Flashcards in Renal Pharmacology Deck (75):
List three disease states in which you get oedema
Congestive heart failure
Hepatic cirrhosis with ascities
List 6 factors that contribute to oedema
1. Increased hydrostatic pressure
2. Reduced oncotic pressure within blood vessels
3. Increased tissue oncotic pressure.
4. Increased blood vessel wall permeability e.g. inflammation;
5. Obstruction of fluid clearance in the lymphatic system
6. Changes in the water retaining properties of the tissues themselves.
How to thiazides and loop diuretics get into the cell at its apical membrane?
Pass into filtrate bound by plasma proteins. They are then secreted by organion anion transporters into the filtrate.
Are thiazide diuretics acidic or basic drugs?
After secretion, is the concentration of the diuretic in the filtrate higher or lower than that of the blood.
Higher concentration in the filtrate.
Where do loop diuretics work?
Thick ascending limb of the loop of henle
What channel do loop diuretics block?
Briefly describe the mechanism of action of loop diuretics.
1. Na+/K+/2Cl- co-transporter blocked
This stops sodium from being reabsorbed into the tubular epithelium.
2. The tonicity if the medullary interstitium is decreased
3. Because magnesium and calcium reabsorption in the thick ascending limb is dependent on the positive lumen voltage gradient set up by potassium recycling through renal outer medullary potassium channel, loop diuretics also inhibit their reabsorption.
Where on the Na+/K+/2Cl- co-transporter do loop diuretics bind?
Name two loop diuretics
`How would you administer furesomide in acute pulmonary oedema?
Why is there increase excretion of magnesium and calcium with loop diuretics.
The reabsorption of these is dependant on the positive voltage gradient set up by pottassium recycling.
Is the tonicity of the medulla interstitium increased or decrease by loop diuretics?
What other indirect action do loop diuetics have, other that diuresis?
Are loop diuretics acidic or basic drugs?
Which drugs create a stronger diuresis; thiazide or loop diuretics?
List some adverse effects of loop diuretics
Depletion of calcium and magnesium
Hyperuricaemia (causes gout)
What channel do thiazide diuretics block?
The Na+/Cl- co transporter
Where do thiazide diuretics bind on the Na+/Cl- channel?
What indirect action do thiazide diuretics have on blood vessels?
What two conditions are thiazide diuretic most often used in?
Mild heart failure
Where is the nephron do thiazide diuretics work?
Distal convoluted tubule
Name two thiazide diuretics
Briefly describe the mechanism of thiazide diuretics
Bind to Cl- aspect on Na/Cl channel and inhibit its action. This means sodium is not reabsorbed and therefore neither is water.
Which diuretic causes depletion of calcium.
Loop. Thiazides do not cause deplection of calcium.
Which diuretic is more likely to cause erectile dysfunction
Why might diuretics cause a metabolic alkalosis?
H+ ions are washed away by increasing urinary flow.
What does aldosterone do at a cellular level in the kidneys?
It is a steroid hormone and so acts via cytoplasmic recpetors to increase the synthesis of the Na+/K+ ATPase.
It also increases synthesis of a protein that activates the epithelial Na+ channel
Overall would increase sodium retention
How does ADH work?
A peptide hormone which acts via G protein coupled receptors to increase the number of aquaporins (water channels) in the cell membrane.
Why do thiazide and loop diuretics cause hypokalaemia?
Pottassium is excreted into the filtrate in response to sodium being reabsorbed.
How does spiranolactone work?
It competes with aldosterone for binding to intracellular receptors causing decreased gene expression and reduced synthesis of a protein that activates Na+ channels in the apical membrane.
2. Decreases numbers of NA+/K+ ATPase pumps in the basolateral membrane
Name 4 potssium sparing diuretics
How do amiloride and triamterene work?
Block the apical sodium channel and decrease sodium reabsorption.
Describe the effect of spiranolactone on Na+ and K+ excretion.
Increases excretion og sodium and decreases excretion of pottassium.
Why would you use a potassium sparking diuretic?
In conjunction with other diuretics that cause pottassium loss.
Give an example of an osmotic diuretic
What is an osmotic diuretic?
A type of diuretic that inhibits reabsorption of water and sodium.
