Liver Disease - 1 - Flashcards in University Pharmacy

What are the main functions of the liver? (1)

Metabolism (carbohydrate, protein, fat, steroid hormones, insulin, aldosterone, bilirubin, drugs). Synthesis (proteins e.g. albumin, clotting factors, fibrinogen, cholesterol, 25-OH of vit D, gluconeogenesis/glucose from fat and protein)

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What are the main functions of the liver? (2)

Immunological (Kupffer cells). Storage (fat soluble vitamin A, D, E, K, B12, folic acid). Homeostasis (glucose). Production of bile (secretion of bile salts, enterohepatic circulation). Clearance (bilirubin, drugs, toxins)

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Describe features of the liver (1)

Ability to regenerate. Liver disease can manifest in a broad spectrum of conditions. Can range from mild and self-limiting to severe with high mortality. Many patients can be asymptomatic until development of hepatic complications

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Describe features of the liver (2)

Long time interval between disease occurrence and detection. Increase in premature mortality rates. Most drugs metabolised in liver. Clotting factors (INR), fibrinogen (clotting cascade). LFT (metabolic/synthetic function of liver)

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Describe features of the liver (3)

Bile (aids absorption, digestion of fats/soluble vitamins). Glycogen to glucose. Patients - alcoholics, viruses, fibrosis, scarring of liver

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Describe features of the liver (4)

Compensated liver disease - functional loss, doesn't manifest, able to continue functioning, LFT normal, asymptomatic. Decompensated - ascites, jaundice. Could drink alcohol for years with no signs of liver dysfunction for a long period of time

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What is the aim of the treatment for liver disease?

Extend quality of life in patients with liver disease (extend life before liver transplant)

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Outline the anatomy of the liver

Largest internal organ. Located near stomach, pancreas, gall bladder. Left lobe (smaller) and right lobe of liver

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Outline the classification of liver disease

Classified based on pattern of damage and time course over which damage occurs. Main patterns of damage initially classified as cholestatic or hepatocellular (overlap can occur). Both of these can lead to fibrosis and cirrhosis

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Describe features of cholestasis (1)

Disruption of bile flow (stagnation of bile in bile ducts). Intrahepatic (biliary ductules have stricture/blockage, PBC, drugs, inflammation)

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Describe features of cholestasis (2)

Extrahepatic - cancer outside liver, stops bile flowing out of liver, mechanical obstruction e.g. inflammation of bile ducts, strictures, gall stones. Impaired biliary excretion and reduced absorption of fatty substances

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Describe features of cholestasis (3)

Accumulation of bile salts can lead to damage to hepatocytes

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Describe features of hepatocellular disease

Injury to hepatocytes e.g. toxins, viruses. Fatty infiltration - steatosis, accumulation of fat within hepatocyte, micro vs macro vesicular. Inflammation - hepatitis (acute/chronic, small/widespread). Cell death - necrosis

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Describe the classification of liver disease - fibrosis and cirrhosis (1)

Persistent, extensive hepatocyte damage, active deposition of collagen formation of scar tissue - fibrosis. Disruption of blood flow. Erratic regeneration and nodules can form. Cirrhosis. F0 (patient without fibrosis)

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Describe the classification of liver disease - fibrosis and cirrhosis (2)

F1/2/3 (fibrosis, initial/intermediate/advanced), production of fibrinogen, stiffness in liver - fibrosis is reversible (e.g. patient stops drinking, reverse condition). F4 - cirrhosis (irreversible). Treat cause of being cirrhotic

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Describe the classification of liver disease - fibrosis and cirrhosis (3)

Can be partly fibrotic (reversible part, detected on scan). Etiological factors (alcohol abuse, viral infections, NAFLD, others)

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Describe features of acute vs chronic (1)

Acute - history of onset of symptoms doesn't exceed 6 months. Acute liver failure - hyperacute, acute or subacute, depending on time from jaundice to encephalopathy

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Describe features of acute vs chronic (2)

Chronic - persist for more than 6 months, permanent structural changes following long standing cell damage, long term alcohol use, hep C, can be undiagnosed/untreated. Compensated vs decompensated disease

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Describe features of bilirubin in the LFT (1)

Usual range 5-20 micromol/L. Product of rbc breakdown. Transported to liver in serum attached to albumin. Transformed into water soluble conjugate to be excreted via bile into intestine

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Describe features of bilirubin in the LFT (2)

Levels increased (haemolysis/possibly congenital disease, hepatocellular damage, cholestasis/build-up of bilirubin). Clinical jaundice when bilirubin > 50 micromol/L. High bilirubin, yellow skin, jaundice. Reduced metabolic function, no conjugation

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Describe features of AST and ALT in the LFT (1)

