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Pharmacology Flashcards

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1
Q

List the different types of diuretic

A

Loop
Thiazide
Osmotic
Carbonic anhydrase inhibitors

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2
Q

How to diuretics work (generally)

A

They cause the excretion of electrolytes (particularly Na and Cl)
This triggers the excretion of water by osmosis

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3
Q

List diseases that produce oedema

A

Nephrotic syndrome
Congestive heart failure
Hepatic cirrhosis with ascites

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4
Q

What causes oedema

A

An imbalance between the rate of formation and absorption of interstitial fluid

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5
Q

How does nephrotic syndrome lead to oedema

A

In this condition, large proteins are allowed into the filtrate from blood
This causes fluid to also move out of blood - enters interstitium
The lower blood volume and renal perfusion activates the RAAS system
This leads to further water retention

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6
Q

How does congestive heart failure lead to oedema

A

In HF there is reduced cardiac output and therefore reduced renal perfusion
This activates RAAS which leads to water and Na retention

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7
Q

How does cirrhosis lead to oedema (ascites)

A

Fibrosis in the liver produces a resistance to blood flow, increased liver pressure and decreased albumin
This causes fluid to be lost to the peritoneal cavity = ascites
RAAS is again activated

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8
Q

How do diuretics mobilize the oedema fluid

A

Diuretic causes excretion of salt and water – blood in kidney becomes more concentrated which draws water from the interstitial fluid (reduced oedema)

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9
Q

Where in the nephron do carbonic anhydrase inhibitors work

A

Proximal convoluted tubule and the early distal convoluted tubule
Work on the Na/H exchange
Weak diuretic

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10
Q

Where in the nephron do loop diuretics work

A

Loop diuretics block the triple transporter in the loop of Henle – very strong action

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11
Q

Where in the nephron do thiazide diuretics work

A

Early distal convoluted tubule

Act on the Na/Cl co-transporter

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12
Q

Where in the nephron do potassium sparing diuretics work

A

Collecting tubule and duct

Block Na/K exchange

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13
Q

Diuretics usually work at the basolateral membrane of tubular cells - true or false

A

False

They mostly act on the apical membrane as this is where the transporters are

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14
Q

How do diuretics enter the filtrate

A

If not bound to large proteins they can enter by glomerular filtration
Organic anion transporters move acidic drugs into the filtrate
Organic cation transporters move basic drugs into the filtrate

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15
Q

Which diuretics are acidic

A

Thiazide and loop agents

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16
Q

Which diuretics are basic

A

triamterene and amiloride

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17
Q

How does the organic anion transporter (OAT) work

A

Na+/K+ works at basolateral membrane
Allows Na to move down the conc gradient – a-KG is co-transported by this
This movement drives OA to enter the cell in exchange for the a-KG leaving the cell again
OA is actively pumped out of apical membrane by a transporter using ATP (primary active transport)
Some OA can be reabsorbed on another antiport system – exchange of OA and a-KG

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18
Q

How does furosemide increase your risk of gout

A

It reacts with urate in the tubular cells

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19
Q

How does the organic cation transporter work

A

OC enters the cell against a chemical gradient – driven by electrical gradient
OC is pumped out by primary active transport
Also in the apical membrane the MATE transporter which moves OC out in exchange for H+ ions

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20
Q

How are calcium and magnesium absorbed in the kidney

A

The negative charge created by the triple transporter drives their movement
They are moved through specific proteins into the interstitium - paracellular route

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21
Q

How does the triple transporter work

A

2 Cl- move downhill by the triple transporter
Cl leaves the basolateral membrane via a chloride channel
K+ must move uphill – energy comes from Na+ movement
K+ re-enters the tubule and also moves out of the BL membrane via a channel
Movement of 1 Na and K and 2 Cl

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22
Q

How does the triple transporter end up giving the cell negative potential

A

positive move in and so do 2 negatives. However, the K+ is recycled back into tubule so cell has negative potential

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23
Q

How do loop diuretics work

A

They block the triple transported in the ascending loop of Henle
This alters the electrolyte balance (less reabsorption) and reduces water reabsorption

