Clinical science Flashcards
Canakinumab MOA?
targets IL-1 beta
- used in systemic JIA, adult onset Still’s
what organs are in direct contact with the left kidney?
- Left suprarenal gland
- Pancreas
- Colon
what organs are in direct contact with the right kidney?
- Right suprarenal gland
- Duodenum
- Colon
p53 gene is located on which chromosome?
17p
role of p53 tumour suppressor?
preventing entry into the S phase until DNA has been checked and repaired.
- key regulator of apoptosis
What is responsible for rapid depolarisation of myocardial cells?
rapid sodium influx
What is responsible for early repolarisation of myocardial cells?
efflux of K+
What is responsible for the plateau before full repolarisation of myocardial cells?
slow influx of calcium
what is responsible for final repolarisation of myocardial cells?
efflux of K+
what is responsible for restoration of ionic concentrations of myocardial cells?
resting potential restored by Na+/K+ ATPase
What part of the heart is responsible for the fastest conduction?
purkinje fibres
- large diameter, velocities of 2-4m/s
IX of homocystinuria?
- Increased homocysteine levels in serum and urine
- cyanide-nitroprusside test: *also + in cystinuria
Mx of homocystinuria?
Pyridoxine Vit B6 supplements
Causes of increased lung compliance?
ie. greater change in lung volume/ unit change in airway pressure
- age
- emphysema - this is due to loss alveolar walls and associated elastic tissue
Causes of decreased lung compliance?
ie. decreased change in lung volume/ unit change in airway pressure
- pulmonary oedema
- pulmonary fibrosis
- pneumonectomy
- kyphosis
Function of leukotrienes?
- mediates inflammation/ allergic reactions
- causes bronchoconstriction, mucous production
- increases vascular permeability, attracts leukocytes
Leukotriene in NSAID induced bronchospasm in asthmatics?
NSAID induced bronchospasm in asthmatics is secondary to the express production of leukotrienes due to the inhibition of prostaglandin synthetase
Which technique would be most suitable to detect and quantify a viral protein?
Western blot
- detects *PROTEINS using gel electrophoresis
Function of Vit D?
- increases plasma calcium + phosphate
- increases renal tubular reabsorption and gut absorption of calcium
- increases osteoclastic activity
- increases renal phosphate reabsorption
Characteristic features of Rubella maternal infection in babies?
S.H.E.
- Sensorineural deafness
- Eyes: Congenital cataracts, Glaucoma
- Congenital heart disease (e.g. patent ductus arteriosus)
Characteristic features of Toxoplasmosis maternal infection in babies?
- Cerebral calcification
- Chorioretinitis
- Hydrocephalus
Characteristic features of CMV maternal infection in babies?
- Growth retardation
- Purpuric skin lesions
Differences between Toxoplasmosis and CMV maternal infection in baby?
Toxo: hydrocephalus
CMV: microcephaly
What cells are mostly responsible for creating granulomas?
macrophages
what cytokine is the main agent in macrophage activation?
IFN-gamma
Which cytokines are responsible for neutrophil chemotaxis?
IL-8, TNF alpha
which cytokines induce fever?
IL-1, IL-6, TNF-alpha
Which cytokine is an anti-inflammatory cytokine?
IL-10
MOA of growth hormone?
- acts on transmembrane R for growth factor
- binding of GH -> receptor dimerization
- acts directly on tissues + indirectly via IGF-1
where is IGF-1 primarily secreted?
liver
what decreases/ inhibits GH secretion?
glucose, somatostatin
What are funnel plots used for?
primarily to demonstrate existence of publication bias in meta-analyses
- treatment effects on horizontal axis, study size on vertical axis
Interpretation of a funnel plot?
a symmetrical inverted funnel shape (ie. triangle) -> suggests publication bias is unlikely.
if asymmetrical: indicates rs between tx effect and study size, indicating either publication bias or a systematic difference between larger and smaller studies
Features of Fabry disease?
- burning pain/paraesthesia in childhood- triggered by stress/heat/cold
- angiokeratomas
- lens opacities
- proteinuria
- early cardiovascular disease
genetics of Fabry disease?
X linked recessive -> deficiency of alpha-galactosidase A
proteinuria + early strokes/ MI + rash known as angiokeratomas?
Fabry disease
Subcortical infarcts and leukoencephalopathy + history of migraines and multiple strokes?
CADASIL
cerebral auto dominant arteriopathy with subcortical infarcts
MELAS =?
mitochondrial encephalopathy with lactic acidosis and stroke symptoms
what are the 5 layers of the epidermis?
