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MD3002 - RENAL > Drugs And The Kidneys > Flashcards

Drugs And The Kidneys Flashcards

1
Q

Loop Diuretics - Examples

A

Furosemide and Bumetanide

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2
Q

Loop Diuretics - Mechanism of Action

A

Inhibits the Na+/K+/2Cl- Co-transporter in the luminal membrane of the Thick Ascending Limb of the Loop of Henle. The inhibition of NaCl transport into the interstitium reduces the osmotic gradient in the medulla of the kidney and less water is recovered. This means there is profound diuresis.

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3
Q

Loop Diuretics - Indications

A
  • Oedema - Heart Failure, Pulmonary, Ascites, Nephrotic Syndrome, Renal Failure
  • Resistant Hypertension
  • Hypercalcaemia
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4
Q

Loop Diuretics - Side-effects

A
  • Hypovolaemia, hypotension
  • Electrolyte disturbances - e.g. low Na, K, Mg, Ca
  • May produce a metabolic alkalosis due to loss of H+ ions
  • Hyperuricaemia - Gout
  • Renal impairment
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5
Q

Thiazide Diuretics - Examples

A

Bendroflumethiazide and Indapamide

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6
Q

Thiazide Diuretics - Mechanism of Action

A
  • Inhibits the NaCl Co-transporter in the Distal Convoluted Tubule, this means less NaCl reabsorbed causing moderate diuresis, which reduces oedema and blood pressure.
  • Also has a direct relaxant effect on vascular smooth muscle which reduces blood pressure.
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7
Q

Thiazide Diuretics - Indications

A
  • Hypertension
  • Mild heart failure
  • Severe resistant oedema (plus loop diuretics)
  • Nephrogenic diabetes insipidus
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8
Q

Thiazide Diuretics - Side-effects

A
  • Hypovolaemia, hypotension
  • Low K, Na, Mg
  • Promotion of calcium retention/hypocalciuria
  • Metabolic alkalosis
  • Gout
  • Erectile dysfunction
  • Hyperglycaemia, hyperlipidaemia
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9
Q

Aldosterone Antagonists - Examples

A

Spironolactone and Eplerenone

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10
Q

Aldosterone Antagonists - Mechanism of Action

A

Potassium sparing weak diuretics. Antagonise aldosterone receptors and mineralocorticoid receptors in Collecting Duct.

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11
Q

Aldosterone Antagonists - Indications

A
  • Oedema (heart, liver, nephrotic syndrome)
  • Hypertension
  • Conn’s Syndrome (Primary Aldosteronism)
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12
Q

Aldosterone Antagonists - Side-effects

A
  • Renal impairment
  • Hyperkalaemia
  • Hyponatraemia
  • GI upset
  • Metabolic Acidosis
  • Gynaecomastia (Spironolactone)
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13
Q

Amiloride - Mechanism of Action

A

Potassium sparing weak diuretic which acts by directly blocking epithelial sodium channels in the Collecting Duct so less sodium is reabsorbed, causing diuresis.

Usually synergistically combined with thiazide or loop diuretic.

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14
Q

Amiloride - Indications

A

Oedema, Ascites, Hypertension

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15
Q

Amiloride - Side-effects

A
  • High potassium (care if renal impairment)
  • GI upset
  • Metabolic Acidosis
  • Renal Impairment
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16
Q

Osmotic Diuretics - Example

A

IV Mannitol

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17
Q

Osmotic Diuretic - Mechanism of Action

A

Modify filtrate content in the glomerulus, increasing amount of water excreted.

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18
Q

Osmotic Diuretics - Indications

A

Cerebral oedema and raised intra-ocular pressure

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19
Q

Carbonic Anhydrase Inhibitors - Example

A

Acetazolamide

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20
Q

Carbonic Anhydrase Inhibitor - Indications

A

Glaucoma, altitude sickness

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21
Q

Syndrome of Inappropriate ADH Secretion (SIADH)

A

Excess anti-diuretic hormone secreted by the posterior pituitary gland regardless of what the serum osmolality is….

