Pharmacology and Kidneys Flashcards
2 names of loop diuretics?
Furosemide
Bumetanide
Indication for loop diuretics?
- Pulmonary oedema
- CHF
- CKD
- Hepatic cirrhosis with ascites
- Diuretic-resistant oedema (in combo with thiazide)
- Add on for HT
- Reduce acute hypercalcaemia
Mode of action for loop diuretics?
-Absorbed in GI tract | -Bind to Plasma proteins | Enter nephron by OAT | Targets Cl- site & blocks the NKCC2 triple transporter on the apical surface of the tubular epithelium (thick ascending loop of henle TAL) | Decrease tonicity of the medullary interstitium -Prevent dilution of filtrate in TAL -Increase Na+ load delivered to distal nephron (causing K+ loss_ -Increase Ca2+ and Mg2+ excretion -Additional venodilator action
What is an OAT?
Organic anion transporter
What site do loop diuretics target?
Cl-
What is result of Loop diuretics blocking NKCC2 triple transporter?
Prevents dilution of filtrate in TAL
-Increasing Na+ load delivered to distal nephron
Contraindications for loop diuretic?
Hypovolaemia/dehydration
Be cautious of what with loop diuretics?
Hypokalaemia
Hyponatraemia
Hepatic encephalopathy
Gout
Side effects of loop diuretic?
- Hypokalaemia
- Metabolic acidosis (increased H+ secretion)
- Hypocalcaemia
- Hypomagnesaemia
- Hypovolaemia & hypotension
- Hyperuricaemia (can precipitate acute gout)
- Dose related hearing loss
Example of thiazide diuretic?
Bendroflumethiazide
Indications for thiazide diuretic?
HT Mild heart failure Severe resistant oedema (combo with loop) Renal stone disease Nephrogenic diabetes insipidus
Mechanism of thiazide diuretic?
- Absorbed from GI Tract to enter nephron by OAT
- Target CL- site and Block Na+/Cl- co-transporter
- Prevents dilation of urine in early DCT
- Increases Na+ load going to Collecting tubule (K+ loss)
- Increases reabsorption of Ca2+
- Additional vasodilator action
Where is the Cl-/Na+ cotransporter?
Tubular epithelium of early distal convoluted tubule
Main mechanism of thiazide/thiazide-like diuretic?
Increases reabsorption of Ca2+
Contraindications of thiazide/thiazide-like diuretic?
Hypokalaemia
Be cautious using thiazide/TL diuretics if patient has?
Hyponatraemia
Gout
Side effects of thiazide/TL diuretics?
- Hypokalaemia
- Metabolic alkalosis
- Hypovolaemia & hypotension
- Hypomagnesaemia
- Hyperuricaemia (poss lead to gout)
- Erectile dysfunction
- Impaired glucose tolerance in diabetics
Examples of thiazide-like diuretics?
- Chlortalidone
- Indapamide
- metolazone
Indications for thiazide like diuretics?
HT Mild heart failure Severe resistant oedema (combo with loop) Renal stone disease Nephrogenic diabetes insipidus
Mechanism of thiazide like diuretics?
- Absorbed from GI Tract to enter nephron by OAT
- Target CL- site and Block Na+/Cl- co-transporter
- Prevents dilation of urine in early DCT
- Increases Na+ load going to Collecting tubule (K+ loss)
- Increases reabsorption of Ca2+
- Additional vasodilator action
Example of potassium sparing diuretics?
Spironolactone
Eplerenone
Amiloride hydrochloride
Triamterene
Indications for potassium sparing diuretics?
- Heart failure
- Primary
- Hyperaldosteronism (Conns)
- Resistant HT
- Secondary hyperaldosteronism
Used in combo with thiazides and loops to prevent hyperkalaemia
Mechanism of potassium sparing diuretics?