- stratum corneum
- stratum lucidum
- stratum granulosum
- stratum spinosum
- stratum germinativum - the basement membrane
which layer of the epidermis gives rise to keratinocytes/ contain melanocytes?
bottom layer- stratum germinativum
which layer of the epidermis is the thickest layer of epidermis?
stratum spinosum
what type of receptors does adrenaline work on?
G-protein coupled receptors
mitochondrial diseases known for…?
poor genotype: phenotype correlation -
within a tissue or cell, there can be different mitochondrial populations (aka heteroplasmy)
Examples of Mitochondrial diseases?
- Leber’s optic atrophy
- MELAS
- MERRF: myoclonus epilepsy with ragged red fibres
- Kearns- Sayre: external ophthalmoplegia, retinitis pigments, ptosis
- sensorineural hearing loss
muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria
mitochondrial diseases
most common renal abnormality in Turner’s syndrome
Horseshoe kidney - occur in 10%.
- usually causes higher risk of ureteropelvic junction obstruction +/- UTI
Fanconi syndrome features / investigation findings?
- glucose +++ Protein ++ on urinalysis
(due to Proximal tubular cells not reabsorbing glucose and aas) - HypoK, HypoCa, HypoPO4
(failed reabsorption of electrolytes)
what part of the kidney is implicated in Fanconi syndrome?
proximal convoluted tubule
Features of phenylketonuria?
- usually presents by 6 mo with developmental delay
- classically fair hair, blue eyes
- learning difficulties
- seizures, typically infantile spasms
- eczema
- “musty” odour to urine and sweat
Defect in phenylketonuria?
defect in phenylalanine hydroxylase
- leading to high levels of phenylalanine *neurotoxic
what cell type mediates hyper acute organ rejection?
B cells
What cell types mediate acute/ chronic organ rejection?
T cells
features of Bartter’s syndrome?
- metabolic alkalosis
- low Na, K, Cl
- polyhydramnios typical in neonatal form
gene defect assoc w Li-Fraumeni?
p53
which part of the cell cycle determines the length of the cell cycle?
G1
shortest phase of the cell cycle?
M phase: mitosis
brown/bluish pigment of the ear cartilage or sclera, arthropathy, renal stones, cardiac valve involvement and coronary calcification.
Alkaptonuria
- auto reccessive
- elevated Homogentisic acid (HGA) which polymerises and deposits in connective tissue throughout the body
features of alkaptonuria?
- pigmented sclera
- urine turns black if exposed to air
- intervertebral disc calcification may result in back pain
- renal stones
pathophysiology of alkaptonuria?
auto recessive. build up of toxic HGA (Homogentisic acid)
treamtent of alkaptonuria?
high dose vit c, dietary restriction of phenylalanine and tyrosine
what complement deficiency causes one to be particularly prone to Neisseria meningitidis infection?
C5-9
- encodes the MAC
what complement deficiency predisposes to Leiner disease: recurrent diarrhoea, wasting, seborrheic dermatitis?
C5 deficiency
E.g.s of Type IV T cell mediated hypersensitivity reactions?
- Tuberculosis / tuberculin skin reaction
- Graft versus host disease
- Allergic contact dermatitis
- Scabies
- Extrinsic allergic alveolitis (especially chronic phase)
- Multiple sclerosis
- Guillain-Barre syndrome
Examples of type V mediated hypersensitivity reactions?
Graves disease, myasthenia gravis
- antibodies that bind cell surface receptors and either block/ stimulate
equation for standard error of the mean?
-ie. measure of the spread expected for the mean of the observations.
SEM = Standard deviation/ Square root (n= sample size)
What is the lower/ upper limit of a 95% confidence interval?
LOWER LIMIT: mean - (1.96 * SEM)
Upper limit: mean + (1.96 * SEM)
what percentage of values lie within 1/ 2/ 3 SD of the mean?
- 3% - 1 SD
- 4% - 2 SD
- 7% - 3 SD
equation relating standard deviation from variance?
SD = square root (variance)
Homocystinuria features?
- fine fair hair
- Arachnodactyly, marfinoid, osteoporosis/ kyphosis
- neuro: LD, seizures
- ocular: myopia, inferonasal lens dislocation
- increased risk of VTE/ arterial clot
- malar flash/ libero reticularis
Diabetic nephropathy histological findings?
Kimmelstiel-Wilson lesions, nodular glomerulosclerosis
what nerves go through the optic canal?
CN II - optic
What nerves go through the superior orbital fissure?
CN III, IV, V1, VI
what nerves go through the inferior orbital fissure?
Zygomatic nerve and infraorbital nerve of maxillary nerve (CN V2), Orbital branches of the pterygopalatine ganglion
what nerve goes through the foramen rotundum?
CN V2 - maxillary nerve
what nerve goes through the foramen ovale?
mandibular nerve - CNV3
what nerves go through the jugular foramen?