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24
Q

Loop diuretics have a venodilator effect - true or false

A

True

This is useful in treating pulmonary oedema

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25
Loop diuretics have rapid action - true or false
True Especially with IV administration Used in emergency treatment of acute pulmonary oedema
26
What are the clinical indications for loop diuretics
``` Acute pulmonary oedema Chronic heart failure Chronic kidney failure Hepatic cirrhosis with ascites Nephrotic syndrome Hypertension Increase urine volume in acute kidney failure Reduce acute hypercalcaemia ```
27
which loop diuretic is best for those with heart failure
Bumetanide | Furosemide absorption can be unpredictable in CHF
28
How are loop diuretics processed by the body
Absorbed in the GI tract Strongly bind to plasma proteins Enter nephron by the OAT mechanism
29
When are loop diuretics contraindicated
Severe hypovolaemia or dehydration Must take caution with severe hypokalaemia or hyponatraemia, hepatic encephalopathy and gout
30
What are the adverse affects of loop diuretics
``` Hypokalaemia Metabolic alkalosis - more H+ is secreted Hypocalcaemia and hypomagnesaemia Hypovolaemia and hypotension - elderly Hyperuricaemia - may precipitate gout Dose related loss of hearing ```
31
How do thiazide diuretics work
Inhibit the Na/Cl carrier Prevents dilution of filtrate in the distal tubule Increases the load of Na in the collecting tubule - causes K loss Causes more Na excretion = modest diuresis
32
Thiazide diuretics have a vasoconstrictor effect - true or false
False | It is a vasodilator effect which helps with hypertension treatment
33
How are thiazide diuretics absorbed
Well absorbed in GI tract | Enter nephron by OAT mechanism
34
What are the clinical indications for thiazide diuretics
``` Mild heart failure Hypertension Severe resistant oedema - with a loop Renal stone disease - reduces amount of Ca in filtrate Nephrogenic diabetes insipidus? ```
35
List examples of thiazide diuretics
Bendroflumethiazide | Indapamide, metolazone - thiazide like
36
When are thiazide diuretics contraindicated
Hypokalaemia | Must be cautious in hyponatraemia and gout
37
What are the adverse effects of thiazide diuretics
``` Hypokalaemia Metabolic alkalosis Hypovolaemia and Hypotension Hyperuricemia - may precipitate gout Erectile dysfunction Impaired glucose tolerance in diabetics ```
38
How can thiazide diuretics be used in osteoporosis
They help reabsorb calcium
39
How does aldosterone act in the kidney
It acts on cytoplasmic receptors to active the ENaC channel This allows more Na reabsorption Aldosterone also increases abundance of Na/K ATPase so you can also pump the excess Na out of the cell as well
40
How do the potassium sparing diuretics work
Amiloride and Triamterene - block apical sodium channel and decrease its reabsorption Spironolactone and eplerenone - compete with aldosterone to prevent it activating ENaC
41
How do loop and thiazide diuretics cause K+ loss
The increase the load of Na in the filtrate Some is reabsorbed which makes the lumen more negative These both increase driving force for K+ secretion into filtrate and it is lost in the urine
42
How are spironolactone and eplerenone absorbed by the body
Well absorbed from GI tract | Spironolactone is rapidly metabolised to canrenone which is the active part
43
How are amiloride and triamterene absorbed in the body
T is well absorbed in the GI tract, A is not | Enter nephron via OCT in proximal tubule
44
When are potassium sparing diuretics contraindicated
Severe renal impairment Hyperkalaemia Addison's disease
45
What are the clinical indications for potassium sparing diuretics
Used alongside other diuretics to counteract potassium loss Heart failure Hyperaldosteronism - Conns Resistant hypertension secondary hyperaldosteronism (due to hepatic cirrhosis with ascites)
46
How do osmotic diuretics work
They enter the nephron by glomerular filtration Increase the osmolarity of the filtrate which opposes the absorption of water They also decrease sodium reabsorption in the proximal tubule - higher fluid volume so Na conc decreased
47
Where is the major site of action of osmotic diuretics
Proximal tubule | As this is where most isosmotic reabsorption of water occurs
48
When are osmotic diuretics used
In prevention of acute hypovolaemic renal failure - maintains urine flow In urgent treatment of raised intracranial and intraocular pressure
49
How do osmotic reduce intracranial and intraocular pressure
Solute itself doesn't get into eye or brain (due to BBB) but increases plasma osmolarity This creates a osmotic gradient that draws fluid into the blood – reducing pressure
50
what are the adverse effects of osmotic diuretics
