finals Flashcards
Huntingtons - chromosome, repeat, pathology
Chromosome 4 - cag repeat - huntingtin protein
Decreased GABA neurons in basal ganglia leads to increases stimulation of thalamus and cortex by global pallidus
Alzheimer’s - pathology
Beta amyloid plaques
Neurofibrillary tangles - tau proteins
Cerebral atrophy, peri ventricular degeneration
Affects posterior parietal lobe
Alzheimer’s drug treatment?
If mmse >12 - acetylcholinesterase inhibitors - donepezil, rivastigmine, galantamine
<12 - nmda receptor antagonist - memantine
Lewy body dementia - pathology, treatment
Lewy bodies (eosinophilic aggregates, ubiguitin) - widespread in subcortical areas and temporal cortex No treatment - avoid antipsychotics as they may be neuroleptic sensitive - get very bad epse's
Frontotemporal dementia - picks disease - pathology
Frontotemporal atrophy, knife blade atrophy, picks bodies (contain tau)
Neurosyphilis
General paresis - dementia, frontal lobe dysfunction, ar pupils
Tabes dorsalis - shooting pains, ataxia
Alcohol dependence
Primacy Compulsion to drink Narrowing of repertoire Increased tolerance Withdrawal symptoms Continuing drinking to avoid withdrawal Reinstatement after abstinence
Delirium tremens
72 hrs after last drink
Tachycardia hypertension, tremor, fits, visual tactile hallucinations, worse at night
Rx: bdz reducing regime (chlordiazepoxide), thiamine b1
Maintenance of alcohol detox
Disulfiram - Antabuse - acetaldehyde
Acamprosate - reduces cravings by enhancing GABA
Naltrexone - partial opioid receptor antagonist - reduces cravings
Wernickes encephalopathy
B1 deficiency causes mammillary body damage
Nystagmus Ataxia Peripheral neuropathy Clouding of consciousness Ophthalmoplegia
Rx - pabrinex
Korsakoffs psychosis
Anterograde amnesia
Retrograde amnesia
Preservation of immediate recall
Confabulation
Irreversible
Give oral thiamine
Opioid dependence - treatment
Methadone
Buprenorphine - partial opioid receptor antagonist - start when not using very much meth
Naltrexone - opioid receptor antagonist - use after stopped to prevent relapse
Naloxone - for overdoses
Benzodiazepines - how do they work
Enhance GABA activity
Cocaine - neurotransmitters involved?
Dopamine, serotonin, noradrenaline - blocks reuptake
Test for cystic fibrosis
Immunoreactive trypsinogen
ECG changes in PE?
Rv hypertrophy
Sinus tachycardia
S1Q3T3
ECG changes in left atrial hypertrophy?
P mitrale - broad bifid p waves - due to mitral stenosis
ECG changes in right atrial hypertrophy?
P Pulmonale - peaked p wave - tricuspid stenosis or pulmonary hypertension
What type of drug is a statin?
Hmg coa reductase inhibitor
Sfx - muscle pain, rhabdomyolosis, elevated lfts
What is cushings disease?
ACTH excess causing high cortisol levels
Hormonal treatment for acromegaly?
Octreotide - a somatostatin analogue
What is kallmans syndrome?
Failure of gnrh secretion - 50% have loss of smell
What is Hashimoto’s thyroiditis?
What are the antibodies?
Atrophic changes with regeneration leading to goitre formation
Thyroid peroxidase antibodies
Graves’ disease antibodies and special features?
Tsh receptor antibodies
Specific eye signs - Ophthalmoplegia and exophthalmos
What is extramedullary haematopoeisis and when does it occur?
Haematopoesis that starts occurring in liver and spleen and places other than marrow - occurs in states where marrow has been replaced eg myelofibrosis, myeloproliferative disorders, and in excessive demand eg haemoglobinopathies
What cells are produced from common myeloid progenitors?
Megakaryocytes, erythrocytes, mast cells, basophils, neutrophils, eosinophils, monocytes
What cells are produced from common lymphoid progenitors?
natural killer cells, t lymphocytes, b lymphocytes
Where do lymphocytes mature?
