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Renal and Urology > Drugs That Have Effects on the Kidney > Flashcards

Drugs That Have Effects on the Kidney Flashcards

1
Q

What are the important functions of the kidney?

A
  • Regulation of extracellular volume (H2O)
  • Regulation of plasma electrolytes (Na+, Cl-, K+, Ca2+, Mg2+, PO4 3-)
  • Regulation of acid-base balance (H+, HCO3-)
  • Elimination of waste products (urea, creatinine, uric acid, drugs)
  • Conservation of essential nutrients (amino acids, vitamins)
  • Endocrine function (erythropoietin, calcitriol, renin)
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2
Q

What proportions of water are in the different compartments?

A

-Blood (intravascular) volume- 4L
=Heart
=Arteries/ arterioles
=Capillaries (equilibrium with extracellular fluids)
=Veins (50-60% blood volume, acts as reservoir regulating venous return to heart but able to divert this volume into the other parts of the circulation)
-Extracellular (interstitial) fluid- 12L
-Intracellular fluid- 32L

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3
Q

What is the role of the kidneys in extracellular volume?

A
  • Renal blood flow= 1.25L/min (25% cardiac output)
  • Glomerular filtration rate (GFR)= 100mL/min (150L/day)
  • Urine output= 1mL/min (1.5L/day)
  • extracellular blood and blood volume dependent on overall hydration of the body which is regulated by the kidney
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4
Q

What are the hormones that act on renal tubules?

A

-Aldosterone
=Stimulates Na+ reabsorption in the distal tubule
-Vasopressin
=stimulates water reabsorption in the collecting duct
-Parathyroid hormone
=stimulates Ca2+ reabsorption

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5
Q

When is erythropoietin released?

A
  • In response to hypoxia (low levels of oxygen at tissue level) in the renal circulation
  • Stimulates erythropoiesis (production of red blood cells) in the bone marrow
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6
Q

What does Calcitriol do?

A
  • The activated form of vitamin D

- Promotes intestinal absorption of calcium and the renal absorption of phosphate

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7
Q

When is renin released?

A
  • Released from juxtaglomerular apparatus in response to reduction in tubular flow or sodium content
  • Regulates angiotensin and aldosterone levels
  • Combined with regulation of volume and plasma electrolytes= influence on blood pressure
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8
Q

What helps anchor the kidney in place?

A
  • Tough connective tissue layer= renal fascia

- Capsule of peri-renal fat

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9
Q

How many pyramids are there in the kidney?

A

Around 8

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10
Q

What is the lobe of the kidney?

A

Renal pyramids along with adjoining cortical region

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11
Q

Describe the renal arteries

A
  • Split into segmental and then several inter-lobar arteries which run through the renal columns to supply the renal lobes
  • Inter-lobar arteries split at the junction of the renal cortex and medulla to form bow-shaped arcuate arteries that form arcs along the base of the medullary pyramids.
  • Radiating arteries branch into numerous afferent arterioles (that supply the glomerular capillaries), the efferent arterioles (drain capillaries) and vasa recta (supply renal tubule associated with each glomerulus.
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12
Q

How is the water in the compartments in equilibrium?

A
  • Across capillary walls of tissues (intravascular and interstitium)
  • Dependent on relationship between hydrostatic pressure (favours filtration of water across capillary endothelium into interstitium) and oncotic pressure (produced by plasma proteins that tends to pull water back into intravascular space)
  • Interstitial fluid in equilibrium with intracellular across cell membrane
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13
Q

Describe the PCT

A
  • 65% reabsorption Na+, K+, Cl- ions by passive transport
  • 80-90% filtered bicarbonate
  • Almost all filtered glucose and amino acids (sodium)
  • Calcium and magnesium (compete for exchange with Na) and most phosphate
  • 50% filtered urea reabsorbed
  • Water through aquaporins osmotically
  • Active excretion of creatinine, uric acid and many drugs
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14
Q

Describe the Loop of Henle

A
  • Descending limb=- water
  • 25% NaCl ions thin and thick ascending limb by specialised symporter protein along with a K+ and Cl- ion
  • Calcium and phosphate ions in thick ascending limb passively
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15
Q

Describe the DCT

A

-10% NaCl
=First part= symporter
=sodium in exchange for K+ or H+ (aldosterone)
-Calcium reabsorption= PTH

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16
Q

Describe the macula densa

A
  • Area of closely packed specialised juxtaglomerular cells lining renal tubule at transition between LoH and DCT
  • Sensitive to concentration of NaCl in tubular fluid, pressure in afferent artery and signals from sympathetic NS (beta 1)
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17
Q

Actions of renin

A
  • Constrict efferent arteriole (increase glomerular capillary pressure and filtration)
  • Vasoconstriction
  • Stimulates thirst
  • Vasopressin (water-conserving)= posterior pituitary
  • Aldosterone (sodium-conserving)= adrenal gland
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18
Q

What is pre-renal renal impairment?

