Drugs and the Kidney Flashcards
What is the mechanism of action of loop diuretics?
- To inhibit the Na+/K+/2Cl- co-transporter in the luminal membrane of the TAL of Henle’s loop
- Inhibiting transport of NaCl ot of the tubule into the interstitial tissue
- Reducing osmotic gradient in the medulla of the kidney, less water recovered
Give two examples of loop diuretics
- Furosemide
- Bumetanide
What are some indications for loop diuretics?
- Pulmonary oedema
- Resistant hypertension - Hypercalcaemia
What are some side-effects of loop-diuretics?
- Hypovolaemia, hypotension
- Electrolyte disturbances - e.g low Na, K, Mg, Ca
- May produce metabolic alkalosis due to loss of H+ ions
- Hyperuricaemia - Gout
- Renal impairment
What are 2 examples of thiazide diuretics?
- Bendroflumethiazide
- Indapamide
What is the mechanism of action of thiazide diuretics?
- Inhibits the NaCl co-transporter in the distal tubule so less Na/Cl reabsorbed
- Causes moderate diuresis, reducing oedema and BP
- Direct relaxant effect on vascular smooth muscle (reduces BP)
What are the indications for use of thiazides?
- Hypertension
- Mild HF
- Severe resistant oedema (plus loop)
- Nephrogenic diabetes insipidus
What are the side-effects of thiazides?
- Hypotension, hypovolemia
- Low K, Na, Mg
- Promotion of calcium retention / hypocalciuria
- Metabolic alkalosis
- Gout
- Erectile dysfunction
- Hyperglycaemia, hyperlipidemia
What is the mechansim of action of aldosterone antagonists?
- Antagonise the aldosterone receptor in the collecting tubule
GIve 2 examples of aldosterone antagonists
- Spirolanactone
- Eplerenone
What can aldosterone antagonists also be known as?
- Potassium sparing weak diuretics
- Mineralocorticoid receptor antagonists
What are the indications for aldosterone antagonists?
- Oedema (hert, liver nephrotic syndrome)
- Hypertension
- Conn’s syndrome (primary hyperaldosteronism)
What are the side-effects of aldosterone antagonists?
- Renal impairment
- Hyperkalaemia
- Hyponatraemia
- GI upset
- Metabolic acidosis
- Gynaecomastia with spiro
What is amiloride?
- Potassium sparing weak diuretic
- Acts by directly blocking epithelial Na+ channels in the collecting tubule so less Na+ reabsorbed, causing diuresis
- Usually synergistically combined with thiazide or loop diuretic
What are the indications for amiloride?
Oedema inc. ascites, hypertension
What are the side-effects of amiloride?
- High K+ (care if renal impairment)
- GI upset
- Metabolic acidosis
- Renal impairment
How do osmotic diuretics work?
Modify filtrate content increasing amount of water excreted (e.g mannitol IV)
Give an example of an osmotic diuretic
mannitol IV
What are the indications for osmotic diuretics?
- Cerebral oedema + raised intra-occular pressure
Give an example of a carbonic anhydrase inhibitor?
Acetazolamide (v. weak diuretic)
What are the indications for carbonic anhydrase inhibitors (e.g acetazolamide)?
- Glaucoma
- Altitude sickness
What is syndrome of inappropriate ADH secretion caused by?
Excess ADH secreted by posterior pituitary gland regardless of what serum osmolality is
What does syndrome of inappropriate ADH secretion result in?
- Hyponatraemia (<135)
- Low serum osmolality
- Inappropriately elevated urine osmolality (>plasma osmolality)
- Euvolaemia
What are the mild symptoms of SIADH?
- Nausea
- Vomitting
- Headaches
- Anorexia
What are the moderate symptoms of SIADH?
- Muscle cramps
- Weakness
- Tremor
- Mental health disorders
What are the severe symptoms of SIADH?
- Drowsiness
- Seizures
- Coma
What are the different causes of SIADH?
- Neurological cases e.g tumour, trauma, meningitis, SAH
- Pulmonary causes e.g lung small cell ca, pneumonia
- Malignancy
- Hypothyroidism
- Drugs e.g thiazide and loop diuretics, ACEis, SSRIs and PPIs
How is SIADH treated?
- Correct underlying cause
- Fluid restrict (500-1000ml daily)
- Monito plasma osmolality, serum sodium and bodyweight
What are some of the medictions used to treat SIADH?
- Demeclocycline - antibiotic, also inhibits action of ADH on kidneys
- Tolvaptan - ADH V2 antagonist in renal collecting ducts
- Hypertonic sodium chloride in severe cases only
Hoe is anaemia of renal disease treated?