Thymus
Which white blood cells are granulocytes
basophils, eosinophils, neutrophils, nk cells
Role of neutrophils
Engulf & kill bacteria Release cytokines (IL1, TNFalpha) and chemotaxins (adhesion molecules)
Role of eosinophils
Similar function to neutrophils
Act against parasites
Involved in hypersensitivity
Role of monocytes
Migrate to tissues and become either dendritic cells (present antigens) or macrophages (engulf pathogen and present antigens)
Role of basophils & mast cells
Mediate parasite and allergic reactions, like eosinophils
Have surface receptors for IgE
Release heparin and histamine
Mast cells = v similar but stay on connective tissue not blood
Role of T lymphocytes
CD4 helper cells - bind to MHCs on antigen presenting cells and produce cytokines which activate B cells and macrophages
CD8 cytotoxic cells - bind to MHCs on antigen presenting cells and kill cells infected by pathogens
Role of natural killer cells
Destroy native cells which are abnormal or infected by pathogens - part of innate response - important in the bodys response to cancer
Role of B lymphocytes
When activated by T helper cells, some become plasma cells and produce antibodies, some become memory cells which stay around after the infection and have v sensitive immunoglobulins which will detect and respond to low levels of the same pathogen in the future
Roles of the spleen
Phagocytosis of old RBCs
Pools WBC and platelets, can be rapidly mobilised when needed
Some first-line immunological defence
Extramedullary haematopoesis
Causes of massive splenomegaly
CML Myelofibrosis Chronic malaria Leishmaniasis Gauchers (lysosomal storage disease --> lipid accumulation)
Complications of splenectomy
Infection - vaccinations & lifelong oral Pen V
Thromobocytosis for 2-3 wks afer
Abnormal RBC morphology - Howell-Joly bodiesm Pappenheimer bodies, target cells etc
Causes of splenic atrophy
Sickle cell disease (infarctions)
Coeliac disease
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Sideroblastic anaemia
Anaemia of chronic disease
Causes of macrocytic anaemia
Megaloblastic - B12 and folate def
Normoblastic - liver disease, hypoTH, alcohol, drugs, aplastic anaemia, pregnancy, myeloma
Causes of normocytic anaemia
Haemorrhage, haemolysis, anaemia of chronic disease
What is sideroblastic anaemia?
Consider if microcytic anaemia does not respond to Fe
DIsorder of haem synthesis resulting in refractive anaemia, microcytics hypochromic RBCs, ring sideroblasts in BM
May be due to myelodysplasia, alcohol, isoniazid
Causes of red cell aplasia
Diamond blackfan
Transient erythroblastopenia of childhood (post viral)
Parvovirus B19
Causes of aplastic anaemia
Fanconis anaemia (AR) Idiopathic Cytotoxic drugs Radiation Infection
Investigations for Fe def anaemia
Low Hb, low MCV, low MCHC Low ferritin Low Fe High total iron binding capacity (as liver produces more transferrin) Endoscopy - in older people Coeliac serology
Drugs which may cause folate deficiency?
Trimethoprim, methotrexate, phenytoin, sulfasalazine
Causes of haemolytic anaemia
Inherited RBC abnormalities - spherocytosis, G6PD def, thalassaemia, sickle cell
Immune - newborn, blood transfusions
Autoimmune - warm & cold
Mechanical - DIC, HUS, heart valves, marching
Inheritance and pathophysiology of hereditary spherocytosis
AD
Mutation of RBC membrane protein eg spectrin - increased permeability to Na - spheroidal shape- destroyed in spleen
Differential diagnosis of spherocytosis
Hereditary spherocytosis
Autoimmune haemolytic anaemia - direct Coombes test +ve
Inheritance and pathophysiology of G6PD deficiency
X-linked
G6PD is enzyme which maintains glutathione levels and prevents oxidative damage to RBCs - without it, oxidant-induced haemolysis occurs
Warm haemolytic anaemia - antibody type and causes
IgG
SLE, lymphoma, CLL, carcinomas, drugs
Cold haemolytic anaemia - antibody type and causes
IGM
Infection, paroxysmal cold haemolysis
Triggers for haemolysis in G6PD deficiency
Infection, fava beans, quinine, ciprofloxacin, nitrofurantion, sulphonylureas
Sickle cell disease pathology
Mutation in gene for Beta-globin chain --> HbS gene - valine instead of glutamine If homozygous (HbSS) - nearly all Hb is HbS, which polymerises in low oxygen states, making RBCs sickle shaped and rigid and fragile
4 crises in sickle cell disease
-Vasocclusive - painful - dactylitis, pain, avascular necrosis, priapism, stroke
-Sequestration - spleen engorged
-Aplastic - due to Parvovirus
-Haemolytic (rare)
Also increased risk of infection & sepsis
Management of sickle cell crisis
analgesia (opioids), hydration, abx if infection, exchange transfusion if severe
Drug used to reduce rate of crises in sickle cell
Hydroxyurea/hydroxycarbamide - increased concentration of foetal Hb
B thalassaemia pathophysiology
Imbalance of production of alpha and beta chains - beta chain production decreased so cant make HbA - make more HbF and HbA2 instead
Major form - severe anaemia, need regular transfusions + iron chelation (desferrioxamide)
A thalassaemia pathophysiology
Problem with genes for alpha globin - fewer normal a globin genes means more b globin chains
Most severe is major (all 4 deleted) -fatal
3 deleted - mild anaemia
1/2 deleted - asymptomatic
Haemophilia - what is deficient in each type?
