JD Renal & Pharma Flashcards

Question

Why do people with diabetes end up with sweet urine?

Answer 1

Important medically for diabetes (too much urine) mellitus (sweet) – urine is sweet Too much glucose in the blood – too much in the primary filtrate – uptake systems have a max capacity to uptake Once the reabsorption level is saturated – we excrete glucose

Answer 2

Organic molecules - drugs and metabolites SLC22 family: Organic anion transporters (OATs) Organic cation transporters (OCTs) Organic Cation/ Carnitine transporters (OCNTs)

Answer 3

1. Organic cation drifts into the cell down its gradient (bottom right) using the OCT2 channel 2. Na+/H+ sets up H+ gradient in filtrate (use Na+ again to set up H+ gradient) 3. MATE antiporter (SLC22A1) moves H+ down the gradient into the cell while exporting organic cations into the urine 4. There is also a ATP driven transporter – ABCB1 – pump out organic cations directly Note this setup 'safe' for the cell - in the sense that cations drift into the cell and are pumped out. The cytoplasmic concentration should therefore not exceed that of plasma.

Answer 4

Organic anion transporter – Organic anion transporting polypeptides (OATPs) – transport larger and somewhat hydrophobic organic anions Organic anion moves into the cell on the basal side and exits on the apical side - story is incomplete.

Answer 5

Organic anion transporter – Na+/K+ ATPase sets up a Na+ gradient on the basal membrane, which is then used to set up an alpha-ketoglutarate gradient, which can then be used to to pump in organic anions, which can then be drift out on the apical side down the conc. gradient. Takeaway - Ketoglutarate gradient set up using the Na+ gradient at the basolateral side - Ketoglutarate gradient is then used to pump in organic anions (antiporter)

Answer 6

Dangerous – we have a pump in and drift out (different from drift in and pump out) - metabolite can accumulate in cell Depending on the efficiency of drift out – the metabolite can accumulate and be toxic to kidney cells – important when thinking about drug metabolism and pharmacodynamics of the drug You have blockers to prevent excessive uptake of organic anions to prevent toxicity on kidney cells – examples probenecid

Answer 7

Proximal tubule Phosphate recovery – once again using our sodium gradient (Na+/K+ ATPase) to drive in phosphate into the cell on the apical side – can be further exported out on the basal side

Answer 8

Recovering bicarbonate – we want to keep to help maintain pH 1. In the urine we find our filtered bicarbonate – bonds to H+ forming carbonic acid – carbonic anhydrase catalyzes the formation of H2O and CO2. 2. CO2 diffuses into the cell (move through membranes as non-polar) and converted to back into carbonic acid in the cell using carbonic anhydrase 3. Bicarbonate reformed, releasing H+, which can can then be pumped out, resulting in no net change in H+ thus making it a pH neutral reaction 4. HCO3- can then move out on the basal side either using a Cl- antiporter or Na+ symporter

Answer 9

If there is excess protons (acidosis) and bicarbonate is low, protons can be exported using the H+/Na+ antiporter (encountered before). The H+ can then be mopped up by phosphate anion and excreted in the urine. Reaction is not pH neutral

Answer 10

If there is excess protons (acidosis) and bicarbonate is low, protons can be exported using the H+/Na+ antiporter (encountered before). The H+ can then be mopped up by ammonia and excreted in the urine as ammonium. Reaction is not pH neutral

Answer 11

Ammonia produced from glutamine – glutamine pathway creates ammonia, proton and bicarbonate 1. Ammonia can be exported 2. Proton – exported out as is or bound in ammonium 3. Reaction also produced bicarbonate – can be exported from the cell to help reduce acidosis Example showing you how the kidneys try to maintain acid/base balance in a state of acidosis - excrete protons into filtrate and create bicarbonate that enters circulation to buffer.

