eScript 3 Flashcards
What is an electrolyte abnormality caused by spironolactone?
hyperkalaemia
are ACE inhibitors contraindicated in severe liver disease?
yes
In severe liver disease, the patient relies in part on activation of the renin-angiotensin system to maintain peripheral vascular resistance. Administration of an ACE inhibitor can lead to a rapid drop in blood pressure and the development of renal failure.
signs on examination of chronic liver disease?
Spider naevi Clubbing Jaundice Loss of secondary sexual hair Gynaecomastia Ascites Splenomegaly Peripheral oedema
tests to evaluate hepatic function?
Albumin, prothrombin time, bilirubin
USS
what is child pugh score?
The Child Pugh score was developed to evaluate operative risk in patients with liver cirrhosis, but it remains one of the easiest bedside scores to calculate. It considers five variables; the severity of ascites and of encephalopathy, serum bilirubin, serum albumin and clotting time. It stages patients as Child class A, B or C, with class C patients having the most severe liver dysfunction.
what liver complications can flucloxacillin cause?
hepatitis and cholestatic jaundice
the onset may be delayed for up to 2 months
name some commonly prescribed drugs that can cause acute liver injury?
Paracetamol causes a dose-dependent acute liver injury that can lead to acute liver failure.
Co-amoxiclav and flucloxacillin can cause cholestatic hepatitis that resolves in most cases after withdrawal of the drug.
NSAIDs (e.g. ibuprofen, naproxen, diclofenac) can cause an ideosyncratic hepatitis that resolves in most cases after withdrawal of the drug. Aspirin can also cause hepatitis but it tends to be dose related.Ibuprofen classically causes a cholestatic hepatitis.
Antituberculosis drugs (e.g. rifampicin) can cause liver injury.
Methotrexate can cause severe fibrosis and cirrhosis if not adequately monitored.
Amiodarone can cause a steato hepatitis.
how does paracetamol OD cause toxicity?
Paracetamol is primarily metabolised in the liver and metabolism of paracetamol is required prior to hepatotoxicity. Liver injury does not occur until glutathione is depleted. After this, the reactive metabolites of paracetamol bind to cellular macromolecules, causing lethal damage to the hepatocyte.
when is NAC treatment commenced?
Treatment should be commenced if a patient has taken more than 150 mg/kg in any 24-hour period, unless:
The plasma-paracetamol concentration is undetectable
The patient is asymptomatic
LFTs, serum creatinine and INR are all normal
what happens if a patient presents after 8 hours who has taken potentially toxic amounts of paracetamol, even if plasma concs are not available?
given NAC
what are the 2 phases of drug metabolism?
Phase 1 - The cytochrome P450 group of enzymes is responsible for the majority of Phase 1 reactions. In cirrhosis, the activity of these enzymes can be markedly reduced.
Phase 2 - conjugation, which results in a water soluble compound that is usually inactive and more easily excreted in the urine or bile.
what is first pass metabolism?
They will pass through the liver and be partially or wholly metabolised before reaching the systemic circulation, reducing oral bioavailability.
If the blood flow through the liver is slowed, a drug may be subject to increased metabolism, as it may stay in the liver for longer.
However, patients with cirrhosis often develop collaterals, enabling the blood to bypass the liver, resulting in a decrease in first-pass metabolism
adverse effects of liver disease?
encephalopathy
clotting abnormalities
gastric and oesophageal varices, secondary to portal hypertension
ascites
what medication can be prescribed for hepatic encephalopathy?
lactulose
why are NSAIDs contraindicated in chronic liver disease?
The risk of bleeding is increased. NSAIDs can irritate the gastrointestinal tract, which may increase the risk of bleeding from GI varices. NSAIDs may also increase fluid retention in ascites. Patients with liver failure may depend on renal prostaglandins to maintain blood flow. NSAIDs inhibit prostaglandin production, reducing renal perfusion and can therefore precipitate renal impairment.
how does body composition change with age?
Decrease in lean body mass.
Decrease in body water.
Increase in body fat in relation to total body weight.
Decrease in bone mass.
what is the effect on distribution of drugs in elderly people for water-soluble and lipid-soluble drugs?
