Prescribing in Hepatic and Renal Impairment Flashcards
What does reduced liver function mean to drug bioavailability/dose
reduced dose and therefore therapeutic effect
important for narrow therapeutic drugs
How does liver change as you age
reduced liver volume = liver impairment
What does hypoproteinanaemia cause
reduced protein binding as less protein binding sites in body
What does hypoproteinanaemia mean in terms of drugs and toxicity
it will increase level of free drug in blood, increasing toxicity
What does vitamin k deficiency lead to
increased risk of bleeding
- give Menadiol (water soluble vitamin k) for vitamin k balance
What are the fat soluble vitamins
ADEK
What is Obstructive jaundice
blockage in bile ducks reducing or stopping bile flow from liver into small intestine
What is the difference between intrahepatic and extrahepatic jaundice
Intra- blockage is inside the liver
Extra- blockage is outside the liver
Why does obstructive jaundice affect fat soluble vitamin absorption
reduced bile into small intestine causes lowered emulsification and absorption of fat soluble vitamins
Fusidic acid and obstructive jaundice
- impaired liver
- causes lowered excretion of fusidic acid from liver
- increased fusidic acid levels in blood
- causing toxicity
- impacting its effectiveness on biliary tract infections
Rifampicin and obstructive jaundice
- impaired liver
- causes lowered excretion of rifampicin
- increasing its systemic levels
- can increase liver impairment
What is hepatic encephalopathy
- liver detoxifies ammonia into urea normally
- impaired liver leads to build up of ammonia in blood
- it passes BBB and builds up in brain
- disrupting neurotransmission and brain function
What is Grade I hepatic encephalopathy
Grade I: Subtle cognitive changes, euphoria or depression, mild confusion, and slight tremor.
What is Grade II hepatic encephalopathy
Grade II: Increased drowsiness, lethargy, confusion, disorientation, and asterixis (flapping tremor).
What is Grade III hepatic encephalopathy
Grade III: Stupor, marked confusion, severe disorientation, and incoherent speech.
What is Grade IV hepatic encephalopathy
Grade IV: Coma, unresponsiveness to stimuli, and potential progression to death if untreated.
What drugs can exacerbate hepatic encephalopathy
- Constipating drugs
(opioids, TCAs) - Sedating drugs
(opioids, antihistamine, benzodiazepines) - Hypokalaemic drug
(Loop and thiazide like diuretics)
How to treat hepatic encephalopathy
Lactulose
What drugs can exacerbate Oedema and Ascities
drugs that cause fluid retention
(NSAIDs, Corticosteroids)
Main hepatoxocic drugs
- Antipsychotics
- Amiodarone
- Carbamazepine
- Co-Amoxiclav
- Fluconazole
- Flucloxacilin
- Ketoconazole
- Labetalol
- Methotrexate
- Paracetamol
- Piolitazone
- Rifampicin
- Statins
- Valproate
- Tetracyclines
What are the Signs of liver toxicity
- jaundice (yellow skin, eyes)
- abdominal pain
- nausea / vomiting
- weight loss
- dark urine
- drowsiness or confusion
What does grapefruit do to cytochrome p450
enzyme inhibitor
What does enzyme inhibition cause
increased plasma concentration
What drugs will have increased plasma concentration with grapefruit
- CVS drugs
- CNS drugs
- Immunosuppressants
- Colchicine
- Sildenafil
What CVS drugs interact with grapefruit juice
- amiodarone
- statins
- verapamil
- CCB (amlodipine)
- dihydropyrdine
What CNS drugs interact with grapefruit juice
- Quetiapine
- Sertraline
What immunosuppressants drugs interact with grapefruit juice
- Tacrolimus
- Ciclosporin
What factors are HIGH in liver function test in liver impairment
- ALT
- AST
- ALP
- GGT
- Bilirubin
- Prothrombin time / INR
What factors are LOW in liver function test in liver impairment
Albumin
When is ALT raised in a liver function test when there is liver impairment
raised transaminases in hepatocellular damage
When are AST and ALP raised in a liver function test when there is liver impairment
raised in obstructive jaundice
(found mainly in bile duct)
What is bilirubin
it is a pigment in the bile that causes jandice
Why is Albumin LOW in liver function test when there is liver impairment
because the liver can’t make the protein as much in hepatic impairment
What does reduced renal excretion of drugs cause
toxicity, as plasma concentration of the drug isn’t excreted
How should you handle the dose of a narrow therapeutic drug in renal impairment
close monitoring of plasma concentration and clinical response
What does renal impairment do to plasma half life of drugs
increases it
Why is renal impairment a problem in half life drugs
- some drugs require a loading dose before regular use
- it will take longer to reach the drug steady state
What are the signs of acute kidney injury
- reduced urine output
- fluid retention
- dehydration
- nausea / vomiting
- fatigue
- High BP
- confusion
What will lab results show for acute kidney injury
- reduced eGFR
- reduced creatinine clearance
- high serum creatinine
Examples of Nephrotoxic drugs
- ACE inhibitors
- Aciclovir
- NSAIDs
-Tetracyclines - Quinolones
- Aminoglycosides
- Aminosalicylates
- Cephalosporins
What is the most significant risk factor or AKI
Dehydration
What are renal impairment sick day rules
when unwell, stop taking certain medications
When should you restart sick day rule medications
24-48 hours after eating and drinking normally
What medications should you stop taking when feeling unwell with AKI (sick day rule medication)
- Diuretics
- ACE Inhibitors
- Metformin
- NSAIDs
Why should you stop taking Diuretics when feeling unwell with AKI
it exacerbates dehydration and electrolyte disturbances
Why should you stop taking ACE Inhibitors when feeling unwell with AKI
they are nephrotoxic and they reduce eGFR
Why should you stop taking Metformin when feeling unwell with AKI
increases risk of lactic acidosis in renal impairment
Why should you stop taking NSAIDs when feeling unwell with AKI
they are nephrotoxic and they reduce eGFR, sodium and water retention
Which equation do you use to calculate creatinine clearance
Cockcroft-Gault formula
What is the Cockcroft-Gault formula
Serum creatinine
What is the Cockcroft-Gault formula constant for men and women
Men: 1.23
Women: 1.04
If BMI is less than 18 what weight should be used in the Cockcroft-Gault formula
actual body weight
if major contributor to high body weight is fat, what weight should be used in the Cockcroft-Gault formula
ideal body weight
how to calculate ideal body weight
Constant + 0.91(height -152.4)
What is the constant for men and women for the ideal body weight formula
Men: 50
Women: 45.5
If eGFR is above 60 and the ACR is below 3 than what is the status of the kidney
Normal
What is urine ACR
the ration between the amount of albumin to the amount of creatinine in the urine
What drugs colour urine and bodily secretions RED
- Dantron
- Doxorubicin
- Levodopa
What drugs colour urine and bodily secretions RED-ORANGE
- Rifampicin
What drugs colour urine and bodily secretions ORANGE
- Sulfasalazine
What drugs colour urine and bodily secretions YELLOW-BROWN
- Nitrofurantoin
- Senna
What drugs colour urine and bodily secretions PINK O ORANGE
- Phenindone
What drugs colour urine and bodily secretions BLUE
- Triamterene
What drugs colour urine and bodily secretions BLACK/TARRY
- Iron
- Bismuth
What drugs colour urine and bodily secretions BROWN
- Prostoglandin Analogues
(latanoprost eye drops)