Answer 12

Intercalated cells **A Cells** push protons out – directly with H+ ATPase or using a H+/K+ antiporter – proton released from carbonic acid **B Cells** pump H+ back into the body and bicarbonate out

Answer 13

Calcium moves across junctions driven by osmosis – urine becomes more concentrated, relative to plasma, once water has been removed Drives Ca2+ down downgradient – into the body through the leaky junctions

Answer 14

Protein uptake – huge proteins in the proximal tubule cells stick to proteins in the tubule, which then drives movement via endocytosis

Answer 15

All of this movement of ions is trying to reduce the osmolarity of the tubule – removing species form the filtrate – in order to drive water out of the filtrate back into the body – recovery

Answer 16

Has a large surface area to maximise solute and water recovery! 1. Microvilli 2. Pack a lot of length into a small space

Answer 17

Extra notes * PCT recovers 65% of the water and solutes! * Urine will still be at the same concentration after proximal convoluted tubule – as reduction is proportionate – both molecule/ion and water quantities drop by the same amount – concentration is similar * Some acid/base changes taken place but not the sophisticated changes

Answer 18

We have no water pumps, so we rely on osmosis and creating differential concentrations of solutes across membranes. If the environment around the tubules is more concentrated (which we can make), then water will naturally flow out!

Answer 19

Area of the kidney responsible for concentration - ascending thin limb **SLC12A2** – uses Na+ gradient to pump in Na+, K+ and 2Cl- -> subsequently on the basal end, Cl- is diffuses out with 3Na+ In this region there are no aquaporins and tight junctions are present – prevents movement of water along with ions – help to create a hypertonic solution outside of the urine

Answer 20

Loop Henle – hairpin loop 1. Descending thin limb 2. Ascending thin limb 3. Thick ascending limb

Answer 21

1. Ascending thin limb – concentrates the the environment around the LoH (kidney medulla) – allowing for ions + urea to leave but is impermeable to water following 2. Urine travelling down the descending limb will experience a strong osmotic pull – result in water moving out/recovered (Cells in the thin descending limb have lots of aquaporins but little ion transport) 3. But once the urine in the descending limb reaches the ascending thin limb the urine will already be more concentrated – making the action of the ion transporters more efficient at concentrating the limb (Positive loop) 4. Thick ascending limb – the solution becomes more dilute as everything would have been pumped out in the ascending thin limb

Answer 22

Mechanism recovers 10% of filtered water and 25% of Na+ and Cl- Running total – 75% water 90% NaCl

Answer 23

Anatomy (1): we have all of the loops in the same area and all of the renal corpuscles somewhere else Anatomy (2): we are careful with the way we organize the blood system, which would be the main transport system that could mess this up.

Answer 24

The blood vessels emerging from the glomerulus go on to form a secondary capillary system – the vasa recta We want to avoid that the solutes can taken up by the blood and carried away – removing the hypertonicity of the area

Answer 25

Concept - **counter current flow exchange** 1. Blood coming down – water will be drawn out of the blood (into the hypertonic environment) and ions will move into the blood (down the concentration gradient) 2. Bottom of the loop – blood is very concentrated and salt 3. Blood going up – water drawn in to, ions out drawn out In agreement with the loop of Henle – no net effect – both sides are cancelling each other out

Answer 26

Coming out of the LoH – dilute urine with low volume At the end of the distal tubule 95% of NaCl recovered and 75% of water – 5% more of NaCl recovered in distal convoluted tubule

Answer 27

Collecting duct follows the DCT and travels back down to the core of the kidney into the ureter As the collecting duct travels down, water is drawn out water due to the increased salinity of the medulla - transport via aquaporins Aquaporin two – can be in the cell membrane or locked up in vacuoles/vesicles - this is regulated by vasopressin – AVP drives movement to apical membrane allowing for water efflux from urine

Answer 28

Yes, the collecting duct can also leak urea into the medulla – also regulated by vasopressin Allowing some of it back – due to the concentration gradient - high concentration in collecting duct relative to surrounding environment