What do osmotic diuretics do to the osmolarity of the blood and renal filtrate?
Increase the osmolarity of both.
How do you give osmotic diuretics and why?
IV. Because they are pharmacologically inert
Briefly describe how osmotic diuretics work
The enter the nephron by glomerular filtration but are not reabsorbed. They oppose the absorption of water in freely permeable parts of the nephron and cause secondarily decrease in sodium reabsorption in the proximal tubule. Large fluid volume decreases sodium concentration and electrochemical gradient for reabsorption.
What is the major site of action of osmotic diuretics?
When would you use an osmotic diuretic?
For the prevention of acute hypovolaemic renal failure to maintain urine flow. Used in accutely raised intracranial or intra occular pressure
How do osmotic diuretics work to reduce intra cranial or intra occular pressure?
Solute does not enter they eye pr brain but increases plasma osmolality extracts water from these compartments.
Give an example of a carbonic anhydrase inhibitor
What do carbonic anhydrase drugs do?
Increase the excretion og NCO3 as well as NA, K and H20. Results in an alkaline diureses and metabolic acidosis.
When would you use carbonic anhydrase inhibitors?
Open angle gluacoma to reduce formation of aqueous humour.
Prophlaxis of altitude sickness.
What action does aldosterone have at the collecting tubule?
Enhanced reabsorption of sodium and salt retention
What is the action of ADH at the collecting tubule?
Enhanced water reabsorption.
What effect does alcohol have on the secretion of ADH?
What is neurogenic diabetes insipidus?
Lack of ADH secretion from the posterior pituitary
How do you treat neurogenic diabetes insipidus?
What drug might be useful in the treatment of bedwetting in children older than 10?
What is nephrogenic diabetes insipidus?
Inability of the nephron to respond to vasopressin
Mutations in what gene cause nephrogenic diabetes insipidus?
How do vaptan drugs work?
Act as competitive antagonists of ADH receptors
Briefly describe how vaptans work?
Block ADH receptors which causes excretion of water without excretion of sodium. Therefore the plasma concentration of sodium is raised.
What drug is used is the syndrome of innappropriate ADH secretion?
Where do SGLT2 inhibitors work?
At the SGLT2 co transporter in the proximal tubule
How do SGLT2 transporters work to reabsorb glucose?
1. Secondary active transsport at the apical membrane
2. Facilitated diffusion at the basolateral membrane.
Give an example of an SGLT2 inhibitor
What do the prostoglandins synthesised in the kidney do?
Act as vasodilators. Are importnt in compensatory vasodilation when there are condition of vasoconstirction or decreased effective arterial flow.
When is production of prostoglandins by the kidney stimulated?
In response to ischaemia, trauma, angiotensin 2, ADH and bradykinin
Name two ways in which prostoglandins affect GFR
Direct vasodilator effect upon the afferent arteriole
Release of renin leading to increased levels of angiotensis 2 that vasoconstricts the efferent arteriole leading to an increased filtartion pressure.
When will NSAIDS precipiate acute renal failure?
In conditions where renal blood flow is dependant of vasodiltor prostoglandsins (liver cirrhois, heart failure, nephrotic syndrome.
What drugs make up the "triple whammy effect"?
ACEI (or ARB) diuretic and NSAID.
How do uricosuric agents work?
Block the reabsorption of urate in the proximal tubule
What two uricosuric agents can be useful in gout?
What kind of drug is verapamil?
Rate limiting calcium channel blocker
What kind of drug is amioderone?
Calcium channel blocker that restores rhythm in AF
How do NSAIDs lead to decreased renal perfusion?
Block COX 2 which blocks prostoglandins
What do you usually have to do to the insulin dose in a person who has kidney damage.
Reduce it. If the kidney is injured then the insulin will stay around in the blood more often and cause hypoglycaemia.
Why is salbutamol given to people with hyperkalaemia?
Pushes a little bit of pottassium into the cells.
Does hyperkalaemia cause acidosis or alkalosis?
Do ACE inhibitors cause hyperkalaemia or hypokalaemia. Why?
Hyperkalaemia. They block the RAAS system which then reduces excretion of pottassium and leads to hyperkalaemia