Limited diuretic action
- Competitive antagonists of aldosterone at cytoplasmic aldosterone receptors
- increase Na+ excretion
- Decrease K+ excretion
- Block luminal Na channels in collecting tubules
- Increase Na+ excretion
- Decrease K+ excretion
- Enter nephron via OCT in proximal tubule
What is spironolactone metabolised to?
Rapidly spironolactone metabolised to canernone
Contraindications of potassium sparing diuretic?
- Severe renal impairment
- Anuria
- Hyperkalaemia
- Addison’s disease
Cautions for potassium sparing diuretic?
Acute porphyria’s
Side effects of potassium sparing diuretic?
Metabolic acidosis
AKI
Other random stuff
Triamterene has what type of GI absorption?
Good GI absorption
Amiloride has poor GI absorption. True or False?
True
Cautions using triamterene?
DM
Gout
Can cause blue fluorescence of urine
Side effects of triamterene?
Diarrhoea
Hyperkalaemia
Uncommon- hyperuricaemia, reversible renal failure
Example of osmotic diuretics?
Mannitol (IV)
Indications for osmotic diuretics?
Prevention of acute hypovolaemic renal failure: maintains urine flow
-Emergency treatment of acutely raised intracranial pressure/intraocular (increases plasma osmolarity which extracts water from these compartments)
Mechanism of osmotic diuretic?
IV infusion enters nephron via simple glomerular filtration
- Remains in filtrate (too polar for reabsorption)
- Creates osmotic potential for water
- Dilutes solute in proximal tubule (decreases force for sodium to move from tubular fluid into interstitium)
Contraindications for osmotic diuretic?
Anuria Intracranial bleeding Severe cardiac failure Severe dehydration Severe pulmonary oedema
Caution using osmotic diuretics if?
Extravasation causes inflammation and thrombophlebitis
Side effects of osmotic diuretic?
Pretty generic (wow specific)
Example of carbonic anhydrase inhibitors?
Acetazolamide
Indications for carbonic anhydrase inhibitors?
NOT USED AS DIURETIC ANYMORE
- Glaucoma
- Altitude sickness prophylaxis
Mechanism of carbonic anhydrase inhibitors?
Increase HCO3- excretion with Na+, K+, H20
Contraindications of carbonic anhydrase inhibitors?
- Adrenocortical insufficiency
- Metabolic acidosis
- Hypokalaemia
- Hyponatraemia
Caution if using carbonic anhydrase inhibitors if?
DM
Elderly
Renal calculi (stones)
Side effects of carbonic anhydrase inhibitors?
Metabolic acidosis
Haemorrhage
Nephrolithiasis
Indications for citric acid with potassium citrate?
Relief or discomfort i mild UTIs
-Alkalises urine
-May help prevent renal stone formation (ionised form is preferred- rather than crystal)
Contraindications for citric acid with potassium citrate?
Avoid in severe renal impairment
Side effects of citric acid with potassium citrate?
Hyperkalaemia
Nausea
Vomiting
Name for synthetic ADH analogue?
Desmopressin
Indications for synthetic ADH analogue?
Treatment for neurogenic diabetes insipidus
-Primary nocturnal enuresis
-Post-operative polyuria/polydipsia
(also an investigation)
Mechanism of Synthetic ADH analogue?
Specific to V2 receptor (found only in kidneys)
Acts to replace ADH that is otherwise not being secreted from the pituitary gland
Contraindications for synthetic ADH analogue?
- Cardiac insufficiency
- Conditions treated with diuretics
- History of hyponatraemia
- Polydipsia in alcohol dependence
- SIADH
Cautions with synthetic ADH analogue?
Conditions aggravated by water retention, CF
Side effects of synthetic ADH analogue?
HYPONATRAEMIA
Example of aquaretic/Vapten?
Tolvaptan
Indications for aquaretic?
-Hyponatraemia secondary to syndrome of inappropriate ADH secretion
Mechanism of aquaretic?