CN IX, X, XI
what statistical test is used to compare proportions or percentages following 2 different interventions?
Chi squared test
What cell receptor is a co-receptor for MHC Class I molecules?
CD8
what cell receptor is a co-receptor for MHC Class II molecules?
CD4
what cell receptor is expressed on Reed-Sternberg cells?
CD15, CD30
what cell receptor is receptor for EBV?
CD21
What cell receptor acts as the FAS receptor involved in apoptosis?
CD 95
immunological changes seen in progressive HIV infection?
increased B2-microglobulin, polyclonal B cell activation.
- decreased CD4, IL-2, NK cell function, reduced delayed hypersensitivity responses.
what hormone lowers appetite?
leptin
- produced by adipose tissues, works on satiety centres in the hypothalamus
what hormone increases appetite?
ghrelin
- produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas.
- Ghrelin levels increase before and decrease after meals
northern blotting used to..?
detect RNA
SNOW- DROP
Southern blotting used to…?
detect DNA
SNOW - DROP
what stage of the cell cycle is under p53 influence (regulating apoptosis)?
G1
What does endothelin do?
potent, long acting vasoconstrictor and bronchoconstrictor
what promotes release of endothelin?
- angiotensin II
- ADH
- hypoxia
- mechanical shearing forces
what inhibits release of endothelin?
- nitric oxide
- prostacyclin
where is endothelin secreted from?
secreted initially as a prohormone by the vascular endothelium
- later converted to ET-1 by endothelin converting enzyme.
what stimulates respiration in the central chemoreceptors of the brain??
raised [H+] (more acidic)
what stimulates respiration in the peripheral chemoreceptors of the body??
carotid + aortic bodies: raised pCO2 & [H+],
to a lesser extent low pO2
what is the Hering-Bruer reflex?
lung distension causes slowing of respiratory rate
sensed by stretch receptors
Management of Fabry disease?
enzyme replacement therapy with agalsidase alfa (alpha-galactosidase A.)
the addition of mannose-6-phosphate to proteins designates transport to which organelle?
lysosome
what does trop T bind to?
tropomyosin,
forming a troponin-tropomyosin complex
what does Troponin C bind to?
calcium ions.
- trop C is released by damage to both skeletal and cardiac muscle, making it an insensitive marker for myocardial necrosis
what does Troponin I bind to?
binds to actin,
to hold the troponin-tropomyosin complex in place,
specific to myocardial damage
how to calculate odds?
number of people who incur a particular outcome / no of ppl who do not incur the outcome..
odds ratio?
odds ratio = ratio of odds of a particular outcome with experimental treatment and that of control
how to calculate pulse pressure?
systolic pressure - diastolic pressure
factors which increase pulse pressure?
- less compliant aorta (tends to occur w advancing age),
- increased stroke volume
how to calculate systemic vascular resistance?
mean arterial pressure/ cardiac output
How to calculate likelihood ratio for a positive test result?
sensitivity/ (1- specificity)
- how much the odds of the disease increases by when test is positive
How to calculate likelihood ratio for a negative test result?
(1- sensitivity)/ specificity
- how much the odds of the disease decreases by when test is negative
mean/ median/ mode for Normal distributions?
mean = median = mode
mean / median/ mode for positively skewed distributions?
mean > median > mode
mean / median/ mode for negatively skewed distributions?
mean < median < mode
which part of the antibody binds to antigens?
Fab (antigen-binding fragment) region
which part of the antibody binds to immune cells?
Fc region (fragment crystallisable region- tail region of an antibody that interacts with cell surface receptors)
conditions assoc w HLA-DR3?
- dermatitis herpetiformis
- Sjogren’s syndrome
- primary biliary cirrhosis
HLA- A3?
haemochromatosis
HLA-B51?
Behcet’s disease
HLA-B27?
- ank spond
- reactive arthritis
- acute ant uveitis
HLA-DQ2/8?
Coeliac
HLA-DR2?
narcolepsy, Goodpastures
HLA-DR4?
- T1DM
- Rheumatoid arthritis (in particular DRB1 gene)
oncogene assoc with neuroblastoma?
n-MYC
oncogene assoc with follicular lymphoma?
BCL-2
oncogene assoc with MEN?
RET oncogene
dry beri beri?
peripheral neuropathy
- secondary to thiamine deficiency
conditions assoc with thiamine deficiency?
- Wernicke’s encephalopathy: nystagmus, ophthalmoplegia and ataxia
- Korsakoff’s syndrome: amnesia, confabulation
- dry beriberi: peripheral neuropathy
- wet beriberi: dilated cardiomyopathy
mitochondrial inheritance + rapid onset visual loss?
Leber’s hereditary Optic neuropathy
stroke like episodes + seizures + lactic acidosis?