A - factor VIII
B - factor IX
Clotting function test results in haemophilia and VW disease
Haemophilia - prolonged APTT
VW - prolonged APTT, prolonged bleeding time (as platelet function abnormal as well as decreased factor VIII)
Both have normal prothrombin time
Treatment of haemophilia and VW disease
Replace deficient factor
Desmopressin
Polycythaemia rubra vera pathophysiology
Excess proliferation of RBC ± platelets and other cells
95% due to JAK2 mutation –> activates tyrosine kinase
Treatment of polycythaemia rubra vera
venesection
chemo - hydroxycarbamide & busulfan to decrease plt count
low dose aspirin
allopurinol
WHO definition of osteporosis
BMD at least 2.5 standard deviations below the mean (between -1 and -2.5 is osteopenia)
Risks associated with oestrogen
Breast cancer Endometrial cancer (if unopposed) Venous thromboembolic disease Stroke Vaginal bleeding
What is raloxifene?
Selective oestrogen receptor modulator - acts on oestrogen receptors in bone to increased BMD, but does not affect receptors in endometrium and breast - which is good!!
Sfx - increases menopausal symptoms, increased risk of VTE
What is denosumab?
Fully human monoclonal antibody to RANKL - for osteoporosis
What is strontium ranelate?
dual action bone agent for osteoporosis - increases bone formation AND decreases bone resorption
Risk factors for osteomalacia
Lack of sunshine, dark skin, anticonvulsants, malabsorption, CKD
RA + splenomegaly = ?
Feltys syndrome
Extra-articular features of Ank spond?
Anterior uveitis
Aortitis/aortic regurg
Apical lung fibrosis
Amyloidosis
Which crystals are present in gout and pseudogout?
Gout - monosodium urate - negatively birefringent
Pseudogout - calcium pyrosphosphate - positively birefringent
Side effects of corticosteroids
Weight gain Osteoporosis Think skin, bruising, poor wound healing Hypertension/oedema Infection Hyperglycaemia Psychosis Cataracts Muscle weakness/myopathy Adrenal/pituitary suppression Pancreatitis Impaired growth
What is rituximab?
Anti-CD20 antibody - causes lysis of B cells
What are the anti TNF drugs?
Infliximab - monoclonal antibody against TNF
Etanercept - TNF receptor fusion protein
Adalimumab - monoclonal antibody against TNF
What are complications of blood transfusion? Early & late
Early - ABO incompatibility, fluid overload, febrile reaction, urticarial reaction, transmission of infection
Late - RhD and other sensitisation, delayed transfusion reaction, Iron overload, transmission of infection
Causes of red eye
Conjunctivitis, keratitis, scleritis, episcleritis, uveitis, acute glaucoma, endophthalmitism subconjunctival haemorrhage
What is the 4th generation test for HIV?
ELISA or western blot for HIV antibodies
Test for p24 antigen
Treatment of urge incontinence
Anticholinergics - oxybutynin, tolterodine
Sacral neuromodulation
Intravesical botox
Surgery - detrusor myomectomy, cystoplasty
Physiotherapy
Behavioural therapy
Treatment of stress incontinence
Pelvic floor exercises, vaginal cones
Weight loss
Surgery - TVT, TOT
Duloxetine (SNRI)
What are the most common types of testicular tumour?
90% are germ cell tumours
- seminomas 48%
- non-seminomatous 42% - teratoma, yolk sac, choriocarcinoma
What are the tumour markers for testicular ca?
beta hcg, afp, palp (placental ALP), LDH
Which drug can reverse the effects of benzos?
Flumazenil (benzodiazepine antagonist)
What are the beta lactam abx?
Penicillins, cephalosporins and carbapenems
They inhibit cell wall synthesis
Bacteriocidal
What are the aminoglycoside antibiotics?
Gentamycin, streptamycin, neomycin
They inhibit protein synthesis
Bacteriocidal
What are the macrolide antibiotics?
clarithromycin, azithromycin, erythromycin,
They inhibit translocation of proteins
Bacteriocidal/static
What are the tetracycline antibiotics?
Doxycyline, oxytetracycline
Inhibits protein synthesis
Bacteriostatic
What is trimethoprim?
A folic acid inhibitor
Bacteriostatic
What is the innervation to the pupil?
Afferent - CN2 (optic nerve) - chiasm –> optic tracts –> synapses in lateral geniculate nucleus –> optic radiations –> occipital cortex
Efferent
-Parasympathetic - with CN3 (oculomotor) - arises from Edinger-Westphal nucleus
-Sympathetic - from cervical spinal cord
Causes of miotic pupil
Old age Opiates Pilocarpine Horner's Pontine lesion Argyll Robertson pupil (neurosyphilis)
Causes of mydriatic pupil
Arousal
Damage to eye eg acute glaucoma, trauma, iritis
Anticholinergics - atropine, oxybutynin, antidepressants
Sympathetic stimulants - cocaine
3rd nerve palsy - eg DM
Midbrain lesion
Holmes Adie pupil
What is Bell’s palsy?