The distribution of lipid-soluble drugs (e.g. diazepam) may increase, resulting in a prolonged action or a ‘hangover effect’.
The distribution of water-soluble drugs (e.g. paracetamol, digoxin, ethanol) may decrease resulting in a higher initial plasma concentration for any dose based on body weight.
what is the clinical relevance in decrease in lean body mass?
doses may need to be reduced e.g. digoxin
what are the changes to drug metabolism as you get older?
decrease in hepatic function
decline in hepatic blood flow
name some drugs that can cause toxicity due to a decline in renal function with age?
Aminoglycosides (e.g. gentamicin) Digoxin Lithium salts Metformin Thiazide diuretics
What should be calculated to estimate a decline in renal function in elderly people with extremes of weight?
creatinine clearance- eGFR not accurate
what drugs can cause hypothermia in older people?
- sedatives- benzos, opioid analgesics, TCAs
- impair awareness of temp- chlorpromazine
- decrease motility- antipsychotics, antiparkinsonian drugs
- cause vasodilation- e.g. amlodipine
what drugs can cause peripheral oedema resistant to diuretics?
calcium channel blockers e.g. amlodipine
drugs that can cause confusion and affect cognition?
Anticholinergics Antihistamines Beta-blockers Hypnotics Opioid analgesics Tricyclic antidepressants
when can benzodiazepines be contraindicated?
they can cause respiratory depression
when is haloperidol contraindicated?
in the presence of long QT
Haloperidol is a ‘typical’ antipsychotic, which can cause extrapyramidal side-effects such as tremor and restlessness (akathesia).
ADRs of anti-muscarinics e.g. TCAs and anti-spasmodics?
Memory loss
Urinary retention
Constipation
Exacerbation of glaucoma
ADRs of hypnotics/anxiolytics e.g. diazepam, zopiclone?
Falls
Confusion
Postural hypotension
ADRs of opioid analgesics such as codeine, dihydrocodeine and morphine sulfate?
Constipation
Drowsiness
Falls
why can amiodarone cause low mood and fatigue?
it can cause hypothyroidism
what is the criteria for a possible covid-19 case?
Requiring admission to hospital (i.e. hospital practitioner decided that admission to hospital is required with expected stay at least one night) AND
Have either clinical or radiological evidence of: - Pneumonia; OR
- Acute respiratory distress syndrome; OR
- Influenza like illness (fever ≥ 37.8oC and ≥ one acute
respiratory symptom: persistent cough (with or without
sputum), hoarseness, nasal discharge or congestion,
shortness of breath, sore throat, wheezing, sneezing)
Patients admitted who have symptoms that meet the above criteria should be tested, irrespective of contact or travel history.
Ix for covid-19?
Urea and electrolytes (calculate the patient’s CURB-65 score)
Other biochemistry
Full blood count
Clotting - Prothrombin time (PT) or INR, D-dimers, Fibrinogen (DIC)
Liver function tests
Arterial blood gases (if O2 saturations < 92% on air)
Blood cultures and other microbiology, as per standard practice and indications
Imaging: Chest X-ray +/- CT thorax
Coronavirus swabs
abnormal blood test results on covid-19?
U&E’s: ↑ creatinine
Other biochemistry: ↑CRP, ↑Ferritin, ↑LDH, ↑troponin
Full blood count: Lymphocytopaenia, ↓Platelets
Clotting: ↑ Prothrombin time (PT) or INR, ↑D-dimers, Fibrinogen (DIC)
Liver function tests: ↑Bili, ↑ALT/AST
Arterial blood gases: hypoxia, ↑Lactate
CXR findings of covid-19?
May appear clear / unchanged
Local consolidation
Ground-glass opacity
Bilateral pulmonary infiltrate (basal / peripheral)
moderate features of deterioration in covid-19?
Oxygen requirement of more than 4 litres/min or inspired oxygen > 28% to maintain target saturations
severe features of deterioration in covid-19?
Unable to maintain target saturations (92–96% or 88–92% in type 2 respiratory failure risk group)
Inspired oxygen ≥ 50% to maintain target saturations
Respiratory Rate > 30 despite oxygen
pH < 7.2
Systolic BP < 90 mmHg
Other organ failure (e.g. liver/kidney/heart/brain)
Decreased conscious state
other complications of covid-19?