Answer 29

Anatomical arangement 1. The normal and hypertonic zones are seperated - cortex and medulla 2. Route taken by urine passes twice through the hypertonic zone - LOH and collecting duct All nephrons are arranged in a way that makes this happens: * glomeruli, DCT and PCT clustered in the cortex * LOH and collecting duct present in the medulla

Answer 30

Finer vessels come off to supply the nephrons Given the fact that the arteries/arterioles and the veins/venules run next to each other, we get exchange of O2, which means that quite a bit of oxygen get shunted from arteries to veins before the blood enters capillaries. The consequence of this is that the kidney cells later down the line (especially in the renal pyramid - LoH and collecting ducts) receive low amounts of oxygen – making these areas more sensitive to ischemia/states of low O2 Adaptation - Explains why the kidney's are responsible for EPO release to increase RBCs/oxygen delivery

Answer 31

Three things that can regulate BP 1. Systemic blood pressure 2. Constriction/relaxation of afferent arterioles 3. Constriction/relaxation of efferent arterioles

Answer 32

Yes, the glomerulus is able to effectively maintain blood pressure levels – stable between 80 and 180mmHG

Answer 33

1. Direct pressure sensing in the afferent arteriole – the myogenic mechanism. 2. Monitoring the performance of the nephron - tubuloglomerular feedback - each nephron relays information (salinity), which is used to modulate the blood pressure in glomeruli (distal tubule is actually located close to the glomerulus) Note - there are also systemic inputs from baroreceptors around the body

Answer 34

**Elevated pressure** – filtrate flows quicker - less time for solute recovery – macula densa pumps out more salt because there is more NaCl to begin with – in response to this JG cells release adenosine – acts on afferent arteriole and constricts – reducing glomeruli blood flow **Low pressure** – filtrate flows slower through tubules – more time for recovery/less NaCl in distal tubules – macula densa cells pump out less NaCl because there is less to begin with – JG cells respond to this can release less adenosine – afferent arteriole dilates in response to lower adenosine - increase glomerular blood pressure

Answer 35

Renin is an important player in blood pressure control - released by juxtaglomerular cells (located next to macula densa cells) Recap - Renin converts angiotensinogen into AngI, and Angiotensin converting enzyme (ACE) converts AngI into AngII - which is the main active player At the level of the kidney... 1. Macula densa cells detecting the salinity of the filtrate - high salinity = high pressure - inhibit renin release by JGCs / low salinity = low pressure - promote renin release by JGCs 2. Baroreceptors in JGCs - detect pressure directly - high pressure = inhibition of renin release / low pressure = stimulation of renin release. Renin increases - Ang II increases - efferent arteriole constricts - increases glomerular pressure

Answer 36

Renin – Ang – AngI - ACE – AngII – has a whole bunch of effects on the body Focus on... 1. Vasoconstriction of arterioles – increase blood pressure 2. Stimulates sympathetic activity 3. AngII directly stimulates salt resorption in kidney tubules (independent of aldosterone) 4. Increased salt recovery via aldosterone 5. Water retention - stimulation of ADH

Answer 37

AngII acts on cells in the PCT (AGTR1) – increases the activity of this exchanger – SLC9A3 – driving increase in sodium uptake

Answer 38

Aldosterone effects in the Kidney – it is a steroid and therefore targets gene transcription **Principal** – drives expression of two genes – increases Na/K ATPase and increases expression of sodium intake channel (ENac/ASC) resulting in sodium reuptake. Potassium is pumped countercurrent, so aldosterone also has the effect of driving K+ out (aldosterone also responds to levels of K+ in the body) **Intercalated** – drives expression of H+ ATPase – absence of aldosterone H+/K+ only present, so K+ pumped in while H+ is pumped out - but when Aldosterone is present the protons exit via the ATPase so less K+ in pumped in – net effect excretion of K+