MELAS- mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.
- mitochondrial inheritance
what is the Bohr effect in respiratory physiology?
Increasing acidity or pCO2 -> O2 binds less well to Hb
What is the Haldane effect in respiratory physiology?
increased pO2 means CO2 binds less well to Hb
what chromosome has the genes for HLA antigens?
chromosome 6
most common genetic cause of Prader-Willi syndrome?
microdeletion of paternal 15q11-13 (70% of cases)
what significance test is appropriate to calculate correlation between two things?
Spearman’s rank correlation coefficient, Kendall rank
mitochondrial inheritance +
onset < 20-years-old +
external ophthalmoplegia +
retinitis pigmentosa
Kearns-Sayre syndrome
which cell surface protein is used by HIV to enter T cells?
CD4
what is intention to treat analysis?
analyse all data, regardless of whether they completed/ received the treatment.
- to avoid effects of crossover and drop-out
Which part of the renal tubule is impermeable to water?
ascending limb of loop of Henle
what increases absorption of iron in the gut?
vit c, gastric acid
what decreases absorption of iron in the gut?
PPI, tetracycline, gastric achlorhydria, tannin (found in tea)
developmental delay and cherry red spot on the macula, without hepatomegaly or splenomegaly
Tay-Sachs disease
- accumulation of GM2 ganglioside within lysosomes
hepatosplenomegaly + cherry red spot on the macula
Niemann-Pick disease
hepatosplenomegaly + aseptic necrosis of the femur
Gaucher’s disease
- accumulation of glucocerebrosidase in brain, liver, spleen
Maxillary nerve goes through?
foramen rotundum
Mandibular nerve goes through?
foramen ovale
X linked dominant conditions?
Alports syndrome
Rett syndrome
Vit D resistant rickets
what occurs in phase I drug metabolism?
oxidation, reduction, hydrolysis
what occurs in phase II drug metabolism?
conjugation
Drugs exhibiting zero-order kinetics?
e.g. enzyme saturated
phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol
Drugs affected by deficiency in hepatic N-acetyltransferase?
isoniazid procainamide hydralazine dapsone sulfasalazine
causes of oculogyric crises?
antipsychotics, metoclopramide, postencephalitic Parkinsons disease
mx of oculogyric crisis?
IV benztropine/ procyclide (antimuscarinic)
Infliximab MOA? used in?
anti-TNFa
- used in rheumatoid arthritis, Crohn’s
Rituximab MOA? used in?
anti-CD20
- used in Rheumatoid arthritis, non-Hodgkins lymphoma
Cetuximab MOA? used in?
Epidermal growth factor receptor antagonist
- used in metastatic colorectal cancer, H+N cancer
Trastuzumab MOA? used in?
HER2/ neu receptor antagonist
- used in metastatic breast ca
Alemtuzumab MOA? used in?
anti-CD52.
- used in CLL
OKT3 MOA? used in?
anti-CD3.
- used to prevent organ rejection
IV sodium bicarb in lithium toxicity?
works to increase urinary alkalinity to promote lithium excretion
- preferred treatment in severe cases would be haemodialysis
what abx is CI in G6PD deficiency?
ciprofloxacin
e.g.s of mixed alpha and beta antagonists?
carvedilol, labetalol
alpha 1 blocker?
doxazosin
alpha 1 a blocker?
tamsulosin - acts mainly on urogenital tract
alpha 2 blocker?
yohimbine
non selective alpha blocker?
phenoxybenzamine
beta 1 blocker?
atenolol
non selective beta blocker?
propranolol
fomepizole MOA?
competitive inhibitor of alcohol dehydrogenase
How does COHb affect the oxygen dissociation curve?
left shift of oxygen dissociation curve
causes of drug induced thrombocytopenia?
- quinine
- abciximab
- NSAIDs
- diuretics: furosemide
- antibiotics: penicillins, sulphonamides, rifampicin
- anticonvulsants: carbamazepine, valproate
- heparin
which electrolyte abnormalities predispose to digoxin toxicity?
hypoK,
HypoMg,
HyperCa, HyperNa
alpha 1 agonist?
phenylephrine
alpha 2 agonist?
clonidine
beta 1 agonist?
dobutamine
Moa of digoxin?
inhibition of Na/K ATPase pump
first line therapy for hypotension or arrhythmias in TCA OD?
IV bicarbonate
management of motion sickness?
- hyoscine (transdermal patch)
- cyclizine (antihistamine)
- Sedating- promethazine
Aspirin MOA?
blocks Cox 1 and COX2
- > blocks thromboxane A2 formation in platelets
- > decreases ability of platelets to aggregate
blood test to monitor LMWH?
anti-factor Xa levels
blood test to monitor heparin?
