen) when virus is replicating rapidly
- Hbe-antibody to e antigen indicates the virus has stopped replicating as rapidly
- HBV DNA indicates the viral load
- HbcAg (core antigen) does not circulate in the blood so is not tested
- HbcAb is IgM high in acute infection IgG is high in chronic or cleared infection
Therefore
Acute infection: HbsAg +, HbeAg +, HbcAb IgM +, HBV DNA +
Chronic infection: HbsAg and HbcAb +, HBV DNA + and HbeAg may be positive
Vaccination: HbsAB +ve only
Cleared infection: HbcAb + only
Chronic carrier state: HbsAg +, HbcAb + and HBV DNA negative
What is the management of Hepatitis B?
Management is with screening for hepatitis D, A, C, HIV, and syphilis.
Refer to hepatology or infectious diseases. Treatment is based on the stage of infection and pattern of disease. Some will clear the infection so 6 months until treatment should be started.
Some treatment options are Tenofovir, Entecavir and Peg interferon. GUM will also provide vaccination and partner notification.
What is the natural history of Hepatitis C?
Hepatitis C is an RNA virus with a 1% prevalence and the majority are asymptomatic. This is a curable infection and is transmitted parentally and rarely sexually/vertical. There is a long incubation period of 4-20 weeks and can be longer in HIV co-morbidities.
GUM is involved because risks include Chemsex (recreational drug use), traumatic anal sex, fisting, group sex, sharing lubricant, sero-sorting and having a partner with HIV. Vertical transmission is higher if the mum also has HIV.
What are the symptoms of hepatitis C?
60% are asymptomatic, some experience serious fatigue which improves with treatment. Diagnosis is with bloods for Anti HCV and HCV RNA (viral load). Management is done by the regional MDT which involves directly acting
Describe the pharmacokinetic changes in pregnancy via ADME?
Absorption: Decreased gastric emptying, decreased small bowel motility, nausea, vomiting, and increased gastric pH
Metabolism: Increased hepatic blood flow and increased rate of hepatic metabolism
Distribution: Increased cardiac output, increased plasma volume, increased total body fat and water, and decreased plasma albumin
Excretion: Increased glomerular blood flow, increased glomerular filtration rate, and thus enhanced clearance.
What are some of the issues involved with prescribing drugs in pregnancy?
Pharmacology in pregnancy is complicated by research factors as pregnant women are excluded from clinical trials, most drugs are not tested for use in pregnancy and therefore there is limited guidance on dosing and efficacy in pregnancy. Animal studies cannot be trusted for human research.
Spontaneous reporting of side effects is done through the yellow card scheme. There are also congenital malformation registries, pregnancy registries (epilepsy) and population registries (GPRD). These are observational methods. These fail to consider co-factors.
Teratogenesis are fetal adverse effects arising from drug and chemical exposure. Congenital malformations occur in 2-3% of pregnancies and 1% of these are caused by drugs. The highest risk is during organogenesis (1st trimester), but there are also risks in growth and neurodevelopment in the 2nd and 3rd trimester. Exposure at term carries the highest risk of neonatal toxicity or withdrawal from drugs.
In preconception, drugs can prevent implantation. Alcohol causes fetal growth restriction. In the 3rd trimester anticoagulation can increase the post-partum bleeding risk. Transmission of drugs in breastmilk should always be considered. Prescribing in pregnancy is about managing the risk of harm to the mother by not taking their medication and the risk to the neonate from teratogenesis.
Describe in detail the changes to metabolism of drugs in pregnancy
Increased hepatic blood flow, increased cytochrome P450 enzymes and so increased hepatic metabolism. CYP3A4 is a P450 enzyme that is responsible for the metabolism of over 50% of all drugs. The activity of P450 enzymes can be increased or reduced by oestrogen.
Give some examples of CYP3A4 metabolized drugs
Citalopram, amlodipine, diltiazem, methadone, midazolam, nifedipine, and oxycodone
Give some examples for CYP2D6 metabolised drugs
Amitriptyline, codeine, fluoxetine, metoprolol, propranolol, venlafaxine, and haloperidol
What is the general pharcological advice in pregnancy?