A

Physiological function of a kidney declines because of a failure to deliver sufficient blood flow to renal cortex

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19
Q

What are the causes of pre-renal impairment?

A
  • Systemic dehydration because of intercurrent illness or the effects of diuretics
  • Reduced renal perfusion because of low arterial blood pressure secondary to the effects of drugs or haemorrhage
  • Blockage of major renal arteries because of atherosclerosis or thrombosis
  • Vasoconstriction of cortical vessels because of drugs (NSAIDs)
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20
Q

What are renal causes of impaired function?

A

-Direct injury to renal tissue
=intrinsic renal disease (glomerulonephritis)
-Effect of drugs and toxins

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21
Q

What are post-renal causes of impaired function?

A

-Obstruction to urinary tract
=Compression of ureter between kidney and bladder as a result of a retroperitoneal or pelvic tumour
=Obstruction of the bladder outflow (common secondary to prostate disease)

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22
Q

What are the types of diuretics?

A

-Loop= act on thick ascending limb of LoH
(furosemide, bumetanide)
-Thiazide= act on DCT (Bendroflumethiazide, chlortalidone)
-Potassium-sparing= inhibit Na reabsorption in exchange for K+/H+ at end of DCT and early collecting duct
-Osmotic= small molecules filtered to exert osmotic pressure to prevent water reabsorption (cerebral oedema, mannitol)
-Carbonic anhydrase inhibitor= reduces production of hydrogen and bicarbonate ions (acetazolamide, prevent altitude sickness and glaucoma)

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23
Q

What drugs act on glomerular function?

A
  • Angiotensin-converting enzyme inhibitors (Ramipril, lisinopril)= less angiotensin 2
  • Angiotensin receptor antagonists (losartan, candesartan)= block effect of angiotensin 2 at receptor= dilates arterioles, reduces peripheral vascular resistance, reduce blood volume and pressure
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24
Q

What drugs act at the PCT?

A

-Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin)= inhibit co-transporter protein that reabsorbs glucose with sodium, increases urinary excretion of glucose (type 2 DM)
-Uricosuric drugs (febuxostat, sulfinpyrazone)= block reabsorption of uric acid, indicated for long-term prevention of gout
=Probenecid used to prevent excretion of penicillin

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25
Q

What drugs act on the DCT?

A

-Parathyroid hormone produced by recombinant DNA technology can be administered to maintain reabsorption and calcium concentration in patients with chronic hypoparathyroidism

26
Q

What drugs act on the collecting duct?

A

-Vasopressin analogues (desmopressin)= used in high urinary flow (diabetes insipidus) and develop dehydration
-Vasopressin inhibitors (demeclocycline)= used in SIADH (causes excess water retention and hyponatraemia), tetracycline antibiotic that inhibits responsiveness of collecting duct cells to vasopressin and reduces water reabsorption
=Tolvaptan= specific vasopressin V2 receptor antagonist

27
Q

What drugs replace renal products?

A
  • Epoetins (epoetin beta, darbepoetin alfa)= recombinant human erythropoietin to treat anaemia associated with erythropoietin deficiency in chronic renal failure
  • Vitamin D (hydroxylated derivatives alfacalcidol, calcitriol)= severe renal impairment
  • Sodium bicarbonate (supplements)= usually reabsorbed in PCT, metabolic acidosis
28
Q

What are the mechanisms by which drugs can have adverse effects on renal function?

A
  • Reduced extracellular fluid volume (diuretics)
  • Direct effects on renal blood vessels (NSAIDs, drugs affecting renin-angiotensin system)
  • Toxic effects on renal cells= acute tubular necrosis and acute interstitial nephritis
29
Q

How does reduced extracellular fluid volume cause adverse renal effects?

A

-Excessive fluid losses
=Decrease arterial blood pressure and tissue perfusion
=Initiates protective reflexes like sympathetic NS and renin-angiotensin system
=If perfusion pressure of renal cortex and glomerular vessels fall- generation of angiotensin 2 constricts efferent artery
=Progressive dehydration= glomerular filtration fail and clearance of waste products of metabolism compromised

30
Q

How does dehydration cause reduced renal perfusion?