Dysfunction of CN7 (facial nerve) –> unilateral facial weakness
(LMN so does NOT spare forehead like a UMN problem would)
What is mild non-proliferative diabetic retinopathy?
At least 1 microaneurysm
What is moderate non-proliferative diabetic retinopathy?
Microaneurysms or dot/blot haemorrhages ± cotton wool spots, venous beading, IRMAs, hard exudates
What is severe non-proliferative diabetic retinopathy?
Blot haems + microaneurysms in 4 quadrants
Venous beading in at least 2 quadrants
IRMA in at least 1 quadrant
What is proliferative diabetic retinopathy?
Retinal neovascularisation (may cause vitreous haem) Fibrous tissue forms anterior to retinal disc
What is maculopathy?
Any background changes, haemorrhage, oedema or ischaemia of the macula –> may affect vision
Management of diabetic retinopathy
Glycaemic & risk factor control
Focal or panretinal photocoagulation
Anti-VEGF - Pegaptanib, bevacizumab and ranibizumab
Intravitreal steroids
Hypertensive retinopathy - grades
1 - barely detectable arterial narrowing (silver wiring)
2 - arterial narrowing & focal irregularities (AV nipping)
3 - + flame haemorrhages, exudates, cotton wool spots
4 - + disc swelling
May also get Elschnig spots & Siegrist streaks
Management of glaucoma
Decrease secretion - topical beta blockers, topical/PO carbonic anhydrase inhibitors (acetazolamide)
Increase outflow - topical prostanoids, topical alpha agonists
Laser - trabeculoplasty, iridotomy
Surgical - trabeculectomy
If acute closed angle - IV acetazolamide, beta blockers, pilocarpine (parasympathomimetic, constrict pupil to open angle), iridotomy
Prevention of thyroid eye disease in Grave’s?
Stop smoking!
What are the symptoms and signs of chronic open angle glaucoma?
May be no visual changes
May get loss of peripheral fields, starting nasally, ending up with tunnel vision
O/e - optic disc cupping with notched rim
With gonioscopy lens - open angle visible at iridocorneal angle
What are the symptoms and signs of acute closed angle glaucoma?
Sudden onset severe eye pain - worse with mydriasis Blurred vision Watering Photophobia Visual haloes N, V, abdo pain Fixed semidilated pupil Cloudy cornea
SIgns and symptoms of retinal artery occlusion
Sudden painless visual loss
PALE retina, cherry red spot at fovea
Signs and symptoms of retinal vein occlusion
Sudden painless loss of vision
Severe haemorhages, tortuous dilated retinal veins, macular oedema, cotton wool spots - cheese and tomato pizza!
Causes of anterior ischaemic optic neuropathy
Arteritis - eg temporal!
Atherosclerosis
How to manage a pregnant woman exposed to chicken pox?
If >20wks gestation - v low risk of transmission If <20wks... -Check antibodies -If not immune, give VZ immunoglobulin -If rask present, give aciclovir
Classification of hypertension in pregnancy
Pre-existing hypertension = 140/90 before 20 wks
Pregnancy-induced hypertension = 140/90 after 20 wks, no proteinuria
Pre-eclampsia = 140/90 after 20 wks + proteinuria >0.3g/24hrs
What is Meig’s syndrome?
Benign ovarian tumour (normally fibroma) + ascites + pleural effusion
Most common benign ovarian tumour in young women
Dermoid cyst (teratoma)
Most common cause of ovarian enlargement in women of reproductive age
Follicular cyst
Which HPVs are associated with cervical ca?
16,18, 33
6 and 11 are warts
Risks associated with HRT?
Increased risk of breast ca, endometrial ca (reduced by adding progestogen), VTE, stroke, ischaemic heart disease
What is Fitz Hugh Curtis syndrome?
RUQ pain and perihepatitis caused by PID
Treatment of chlamydia?
Single dose azithromycin or 7 days doxycycline
Benefits of HRT?
Alleviates vasomotor symptoms (flushing, headaches etc)
Prevents osteoporosis
Reduces risk of colorectal ca
Why can you get symptoms of thyrotoxicosis with hydatiform moles?
Because the high levels of hCG can mimic TSH
What disease does Coxsackie A16 virus cause in children?
Hand foot and mouth disease = sore throat, fever, vesicles in mouth and on palms and soles
What is Scarlet fever?
Reaction to erythrogenic toxins produced by Group A haemolytic streptococci
Fever, malaise, tonsillitis
‘Strawberry’ tongue
Rash - fine punctate erythema sparing face
Rx - Pen v
How does Rubella infection in a chid present?
Rash: pink maculopapular, initially on face before spreading to whole body, usually fades by the 3-5 day
Lymphadenopathy: suboccipital and postauricular
What is seborrhoeic dermatitis?