All drugs should be avoided In the first trimester. All known teratogens should be avoided and any drug which has to be continued should be done so at the lowest effective dose. High dose folic acid supplementation should be advised and older drugs which are known to be safe in pregnancy should be first line options.
Give some examples of teratogens
ACE inhibitors: Renal dysfunction and decreased skull ossification
Aminoglycosides: Deafness and vestibular damage
Cytotoxic drugs: Multiple defects and miscarriage
Anti-thyroid drugs: Foetal goitre
Carbamazepine: Neural tube defects
Diethylstilboestrol: Vaginal carcinoma
Lithium: CVS defects include ebstein’s anomaly
Phenytoin: Foetal hydantoin syndrome
Retinoids: Craniofacial, cardiac and CNS defects
Sodium valproate: Neural tube defects
Warfarin: Foetal warfarin syndrome
What drugs are fetally toxic in the 3rd trimester?
Tetracyclines: Tooth discoloration
Warfarin: Fetal intracranial hemorrhage
Androgens: Masculinization of female feotus
NSAIDs: Closure of fetal ductus arteriosus
Opioids: Withdrawal effects in neonate
Theophylline: Neonatal irritability
SSRIs: Neonatal irritability
How should anti-epileptic drugs be managed in pregnancy?
Antiepileptics: With reduced medication there are increased risks of mortality for the mother, as well as injury, SUDEP and placental abruption. Risks for the fetus from antiepileptics include hypoxia, fetal death, prematurity, and malformation. Children exposed to sodium valproate have a 10% increased risk of congenital malformation and there are longer term effects on neurodevelopmental delay and behaviour.
AEDs that can be used are Lamotrigine and Levetiracetam.
When should palliative neonatal referrals be made?
Palliative neonatal referrals are made when there has been a diagnosis of a life-limiting/life-threatening illness made in the antenatal period. The foetus must be older than 23/40 weeks and thus classed as viable and the parents have decided to continue with the pregnancy.
What is a parallel birth plan?
A parallel birth plan encompasses normal discussion around a birth plan such as method, pain relief, birthplace and management but also include medical management after birth, religious beliefs, baby’s place of death if that happens and the role of the neonatal unit. Palliative, funeral, and post-mortem decisions. Organ donation can be considered.
When the baby is born, they may be given end of life care or active treatment. Even if the baby is considered for active treatment the parallel plan remains in place just in case. Post bereavement care is also offered.
How should suspected PID be managed?
There should be screening for other STIs before commencing antibiotics so that a diagnosis can be made, and it is not compromised. Antibiotics should be started as a priority if PID is suspected and should not be delayed whilst awaiting an appointment or swab results.
She should be counseled to avoid sexual intercourse until the improvement of symptoms and advised about barrier methods of contraception if this is unlikely or not possible. All partners of a woman in the last 6 months should be traced and managed appropriately.
How should suspected chlamydia or gonorrhoea be treated before swab results?
Whilst awaiting the chlamydia and gonorrhoea results the patient should be offered empirical treatment of a broad-spectrum antibiotic such as doxycycline 100mg BDO for 1/52. If the results come back as positive then treat the partners as well.
The patient should be advised to complete the course of antibiotics even if the swabs are negative because this will reduce the risks of long-term complications such as PID, infertility, ectopic pregnancy, and chronic pelvic pain. You should advise sexual abstinence until both partners have completed their antibiotics.
You should advise that in future a barrier contraception method should be used as this greatly reduces the risk of re-infection and protect against STIs.
How can tubo-ovarian abscesses and PID be differentiated?
TOA: This is diagnosed with a mass on CT or laparoscopy. There will be persistent high temperature and infection markers. This should be treated with drainage of the abscess. Micro-organisms can include e coli, and actinomyces Israeli.
PID: No presence of mass on CT. Infection markers will improve with antibiotics. This is seen in chlamydia and gonorrhea.
How should PID be treated?
Follow the BASHH Guidelines for PID. This suggests IV Ceftriaxone 2g daily plus IV doxycycline 100mg BDO. IV therapy should be continued until 24 hours after clinical improvement and then switched to oral doxycycline 100mg BD and metronidazole 400mg BD for 2/52. Remember to include a STOP/Review date.
Alternatives can include clindamycin, gentamicin, oflaxacin and ciprofloxacin. Warfarin interacts with antibiotics so this will require monitoring of the INR.