Answer 39

AVP/ADH - drives movement of aquaporins from the vesicle to the membrane – allows for increased water uptake from the collecting ducts

Answer 40

Increased renin results in increases sympathetic activity that drives NA release in renal nerves. This constricts both afferent and efferent arterioles – reducing flow through the glomeruli – filtering less blood – losing less water

Answer 41

1. Salt recovery 2. Increase water adsorption via AVP 3. Filtering less blood – less water lost All these things promote water uptake and limit fluid loss

Answer 42

When the blood pressure is too high, ANP (atrial natruietic peptide) from heart is released. This blocks Na+ re-uptake channes, causing more sodium and fluid loss.

Answer 43

Low Ca+ - parathyroid gland – secretes PTH – acts on the kidney

Answer 44

**PCT** - Ca2+ simply follows other ions/water down loose junctions between cells So to increase the amount of **free** Ca2+ in the blood, the body decrease phosphate reabsorption (phosphate normally binds to Ca2+) **DCT** - calcium uptake system PTH – Activates TRPV5 and activates the exit channel – increase re-uptake Ca2+ move through the cell bound to chaperone proteins - Calbindin – prevents second messenger cascades from being triggered that are regulated by Ca2+ Labelled components (calbindin and exit channel) require vitamin D for synthesis – won’t be produced without Vit-D – calcium re-uptake is lost – can lead to Rickets Takeaway - PTH results in... 1. Decrease phosphate reabsorption 2. Increase calcium reabsorption

Answer 45

We have covered automatic system in the PCT – bicarbonate, ammonia, and phosphate systems But there are also other mechanisms... Body in acidosis – fall in intracellular pH – apical Na+/H+ becomes more active – H+ excreted into urinary space H+ will complex with the same buffers in the urine – phosphate and ammonia

Answer 46

Nephron - 90% reabsorbed here - little regulation Collecting duct - 10% reabosrbed here - regulated by aldosterone

Answer 47

Collecting duct 1. Intercalated cells - Aldosterone drives expression of H+ ATPase – drives H+ out – taking away H+ for H+/K+ antiport – resulting in less K+ import - increasing K+ excretion 2. Prinicipal cells - aldosterone drives expression of Enac and Na/K ATPase – drives Na+ import and only way out for K+ is apically – driving potassium export

Answer 48

Note - Aldosterone changes are much quicker than the effects observed below with tyrosine phosphorylation (longer term changes) Chronic changes: 1. Low K+ diets causes phosphorylation of tyrosine in apical K+ channels – results in channels being removed from membrane – reducing potassium export 2. High K+ - high potassium diet - dephosphorylation of tyrosine on apical K+ channel - channels remain - increasing K+ export

Answer 49

**Cell/body in alkalosis** (acute or chronic) – H+ efflux and K+ influx will be low as the H+/K+ antiporter will be working less – less K+ is taken up because the antiporter is not working at high levels – effect of this that the body goes into a state of hypokalaemia (high levels of K+ loss) when in a state of alkalosis AND apical K+ channel activity increased in principal cells and so is the Na+/K+ ATPase (minor effect but still contributes to increase K+ efflux) – alkalosis results in hypokalaemia **Acute acidosis** – reverse happens - increased re-uptake by antiporter as the body is expelling excess H+ and the apical K+ channel becomes less active, both of which result in hyperkalaemia **Chronic acidosis** – not a problem in chronic acidosis as the Na pump is less efficient in PCT – urine more dilute and helps flush K+ - preventing hyperkalaemia

Answer 50

1. Control of oedema 2. Control of hypertension 3. Control of ion imbalances 4. Control of acid-base disturbances Focus on the first 2

Answer 51

Increasing the amount of water (+ salts) lost from the body If you lose them together (water and salt), you don’t mess up plasma salinity

Answer 52

Targets the ascending limb of loop of henle – cells good at moving salts from the urinary space into the medullary region – block these cells we can minimize water re-uptake Block SLC12A2 – stop export of salts – medulla becomes less salty – less water recovery – less osmotic pull in both the loop of henle and the collecting ducts – 20% more urine output (based on recovery that each region is responsible)

Answer 53

They are very powerful (up to 20% of filtrate to bladder: usually around 0.4%) Useful for reducing fluid overload/oedema.

