Week 5 - D - Drugs acting on the kidney 3 - PGE&I2, Gout and SGLT2 Flashcards
What acid are prostoglandins formed by? And what are the enzymes that carry this out?
They are formed from arachdonic acid by the enzymes cyclooxygenase 1and2 (COX1&2)
What are the two most important prostoglandins in the kidneys?
This would be PGE2 and PGI2
What effect do the prostoglandins have on the kidneys?
They increase renal perfusion by causing vasodilation of the afferent arteriole
What are the drugs which inhibt COX and may precipitate renal failure renal failure due to this?
This would be NSAIDs - they cause vasoconstriciton of the afferent arteriole becuase the prevent they prostoglandins (PGE2 and PGI2) from being produced
Why is it that giving NSAIDs could be a bad in a condition such as CHF?
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
In an acute gout attack, what are the 1st, 2nd, and 3rd line treatment?
1st - NSAID (naproxen % diclofenac) 2nd - Colchicine 3rd - Steroids (prednisolone)
What is a known side effect of colchicine?
Known to cause diarrhoea
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?
The drugs are given 2 weeks after the acute attack Primary - allopurinol, secondary - febuxostat They are both xanthine oxidase inhibitors
If the gout is resistant to the xanthine oxidase inhibitors, what drug can be given? (give examples)
Give uricosuric acid agents - eg probenecid or sulfinpyrazone
How do uricosuric agents work? name 2?
They work by blocking the active transport of organic ions therefore reducing net reabsorption and build up of uric acid Probenecid and sulfinpyrazone
When are uricosuric agents no suitable?
Not suitable if there is a history if renal impairment or renal stones as they will be unable to be filtered
What is the newer uricosuric agent that may be tolerated in mild renal impairment?
Benzbromarone
2 drugs also exhibit mild uricosuric properties, what are these 2 non uricosuric agents that have similar properties?
Losartan and fenofibrate
What type of drugs are losartan and fenofibrate?
Losartan - angiotensin receptor blocker Fenobriate - lipid lowering drug
Usually if a patient has hypertension, ACE is first line If a patinet has HBP and gout, what would then be first line?
Losartan
Why is it encourgaed for patinets to drink lots of fluids when have uricosuric agents?
This is becuase crystalization of the urate can occur and this may lead to uric acid stones
Why may a high protein diet also lead to uric acid stone formation?
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
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?
It can deposit as monosodium urate crystals in the synovial joints leading to inflammation and swelling/pain
Dapagliflozin Canagliflozin Empagliflozin What are these and where do they act on?
These are sodium glucose co-transporter 2 inhibitors (SGLT2 inhibitors) and they act on the proximal convoluted tubule
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?
SGLT2 - 90% of the glucose transporters in the kidneys SGLT1 - majority in the intestine
What is the transport maximum for glucose to travel from the tubules into the blood?
The transport maximum for glucose is 2mmol/min
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?
It is a Na+/Glucose co-transporter which is secondary active transport
What are the benefits of SGLT2 inhibitors?
The decrease HbA1c They also increase excretion of glucose They promote weight loss - both glucose and water (osmotic drift) are lost
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?
Genital and urinary tract infections due to the ideal feeding grounds of bacteria as there is an energy supplying in the urinary tract
What does HbA1c measure?
It meaures the glycated haemoglobin This is a measure over theglycaemic control over the previous 3 months (basically measures the glucose in the blood)