Monitoring requirements include INR, infection markers and swab results to ensure antibiotics are working
How should high INR on warfarin be managed around surgery?
Warfarin needs to be reversed. Pre-operatively the aim of under. if surgery can be delayed for 6-8 hours then use Vitamin K 5mg IV (phytomenadione). If the surgery cannot be delayed then anticoagulation can be reversed with pro-thrombin complex concentrate. This should be discussed with the haematologist.
What are the HRT options post-hysterectomy?
She can have either oral or transdermal options and the drug will be estradiol or conjugated equine oestrogens.
Tablets: Elleste Solo, Premarin, Progynova and Zumenon
Transdermal patches: Evorel, Elleste Solo Mx, Estradot or Progynova TS
Transdermal gel: Sandrena or Oestrogel
In women with a uterus, Oestrogen only HRT can increase the risk of endometrial cancer which is reduced by the addition of progesterone. In women with a history of endometriosis, endometrial foci may remain despite hysterectomy and the addition of progesterone should be considered in these circumstances.
How long is contraception required for after menopause?
Women are considered potentially fertile for 2 years after their last menstrual period if under 50 and 1 year if over 50.
What are the advantages and disadvantages of HRT in tablet, patch, and gel form?
Tablets
Advantages: Easy to take, convenient and variety of doses.
Disadvantages: Cannot be used if VTE risk, migraines, stroke risk, GI disorders affecting absorption, and gallbladder disease
Patches
Advantages: Lower risk of N&V than other forms, lower VTE risk, less chance of causing migraines, easy to use, able to shower, swim and bathe.
Disadvantages: If it begins to peel off it will become defective, can cause local irritation, increased absorption in hot climates, and plaster marks
Gels
Advantages: As per patches and dose can be easily adjusted
Disadvantages: Only available as oestrogen and patients who need higher doses need to use vast quantities of gel.
What HRT options are there for peri-menopause?
A patient that is peri-menopausal so should be started on sequential therapy (cyclical combined HRT). Sequential therapy is where oestrogen and cyclical progesterone is used for at least 10-14 days within 28 days to mimic the cycle. The patient will still have a withdrawal bleed. This can be prescribed as Elleste duet, femoston, prempak C, evorel sequi or femSeven sequi. Other options include Mirena intrauterine system, medroxyprogesterone (provera) tablets, and Micronized progesterone (Utrogestan) capsules.
If her symptoms were vaginal/bladder related due to urogenital atrophy only then treatment should be a topical vaginal oestrogen such as Estradiol (Vagifem or Estring) or Estriol (Ovestin cream, Imvaggis pessary or Blissel vaginal gel). Tablets and creams should be used nighly for 2 weeks and pessaries/gels for 3 weeks. The patient should then continue twice weekly as maintenance. This can be continued long-term
When should continuous HRT be prescribed?
Continuous combined HRT regimens are indicated in patients who have not had a hysterectomy and are either post-menopausal (last period more than 12 months ago) or in patients once they reach the age of 54 or have been on HRT for 5 years. Continuous combined HRT is classed as ‘bleed-free’.
How is HRT associated with cancer risk?
Over 5 years there is a higher risk of breast cancer with 5 years treatment with new HRT preparation. There is also a higher risk of VTE. All types of HRT can increase the risk of breast cancer after 1 year of use. The risk is higher for combined oestrogen-progesterone HRT (especially continuous preparations). The longer the duration the higher the risk. Vaginal preparations are considered low risk for breast cancer.
Long term use of combined or oestrogen only HRT is associated with a small increased risk of ovarian cancer, and the risk reduces a few years after stopping HRT. The risk of VTE is increased when using these HRT types, especially in Y1. Risk is lower transdermally. They also slightly increase the risk of stroke.
What are some of the side effects of HRT?
Oestrogen related: Breast tenderness, bloating, nipple sensitivity, leg cramps, nausea, heartburn, headaches and fluid retention. These should settle within 3 months or dose may need to be lowered. Changing the type of oestrogen or administration may also help
Progesterone related: Breast tenderness, fluid retention, headaches, mood swings, PMT-like symptoms, bloating, acne and greasy skin. This should be managed by changing the type of progesterone, reducing the dose if possible, changing the route, altering the duration and changing the regimen.