- Epoetin Alfa, Darbopoetin - IV/SC route
- Reduce need for blood transfusions
- Boost production of RBCs
- Improve survival
- Reduce CV morbidity
- Enhance quality of life
What can Erythropoietin Stimulating Agents cause e.g Epoetin alfa, darbopoetin?
- Flu-like symptoms
- Avoid over or too rapid correction of haemoglobin - increases risk of hypertension and CV effects
What are vasopressin (ADH) receptor agonists used to treat?
- Diabetes insipidus (Desmopressin)
- Oesophageal varices (Terlipressin)
What are Sodium-Glucose Co-transporter- 2 (SGLT-2) inhibitors used to treat?
- Type 2 diabetes (e.g. canagliflozin)
Give an example of a uricosuric drug used to treat gout?
Sulphinpyrazone (rarely used now)`
What drugs affect the pH of urine?
Ascorbic acid (acidify), potassium citrate (alkalinise) for urine infection symptoms or kidney formation. Rarely done
What drug is used first line to treat type 2 diabetes?
Metformin
What should be considered before prescribing in relation to kidney diseases/impairment?
- Degree of renal impairment
- Whether acute or chronic kidney disease
- Proportion of drug renally excreted
- Does the drug have a narrow/wide therapeutic window?
- Is the drug potentially nephrotoxic
- Is this patient established on renal impairment therapy
How is renal function usually estimated?
- Creatinine clearence
- eGFR
Depends on the drug
How is Creatinine clearence calculated (CrCl) using Cockroft and Gault (C&G)? (do not need to remember)
Crcl = [(140-age) x weight x F]/ [serum creatinine]
- F = 1.04 for F, 1.23 for Males
- In obese patients ideal body weight
- serum creatinine in micromol/L
What are the pros and cons of estimating Creatinine clearence from C&G?
- Good validated formula
- Advised for narrow therapeutic index drugs
- Inaccurate for rapidly changing creatinine levels and in severe renal disease
- Need to use IBW at extremes of body weight
- Adults only
What factors vary eGFR?
creatinine, age, sex, ethnicity
eGFR can only be validated in adults of what races?
WHite and black
What are the pros of using eGFR?
- Easy reporting allows early detection of CKD
- BNF offers a broad range for guidance on dosage based on eGFR
- eGFR increasingly being used to alter drug dosing and evidence growly regarding accuracy
What are the cons of using eGFR?`
- Not validated in some patient groups e.g acute kidney failure, pregnancy, oedematous sates and malnourished, extremes of weight
- As not validated for drug dose calculations - risk of drug toxicity or therapeutic failure
What should be done in a pateint with renal impairment but a therapeutic outcome must be met immedeatly?
- Renal disease can prolong half-life of some drugs
- Can take longer to get to steady state
- Normal loading dose as per normal renal function to reach target therapeutic serum drug concentrations then reduce maintenance dose
Give examples of potentially nephrotoxic drugs?
- ACE inhibitors, ARBs
- NSAIDs
- Diuretics
- Lithium
- Digoxin
- Aminoglycosides
- Vancomycin
- Metformin
- Iodinated contrast media
- Opoids
How can acute kidney injury be divided?
- Pre-renal
- Intra-renal
- Post-renal
What is generally used to treat Pre-renal AKI?
Diuretics
What is generally used to treat intra-renal AKI?
Gentamicin, ciclosporin
What is generally used to treat post-renal AKI?
- Anticholinergics (amitriptyline), opoids, cemotherapy
How is CKD managed?
- Prevent or reverse worsening
- Review all meds, check doses appropriate
- Manage concurrent conditions
How can CKD be classified?
stage 1 through 5 (mild to severe impairment)
How are AKIs managed?
- Treat any sepsis or uro obstruction
- Aim for good fluid / electrolyte balance
- Optimise BP
- With-hold toxins
- Review drug doses and side effect profile
- Monitor U&Es refer nephrology / urology if worsening
What else can AKI cause?
- Low BP - sepsis, DV, poor oral intake
- Low CO
- Reduced blood volume - GI bleed, burns, intra- op losses
- Post-renal obstruction - prostate, constipation, blocked catheter
- Intra-reanl - e.g. rhabdomyolysis, myeloma, vasculitis
When should riveroxaban be avoided?
- When creatinine clearence is less than 15mL/minute
- Too high dose may have worse outcomes with respect to bleeding risk
- Too low dose may result in an increase in embolic events and resilr in potentially preventable strokes
What are the principles of prescribing in renal impairment?
- Check Us and Es, including eGFRs and creatinine
- Look at basetrends in renal function
- Consider stopping or with-holding nephrotoxic drugs
- Check resources
- Chose non-nephrotoxic drug if possible
- Reduce size of dose or increasing dosing interval or stop or with-hold
- Use therapeutic drug monitering to guide dose / frequency if appropriate
- Continue to monitor U&Es, BP and clinical response