-Competitive antagonists to V1 or V2 receptor (target the Hs protein specifically)
Blocks ADH effect
-Reduced permeability at apical membranes & enhanced water excretion via aquaporins (Na not removed with water)
Contraindications for aquaretics?
Anuria
Hypernatremia
Hypovolemic
Volume depletion
Cautions when using aquaretics?
Abnormal LFTs
Diabetes mellitius
Risk of dehydration
Urinary outflow obstruction
How thiazide and loop diuretics cause K+ loss?
- Increase Na+ load (loop/thiazide diuretics) produces enhanced Na+ reabsorption
- Results in charge separation= lumen more -ve causing DEpolarization of luminal vs basolateral membrane
- Increased driving force of K+ across luminal membrane enhanced K+ secretion (number of ROMK channels increase)
- Secreted K+ is washed away by increased urinary flow rate
Syndromes that mimic diuretic effects?
Gitelman Syndrome
Bartter syndrome
Major sites of diuretic action in the nephron?
PCT
Thick ascending loop of Henle
Early distal convoluted tubule
Collecting tubule and duct
What exchanges happen in PCT?
- Na+ (passive Cl- reabsorption)
- Na+/H exchange
Exchange in the thick ascending limb of loop of henle?
Na+/K+/Cl- co-transport
What is transport in thick ascending limb of loop of Henle blocked by?
Loop diuretics- significant diuresis
What is transport in PCT blocked by?
Carbonic anhydrase inhibitors
-Mild diuresis
Inhibit production of H2CO3 H+ and HCO3-
Transport in early distal convoluted tubule?
Na+/H+ exchange
Na+/Cl- co-transport
What is Na+/H+ exchange blocked by?
Carbonic anhydrase inhibitors (mild diuresis)
What is Na+/Cl- co-transport blocked by?
Thiazide diuretics: modest diuresis
What occurs in collecting tubule and duct?
Na+/K+ exchanged
What blocks Na+/K+ exchange in Collecting tubule and duct?
Potassium sparing diuretics
Site of diuretic action in nephron?
Apical membrane
OATs secrete what into PCT?
Acidic drugs: thiazides, loop agents
OCTs secrete what into PCT?
Basic drugs: triamterene, amiloride
Where do loop diuretics work on?
Thick ascending loop of Henle
If you use loop diuretics what will build up in the tubule?
Na
2Cl
K+
What does both loop and thiazide diuretics cause?
Hypokalaemia
What can loop diuretics cause?
Hypocalcaemia
What don’t thiazide diuretics cause?
Hypocalcaemia
THEY = ORMOCALCAEMIA
If an old person with osteoporosis needs diuretics which should you give them?
THIAZIDE DIURETICS
What are prostaglandins synthesized in response to?
Ischaemia Mechanical trauma Angiotensin II ADH Bradykinin
What would a NSAID and ACI combo be?
DETRIMENTAL
Effects of prostglandins?
Vasodilators
Natriuretic
What do NSAIDs inhibit?
Enzyme cyclo-oxygenase 1 and cyclo-oxygenase 2
What is cyclo-oxygenase 1 & 2 required for?
Prostaglandin and thromboxane synthesis
What effect do prostaglandins have?
Vasodilatory effect on renal afferent arteriole, thereby increasing GFR
How heavy is role of prostaglandins in a healthy individual?
Minimal
In states of volume depletion how effective are prostaglandins?
Prostaglandin induced vasodilation is vital compensatory mechanism (Heat fauilure, dehydration)
Why avoid NSAIDs in patients with renal impairment?
Inhibition of renal prostaglandin synthesis can result in vasoconstriction of afferent arteriole and decreased GFR
Angiotensin induces what?
Vasoconstriction of efferent arteriole, therefore increasing intraglomerular perfusion pressure and GFR
What happens to GFR when angiotensin is blocked by ACEis/ARBs?
Reduced
What can ACEis/ARBs cause?
Hyperkalemia