APTT
heparin induced thrombocytopenia- what are antibodies formed against?
complexes of platelet factor 4 (PF4) and heparin
drugs that commonly cause urticaria?
aspirin,
penicillins,
NSAIDs,
opiates
features of organophosphate insecticide poisoning?
- inhibition of acetylcholinesterase -> upregulation of cholinergic neurotransmission
- Salivation
- Lacrimation
- Urination
- Defecation/ diarrhoea
- CV: bradycardia, hypotension
What CV effects are seen in organophosphate insecticide poisoning?
bradycardia, hypotension
management of organophosphate insecticide poisoning?
atropine
Drugs known to cause impaired glucose tolerance?
- thiazides, furosemide
- steroids
- tacrolimus, ciclosporin
- IFN-alpha
- nicotinic acid
- antipsychotics
- beta blockers can cause a slight impairment
management of accidental injection of adrenaline?
local infiltration of phentolamine
what electrolyte changes does Adrenaline have on the body>
hyperglycaemia, high lactate, hypokalaemia
Pilocarpine MOA?
muscarinic agonist
uses of somatostatin?
- acute treatment of variceal haemorrhage
- acromegaly
- carcinoid syndrome
- prevent complications following pancreatic surgery
- VIPomas
- refractory diarrhoea
SE of somatostatin?
gallstones - secondary to biliary stasis
management of cocaine-induced hypertension?
benzodiazepines + sodium nitroprusside
management of cocaine-induced chest pain?
benzodiazepines + GTN
King’s College Hospital criteria for liver transplantation (in paracetamol OD)?
Arterial pH <7.3, 24h after ingestion
OR all of the following:
- PT >100 seconds
- Cr >300
- Grade III/ IV encephalopathy
What is the most appropriate time to take blood samples for therapeutic monitoring of phenytoin levels?
trough levels, immediately before dose
E.g.s of Class Ia antiarrhythmics?
- Quinidine
- Procainamide
- Disopyramide
MOA- bocks Na channels, increases AP duration
E.g.s of Class Ib antiarrhythmics?
- Lidocaine
- Tocainide
- Mexiletine
MOA- bocks Na channels, increases AP duration
E.g.s of Class Ic antiarrhythmics?
- Flecainide
- Encainide
- Propafenone
MOA- bocks Na channels, no effect on AP duration
E.g.s of Class II antiarrhythmics?
Propranolol
Atenolol
Bisoprolol
Metoprolol
MOA: Beta blockers
E.g.s of Class III antiarrhythmics?
- Amiodarone
- Sotalol
- Ibutilide
- Bretylium
MOA: blocks K+ channels
E.g.s of Class IV antiarrhythmics?
- Verapamil
- Diltiazem
MOA: CCB
Cardiovascular effects of cocaine use?
- coronary artery spasm → myocardial ischaemia/infarction
- both tachycardia and bradycardia may occur
- hypertension
- QRS widening and QT prolongation
- aortic dissection
Neurological effects of cocaine toxicity?
- seizures
- mydriasis
- hypertonia
- hyperreflexia
Psychiatric effects of cocaine toxicity?
agitation
psychosis
hallucinations
systemic effects of cocaine toxicity?
- ischaemic colitis
- met acidosis
- rhabdo
- hyperthermia
Nivolumab MOA? used in?
PD-1 (programmed cell death) inhibitor.
- used in lung cancer
SE of ciprofloxacin?
- lowers seizure threshold -> more seizures
- tendon damage/ rupture
- cartilage damage (hence, generally avoided in children)
- lengthens QT
Contraindications for ciprofloxacin?
Breastfeeding/ Pregnancy
- G6PD
MOA of tamsulosin?
Alpha 1a Blocker
Drugs that can be cleared with haemodialysis?
BLAST
- Barbiturate
- Lithium
- Alcohol (inc methanol, ethylene glycol)
- Salicylates
- Theophyllines (charcoal haemoperfusion is preferable)
Drugs which cannot be cleared with haemodialysis?
- TCAs
- benzodiazepines
- dextropropoxyphene (Co-proxamol)
- digoxin
- beta-blockers
Causes of low Mg?
- Drug: diuretics, PPI
- TPN
- Diarrhoea
- Alcohol
- HypoK
- HyperCa: Ca + Mg compete for transport in the thick ascending limb of the loop of Henle
- Gitelmans/ Bartter’s metabolic disorders
Gentamicin Contraindications?
myasthenia gravis
which calcium channel blocker causes constipation as a side effect?
verapamil
which antibiotic inhibits DNA synthesis?
quinolone e.g. ciprofloxacin
which antibiotic damages DNA?
metronidazole
flecainide in patients with heart failure?
contraindicated in structural heart disease e.g. heart failure,
+ has a negative inotropic and pro arrhythmic effect
Features of mercury poisoning?