Common benign greasy scaling rash caused by yeast (Malassezia sp) - may cause cradle cap in infants
Combined test for Downs?
Beta hcg + PAPPA + nuchal translucency - at 11-14 weeks
Consequences of congenital rubella
Sensorineural deafness
Congenital cataracts
Congenital heart disease (e.g. patent ductus arteriosus)
Glaucoma
Consequences of congenital toxoplasmosis
Cerebral calcification
Chorioretinitis
Hydrocephalus
Consequences of congenital CMV
Growth retardation
Purpuric skin lesions
Treatment of threadworm (pinworm)?
Mebendazole & hygiene measures for child & all family
What are muscle fibres made up of?
Many myofibrils - which have thick myosin and thin actin filaments - actin filaments have troponin and tropomyosin attached for linking to cross bridges on myosin
What receptors monitor how much a muscle fibre is being stretched?
Muscle-spindle stretch receptors - wrapped round intrafusal muscle fibres
Which receptors monitor how much tension a muscle is under?
Golgi tendon organs
Pathophysiology of Parkinsons
Degeneration of substantia nigra in brainstem –> less dopamine released in basal ganglia –> motor cortex activated less
Drugs for Parkinsons?
Dopamine agonists - ropinirole
Monoamine oxidase B (enzyme breaks down Da) inhibitors - selegeline
Dopamine precursors - Levodopa + peripheral decarboxylase inhibitor
What are the amine hormones?
Thyroid hormones, catecholamines and dopamine
What are the steroid hormones?
Cortisol, aldosterone, testosterone, estradiol, 1,25-dihydroxyvitamin D
What are the majority of hormones?
Peptides
What hormones are secreted by each part of the adrenal glands?
Cortex
ZG - aldosterone
ZF/ZR - DHEA, androstenedione, cortisol
Medulla - adrenaline, noradrenaline
Enzyme necessary for producing thyroid hormones from iodine and thyroglobulin
Thyroid peroxidase (TPO) nb anti-TPO antibodies are present in Hashimotos thyroiditis
Actions of thyroid hormone
Increased basal metabolic rate
Regulate bone growth and neural maturation
Increase bodys sensitivity to catecholamines
Increase body temperature
Fat mobilisation & breakdown
Carbohydrate metabolism
Growth & development in children
Increase heart rat, contractility and cardiac output
Allow normal fertility
What is Addisons?
Primary adrenal insufficiency
What is Conns?
Aldosterone producing adenoma
What is Cushings disease?
Cushings syndrome due to ACTH-secreting tumour of pituitary gland
Major effects of growth hormone?
Induces secretion of IGF-1 from liver, chondrocytes and other tissues. IGF-1 –> cell division
Stimulate protein synthesis, esp in muscle
Anti-insulin effects
Which hormones favour bone formation and which favour resorption?
Bone formation: insulin, GH, IGF-1, oestrogen, testosterone, calcitonin
Bone resorption: PTH, cortisol, thyroid hormones
What is released in hypercalcaemia of malignancy?
PTH-related peptide
What is the cause of secondary hyperparathyroidism?
Failure to absorb Vit D in gut or decreased 1,25dihydroxyvitamin D production –> increased PTH –> restores calcium levels but at expense of bone
What is the cause of pseudohypoparathyroidism?
End-organ resistance to PTH (PTH levels are high but ineffective)
What is atrial natriuretic peptide?
A peptide hormone and powerful vasodilator secreted in the atria in response to high blood volume
Increases GFR, decreases sodium reabsorption, inhibits renin, inhibits aldosterone, vasodilates, increases release of free fatty acids from adipose tissue
What is Cushing’s phenomenon?
Traumatic head injury leads to increased intracranial pressure, decreased brain blood flow, and a large increase in arterial blood pressure
(because the pressure exerts force on blood vessels so slow is reduced and metabolites build up in brain interstitial fluid causing powerful stimulation of sympathetic neurons controlling systemic arterioles
Typical causes of AF
Thyrotoxicosis Mitral stenosis Ischaemic heart disease Pulmonary embolism Pneumonia Sepsis Alcohol Cardiomyopathy and other structural / valvular heart diseases.
Which hormones are lipid soluble and where are their receptors?
Steroids, thyroid hormones and 1,25-dihydroxy Vit D
Bind to intracellular receptor proteins - in nucleus or in cytosol - these receptors act as transcription factors or suppressors
Which hormones are water soluble and where are their receptors?
Most hormones, neurotransmitters, paracrine/autocrine messengers (apart from Steroids, thyroid hormones and 1,25-dihydroxy Vit D)
Bind to proteins on extracellular surface of plasma membrane - these may be ligand gated ion channels, enzymes or G-protein-coupled receptors - may activate second messengers inside cell
How do steroids work?