What is the treatment for UTI?
Start empirical treatment such as Nitrofurantoin MR 100mg BD for 3 days (if eGFR over 45) or trimethoprim 200mg BD for 3 days. Should also consider paracetamol and oral fluid. There is limited evidence for cranberry containing products.
How is recurrent UTI defined?
A recurrent UTI is defined as 2 or more episodes of LUTI in the last 6 months or 3 episodes in 12 months.
What prophylactic antibiotics are used for recurrent UTI?
1st line: Trimethoprim 100mg at night or nitrofurantoin 50-100mg at night
2nd line: Amoxicillin 250mg at night or cephalexin 125mg at night
The risks of long-term antibiotics include antimicrobial resistance and increased risk of adverse effects. Therefore, it should only be used when essential.
If the patient is started on trimethoprim, she needs to use adequate contraception. Trimethoprim is teratogenic in the first trimester. She should seek immediate advice if she becomes pregnant. Seek urgent attention if UTI symptoms develop and different antibiotics should be used from the prophylaxis if UTi develops.
Define the types of urinary incontinence
Stress urinary incontinence: Involuntary leakage of on effort on exertion, or on sneezing or coughing
Urgency urinary incontinence: Involuntary leakage accompanied by, or immediately preceded by, a sudden compelling desire to pass urine which is difficult to defer. UUI is part of a larger symptom complex known as overactive bladder syndrome (OAB). OAB is defined as urinary urgency, with or without incontinence, which is usually associated with increasing frequency and nocturia. Symptoms usually occur without a UTI or other pathology.
Mixed urinary incontinence: This is both stress and urgency incontinence; involuntary leakage is associated with both urgency and physical stress (exertion/sneeze/coughing).
How should mixed incontinence be managed?
Mixed incontinence should be managed according to their most predominant type of urinary incontinence.
Wha is the pharmacological management of stress urinary incontinence?
Stress incontinence should be managed with duloxetine trials (an SSRI). This should be started at 20mg BDO for 2 weeks and then increased to 40mg BDO. The patient should be reassessed after 2-4 weeks.
How should urge incontinence be managed?
Lifestyle advice should include reducing caffeine intake, maintain balanced fluid intake, advise weight loss if needed and smoking cessation. Bladder training can be considered and pelvic floor exercises.
After 2 months of no improvement of her UUI she should continue bladder training. Pharmacological treatment can include Oxybutynin immediate-release 5mg BD, Tolterodine immediate-release 2mg BD or darifenacin 7.5mg daily. Oxybutynin should not be used in the frail. Mirabegron may be used in patients for whom anti-muscarinic medications are contra-indicated. Treatment should be reviewed after 4 weeks. If effective it should be reviewed again in 12 weeks.
Potential side effects of anti-muscarinic medications can include dry mouth, constipation, dizziness, drowsiness, headache, nausea, vomiting, dyspepsia, palpitations, tachycardia, urinary retention, skin reactions and flushing.
Can’t think, see, spit, pee or poo or:
Blind as a bat (mydriasis), dry as a bone (mouth, sweating and eyes), hot as a hare (increased body temperature), mad as a hatter (delirium) and red as a beet (flushing).
What are the uses of neurosonography in fetal medicine?
This is used to assess skull shape with sutures. It is also useful for brain structures such as the cavum septum pellucidum, lateral ventricles, choroid plexus, thalamus, and cerebellum.
Describe the scanning programme in fetal medicine
- NHS fetal Anomaly Screening Programme (FASP) aims to ensure there is equal access to unform and quality assured screening across England and it is offered to all pregnant women (not mandatory). No screening test is mandatory and it should be noted that additional tests can increase the risk of miscarriage.
- Dating scan should occur between 10-14 weeks. This encompasses the combined test for Trisomy 21 (11+2 to 14+1 weeks). There is also the CRL 45-84mm for combined screening. CRL is crown rump length. This also assesses multiple pregnancy.
- Anomaly scan is undertaken between 18+0 to 20+6 weeks. This aims to identify abnormalities which indicate the baby may die shortly after birth. It also aims to identify conditions which may benefit from treatment before or after birth, plan delivery in an appropriate hospital/centre and there is no requirement to determine gender as very few disorders are related to gender.
