PPT 1 Flashcards
Ciclosporin
Transplant immunosuppression
- Calcineruin inhibitor, inhibits T cell activation
Causes eye inflammation, diarrhoea, renal problems, peptic ulcers
Tacrolimus
Transplant immunosuppression
(Graft rejection prophylaxis)
- Blocks T-cell activation
- Blocks transcription for genes that encode IL-3, 4, 5 and TNFa which are involved in early T-cell activation
Azathioprine
Immunosuppressive
- Inhibits purine synthesis
- Inhibits B and T cells
- Prodrug of 6-mercaptopurine
Causes bone marrow depression, leucopenia, pancreatitis, thrombocytopenia, rarely causes anaemia
Cyclophosphamide
Alkylating agent
Used to treat immune-based renal disease
Causes: agranulocytosis, alopecia, anaemia, bone marrow disorders, sperm abnormalities
Trimethoprim
UTIs
Antibiotic
- Inhibits dihydrofolate reductase (inhibits folic acid synthesis)
- Prevents conversion of DHF-THF in thymidine synthesis pathway
Contraindicated in patients with blood disorders
Causes diarrhoea, electrolyte imbalance, fungal overgrowth, headache, nausea and vomiting
Nitrofurantoin
UtIs
- Inhibits the citric acid cycle and the synthesis of DNA, RNA and protein
Second-line to trimethoprim
Co-amoxiclav
PYELONEPHRITIS
Infections due to beta-lactamase-producing strains
Clavulanic acid + amoxicillin
Clavuanic acid = beta-lactamase inhibitor
Amoxicillin = beta lactam antibiotic
Ciprofloxacin
Second generation fluoroquinolone used for pyelonephrits
Acts on bacterial topoisomerase II (DNA gyrase) and prevents DNA supercoiling
*Can induce convulsions, especially if taken with NSAIDs (the case with all quinolones)
Also associated with tendon damage
Gentamicin
Mainly used for serious gram - infections
Aminoglycoside, 30s inhibitor
Associated with ear and kidney damage
What is beta lactamase?
Enzymes produced by bacteria that allow resistance to beta lactam antibioitcs
How do beta lactam antibioitcs work?
- Contain a beta-lactam ring in their molecular structure
- Bacteriocidal, work by blockingthe snynthesis of the peptidoglycan layer of the bacterial cell wall
- The peptidoglycan layer is needed for structual integrity, particularly in gram + organisms
What is usually prescribed in conjunction with amoxicillin?
Clauvanic acid - beta-lactamase inhibitor thus blocking beta-lactamase degredation
List the antibiotics with a beta lactam ring
- Penicillins
- Cephalosporins
- Carbapanems
- Monobactams
According to kidney disease improving global outcomes (KDIGO) what are the stages of AKI?
●Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L), or reduction in urine output to <0.5 mL/kg per hour for 6 to 12 hours.
● Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in urine output to <0.5 mL/kg per hour for ≥12 hours.
● Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 micromol/L), or reduction in urine output to <0.3 mL/kg per hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of renal replacement therapy, or, in patients <18 years, decrease in eGFR to <35 mL/min per 1.73 m2.
According to kidney disease improving global outcomes, how is AKI defined?
●Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours; or
●Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or
●Urine volume <0.5 mL/kg/h for six hours
What immediate therapy would be given to a patient presenting with AKI?
IV fluid therapy – fluid challenge = 500 mL 0.9% NaCl over fifteen minutes
Withdrawal of nephrotoxins
Withholding of hypotensive agents and diuretics
Withhold atorvastatin
What are the key actions to take when dealing with a patient with AKI?
- Optimise intra-vascular fluid volume: IV fluids
- Optimise BP: withold drugs that alter RAAS and any anti-hypertensives
- Correct any hypovolemia
- Stop drugs that worsen AKI - DAMN
Diuretics
Ace inhibitors
Metformin
NSAIDs
What is the pathophysiology of urea and creatinine increase in AKI in a patient taking diuretics ?