- parasthesiae
- visual field defects
- hearing loss
- irritability
- renal tubular acidosis
Adverse effects of allopurinol?
most significant ones are dermatological, stop immediately if they develop a rash:
- SCAR (severe cutaneous adverse reaction)
- DRESS (drug reaction with eosinophilia and systemic symptoms)
- stevens johnson syndrome
what ethnicities are at increased risk of dermatological side effects of Allopurinol?
chinese, Thai, Korean
what ix should be done if worried about high risk of severe cutaneous adverse reaction when starting allopurinol?
screen for HLA-B*5801 allele
Causes of serotonin syndrome?
- MAO inhibitors
- SSRIs. + St John’s Wort
- ecstasy
- amphetamines
features of serotonin syndrome?
- neuromuscular excitation e.g. myoclonus, rigidity, hyperreflexia
- hyperthermia
- altered mental state
management of serotonin syndrome?
supportive, IV fluids
- benzos
- severe: serotonin antagonists e.g. cyproheptadine, chlorpromazine
management of severe serotonin syndrome?
serotonin antagonists
e.g. cyproheptadine, chlorpromazine
contraindications of flecainide?
- post MI
- structural heart disease. e.g. heart failure
- sinus node dysfunction, 2nd degree or greater AV block
- atrial flutter
management of symptomatic bradycardia secondary to OD if not responding to atropine?
glucagon
acid/ base status in salicylate/ aspirin OD?
mixed met acidosis and resp alkalosis
what serum concentration of salicylate is an indication for haemodialysis?
> 700mg/l
what should be investigated prior to commencing trastuzumab?
echo - as trastuzumab may be cardiotoxic
adverse effects of trastuzumab?
flu like symptoms, diarrhoea - common
- cardiotoxicity
RUQ pain in someone taking octreotide?
biliary stasis and gallstones are a risk
brick red skin + smell of bitter almonds + hypoxia, hypotension, headache, confusion?
Cyanide poisoning
management of cyanide poisoning?
100% oxygen,
IV hydroxocobalamin
or IV sodium nitrite and sodium thiosulfate + inhaled amyl nitrite
what might increase the risk of cardio toxicity with trastuzumab treatment?
anthracyclines
e.g. doxorubicin
what are the different pathophysiologies of Amiodarone-induced thyrotoxicosis types 1 and 2?
AIT Type 1: Excess iodine-induced thyroid hormone synthesis, goitre present
AIT Type 2: Amiodarone-related destructive thyroiditis, goitre absent
management of amiodarone-induced thyrotoxicosis types 1 and 2?
Type 1: Carbimazole or Potassium perchlorate
Type 2: corticosteroids
Should you continue amiodarone treatment in amiodarone-induced thyrotoxicosis / hypothyroidism?
hypothyroidism: can continue
thyrotoxicosis: stop amiodarone
good differentiating feature between methanol and ethylene glycol toxicity?
methanol toxicity: visual problems, including blindness, due to accumulation of formic acid
management of ophthalmological complications with methanol toxicity?
cofactor therapy with folinic acid
renal impairment: which anti-TB drugs should be adjusted?
reduction in Ethambutol dose
smoking - effect on liver enzymes?
inducer of CYP1A2- smokers require more aminophylline
management of ingestion of caustic substances?
- High dose IV PPI
- urgent Upper GI endoscopy to assess degree of ulceration
features of quinine toxicity / OD?
aka cinchonism
- cardiac arrhythmia, flash pulmonary oedema (prolongs QRS/ QT)
- hypoglycaemia
- tinnitus, visual blurring, flushed and dry skin, abdo pain
therapeutic monitoring of ciclosporin?
trough levels, immediately before next dose
Adverse effects of ciclosporin?
high: fluid, hypertension, hyperK, hypertrichosis, gingival hyperplasia, hyperlipidaemia. - nephrotoxicity - hepatotoxicity - tremor
impaired glucose tolerance
MOA of propofol?
GABA agonist
- for rapid onset of anaesthesia
agent of choice for rapid sequence of induction due to extremely rapid onset of action?
Sodium thiopentone
MOA of Ketamine?
NMDA receptor antagonist
suitable agent for anaesthesia in those who are haemodynamically unstable due to minimal myocardial depression?
ketamine
medication causing blue tinge to vision?
sildenafil
- “blue pill”/ blue vision
Features suggesting restrictive cardiomyopathy rather than constrictive pericarditis
- prominent apical pulse
- absence of pericardial calcification on CXR
- the heart may be enlarged
- ECG abnormalities e.g. bundle branch block, Q waves
1st line management in acute glaucoma when patients have a history of asthma?
prostaglandin analogue - latanoprost
Evolocumab MOA?
prevents PCSK9-mediated LDL receptor degradation.