AST (0-40 iu/L) found in liver, heart, skeletal muscle, pancreas, kidney and rbc (less liver specific, shorter t 1/2. level changes quickly after transplant). ALT (5-30 iu/L) liver specific enzyme, levels increase in viral hepatitis

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Describe features of AST and ALT in the LFT (2)

Alcohol related liver injury, drugs, sepsis, level takes longer to change. Not all patients with liver disease have raised ALT

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Describe features of AST and ALT in the LFT (3)

End-stage liver disease – patients very ill but normal LFT due to all liver cells being damaged. Disease progression – ALT generally increases to a certain point (then normalises, close to death, no more liver to kill)

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Describe features of ALP and γ-GT in the LFT (1)

ALP (30-120 iu/L) found in liver, bone, intestine, placenta, increased in cholestasis, infiltrative liver disease, damage to biliary tree. If raised ALP in isolation, may be due to other reasons e.g. Paget's disease

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Describe features of ALP and γ-GT in the LFT (2)

GGT (5-55 iu/L) found in liver, biliary epithelial cells, pancreas, kidneys, prostate, intestine, increased by enzyme inducers, alcohol, cholestasis, carcinoma of pancreas and GIT

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Describe features of albumin and PT in the LFT (1)

Albumin (35-50 g/dL) protein produced by liver, long t1/2 (20-26 days), reduced level in oedema, decreased in chronic liver disease. Indicator of synthetic function, marker of long term liver disease

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Describe features of albumin and PT in the LFT (2)

Lower in patients with oedema/ascites due to albumin in peritoneum (less to vasculature). PT/INR (10-14s) clotting factors produced by liver, short t1/2 (2-3 days), PT/INR increased in acute/chronic liver disease

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Describe features of albumin and PT in the LFT (3)

INR raised due to not creating clotting factors, indicator of synthetic function

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Describe how to interpret LFTs (1)

LFTs fairly non-specific. If 2 x ULN considered abnormal. If liver dysfunction - usually at least 2 will be deranged. Trends not in isolation. Check reference ranges and units. LFTs not always abnormal even in patients with cirrhosis

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Describe how to interpret LFTs (2)

Abnormal LFTs are not necessarily because of liver dysfunction. Never look at one LFT on its own, look at tests as a combination. Review over 3-6 months. Patient may need biopsy

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Describe features of the Child's Pugh scoring system

Points indicated for encephalopathy, ascites, bilirubin, albumin, and INR. Score 0-12, A <6, B 7-9, C >10 (A - best function of liver). Different patients can have the same score but different clinical presentations

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What are the other investigations for liver disease? (1)

Liver ultrasound (check if liver is homogenous, lesions, in liver, cancers in liver, test every 6 months in cirrhotic patients or newly diagnosed). CT scan, ERCP and MRCP (endoscopic scans, stent used for stricture in bile duct, view cells). MRI

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What are the other investigations for liver disease? (2)

Fibroscan (stiffness of liver, more scarring/stiffer/higher scan number >10 - cirrhotic). Liver biopsy to look at cells. MELD and UKELD

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What are the signs and symptoms of liver disease? (1)

Jaundice (yellow skin, yellow eyes, itchy), ascites (can be painful), unexplained bruising and bleeding. Varices. Encephalopathy. Abdominal pain. Pale stools and dark urine. Blood in stools. Gynaecomastia (not metabolising hormones)

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What are the signs and symptoms of liver disease? (2)

Fatty stools (not absorbing/digesting fats), spider naevi. Finger clubbing and pruitis

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Describe features of jaundice (hyperbilirubinaemia)

Yellowing of skin and whites of the eyes. Caused by a build up of bilirubin in the blood and tissues of the body. Common signs - yellowing of skin, eyes and mucus membrane, pale coloured stools (faeces), dark coloured urine

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What is pre-hepatic jaundice?

Disruption occurs before bilirubin has been transported form blood to liver. Caused by conditions such as sickle cell anaemia

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What is intra-hepatic jaundice?

Hepatocellular jaundice. Disruption occurs inside liver. caused by conditions such as Gilberts Syndrome and cirrhosis

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What is post-hepatic jaundice?