Inhibit phospholipase A2 - which inhibits the formation of arachidonic acid (the origin of prostaglandins, prostacyclin, thromboxane and leukotrienes)
In contrast, NSAIDs inhibit COX, and so inhibit formation of prostaglandins, prostacyclin and thromboxane only
Which cells produce the myelin sheath of nerves?
CNS - oligodendrocytes
PNS - Schwann cells
What produces CSF?
Ependymal cells of choroid plexus lining ventricles
Where does CSF go in the brain?
Subarachnoid space (between arachnoid and pia mater)
Where is CSF absorbed?
Arachnoid granulation & lymphatic channels
What controls the shape of the lens in the eye?
The ciliary muscles, and the tension they apply to the zonular fibres
Parasympathetic control
What is presbyopia?
Lens loses elasticity with age - less able to accommodate for near vision
What are the muscles which protect the inner ear from very loud sounds?
Tensor tympani (attaches to malleus and TM) and stapedius (attaches to stapes) - contract reflexively to dampen movements of middle ear bones and transmit less sound to inner ear
What is the uvea?
Choroid, ciliary muscles and iris
What neural pathway is involved in rewards and motivation?
Mesolimbic dopamine pathway
Alzheimers drug rx?
Mild-mod: acetylcholinesterase inhibitors - donepezil, rivastigmine, galantamine
Mod-sev: NMDA receptor antagonist - memantine
Causes of long QT
Hypocalcaemia, hypokalaemia, hypomagnesaemia MI/ischaemia Myocarditis Hypothermia Amiodarone, sotalol, Class 1a's TCA, fluoxetine Jervell-Lange-Neilsen, Romano-ward
Antiplatelet mechanism of aspirin?
Inhibits the production of thromboxane A2
Mechanism of action of clopidogrel
Antiplatelet - inhibits ADP binding to its platelet receptor via inhibition of P2Y12 receptor
Mechanism of action of enoxaparin and fondaparinux
Activates antithrombin III, which in turn potentiates the inhibition of thrombin and coagulation factors Xa
Mechanism of action of bivalirudin
Reversible direct thrombin inhibitor
Mechanism of action of heparin
Activates antithrombin III, which in turn potentiates the inhibition of thrombin and coagulation factors Xa
Management of NSTEMI/unstable angina?
GRACE score (6 month mortality risk) if > 1.5% clopidogrel for 12 months if > 3% angiography within 96 hours + GIIb/IIIa antagonist
Antipsychotics - side effects
Typicals - Antidopaminergic - EPSEs (ADAPT)
Atypicals - Antiserotoninweight gain
Either type
- Antihistaminic - drowsy
- Hyperprolactinaemia - galacttorhea, gynaecomastia, amenorrhoea, impotence
- Antiadrenergic - postural hypotension
- Antimuscarinic - dry mouth, const, blurred vision, retention, increased intraocular pressure
- Prolonged QT
- Neuroleptic malignant syndrome
Clozapine - agranulocytosis
What drug can be used to lessen the dystonia sfx of antipsychotics?
Procyclidine (antimuscarinic)
Side effects of tricyclic antidepressants?
Sedative (esp amitriptyline) Toxic in overdose Arrhythmias Anticholinergic Antiadrenergic
Side effects of SSRIs?
GI upset Headache Sexual dysfunction Withdrawal symptoms (dizzy, lethergy, nausea, headache) Safe in overdose
Side effects of Lithium?
Narrow therapeutic range - check twice weekly then every 3 months
Excreted by kidney - check renal ftn before & every 6m
Can cause hypoTH - check TFTs before & every 6m
Teratogenic
Nausea, metallic taste, thirst, weight gain, oedema, tremor
Define ‘opportunity cost’
The sacrifice in terms of the benefit forgone from not allocating the resources to the next best activity
Define equity
Fairness or justice of distribution of costs and benefits
Define economic evaluation
Comparative study of costs and effectiveness/benefits of different health care interventions
Analysed in terms of increments - eg are the incremental benefits of this new rx worth the incremental costs?
Simplest form is cost-effectiveness analysis, or can use cost-utility analysis
What is cost-utility analysis?
Form of economic evaluation
Measures health in terms of QALYs (utility x life expectancy)
Incremental cost effectiveness ratio (ICER) must be <20,000 to be funded by NICE
ICER = incremental cost/incremental QALY = £X per QALY gained
How do you calculate NNT?
1/Absolute risk reduction
Valve most often involved in infective endocarditis
Tricuspid
ECG signs of digoxin toxicity
Reverse tick (down-sloping ST depression) Short QT
Enlarged heart on CXR without pulmonary oedema?
May be pericardial effusion - often a/w malignancy eg lung tumour
Complications of Paget’s
Bone pain Pathological fractures Nerve deafness Spinal cord compression High-output cardiac failure and Osteosarcoma.
What type of antiemetic are cyclising and promethazine?