Answer 54

1. They result in loss of Na+, K+ and Cl- because of failure to recover in the TAL of LoH 2. They inhibit Na uptake in the macula densa (target the same receptor as the LOH) - So loop diuretics are used more to treat oedema than hyptertension itself - mecula densa receive less sodium, increasing renin release (negates impact of reduce fluid) 3. They can result in hypercalcuria – less pull for Ca2+ recovery, increasing the risk of kidney stones - resulting in hypocalcaemia which is especially bad in osteoporotic elderly. 4. More Na+ getting to the Coll Duct means more uptake there and more K+ loss - system in overdrive - drives hypokalaemia (shown)

Answer 55

Thiazides target channels (SLC12A3 – takes up Na+ and Cl-) in the distal DCT – block salt uptake – less salt uptake – result in less water uptake – osmotic difference is less Macula densa are found before the cells that are targeted by the thiazide drug – will not be affected - hence, renin won't increase Also drives Ca+ recovery – mechanism not understood Better for **hypertension control** – partly as they don’t mess up the RAAS system + appear to have an effect on systemic vascular tone –still being investigated Note - you still lose some K+ as there is more Na+ in the collecting duct

Answer 56

Potassium sparing diuretics – Blocking Na+ uptake (reduces gradient between urine and medulla – decreasing water loss Drug - Amiloride - ASC/ENAC - amiloride sensitive channels Less Na+ is being pumped into the cells = less K+ being exported Don’t have the effect of taking the body into hypokalemia

Answer 57

Spironolactone – acts on the collecting ducts - blocks the action of aldosterone Block aldosterone – blocks ASC/ENAc expression – more Na+ in urine – less water lost (lower gradient) Spironolactone – anti-androgenic hormone – competes with DHT – risk of gyno for men

Answer 58

Carbonic anhydrase inhibitor – more bicarb in the lumen (not imported – therefore reduces activity of Na+/H+ exchanger) Results in more Na+ in the lumen – resulting in less of an osmotic pull

Answer 59

Osmotic agents (eg mannitol): stay in the lumen and resist water egress osmotically - increase pull of water towards the lumen

Answer 60

All cause water and salt loss from body. All useful against excess tissue fluid/ oedema. **Most only weakly effective against hypertension** (maybe because, once bp falls, kidney detects it and RAAS fights back). **Thiazides have an antihypertensive effect**, probably via mechanisms of action additional to diuresis.

Answer 61

Impaired SLC12A2 - Ascending limb of LOH Same effect as loop diuretic – loss of Na and K and H2O (gradient is less – less water taken up) Hypercalcuria Ca2+ follows the other ions

Answer 62

Gitelman's syndrome – impaired SLC12A3 Just like a thiazide diuretic – loss of Na+, K+ and H20 and hypocalcuria Remember thiazide diuretic drives Ca2+ recovery - reduces urine Ca2+ and increases plasma Ca2+

Answer 63

Hyperactivating mutation of the ASC channel - increase sodium uptake, increasing fluid uptake - opposite of diuretic Leads to fluid expansion and hypertension Treated with amiloride

Answer 64

Inactive ASC channel – doesn’t work Result - Na+ loss, K+ retention and high aldosterone as the body is trying to correct this (high K+)

Answer 65

Inactivation of aquaporins - water not taken back up by the collecting duct leading to excessive fluid loss (polyuria and polydipsia)

Answer 66

No aldosterone - decrease uptake of sodium and excretion of K+ Resulting in... Loss of Na+, hyperK+ and hypovolaemia