Obstructive jaundice. Disruption prevents bile (and bilirubin inside it) from draining out of the gallbladder into the digestive system. Caused by conditions such as gallstones and tumours

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Describe features of ascites (1)

Accumulation of fluid in the peritoneal cavity leading to swollen abdomen. 3 theories. Underfill - reduction in circulating plasma volume. Overflow - increased plasma volume. Peripheral artery vasodilation

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Describe features of ascites (2)

Underfill - portal HTN, ascites, decreased effective intravascular volume, RAAS activated, renal Na retention, increased blood volume

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Describe features of ascites (3)

Overflow - increased blood volume due to issues with RAAS. Primary renal Na retention, cirrhosis

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Describe features of ascites (4)

Vasodilation - peripheral arterial vasodilation, decreased effective intravascular volume, activation of RAAS, renal Na retention, increased blood volume

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What is the treatment for ascites? (1)

Restrict Na intake before starting diuretics. Aldosterone antagonist (spironolactone 100-400 mg OD), monitor Na and K (hyperkalaemia hyponatraemia, weight loss between 0.5-1 kg/day, gynecomastia in men/painful, may need to change diuretic)

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What is the treatment for ascites? (2)

Furosemide (loop diuretic, similar monitoring). Amiloride. Can have diuretic resistance (low Na level), low BP. Paracentesis for large volume - need to maintain adequate circulating volume - colloids, albumin, terlipressin (drain 3-10 L of fluid)

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What is the treatment for ascites? (3)

Ensure fluids are replenished with albumin to prevent shock. Transjugular intrahepatic portosystemic shunting (TIPSS) for more refractory ascites (along with paracentesis), reduce portal pressures/ascites reduced

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Describe features of the TIPSS procedure (1)

Prior - PHT causes blood flow to be forced backward, causing veins to enlarge and varices to develop across oesophagus and stomach from pressure in portal vein. Pressure backup also causes spleen to enlarge

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Describe features of the TIPSS procedure (2)

After - shunt allows blood to flow normally through the liver to the hepatic vein. Reduces portal HTN, allows veins to shrink to a normal size helping to stop variceal bleeding

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Describe features of the TIPSS procedure (3)

Cirrhotic liver – blood not entering liver, portal pressure increases, complications of disease, oesophageal/gastral variceals, by-pass blood flow, reduce complications of disease (comes with its own complications)

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What are the cautions with ascites? (1)

Daily U&E (Na, K, Cr). Daily weight (aim for 0.5-1 kg/day loss). Fluid charge (fluid restriction, urine output). Avoid high Na preparations (e.g. soluble preparations). Complications (dilutional hyponatraemia, HRS, gynaecomastia, hyperkalaemia

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What are the cautions with ascites? (2)

HE (due to change in electrolytes). Muscle cramps, spontaneous bacterial peritonitis (SBP)

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Describe features of spontaneous bacterial peritonitis (1)

Infection of ascitic fluid without intra-abdominal source of sepsis. 75% from gut, 25% from skin. Neutrophil count > 250 cells/mm^3. Mortality rate ~ 40%. 3rd generation cephalosporins, co-amoxiclav, Tazocin. Norfloxacin/ciprofloxacin, prophylaxis

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Describe features of spontaneous bacterial peritonitis (2)

SBP – lots of protein/fluid in peritoneum leads to growth of bacteria, tender abdomen, can become septic (broad spectrum antibiotics needed). WCC > 250, grow bacteria – use ciprofloxacin to prevent recurrent (floxacin – not licensed)

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What is hepatic encephalopathy?

Brain dysfunction caused by liver insufficiency and or/***. Manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma. Can occur in acute or chronic liver disease. 4 clinical grades

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What are the theories for the cause of HE?

Accumulation of toxins, increased BBB permeability, increased levels of neurotransmitters

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What are the potential precipitating factors for HE?

Increased protein load, reduced ammonia secretion, electrolyte imbalance/disturbance, infections, dehydration, drugs. Potential correctable. Differential diagnosis - symptoms can be likened to hypoglycaemia, alcohol intoxication, withdrawal

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Describe features of the ammonia cycle

Ammonia metabolised in liver, excreted in kidneys, bacteria in gut produce ammonia, convert urea back into ammonia to be reabsorbed, increased ammonia, cross BBB, cause intra-cerebral swelling, dysfunction

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What are the 4 main clinical grades for HE?

Minimal/grade 1 – patients may not have HE, just confusion/disorientation. Grades 2/3/4 – patients more aggressive, change in behaviour, more drowsy, confused. Grade 4 – coma (diagram/table)

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What is asterixis?

Indication of HE, patient closes eyes, raise hands up, observe flapping tremor. Animal naming test also used to determine precipitation of HE - name as many animals in 60 s (patients may repeat themselves), >15 good, <10 (need treatment)

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What are the treatments for HE? (1)

Lactulose (non-absorbable disaccharide, aim for 2-3 loose stools/day, promotes growth of beneficial microbes, reduce gut protein load, lower colonic pH to discourage bacteria producing ammonia), enemas used when patient is constipated

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What are the treatments for HE? (2)

30-50 mL TDS – not usually tolerated, causes diarrhoea, flatulence. In reality use 15-30 mL BD – titrate with 2-3 loose stools a day. Release of ammonia, increase pH, down regulate bacteria producing ammonia

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What are the treatments for HE? (3)