-> Increasing liver LDLR levels results in associated reductions in serum LDL-cholesterol.
End stage renal failure + painful necrotic skin lesions + calcium deposit in skin biopsy
Calciphylaxis
- tx: reducing calcium and phosphate levels
what drug contributes to calciphylaxis in end stage renal patients?
warfarin
what increases risk of hepatotoxicity in someone who has taken a paracetamol OD?
- liver enzyme inducing drugs e.g. Rifampicin, chronic alcohol excess
- malnutrition (depletion of glutathione stores)
*note acute alcohol excess is not assoc w increased risk
managing hypothyroidism: what should the TSH be with treatment?
0.5 to 2.5 mU/l
Ix (First line) of age related macular degeneration?
slit-lamp microscopy:
to identify any pigmentary, exudative or haemorrhagic changes affecting the retina
ix of choice if wet/ neovascular age related macular degeneration is suspected?
fluorescein angiography:
can guide intervention with anti-VEGF therapy.
*may be complemented with indocyanine green angiography to visualise any changes in the choroidal circulation.
dacrocystitis = ?
infection of the lacrimal sac
risk factors of primary open angle glaucoma?
- increasing age
- family hx
- Afro-Carrib
- *myopia
- hypertension
- diabetes mellitus
- corticosteroids
starting statin as primary prevention of cardiovascular disease, what aim?
aim for a reduction in non-HDL cholesterol of > 40%
which glaucoma medications increases uveoscleral outflow?
- prostaglandin analogues e.g. latanoprost
2. miotics e.g. pilocarpine (muscarinic agonist)
which glaucoma medications reduces aqueous production alone?
- Beta blockers e.g. timolol
2. carbonic anhydrase inhibitors e.g. dorzolamide
which glaucoma medication both reduces aqueous production and increases uveoscleral outflow?
sympathomimetics e.g. brimonidine, an alpha2 adrenoreceptor agonist
e.g. of depolarising muscle relaxant (anaesthetic)
suxamethonium
e.g.s of non depolarising muscle relaxants
atracurium, vecuronium, pancuronium
effects may be reversed by neostigmine
Causes of predominantly hypercholesterolaemia, rather than hypertriglyceridaemia?
- nephrotic syndrome
- cholestasis
- hypothyroidism
conditions associated with retinitis pigmentosa?
- Refsum disease: cerebellar ataxia, peripheral neuropathy, deafness, ichthyosis
- Usher syndrome
- abetalipoproteinemia
- Lawrence-Moon-Biedl syndrome
- Kearns-Sayre syndrome
- Alport’s syndrome
what drugs may precipitate acute glaucoma?
anticholinergics, TCAs
Hypoca/ HyperCa leads to cataracts?
HypoCa
Gitelman’s syndrome: where is the defect?
defect in the thiazide-sensitive Na/Cl transporter in the distal convoluted tubule
Features of Gitelman’s syndrome?
normotension,
- HypoK, HypoMg
- Hypocalciuria
- met alkalosis
Causes of macroglossia?
- hypothyroidism
- acromegaly
- amyloidosis
- Duchenne muscular dystrophy
- mucopolysaccharidosis (e.g. Hurler syndrome)
what causes shift of oxygen to the left? ie. lower affinity to Hb
HbF, methaemoglobin, COHb
- Low [H+]: Alkaline
- Low pCO2
- Low 2-3- DPG
- Low temp
what causes shift of oxygen to the right? ie. higher affinity to Hb
- raised [H+]: acidic
- raised pCO2
- raised 2,3-DPG
- raised temp
Which adrenoceptor causes inhibition of pre-synaptic neurotransmitter release in response to sympathetic stimulation?
alpha 2
- inhibits adenylate cyclase
Which adrenoceptor causes vasoconstriction and relaxation of GI muscle in response to sympathetic stimulation?
alpha 1
- activates phospholipase C → IP3 → DAG
first line medication used for agoraphobia?
sertraline
what statistical measure is used best to analyze survival over time?
Hazard ratio
what drug is appropriate to sedate someone with acute intermittent porphyria?
chlorpromazine
Causes of angioid retinal streaks on fundoscopy?
- pseudoxanthoma elasticum
- Ehler-Danlos
- Paget’s disease
- sickle cell anaemia
- acromegaly
what ophthalmological finding is more common in pseudoxanthoma elasticum?
angioid retinal streaks
causes of Hypokalaemia with hypertension?
- conns
- cushings
- Liddle’s syndrome
- 11 beta hydroxylase deficiency
- drugs: e.g. carbenoxolone (an anti-ulcer drug), liquorice excess
Causes of hypokalaemia without hypertension?