Antihistamines - block h1 receptors in vomiting centre
Sfx - antimuscarinic, sedative
Skin rashes caused by Malassezia?
Seborrhoeic dermatitis
Dandruff
Pityriasis versicolor
What type of antiemetic are haloperidol, chlorpromazine, metoclopramide and domperidone?
Dopamine receptor antagonists - block da receptors in chemoreceptor trigger zone
Sfx - epse, sedation, long QT
Causes of erythema nodosum?
infection: streptococci, TB, brucellosis
systemic disease: sarcoidosis, inflammatory bowel disease, Behcet’s
malignancy/lymphoma
drugs: penicillins, sulphonamides, combined oral contraceptive pill
pregnancy
What type of antiemetic is ondansetron?
5ht3 receptor antagonist - block 5ht3 receptors in chemoreceptor trigger zone and gut
Sfx - qt prolongation, headache, flushing, constipation
Rheumatoid arthritis - antibodies
RF, anti-CCF
RA X ray changes
JS narrowing, periarticular osteopenia & erosions, soft tissue swelling, subluxation
Treatment of RA & psoriatic arthritis?
Methotrexate + a DMARD (steroids for acute attacks)
When dont you use DMARDS?
disease of the spine
Features of sle?
Hair loss butterfly rash discoid rash livedo reticularis photosensitivity depression glomerulonephritis pleuritis pericarditis ulcers raynauds antiphospholipd - CLOTS seizures Libman sacks endocarditis
SLE antibodies
ANA Anti-dsDNA - best Anti-Sm Anti Ro, Anti La Anti-histone - esp drug induced Also low C3, C4
Treatment of SLE
Cyclophosphamide, steroids, sun cream, hydroxychloroquine, NSAIDs, rituximab
Don’t use TNF blockers
Pathology of Sjorgrens
Abnormal B cell activity - antibodies (Ro and La RF, ANA) attack exocrine glands
Pathology of scleroderma
Overactive fibroblasts –> too much collagen –> vascular damage, inflammation
Antibodies for systemic slerosis
Limited - anticentromere
Diffuse - Anti topoisomerase
Clinical features of scleroderma
Cutaneous - linear and morphea skin fibrosis
Systemic
-Limited - CREST, pulm htn, renal crisis
-Diffuse - myocardial fibrosis, pulm htn, renal etc
What is polyarteritis nodosa
Medium vessel vasculitis - necrotising arteritis –> aneurysms - a/w Hep B
Clinical features all related to ischaemia eg post prandial abdo pain, acute tubular necrosis
Arteriography –> aneurysms
Risk factors for gout
Alcohol Seafood meat (with purines in) Male Obesity Diabetes Thiazide diuretics
Gout investigations
Joint aspirate - strongly negatively birefringent monosdium urate crystals
X -ray - erosions, punched out lesions, sclerosis
Treatment of acute gout (and pseudogout)
NSAIDs, colchicine, steroids
Prevention of gout
Allopurinol (xanthine oxidase inhibitor)
Lifestyle - low purine diet, look at drugs
Pseudogout investigations
Joint aspirate - weakly positive rhomboidal calcium pyrophosphate crystals
X - ray - chondrocalcinosis
Bisphosphonates - mechanism
Adhere to hydroxyapatite - inhibit osteoclasts
Alendronate is first line in osteoporosis
Strontium ranelate - mechanism
Dual action - inhibit osteoclasts & promote osteoblasts
Raloxifene - mechanism
SERM
What is denosumab
Monoclonal antibody against RANK - used in osteoporosis
What is teriparatide
Recombinant PTH - used in osteoporosis - anabolic mechanism
Pagets - X-ray?
Sclerosis or lytic lesions, thickening of trabeculae, lose distinction of cortex
Risk factors for osteomalacia
Low vit d or calcium or phosphate
Anticonvulsants
Renal tubular acidosis, renal failure
Malabsorption
What is azothioprine
Purine analogue - inhibits DNA synthesis
What is cyclosporin
Inhibits T lymphocytes and IL2
Monitor kidney function
What are the 5ASA (aminosalicylates)
Sulfasalazine, mesalazine
What hormone in pregnancy causes gestation diabetes?
Human placental lactogen
Causes of microcytic anaemia
Fe deficiency, sideroblastic, thalassaemia
What is sideroblastic anaemia
Can’t use iron in bone marrow –> get ring sideroblasts
Microcytic anaemia not responding to iron!
Low total iron binding capacity
Causes of normocytic anaemia
Haemolytic anaemias
Chronic disease
What is wrong with the beta chain in sickle cell
Replaced glutamic acid with valine
Treatment of spherocytosis
Splenectomy
What is myelodysplasia
Defect in stem cells –> bone marrow failure –> tends to evolve into AML
Old people
Which pathway does prothrombin time measure
Extrinsic - used for warfarin monitoring (INR)
Which pathway does APTT measure
Intrinsic - used for monitoring heparin - increased in haemophilia & VW disease
How do GPIIb/IIIa antagonists work?
