Pharmacology and Kidneys Flashcards by Ellie McMichael

2 names of loop diuretics?

Furosemide

Bumetanide

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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

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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

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What is an OAT?

Organic anion transporter

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What site do loop diuretics target?

Cl-

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What is result of Loop diuretics blocking NKCC2 triple transporter?

Prevents dilution of filtrate in TAL

-Increasing Na+ load delivered to distal nephron

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Contraindications for loop diuretic?

Hypovolaemia/dehydration

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Be cautious of what with loop diuretics?

Hypokalaemia
Hyponatraemia
Hepatic encephalopathy
Gout

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Side effects of loop diuretic?

Hypokalaemia
Metabolic acidosis (increased H+ secretion)
Hypocalcaemia
Hypomagnesaemia
Hypovolaemia & hypotension
Hyperuricaemia (can precipitate acute gout)
Dose related hearing loss

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Example of thiazide diuretic?

Bendroflumethiazide

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Indications for thiazide diuretic?

HT 
Mild heart failure 
Severe resistant oedema (combo with loop)
Renal stone disease 
Nephrogenic diabetes insipidus

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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

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Where is the Cl-/Na+ cotransporter?

Tubular epithelium of early distal convoluted tubule

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Main mechanism of thiazide/thiazide-like diuretic?

Increases reabsorption of Ca2+

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Contraindications of thiazide/thiazide-like diuretic?

Hypokalaemia

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Be cautious using thiazide/TL diuretics if patient has?

Hyponatraemia

Gout

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Side effects of thiazide/TL diuretics?

Hypokalaemia
Metabolic alkalosis
Hypovolaemia & hypotension
Hypomagnesaemia
Hyperuricaemia (poss lead to gout)
Erectile dysfunction
Impaired glucose tolerance in diabetics

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Examples of thiazide-like diuretics?

Chlortalidone
Indapamide
metolazone

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Indications for thiazide like diuretics?

HT 
Mild heart failure 
Severe resistant oedema (combo with loop)
Renal stone disease 
Nephrogenic diabetes insipidus

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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

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Example of potassium sparing diuretics?

Spironolactone
Eplerenone
Amiloride hydrochloride
Triamterene

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Indications for potassium sparing diuretics?

Heart failure
Primary
Hyperaldosteronism (Conns)
Resistant HT
Secondary hyperaldosteronism

Used in combo with thiazides and loops to prevent hyperkalaemia

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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

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What is spironolactone metabolised to?

Rapidly spironolactone metabolised to canernone

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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?

1. Increase Na+ load (loop/thiazide diuretics) produces enhanced Na+ reabsorption 2. Results in charge separation= lumen more -ve causing DEpolarization of luminal vs basolateral membrane 3. Increased driving force of K+ across luminal membrane enhanced K+ secretion (number of ROMK channels increase) 4. 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