- diuretics
- GI loss e.g. D+V
- renal tubular acidosis types 1 and 2
- Bartter’s syndrome
- Gitelman syndrome
Currently, what are the most common causes of viral myocarditis?
Parvovirus B19, HHV 6
what medication may reduce vit B12 absorption, causing B12 deficiency?
metformin
Where is the defect in Bartter’s syndrome?
Defective chloride absorption at Na/K/2Cl cotransporter in the ascending loop of Henle.
e.g. like taking large doses of furosemide
Features of Bartter’s syndrome?
- presents in childhood
- polyuria, polydipsia
- hypoK
- normotension
- weakness
acute onset of unilateral (occasionally bilateral) severe pain, followed by shoulder and scapular weakness several days later. sensory change minimal
brachial neuritis
jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
Whipple’s disease
- caused by Tropheryma whippelii
- malabsorption, arthralgia, LNpathy, skin hyperpigmentation
1st line for generalised anxiety disorder?
sertraline
drugs that cause photosensitivity?
- thiazides
- tetracyclines, sulphonamides, ciproflox
- amiodarone
- NSAIDs e.g. piroxicam
- psoralens
- sulphonylureas
What is the best predictor of mortality post-STEMI in treadmill exercise testing?
exercise capacity
bilateral sensorineural deafness, mild hypothyroidism, goitre ?
Pendred syndrome
- auto recessive
Tx of Pendred syndrome?
thyroid hormone replacement + cochlear implants
MX of oculogyric crisis?
IV antimuscarinic: benztropine or procyclidine
1st line mx for diabetic peripheral neuropathy?
duloxetine
what foods interact with monoamine oxidase inhibitors and might cause a hypertensive reaction?
tyramine containing foods e.g. cheese, pickled herring, Bovril, Oxo, marmite, broad beans
MOA of naftidrofuryl which may be used for peripheral vascular disease?
5-HT2 receptor antagonist
what medication should not be prescribed with statins if there is a history of myalgia (due to risk of muscle toxicity)?
fibrates
Which type of thyroid cancer is most assoc with the RET oncogene?
medullary
- RET oncogene assoc MEN 2
Features of Noonan’s syndrome?
seen as ‘Male turners’
- auto dominant
- cardiac: pulmonary valve stenosis
- coagulation: fXI deficiency
MOA of amiloride?
blocks the epithelial sodium channel in the distal convoluted tubule
- weak diuretic, usually given with thiazides/ loop diuretics
what medication is associated with the unmasking of Churg-strauss syndrome?
montelukast
Genetics of Liddle’s syndrome?
auto dominant
- disorder sodium channels in the distal tubules leading to increased sodium reabsorption
Features of Liddle’s syndrome?
Hypertension + hypoK alkalosis
Management of Liddle’s syndrome?
amiloride/ triamterene
What is the main action of atrial natriuretic peptide?
vasodilation
Irinotecan: MOA of this cytotoxic drug?
inhibits topoisomerase I which prevents relaxation of supercoiled DNA
e.g.s of centrally acting antihypertensive?
- methyldopa
- moxonidine
- clonidine
what increases the risk of fluid retention in patients on pioglitazone?
if patients are also taking insulin
what is pre-test probability?
prevalence
- proportion of people at risk at a specific time (point prevalence) or time interval (period prevalence)
What is post-test probability?
the proportion of patients w that particular test result who have the target disorder
post test probability = post test odds/ (1 + post-test odds)
Pre test odds - what is it?
the odds that the patient has the target disorder before the test is carried out
pre-test odds = pre-test probability / (1 - pre test probability)
post-test odds?
post test odds= pre test odds x likelihood ratio
Features of galactosaemia?
jaundice failure to thrive hepatomegaly cataracts hypoglycaemia after exposure to galactose Fanconi syndrome
painful third nerve palsy?
posterior communicating artery aneurysm
Associations of yellow nail syndrome?
- congenital lymphoedema
- pleural effusions
- bronchiectasis
- chronic sinus infections
Upbeat nystagmus?
cerebellar vermis lesion
Downbeat nystagmus?
Arnold Chiari malformation
- foramen magnum lesions
What CN is involved in a hypersensitive carotid sinus reflex?
CN IX (Glossopharyngeal)
most common cause of death in Friedrich’s ataxia?
HOCM
Difference between Pearson’s correlation coefficient and Spearman’s rank correlation coefficient?
Pearson’s correlation coefficient:
- “R” - measure of association between 2 continuous scale measurements
vs
Spearman’s rank correlation coefficient:
- correlation between ranks of 2 variables
- for categorical (ordinal) variables
regulation of satiety - what controls this in the hypothalamus?
ventromedial nucleus of hypothalamus