Answer 67

Absence of one or more kidney's Bilateral - Rare; fatal after birth - Lack of amniotic fluid causes Potter’s Facies (deformations caused by the lack of amniotic fluid - lack of shock absorption) Unilateral – One kidney missing - Common (1/500) - often no clinical implications unless some bright surgeon removes the working one

Answer 68

Congenital cystic disease – kidney tissue gets destroyed by growing cysts – detectable in the first few decades of life

Answer 69

Supernumerary ureter – two ureters come from one kidney Problematic if the two ureters connect away from the bladder – e.g. past the bladder resulting in incontinence There is also a higher risk of UTIs as infections can spread quicker

Answer 70

Pelvic kidney – kidney stays in developmental area down by the pelvis More problematic in females as the ovary's need the space

Answer 71

Two pelvic kidneys that are connected to eachother - forming a horseshoe shape

Answer 72

Cloacal – common opening for all the exit canals which are separated later in development by folds If folds don’t meet – tubes not separated - resulting in fistulas, such as... 1. Rectovaginal fistula 2. Rectoprostatic fistula 3. Rectoclocal canal (rectum, vagina and urethra unite inside body).

Answer 73

Most common congenital abnormality Urethra zipper is not closed properly Incomplete migraiton of the urethral groove from the base of the penis to the tip.

Answer 74

Important thing to note - Kidney controls the overall volume of the body - 99% of fluid is reabsorbed and 1% is released, means that only we have a urine output of 1.5L/day.

Answer 75

RAAS – defense of renal blood flow, water balance and blood pressure

Answer 76

Even in health we lose a proportion of GFR as we age. Some chronic conditions leads to a more rapid loss of nephrons – e.g. high blood pressure

Answer 77

Think... Pre-renal Renal Post-renal

Answer 78

Hypertension and diabetes are the two main ones!

Answer 79

Diuretics – decrease NaCl absorption, decrease H2O reabsorption (decreased osmotic pull), and therefore increased urine volume Loop diuretics – most powerful

Answer 80

Examples - furosemide (most common), bumetanide and torasemide Mechanism - blocks Na+K+2Cl- symporter in the thick ascending limbs – inhibits reabsorption of 15-25% of glomerular Na+ filtrate – reduces water retention When? * Heart failure - reduce water load on the body (partly due to the activation of the RAAS system – drops in pressure) * Renal failure - retain extra fluid - nephrotic syndrome * Liver cirrhosis with ascites (unable to break down aldosterone) Adverse effects - hypo-Na+, K+, metabolic alkalosis – increased activity of a H+ ATPases - driving metabolic alkalosis - Fluid depletion and incontinence (bladder can’t cope with high volume of urine) - Ototoxicity - ringing of the ear

Answer 81

Thiazide – Bendroflumethiazide – most common Thiazide-like – indapamide (act in a similar manner) **Mechanism** - Inhibit Na+Cl- co-transport in the proximal DCT – maximum effect on Na+ 5-10% (reduces pull on the water into the body) and has a vasodilatory effect **Indications** – hypertension – predominant use Adverse effects - Loss of Na+, K+ and alkalosis (excretion of H+ - presenting more sodium to the distal part of the distal convoluted tubule – increasing H+/K+ exchange) - Hyperuricemia (cause gout – increase uric acid retention) and hyperglycemia (effect on glucose metabolism) - Fluid depletion, incontinence and erectile dysfunction (vascular effect)

Answer 82

Less commonly used than loop and thiazide but still prescribed Two types: * Aldosterone receptor antagonist – spironolactone - block aldosterone action (transcriptional inhibition) * Sodium channel blocker – amiloride – prevents the same exchange as spironolactone (ASC/ENAc inhibition) Mechanism (collecting duct) - Block the effects of aldosterone – block the exchange – prevents Na+ uptake and K+ or H+ excretion (increased retention) Indications – chronic heart failure, liver failure with ascites, resistant hypertension and Conn’s syndrome (hyperaldosteronism) Adverse effects * Hyperkalaemia (more common for patient with renal impairment and are on other drugs) * Gynecomastia (aldosterone receptor antagonist - spironolactone)