  • Hyponatraemia (<135)
  • Low plasma osmolality
  • Inappropriately elevated urine osmolality (higher than plasma osmolality)
  • Euvolaemia
22
Q

Symptoms of SIADH (Syndrome of Inappropriate ADH Secretion)

A
  • Mild - Nausea, vomiting, headaches, anorexia
  • Moderate - muscle cramps, weakness, tremor, mental health disorders
  • Severe - drowsiness, seizures, coma
23
Q

Causes of SIADH (Syndrome of Inappropriate ADH Secretion)

A
  • Neurological Cause e.g. tumour, trauma, meningitis, subarachnoid haemorrhage
  • Pulmonary causes e.g. lung small cell carcinoma, pneumonia
  • Malignancy
  • Hypothyroidism
  • Drugs e.g. thiazide and loop diuretics, ACEIs, SSRIs, and PPIs
24
Q

Treatment of SIADH (Syndrome of Inappropriate ADH Secretion)

A
  • Correct underlying cause, monitor plasma osmolality, serum sodium and body weight.
  • Fluid restrict ( 500-1000ml daily)
  • Demeclocycline
  • Tolvaptan
  • Hypertonic soldium chloride
25
Q

Demeclocycline

A

antibiotic which also inhibits action of ADH on kidneys

26
Q

Tolvaptan

A

Vasopressin/ADH V2 antagonist in renal collecting ducts

27
Q

Hypertonic Sodium Chloride

A

Severe cases only

28
Q

Anaemia of Renal Disease

A

Moderate to severe renal impairment, kidneys produce less EPO, resulting in anaemia.

Erythropoietin (EPO) is a hormone produced by kidney (peritubular interstitial cells), promotes RBC formation in bone marrow.

29
Q

Erythropoietin Stimulating Agents - Examples

A

Erythropoeitin Alfa and Darbopoietin - IV/SC route.

30
Q

Erythropoietin Stimulating Agents - Effects

A
  • Reduce the need for blood transfusions
  • Boost production of red blood cells
  • Improves survival
  • Reduce cardiovascular morbidity
  • Enhances quality of life.
  • Flu-like symptoms
31
Q

Vasopressin Receptor Agonists

A
  • For diabetes insipidus (Desmopressin), Oesophageal Varices (Terliepressin)
32
Q

Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors

A

For type 2 diabetes mellitus e.g. canagliflozin

33
Q

Uricosuric Drugs

A

Sulphinpyrazone, rarely used these days

34
Q

Drugs affecting pH of Urine

A

E.g. Ascorbic acid (acidify), potassium citrate (alkalinise) for urine infection symptoms or kidney stone formation. Rarely used.

35
Q

Why do we need to be careful with prescribing when a patient has kidney impairment?

A
  • Reduced renal excretion of a drug and its metabolites may cause toxicity
  • Sensitivity to some drugs is increased even if elimination is unimpaired
  • Increased risk of adverse drug reaction
  • Some drugs are not effective when renal function is reduced
  • Chronic Kidney Disease increases risk of drug-induced kidney disorders
  • Half-life is increased due to reduced elimination increasing toxicity.
36
Q

Considerations before prescribing?

A
  • degree of renal impairment?
  • AKI or CKD?
  • Proportion of drug which is renally excreted
  • Does drug have narrow or wide therapeutic window?
  • Is drug potentially nephrotoxic?
  • Is this patient established on renal replacement therapy?
37
Q

Estimate Renal Function using….