Rifaximin 550 mg BD. Semi-synthetic rifamycin derivative, poorly absorbed (reduced systemic S/E). Broad spectrum with activity against anerobic/aerobic, Gram +/- organisms. Binds to beta sub-unit of bacterial DNA dependent RNA polymerase

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What are the treatments for HE? (4)

Results in inhibition of bacterial RNA synthesis. Reduces gut bacteria that would produce ammonia, reduce absorption of ammonia from intestinal lumen. Not used in acute infection, held when patient is on broad spectrum antibiotics

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What are the treatments for HE? (5)

Other options - metronidazole, neomycin, sodium benzoate (not commonly used). Dietary protein restriction not recommend (due to condition)

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Describe features of variceal bleeding and portal hypertension (1)

Portal HTN is caused by increased resistance to flow due to disruption of hepatic architecture and compression of hepatic venules by regenerating nodules. Collateral vessels form - enable blood to bypass the liver

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Describe features of variceal bleeding and portal hypertension (2)

Variceal bleeding is a serious complication of pHTN (>12 mmHg) with reduced clotting factors/vitamin K absorption. Bleeding varices - mortality 50% index bleed and 30% for subsequent bleeds

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Describe features of variceal bleeding and portal hypertension (3)

Increased pressure in vessels, thinner blood, not clotting, fatal variceal bleeding

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Describe features of terlipressin (1)

Synthetic analogue of vasopressin, acts on 3 vasopressin receptors. Greater selectivity for V1 and longer t1/2. V1a - potential splanchnic vasoconstriction (liver gluconeogensis, platelet aggregation and release of factor VIII)

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Describe features of terlipressin (2)

Biphasic action - immediate vasoconstriction effect (reduce pressure), prolonged effect with transformation of terlipressin in vivo to lysine vasopressin. Administer in bolus 1-2 mg every 4-6 h (continue until haemostasis achieved)

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Describe features of terlipressin (3)

Monitor - BP, Na, K, fluid balance. S/E - headaches, abdominal cramps, constriction of vessels in hands and feet (with high doses in the long term), ischaemia (monitor extremities)

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Describe features of somatostatin and analogues

Octreotide (somatostatin analogue). Hormone involved in blood vessel tone in GIT. Inhibits splanchnic vasodilation, decrease splanchnic hypervolaemia. Decreases arterial blood supply, reduce pressure in portal circulation. Not commonly used

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Describe features of band ligation

Most commonly endoscopic procedure used. Band off bleed, reduce pressure, stop bleed. OV haemorrhage (band ligation recommended). Complications - oesophageal ulceration (patients put on PPIs to prevent acid eroding band, for 5-7 days/healing)

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Describe features of scleotherapy

Injection of sclerosants (glue) e.g. cyanoacrylate. Complications - oesophageal ulceration, sepsis. GV haemorrhage, sclerotherapy recommended

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Describe features of the balloon tamponade (1)

Temporary measure (<24 h). Several types (e.g. Sengstaken Blakmore tube). Mechanical pressure over bleeding points. Highly effective when deployed but high rates of re-bleed when deflated. High complication rates e.g. oesophageal ulceration

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Describe features of the balloon tamponade (2)

Inflate balloon, pressure in vessels, stop bleed (whilst balloon remains inflated)

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What is common after upper GI bleed in cirrhotic patients?

Infection - major cause of mortality and morbidity. All patients should receive broad-spectrum antibiotic prophylaxis. 7 day antibiotics (decreases mortality), IV broad spectrum antibiotic (Tazocin) or meropenem/ciprofloxacin for pen (allergies)

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Describe features of secondary prophylaxis (1)

Non-selective beta blocker (propranolol, carvedilol), splanchnic vasoconstriction (beta 2 blockade). CO results in reduced portal pressure (beta 1 blockade). Beta blockers prevent re-bleeding, increase survival. Nitrates

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Describe features of secondary prophylaxis (2)

Issues with tolerability, dose titration and monitoring (BP and HR)

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Describe features of spider naevi (1)

Name stems from appearance which is characterised by central red arteriole, representing the body of the spider, surrounded by radial pattern of thin walled capillaries, resembling legs. Raised oestrogen - pregnant women, HRT, OCP

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Describe features of spider naevi (2)

Hepatic disease - failure to metabolic oestrogen. Unexplained bleeding/bruising

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What are the treatments for pruitis? (1)

Colestyramine (get rid of bile salts). UDCA (movement of bile out of liver). Chlorpheniramine, hydroxyzine (sedating antihistamine), loratadine, cetirizine (non-sedating anti-histamine), calamine lotion (store in fridge)

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What are the treatments for pruitis? (2)

Menthol 2% in aq cream, rifampicin (small doses, for patients not responding to other treatments). Ondansetron, naltrexone, naloxone, sertraline

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Liver Disease - 1

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