Answer 83

Examples - mannitol Main actions * freely filtered but non-absorbed creating an osmotic ‘drag' that decreases water and Na+ reabsorption in renal tubule Indications (not perscribed - ICU) * raised intracranial pressure due to cerebral oedema * raised intra-ocular pressure Adverse effects * Initial fluid overload * Hypernatraemia

Answer 84

Main action - interfere with CA, reducing H+ and HCO3-, which is then no longer available for exchange with Na – increases urine Na+ Indications – glaucoma (optic nerve gets damaged) and altitude sickness Adverse effects - metabolic acidosis

Answer 85

Drugs that replace renal products * EPO – stimulates RBC formation * Vitamin D – requires hydroxylation in the kidneys – patients given hydroxylated derivatives * Sodium Bicarbonate – corrects acidosis of renal failure

Answer 86

Drugs that alter renal excretion 1. **Sodium-glucose transport inhibitors** – SGLT-2 inhibitors – PCT reabsorbs glucose – SGLT-2 inhibits at least 90% of renal glucose reabsorption – indicated for type 2 diabetes – shown to improve the outlook for many other patients – group of drugs is taking off 2. **Uricosuric drugs** – prevent uric-acid reabsorption from the PCT – indicated for gout – e.g. sulfinpyrazone

Answer 87

Drugs causing a reduction in extracellular volume - reduced circulating volume - reduced renal perfusion Drugs with direct effects on renal vasculature - Vasoconstriction of the afferent arteriole - Impaired influence of angiotensin on the efferent arteriole Direct toxic effects - acute tubular necrosis - acute interstitial nephritis

Answer 88

Drug causing significant fluid loss – putting pressure/strain on the kidneys

Answer 89

**Drugs interfering with the RAAS system** – kidney is more vulnerable – block the ability for the efferent arteriole to be constricted resulting in low glomerular pressure – minimizing the kidney's ability to modulate renal pressure - important to monitor renal function after prescription **NSAIDs** – reduce cortical blood flow and glomerular perfusion by reducing the production of vasodilating prostaglandins – avoid prescribing to elderly patients

Answer 90

**Acute tubular necrosis** – damage the tubular cells – main example – aminoglycosides (gentamicin – antibiotics) and calcineurin inhibitors (ciclosporin) and radiocontrast agents **Acute interstitial nephritis** – inflammation - antibiotics, NSAIDs and PPI **Other drugs that affect tubular function** – lithium and heavy metals

Answer 91

Mechanisms of drug renal excretion * Glomerular filtration – low molecular weight * Tubular secretion – active, specialized transporters But tubular reabsorption also possible! – if lipid soluble (can move across membranes) and affected by urine pH

Answer 92

Age, dehyrdation, drugs and disease can all influence the kidney's ability to excrete drugs.

Answer 93

Effect of renal impairment – reduced plasma clearance, longer half life and accumulation after repeated disease Solution – dose less frequently and use lower doses Patients for whom caution should be exercised 1. Patients with renal disease 2. Elderly 3. Patients on nephrotoxic drugs

Answer 94

Drugs that impair renal function * Diuretics * Angiotensin-converting enzyme (ACE) inhibitors * Non-steroidal anti-inflammatory drug (NSAIDs)

Answer 95

Vasopressin analogues (e.g. desmopressin) - acts as ADH - increaseing aquaporin expression resulting in more water absorption Vasopressin inhibitors (e.g. demeclocycline, tolvaptan) - decreasing aquaporin expression resulting in less water absorption

Answer 96

Hyperventilation – drive out CO2 – alkalosis – less proton export to help bring the body out of alkalosis but as a result less potassium will be taken up – prolonged – hypokalaemia

JD Renal & Pharma Flashcards

(124 cards)