A
  • Creatinine Clreance or eGFR (depends on drug)

- Cockroft and Gault equation used for Creatinine Clearance

38
Q

Pros & Cons of estimating Creatinine Clearance using Cockroft and Gault

A
  • Pros - good validated formulae, advised for narrow therapeutic index drugs
  • Cons - inaccurate for rapidly changing creatinine levels and in severe renal disease, need to use “ideal body weight” at extremes of body weight, adults only.
39
Q

Pros of eGFR

A
  • Easy reporting allows early detection of CKD
  • BNF offers broad range of guidance on dosage based on eGFR
  • eGFR increasingly being used to alter drug dosing and evidence growing regarding accuracy
  • Good for majority of patients and drugs
40
Q

Cons of eGFR

A
  • Not validated in some patient groups e.g. acute renal failure, pregnancy, oedematous states and malnourished, extremes of weight.
  • As not validated for drug dose calculations - risk of drug toxicity or therapeutic failure.
41
Q

Examples of Nephrotoxic Drugs

A
  • ACEIs and ARBs
  • NSAIDs e.g. ibuprofen
  • Diuretics
  • Lithium
  • Digoxin
  • Aminoglycosides (Gentamicin)
  • Vancomycin
  • Metformin
  • Iodinated Contrast Media
  • Opioids (e.g. morphine)
42
Q

Pre-Renal Drug-Induced AKIs

A
  • Blood flow to kidney restricted = renal underperfusion e.g. NSAIDs
  • Excessive water and electrolyte loss e.g. diuretics
43
Q

Intra-Renal Drug-induced AKIs

A
  • Tubular necrosis or interstitial nephritis or rhabdomyolysis
  • Gentamicin or Ciclosporin
44
Q

Post-Renal Drug-Induced AKIs

A
  • Obstruction of renal tract, or urine retention

- Anticholinergicvs (amitriptyline), opioids, chemotherapy

45
Q

Non-drug-related AKI causes

A
  • Low BP - sepsis, diarrhoea and vomiting, poor oral intake
  • Low cardiac output - MI, heart failure, arrythmia
  • Reduced blood volume - GI bleed, burns, intra-op losses
  • Post-renal obstruction - prostate, constipation, blocked catheter, blood clot
  • Intra-renal - rhabdomyolysis, myeloma, vasculitis
46
Q

Prinicipals of Prescribing in Renal Impairment

A
  • Check U&Es, including eGFR and Creatinine
  • Look at baseline and trends in renal function
  • Consider stopping or with-holding nephrotoxic drugs
  • Check resources
  • Chooses non-nephrotoxic drug if possible
  • Reduce size of dose or increase dosing interval or stop or withhold
  • Use therapeutic drug monitoring to guide dose / frequency if appropriate
  • Continue to monitor U&Es, BP and clinical response
47
Q

Management of AKI

A
  • Treat any sepsis or urogenital obstruction
  • Aim for good fluid / electrolyte balance
  • Optimise BP
  • Withhold/stop toxins
  • Review drug doses and side effect profile
  • Monitor U&Es, refer nephrology/urolgy if worsening
48
Q

Prescribing in CKD

A
  • CKD classified stage 1 (mild) through to 5 (severe impairment)
  • Important risk factor for cardiovascular disease
  • Aim to: prevent or reverse worsening, review all meds, check doses appropriate, manage concurrent conditions e.g. hypertension, sepsis, diabetes, heart failure, renal anaemia, bone disease, electrolyte and acid-base disturbances
49
Q

Patients on Renal Replacement Therapy

A
  • Some drugs actively removed during dialysis - this will affect dose and timing of drug.
  • Many variables - what kind of dialysis?
  • Is drug removed from circulation during dialysis?
  • What is dialyser membrane (filter in machine), blood and dialysate flow rate (rate at which it flows through machine)?
  • Refer to specialist renal team!!!
50
Q

Sick Day Rules

A
  • Stop taking certain drugs when they have a temporary illness like diarrhoea and vomiting which can dehydrate the patient.
  • Medicines which should be stopped include Diuretics (stimulates fluid loss increasing risk of dehydration), ACEIs, ARBs, NSAIDs (the previously listed drugs can impair kidney function when the patient is dehydrated and cause kidney failure) and Metformin (increases risk of lactic acidosis).

MD3002 - RENAL (13 decks)

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