Transient expansion of blood volume | Hyponatraemia
51
When else might osmotic diuresis occur (without use of diuretics)
In hyperglycaemia - the excess glucose in the urine means the filtrate retains fluid As a consequence of iodine radiocontrast dyes - dye is excreted and takes some water with it
52
Give an example of an osmotic diuretic
Mannitol
53
Give an example of a carbonic anhydrase inhibiter
Acetazolamide
54
What are carbonic anhydrase inhibitors used for
Not used as diuretics anymore Reducing intraocular pressure - glaucoma Prophylaxis of altitude sickness Some forms of infant epilepsy
55
How do carbonic anhydrase inhibitors work (in kidney)
Inhibit carbonic anhydrase This increases excretion of HCO3 with Na, K and H20 Gives an alkaline diuresis
56
How is alkalising the urine useful
It can relive dysuria Prevents crystallisation of weak acids - decreases formation of uric acid stones Enhances secretions of weak acids
57
How does vasopression (ADH) work
Released from posterior pituitary Binds to G protein coupled receptor = increased cAMP This increases insertion of aquaporin 2 channels into the apical membrane More water is reabsorbed
58
What causes neurogenic diabetes insipidus
Caused by lack of vasopressin secretion from the posterior pituitary
59
How do you treat neurogenic diabetes insipidus
Desmopressin Synthetic analogue of vasopressin but selective for V2 receptor Doesn't cause the vasoconstriction
60
What substances can affect vasopressin secretion
Ethanol inhibits secretion | Nicotine enhances it
61
What causes nephrogenic diabetes insipidus
Mutations in the V2 gene - usually recessive and X linked This prevents the nephron from responding to vasopressin No current treatment
62
How do aquaretics work
Act as competitive antagonists of vasopressin receptors | This causes excretion of water without accompanying Na
63
Give examples of aquaretics
Tolvaptan | Conivaptan
64
How is tolvaptan used
Syndrome of inappropriate ADH secretion | Role in HF being investigated
65
Where is SGLT2 expressed
In the proximal tubule of the kidney
66
How do SGLT2 inhibitors work
Block SGLT2 to prevent reabsorption of glucose Leads to glycosuria - glucose excreted This decreases HbA1c and leads to weight loss Used in diabetes treatment
67
Name some SGLT2 inhibitors
Dapagliflozin | Canagliflozin
68
SGLT2 inhibitors cause a diuresis - true or false
True | A mild one
69
What are the functions of prostaglandins that are made in the kidney
Vasodilators | They are produced in response to ischaemia, mechanical trauma, angiotensin II, ADH and bradykinin
70
How do prostaglandins affect GFR
Only affect GFR if there is widespread vasoconstriction or decreased blood flow They cause vasodilation of the afferent arteriole and trigger renin release
71
Why might NSAIDs precipitate renal failure
They inhibit COX which decreases prostaglandins | Can lead to issues if the kidneys need to prostaglandin mediated vasodilation
72
What is an adverse drug reaction
Any undesirable reaction (whether expected or not) that leads to detriment in the wellbeing of the patient in the absence of another explanation
73
Give examples of drugs with a low therapeutic index
gentamicin, lithium, digoxin, warfarin, vancomycin, theophylline
74
Adverse drug reactions are common in which groups
The elderly and frail Those with multiple morbidities - renal/hepatic impairment Polypharmacy Drugs with low therapeutic index
75
What is a Type A adverse drug reaction
Due to augmented pharmacological effect | Dose dependant and predictable
76
Give examples of Type A adverse drug reactions
Diuretics can cause pre-renal failure and dehydration if too high a dose is given ACEi shouldn't be taken if you have D&V Drug-drug interaction Drug-food interaction Drug disease interaction
77
What is a Type B adverse drug reaction
Includes bizarre, unpredicted effects of a drug Not dose dependent These are the dangerous ones - can be fatal
78
Give examples of Type B adverse drug reactions
Drug rashes Bone marrow aplasia Hepatic necrosis
79
What is a Type C adverse drug reaction
Chronic effects of the drug Occurs with prolonged therapy Need to monitor these drugs and tell patients about them
80
Give examples of Type C adverse drug reactions
Steroids in Cushing's - osteoporosis | NSAIDs can lead to hypertension
81
What are Type D adverse drug reactions
Delayed effects of a drug May occur years after stopping treatment Often cardiogenic or teratrogenic
82
Give examples of Type D adverse drug reaction
Secondary malignancy post-chemo
83
What are Type E adverse drug reactions
End of treatment effects | Occurs with abrupt withdrawal of a drug as you can get rebound effects
84
What is a Type F adverse drug reaction
Failure of therapy

Renal (18 decks)

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