A

-Contraction of extracellular fluid volume
=Decrease venous return to heart, arterial blood pressure and reduce tissue perfusion
=Changes sensed by arterial baroreceptors and low pressure stretch receptors in the heart
=Initiate protective reflexes= activation of sympathetic NS and renin-angiotensin system
=Sympathetic NS causes vasoconstriction

31
Q

What preserves threatened extracellular volume?

A

-Reduced renal perfusion= reduced volume of blood supplied to glomeruli= reduced filtration because of reduced hydrostatic pressure in glomerular capillaries)= reduced glomerular filtration rate and volume of urine produced

32
Q

What drugs cause dehydration?

A
  • Diuretics (poorly monitored)
  • Laxatives
  • Proton pump inhibitors
  • Antibiotics
  • Chemotherapeutic agents (vomiting)
33
Q

What are the symptoms and signs of dehydration?

A
  • Thirst
  • Dizziness, especially after adopting the upright posture
  • Less urine
  • Reduced blood pressure
  • Decreased skin turgor
  • Postural hypotension
  • Increased urea and creatinine
34
Q

What drugs alter renal perfusion?

A
  • Drugs affecting renin-angiotensin system= ACE inhibitors and angiotensin receptor antagonists
  • NSAIDs
35
Q

How do NSAIDs affect renal vasculature?

A

-PDE2 and PGI2 widely synthesised in kidney where they regulate vasomotor tone and tubular transport
-Act as vasodilators that enhance glomerular perfusion and act as natriuretic by inhibiting sodium-potassium-chloride co-transporter in the thick ascending limb of LoH
-Inhibit generation of prostanoid by cyclo-oxygenase
-Interfere with regulatory mechanism
=Contraindicated in hypertension and heart failure

36
Q

What are the mechanisms of direct toxic effects on the kidneys?

A
  • Acute tubular necrosis= process of direct injury and cell death, obstruct tubules by debris
  • Acute interstitial nephritis= acute hypersensitivity reaction manifesting as inflammation in interstitial spaces around renal tubules
  • Tubular dysfunction
37
Q

What are the causes of acute tubular necrosis?

A

-Aminoglycoside antibiotics (gentamicin)
-Amphotericin B
-Calcineurin inhibitors (ciclosporin),
Chemotherapeutic agents (cisplatin)
-Aciclovir (crystallise and obstruct urinary flow)
-Poisons (ethylene glycol)
-Radiocontrast media in imaging
-Bacterial sepsis
-Renal ischaemia

38
Q

What are the clinical features that suggest acute interstitial nephritis?

A
  • Low grade fever
  • Skin rash
  • Eosinophilia
  • Urine sample containing protein
  • White blood cells
39
Q

What are the causes of acute interstitial nephritis?

A

-Drug-induced
=antibiotics (cephalosporins, sulphonamides)
=NSAIDs (ibuprofen, diclofenac)
-Proton pump inhibitors (omeprazole)

40
Q

What are the causes of tubular dysfunction?

A
  • Lithium is a small cation that can compete with other cations in tubular cells and cause polyuria secondary to impairing urine concentrating ability
  • Proximal tubular function impaired by cumulative exposure to heavy metals (lead, mercury, arsenic, cadmium) manifesting as excessive loss of glucose, amino acids, phosphate and smaller proteins that would normally be reabsorbed
41
Q

What are the types of thiazide diuretics?

A
  • True thiazides= Bendroflumethiazide, hydrochlorothiazide
  • Thiazide-like diuretics= indapamide, chlortalidone (different chemical structure but have similar pharmacological actions)
42
Q

What are the types of potassium-sparing diuretics?

A
  • Directly inhibit actions of aldosterone at its receptors (spironolactone, eplerenone)
  • Indirectly affect the resulting exchange of cations by blocking sodium channels (amiloride, triamterene)
43
Q

What is the mechanism of action of loop diuretics?

A
  • Thick ascending limb of LoH, inhibit co-transporters in luminal membrane by combining with Cl- binding site
  • Direct vasorelaxant properties
44
Q

What are the indications for loop diuretics?

A
  • Heart failure (fluid accumulates in peripheral tissues or lung alveoli)
  • Chronic renal failure
  • Liver cirrhosis with ascites
45
Q

Describe administration of loop diuretics

A
  • Absorbed from GI tract, usually given by mouth
  • Reach LoH after secreted by organic acid transport proteins in PCT
  • Daily dose 40 to 80mg
  • Furosemide can be given IV in emergency (acute pulmonary oedema) or when intestinal absorption impaired (severe chronic congestive heart failure)
46
Q

What are the adverse reactions of loop diuretics?