- Reduced circulating volume due to diuretics causing reduced renal perfusion - low perfusion = lack of creatinine and urea removal thus higher levels in the blood
What are the pre-renal causes of AKI?
- Hypovolemia
- Decreased cardiac output
- Congestive heart failure
- Liver failure
- NSAIDs
- ACEi/ ARBs
- Cyclosporine
What are the post-renal causes of AKI?
- Bladder outlet obstruction
- Bilateral pelvoureteral obstruction
Which drugs interfere with renal perfusion?
- ACEi
- ARBs
- NSAIDs
In the setting of AKI, what GFR be assumed when presciring drugs metabolised and excreted by the kidney?
< 10 mL/min/1.73m2
Which drugs should be stopped or have a dose-reduction in AKI?
- Fractionated heparins
- Opiates
- Penicillin-based antibiotics
- Sulfonylurea-based hypoglycemic drugs
- Aciclovir
- Metformin
Which drugs aggravate hyperkalemia?
- Trimethorprim
- Spironolactone
- Amiloride
Which drugs require close monitoring in AKI?
- Warfarin
- Aminoglycosides (gentamycin, tobramycin)
- Lithium
What is the gold-standard filtration marker for measuring GFR?
Inulin - a physiologically inert substance that is freely filtered at the glomerulusand is not secreted, reabsorbed, synthesised or metabolised by the kidney.
*infrequently used because inulin is expensive and difficult to assay and requires a strict protocol
Which methods are most commonly used to measure eGFR?
- Measurement of creatinine clearance
- Cockcroft-Gault equation
Which is more accurate, eGFR or Cockcroft-Gault?
Cockcroft-Gault because it adds weight into the equation
Are the majority of drugs affected by impaired renal function?
No, 80% of drugs are eliminated by hepatic metabolism
- The kidneys provide the major route of elimination for water soluble drugs and water soluble metabolites
How do aminoglycosides work?
Bind to the 30s ribosomal subunit and cause:
- Misreading of the mRNA codon leading to errors in amino-acid sequencing
- Disruption of polysomes, reducing the efficiency of protein synthesis
- Inhibition of the translocation of tRNA between A and P ribosomal binding sites
What are the adverse effects of gentamicin? (aminoglycoside)
- Damage to cochlear and vestibular apparatus
- Renal damage
Aminoglycosides such as gentamicin are readily taken up by renal proximal tubule cells and cochlear cells
How is gentamycin administered?
Not readily absorbed from the GI tract and is therefore given IV (sometimes IM)
Highly hydrophilic and not distributed into body fat
When calculatingtyhe dose for administration, excess body fat should be taken into consideration - mass without excess fat = ideal body weight
Usually calculate a dose using the lower end of actual body weight
Which order kinetics does gentamicin follow?
First order kinetics - excreted unmodified by the kidneys, cleared from the blood at a rate proportional to its concentration
Describe first order kinetics
Rate of elimination is proportional to the amount of drug in the body - the higher the concentration the greater the amount of drug eliminated per unit time
After a dose the level in the blood decays exponentially
What types of regimens are commonly used when prescribing gentamicin in the UK?
- Pharmacokinetic: tailored to the patient
- Extended interval: single daily dosing, total daily dose is given in one go, little-no tissue accumulation occurs meaning risk of toxicity is reduced, maximises bacterial kill whilst minimising toxicity AKA Hartford dosing
A study in 1996 showed the two regimens are equally efficacious but extended interval gentamicin had reduced toxicity
What is a Hartford nomogram?
Used to plot gentamicin concentration
What should be remembered when taking blood to monitor gentamicin concentration?
- Don’#t take blood from same line used to administer gentamicin
- Take one blood sample of 10mL 6-14hrs after the start of the first infusion
- Take the blood into a plain tube (clotted blood)
- Document on the microbiology request form the exact time and date the infusion was set up and the exact date and time the sample was taken
In extended-interval dosing for gentamicin, what is the initial dose?
7mg/kg