There is emerging evidence that COVID-19 can cause acute myocarditis and heart failure, as the Middle East Respiratory Syndrome (MERS) did. Activation of coagulation pathways, can lead to blood clots, leading to ischaemia and multi-organ failure.
what is stage 1 AKI?
Creatinine rise of 26 micromol/litre or more within 48 hours; or
Creatinine rise of ≥ x 1.5 from baseline in 7 days ; or
Reduced urine output of < 0.5 ml/kg/hour for more than 6 hours.
what is stage 2 AKI?
Creatinine rise of ≥ x 2 from baseline; or
Reduced urine output of < 0.5 ml/kg/hour for 12 hours or more
what is stage 3 AKI?
Creatinine rise of ≥ x 3 from baseline within 7 days
OR
Creatinine rise to ≥ 354 micromol/litre with either:
Acute rise in creatinine of ≥ 26 micromol/litre within 48 hours or
≥ 50% rise from baseline within 7 days
OR
Urine output of < 0.3 ml/kg/hour for 24 hours
OR
Anuria for 12 hours
OR
Any requirement for renal replacement therapy.
common drugs causing nephrotoxicity?
Aminoglycosides: are directly nephrotoxic, causing acute tubular necrosis.
Amphotericin: is directly nephrotoxic. The use of newer liposomal formulations can still result in nephrotoxicity.
Cytotoxic chemotherapy: e.g. cisplatin, which has been associated with renal tubular damage.
Diuretics: can lead to volume depletion.
Immunosuppressants: ciclosporin and tacrolimus cause renal vasoconstriction producing ischaemia.
Lithium salts: can cause tubulo-interstitial damage and chronic kidney disease with long-term use.
NSAIDs/COX-2 inhibitors: renal blood flow often relies on prostaglandins. NSAIDs and cyclooxygenase-2 inhibitors reduce prostaglandin synthesis, and cause renal hypoperfusion, and AKI.
Radiocontrast media: a high ionic load can produce renal vasoconstriction leading to ischaemia.
Other nephrotoxic agents: Synthetic agents: insecticides, herbicides. Naturally occurring agents: alkaloids from plants/fungi, reptile venoms (all rare), cocaine.
what are some pathological states that are nephrotoxic?
Hypoperfusion: reduces oxygen and nutrient supply to the kidney.
Sepsis: endotoxins and inflammatory mediators from infection can damage the renal vascular endothelium resulting in thrombosis.
Rhabdomyolysis: myoglobin released from damaged muscles precipitates in renal tubules and also reduces blood flow in the outer medulla.
Hepatorenal syndrome: patients with end-stage liver disease often have renal vasoconstriction.
when should creatinine clearance be used for estimating eGFR?
Estimating renal function or calculating drug doses in patients with renal impairment
Older adults
Patients at extremes of muscle mass
Patients on a medicine with a low therapeutic index
what is the role of prostaglandins and angiotensin II in renal dysfunction?
Prostaglandins produced within the kidney maintain renal blood flow and GFR, especially under conditions of reduced effective circulating volume (e.g. dehydration, cardiac failure, cirrhosis).
Angiotensin-II is produced by the renin-angiotensin system in response to hypovolaemia or reduced renal perfusion (e.g. with reno-vascular disease). It causes efferent arteriolar vasoconstriction.
what parameters are used to measure fluid balance in AKI?
Pulse - supine and upright (where possible). You may need to sit the patient up in bed if they are unable to stand.
Blood pressure - supine and upright.
Arterial oxygen saturation.
Look for signs of pulmonary oedema - examine for tachypnoea, fine bilateral basal inspiratory crackles, chest X-ray signs.
Fluid overload - check for pitting ankle and sacral oedema. Check the patient’s weight daily (rising daily weights are a very useful indicator of fluid overload).
what fluids are prescribed in AKI?
Sodium chloride 0.9% is an appropriate intravenous fluid in AKI. Sodium bicarbonate 1.26% is a good alternative if the patient has AKI with hypovolaemia and a metabolic acidosis (a serum bicarbonate of less than 20 mmol/litre)
why is hartmann’s unsuitable for AKI?
it has a high potassium content
