Week 5 - D - Drugs acting on the kidney 3 - PGE&I2, Gout and SGLT2

Question 1

What acid are prostoglandins formed by? And what are the enzymes that carry this out?

Answer 1

They are formed from arachdonic acid by the enzymes cyclooxygenase 1and2 (COX1&2)

Question 2

What are the two most important prostoglandins in the kidneys?

Answer 2

This would be PGE2 and PGI2

Question 3

What effect do the prostoglandins have on the kidneys?

Answer 3

They increase renal perfusion by causing vasodilation of the afferent arteriole

Question 4

What are the drugs which inhibt COX and may precipitate renal failure renal failure due to this?

Answer 4

This would be NSAIDs - they cause vasoconstriciton of the afferent arteriole becuase the prevent they prostoglandins (PGE2 and PGI2) from being produced

Question 5

Why is it that giving NSAIDs could be a bad in a condition such as CHF?

Answer 5

This is because since they constrict the afferent arteriole, this decreases renal perfusion and lowers the GFR Therefore more salt and water is within the blood leading to an increase in blood pressure

Question 6

In an acute gout attack, what are the 1st, 2nd, and 3rd line treatment?

Answer 6

1st - NSAID (naproxen % diclofenac) 2nd - Colchicine 3rd - Steroids (prednisolone)

Question 7

What is a known side effect of colchicine?

Answer 7

Known to cause diarrhoea

Question 8

WHat drug is given for long term gout? (recurrent gout) Primary and secondary drug? What type of drugs are they? How long after the acute attack are the drugs given?

Answer 8

The drugs are given 2 weeks after the acute attack Primary - allopurinol, secondary - febuxostat They are both xanthine oxidase inhibitors

Question 9

If the gout is resistant to the xanthine oxidase inhibitors, what drug can be given? (give examples)

Answer 9

Give uricosuric acid agents - eg probenecid or sulfinpyrazone

Question 10

How do uricosuric agents work? name 2?

Answer 10

They work by blocking the active transport of organic ions therefore reducing net reabsorption and build up of uric acid Probenecid and sulfinpyrazone

Question 11

When are uricosuric agents no suitable?

Answer 11

Not suitable if there is a history if renal impairment or renal stones as they will be unable to be filtered

Question 12

What is the newer uricosuric agent that may be tolerated in mild renal impairment?

Answer 12

Benzbromarone

Question 13

2 drugs also exhibit mild uricosuric properties, what are these 2 non uricosuric agents that have similar properties?

Answer 13

Losartan and fenofibrate

Question 14

What type of drugs are losartan and fenofibrate?

Answer 14

Losartan - angiotensin receptor blocker Fenobriate - lipid lowering drug

Question 15

Usually if a patient has hypertension, ACE is first line If a patinet has HBP and gout, what would then be first line?

Answer 15

Losartan

Question 16

Why is it encourgaed for patinets to drink lots of fluids when have uricosuric agents?

Answer 16

This is becuase crystalization of the urate can occur and this may lead to uric acid stones

Question 17

Why may a high protein diet also lead to uric acid stone formation?

Answer 17

Increased protein means increased DNA bases Uric acid is a by product of purine (adenine and guanine) breakdown and therefore this can lead to increased risk of gout

Question 18

Hyperuricaemia can occur in kidney failure due to the inability to secrete uric acid from the vessels to the tubular lumen, where can the uric acid deposit?

Answer 18

It can deposit as monosodium urate crystals in the synovial joints leading to inflammation and swelling/pain

Question 19

Dapagliflozin Canagliflozin Empagliflozin What are these and where do they act on?

Answer 19

These are sodium glucose co-transporter 2 inhibitors (SGLT2 inhibitors) and they act on the proximal convoluted tubule

Question 20

The main types of glucose transporter is sodium glucose co-transporters 1and2 Where are SGLT2 found in more abundance? Where are SGLT1 found in more abundance?

Answer 20

SGLT2 - 90% of the glucose transporters in the kidneys SGLT1 - majority in the intestine

Question 21

What is the transport maximum for glucose to travel from the tubules into the blood?

Answer 21

The transport maximum for glucose is 2mmol/min

Question 22

Glucose reabsorption occurs in the proximal tubule mediated by sodium glucose co-transporters -SGLT 1 & 2 (normally 100% efficient) SGLT2 (S1 segment) and SGLT1 (S2/3 segment reabsorb up to 90% and 10%) of filtered glucose, respectively What type of transport mechanism is the uptake of glucose in the proximal convoluted tubule?

Answer 22

It is a Na+/Glucose co-transporter which is secondary active transport

Question 23

What are the benefits of SGLT2 inhibitors?

Answer 23

The decrease HbA1c They also increase excretion of glucose They promote weight loss - both glucose and water (osmotic drift) are lost

Question 24

They are taken once a day with or without food. Prescribed as monotherapy or in combination with insulin/ other antidiabetic drugs if existing treatment fails to control blood glucose. What are the common side effects of SGLT2 inhibtors?

Answer 24

Genital and urinary tract infections due to the ideal feeding grounds of bacteria as there is an energy supplying in the urinary tract

Question 25

What does HbA1c measure?

Answer 25

It meaures the glycated haemoglobin This is a measure over theglycaemic control over the previous 3 months (basically measures the glucose in the blood)