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MD3002 Pharmacology > Drugs and the Kidney > Flashcards

Drugs and the Kidney Flashcards

1
Q

What is the mechanism of action of loop diuretics?

A
  • 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
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2
Q

Give two examples of loop diuretics

A
  • Furosemide

- Bumetanide

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3
Q

What are some indications for loop diuretics?

A
  • Pulmonary oedema

- Resistant hypertension - Hypercalcaemia

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4
Q

What are some side-effects of loop-diuretics?

A
  • 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
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5
Q

What are 2 examples of thiazide diuretics?

A
  • Bendroflumethiazide

- Indapamide

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6
Q

What is the mechanism of action of thiazide diuretics?

A
  • 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)
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7
Q

What are the indications for use of thiazides?

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

What are the side-effects of thiazides?

A
  • Hypotension, hypovolemia
  • Low K, Na, Mg
  • Promotion of calcium retention / hypocalciuria
  • Metabolic alkalosis
  • Gout
  • Erectile dysfunction
  • Hyperglycaemia, hyperlipidemia
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9
Q

What is the mechansim of action of aldosterone antagonists?

A
  • Antagonise the aldosterone receptor in the collecting tubule
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10
Q

GIve 2 examples of aldosterone antagonists

A
  • Spirolanactone

- Eplerenone

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11
Q

What can aldosterone antagonists also be known as?

A
  • Potassium sparing weak diuretics

- Mineralocorticoid receptor antagonists

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12
Q

What are the indications for aldosterone antagonists?

A
  • Oedema (hert, liver nephrotic syndrome)
  • Hypertension
  • Conn’s syndrome (primary hyperaldosteronism)
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13
Q

What are the side-effects of aldosterone antagonists?

A
  • Renal impairment
  • Hyperkalaemia
  • Hyponatraemia
  • GI upset
  • Metabolic acidosis
  • Gynaecomastia with spiro
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14
Q

What is amiloride?

A
  • 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
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15
Q

What are the indications for amiloride?

A

Oedema inc. ascites, hypertension

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16
Q

What are the side-effects of amiloride?

A
  • High K+ (care if renal impairment)
  • GI upset
  • Metabolic acidosis
  • Renal impairment
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17
Q

How do osmotic diuretics work?

A

Modify filtrate content increasing amount of water excreted (e.g mannitol IV)

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18
Q

Give an example of an osmotic diuretic

A

mannitol IV

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19
Q

What are the indications for osmotic diuretics?

A
  • Cerebral oedema + raised intra-occular pressure
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20
Q

Give an example of a carbonic anhydrase inhibitor?

A

Acetazolamide (v. weak diuretic)

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21
Q

What are the indications for carbonic anhydrase inhibitors (e.g acetazolamide)?

A
  • Glaucoma

- Altitude sickness

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22
Q

What is syndrome of inappropriate ADH secretion caused by?

A

Excess ADH secreted by posterior pituitary gland regardless of what serum osmolality is

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23
Q

What does syndrome of inappropriate ADH secretion result in?

A
  • Hyponatraemia (<135)
  • Low serum osmolality
  • Inappropriately elevated urine osmolality (>plasma osmolality)
  • Euvolaemia
24
Q

What are the mild symptoms of SIADH?

A
  • Nausea
  • Vomitting
  • Headaches
  • Anorexia
25
Q

What are the moderate symptoms of SIADH?

A
  • Muscle cramps
  • Weakness
  • Tremor
  • Mental health disorders
26
Q

What are the severe symptoms of SIADH?

A
  • Drowsiness
  • Seizures
  • Coma
27
Q

What are the different causes of SIADH?

A
  • 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
28
Q

How is SIADH treated?

A
  • Correct underlying cause
  • Fluid restrict (500-1000ml daily)
  • Monito plasma osmolality, serum sodium and bodyweight
29
Q

What are some of the medictions used to treat SIADH?

A
  • Demeclocycline - antibiotic, also inhibits action of ADH on kidneys
  • Tolvaptan - ADH V2 antagonist in renal collecting ducts
  • Hypertonic sodium chloride in severe cases only
30
Q

Hoe is anaemia of renal disease treated?

A
  • Epoetin Alfa, Darbopoetin - IV/SC route
  • Reduce need for blood transfusions
  • Boost production of RBCs
  • Improve survival
  • Reduce CV morbidity
  • Enhance quality of life
31
Q

What can Erythropoietin Stimulating Agents cause e.g Epoetin alfa, darbopoetin?

A
  • Flu-like symptoms

- Avoid over or too rapid correction of haemoglobin - increases risk of hypertension and CV effects

32
Q

What are vasopressin (ADH) receptor agonists used to treat?

A
  • Diabetes insipidus (Desmopressin)

- Oesophageal varices (Terlipressin)

33
Q

What are Sodium-Glucose Co-transporter- 2 (SGLT-2) inhibitors used to treat?

A
  • Type 2 diabetes (e.g. canagliflozin)
34
Q

Give an example of a uricosuric drug used to treat gout?

A

Sulphinpyrazone (rarely used now)`

35
Q

What drugs affect the pH of urine?

A

Ascorbic acid (acidify), potassium citrate (alkalinise) for urine infection symptoms or kidney formation. Rarely done

36
Q

What drug is used first line to treat type 2 diabetes?

A

Metformin

37
Q

What should be considered before prescribing in relation to kidney diseases/impairment?

A
  • 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
38
Q

How is renal function usually estimated?

A
  • Creatinine clearence
  • eGFR
    Depends on the drug
39
Q

How is Creatinine clearence calculated (CrCl) using Cockroft and Gault (C&G)? (do not need to remember)

A

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
40
Q

What are the pros and cons of estimating Creatinine clearence from C&G?

A
  • 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
41
Q

What factors vary eGFR?

A

creatinine, age, sex, ethnicity

42
Q

eGFR can only be validated in adults of what races?

A

WHite and black

43
Q

What are the pros of using eGFR?

A
  • 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
44
Q

What are the cons of using eGFR?`

A
  • 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
45
Q

What should be done in a pateint with renal impairment but a therapeutic outcome must be met immedeatly?

A
  • 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
46
Q

Give examples of potentially nephrotoxic drugs?

A
  • ACE inhibitors, ARBs
  • NSAIDs
  • Diuretics
  • Lithium
  • Digoxin
  • Aminoglycosides
  • Vancomycin
  • Metformin
  • Iodinated contrast media
  • Opoids
47
Q

How can acute kidney injury be divided?

A
  • Pre-renal
  • Intra-renal
  • Post-renal
48
Q

What is generally used to treat Pre-renal AKI?

A

Diuretics

49
Q

What is generally used to treat intra-renal AKI?

A

Gentamicin, ciclosporin

50
Q

What is generally used to treat post-renal AKI?

A
  • Anticholinergics (amitriptyline), opoids, cemotherapy
51
Q

How is CKD managed?

A
  • Prevent or reverse worsening
  • Review all meds, check doses appropriate
  • Manage concurrent conditions
52
Q

How can CKD be classified?

A

stage 1 through 5 (mild to severe impairment)

53
Q

How are AKIs managed?

A
  • 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
54
Q

What else can AKI cause?

A
  • 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
55
Q

When should riveroxaban be avoided?

A
  • 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
56
Q

What are the principles of prescribing in renal impairment?

A
  • 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

MD3002 Pharmacology (7 decks)

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