Block binding of fibrinogen to platelets
How does heparin work
Inactivates thrombin and factor Xa
How does clopidogrel/tacegralor work
P2y12 receptor inhibitors - block platelet activation
How do alteplase, retaplase etc work
Recombinant tissue plasminogen activator - activates plasmin from plasminogen - plasmin breaks down fibrin
Features of PKD?
Hypertension, infections, abdo pain, compression, hepatic cysts, berry aneurysms
Where does renal cell carcinoma arise?
Proximal tubule
Causes of CKD
Congenital disease eg pkd Glomerular disease vascular disease tin urinary obstruction
Complication of CKD
Polyuria Itching Gout Hyperprolactinaemia Polyneuropathy ED, amenorrhoea Anaemia renal osteodystrophy uraemic encephalopathy/pericarditis
How do you treat someone with vit d deficiency and CKD?
Calcitriol (activated vit d)
What do HHV 6 & 7 cause
Roseola infantum
What do the paramyxoviridae cause?
Measles & mumps
What are cestodes?
Tapeworms - from pork and beef
What are nematodes?
Roundworms - hookworm, pinworm, threadworm, whipworm
What are trematodes?
Schistosomiasis
Treatment of schistomiasis?
Praziquantel
What are adrenaline & noradrenaline
Direct sympathomimetics
Adrenaline –> act on beta and alpha - used in anaphylaxis, in CPR, with local anaesthetic, in croup
Noradrenaline –> vasoconstriction via alpha 1 receptors - used to increased systemic vascular resistance
Treatment of whooping cough
Erythromycin
What are phenylephrine and metaraminol?
Alpha agonists - vasoconstriction - sympathomimetics - like noradrenaline but less direct
Treatment of status epilepticus
Ensure safety, ABC, high flow o2
Give buccal midazolam, rectal diazepam or iv lorazepam –> up to 2 doses –> then iv phenobarbitol or phenytoin
If refractory –> iv propofol or thiopentol
What is ephedrine
Mixed alpha and beta agonist sympathomimetic
What is dobutamine
Directly acts on beta1 receptors (heart) –> so is an ionotrope - used in heart failure, pulmonary oedema
Timilol?
Decreases aqueous secretion of ciliary body - used in primary open angle glaucoma
What are alpha 1 receptors?
Causes vasoconstriction of non vital organs & contraction of bladder sphincter (sympathetic nervous system)
What are beta 1 receptors?
Increase contraction of cardiac muscle (sympathetic nervous system)
What are beta 2 receptors?
Relax smooth muscle of bronchus, vasculature and uterus (sympathetic nervous system)
What is digoxin?
Positive ionotrope - used in heart failure and AF
How do nitrates work?
Increase cyclic GMP
Vasodilates veins –> reduce preload (also vasodilate coronary arteries)
GTN - short acting
Isosorbide mononitrate - long acting
How verapamil & diltiazem work?
Block AV node
Histamine antagonists
H1 = antiallergy
Sedating - chlorphenamine, promethazine, cyclizine (also antiemetics)
Non-sedating = cetirizine, loratidine
H2 = parietal cells
Ranitidine, cimetidine
Pathophysiology of paracetamol overdose
Paracetamol usually metabolised by liver conjugation
In overdose the liver conjugation becomes inundated so paracetamol is metabolised by an alternate pathway, creating toxic NAPQ - this is inactivated by glutathione
When glutathione stores are depleted, NAPQ causes necrosis of liver and kidney cells
Rx - N acetyl cysteine
Carbon monoxide poisioning mgmt
High flow oxygen
sats are normal
TCA overdose - mgmt
Charcoal, gastric lavage
IV diazepam, IV sodium bicarbonate
Aspirin overdose - mgmt
Charcoal, gastric lavage
Urinary alkalinisation
Haemodialysis
Ethylene glycol poisoning - mgmt
ethanol or fomepizole - inhibit alcohol dehydrogenase
Digoxin toxicity - mgmt
FAB antibody
Insecticide poisoning - mgmt
Atropine
How to prove someone negligent?
Must be a duty of care Must be a breech of duty of care Are their action supported by others? Did pt come to harm? Did the breech cause the harm?
Effect of lithium on thyroid function?
Inhibits production and release of T3 and T4 –>hypothyroidism
What can cause hypernatraemia with a high urine output?
Osmotic diuresis
Impairment of ADH function (diabetes insipidus)
Causes of diabetes insipidus
Nephrogenic - lithium, CKD, ATN, hypercalcaemia, hypokalaemia
Cranial - trauma, infection, tumours
Diagnosis of diabetes insipidus
Water deprivation - failure to raise urine osmolality to 650 mmol/kg
Give desmopression - if cranial, osmolality will rise to >650, if nephrogenic, it won’t