A

-Hyponatraemia, hypokalaemia and metabolic alkalosis
=increased Na+ to distal nephron increases reabsorption of Na in exchange for potassium and hydrogen
-Hypokalemia= lethargy, drug interactions (increases toxicity of digoxin and type 3 anti-arrhythmias)
-Dehydration and hypovolaemia= hypotension so impaired renal function (rise in urea and creatinine conc)
-Precipitate incontinence and urinary retention
-Gout= greater excretion of Ca2+ and Mg2+ and uric acid
-Dose-related hearing loss= impaired ion transport by basolateral membrane of stria vascularis in inner ear

47
Q

What is the mechanism of action of thiazide diuretics?

A
  • Inhibition of Na+/Cl- co-transporter protein on the luminal membrane by interaction with chloride-binding site
  • Increases loss of K, H, Mg
  • Reduce Ca2+ excretion
  • Vasodilator action
48
Q

What are the indications of thiazide diuretics?

A

-Hypertension
=natriuresis and volume contraction
-Heart failure (with loop diuretics for rapid diuresis)
-Prevent recurrent stone formation in idiopathic hypercalciuria
-Nephrogenic diabetes insipidus

49
Q

Describe the administration of thiazide diuretics

A
  • Once daily by mouth
  • Standard dose of Bendroflumethiazide 2.5-5mg PO daily
  • Active secretion into PCT, involves organic anion transporter proteins that excrete uric acid (compete for excretion)
50
Q

What are the adverse effects of thiazide diuretics?

A
  • Electrolyte disturbances
  • Hyperuricaemia and episodes of gout
  • Hyperglycaemia= affects on ATP-sensitive K+ channels involved in pancreatic beta-cell secretion of insulin
  • Increased urinary frequency, dehydration and incontinence
  • Erectile dysfunction (vasodilation)
  • more potent than loop but less therapeutic efficacy
51
Q

What are the mechanisms of action of potassium-sparing diuretics?

A
  • Aldosterone receptor antagonists= aldosterone binds to receptor and stimulates the formation of the Na+/K+ exchanger in basolateral membrane of DCT
  • Sodium channel blockers= inhibit Na+ reabsorption by blocking luminal sodium channels reducing availability of sodium for exchange with potassium at basolateral membrane
52
Q

What are the potassium-sparing diuretic indications?

A
  • Chronic heart failure
  • Liver failure with ascites
  • Primary hyperaldosteronism (Conn’s syndrome)= aldosterone-secreting tumour of adrenal gland
  • Hypertension (resistant to standard treatment)
  • Combined with other diuretics for reduced risk of hypokalaemia
53
Q

How are potassium-diuretic diuretics administered?

A
  • Oral, once daily

- Metabolite canrenone

54
Q

What are the adverse effects of potassium-sparing diuretics?

A
  • Hyperkalaemia
  • ACE inhibitors, angiotensin receptor antagonists favour potassium retention
  • Monitor electrolytes
  • Gynaecomastia, menstrual disorders and testicular atrophy= acts on progesterone and androgen receptors
55
Q

Describe the mechanism of action of osmotic diuretics

A
  • Create osmotic drag that prevents passive reabsorption of water in parts of renal tubule that are freely permeable to it
  • Increased flow of water through tubule carries electrolytes
56
Q

What are the indications of osmotic diuretics?

A

-Emergency treatment of acutely raised intracranial or intra-ocular pressure

57
Q

What are the adverse effects of osmotic diuretics?

A

-After IV administration
=transient expansion of the extracellular fluid volume (with a risk of precipitating left ventricular failure) and hyponatraemia

58
Q

Describe the mechanism of action of carbonic anhydrase inhibitors

A

-Inhibit enzyme
=inhibits reaction between CO2 and water in renal tubular cells
=reduced production of carbonic acid and dissociated products, bicarbonate and hydrogen ions
=reduces availability of H+ ions at luminal membrane for exchange with Na and bicarbonate ions for co-transport with sodium at basolateral membrane
*mild natriuresis and diuresis, alkalisation of urine and metabolic acidosis

59
Q

How are carbonic anhydrases administered?

A
  • Glaucoma in eye drops to reduce formation of aqueous humour
  • Mouth to accelerate acclimatisation to high altitude
60
Q

What are the adverse effects of carbonic anhydrases?

A
  • Metabolic acidosis because of reduced absorption of bicarbonate ions
  • Idiopathic reactions= rashes, blood dyscrasias, interstitial nephritis (sulphonamides)

Renal and Urology (43 decks)

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