Pharmacology

Question 1

diuretic action of potassium sparing diuretics

Answer 1

These are weak diuretics on their own (the site on which they act accounts for 2% of total sodium reabsorption), they are used as compound preparations with thiazide or loop diuretics, which activate the RAAS system in response to natriuresis and hypovolaemia

Question 2

clinical indications for potassium sparing diuretics

Answer 2

• They potentiate the actions of thiazide and loop diuretics by blocking the effects of aldosterone
• Used to treat primary/secondary hyperaldosteronism, which can cause refractory oedema
• Used to counter K⁺ loss due to more potent diuretics

Question 3

mechanism of action of spironolactone and eplerenone

Answer 3

compete with aldosterone to bind to its receptors

• Decrease gene expression and reduced synthesis of a protein mediator that activates Na⁺ channels in the apical membrane
• Decreased numbers of the Na/K/ATPase pumps in the basolateral membrane

Question 4

mechanism of action of amiloride and triamterene

Answer 4

block the apical Sodium channel in the distal tubule that are controlled by aldosterone’s protein mediator and decrease Na reabsorption

Question 5

is amiloride or triamterene more potent

Answer 5

amiloride - 10x

Question 6

what is spironolactone metabolised inthe liver to

Answer 6

canrenone

Question 7

adverse effects of spironolactone

Answer 7

hormonal disturbances: there is some blocking on androgen and progesterone receptors

• gynaecomastia
• impotence
• menstrual irregularities

note eplerenone doesnt cause these

Question 8

what must potassium sparing diuretics not be adminstered with

Answer 8

potassium supplements and ACEi/ARB - risk of hyperkalaemia

Question 9

clinical used of K sparing diuretic

Answer 9

• Heart failure – moderate to severe CHF
• Secondary hyperaldosteronism, due to hepatic cirrhosis with ascites or nephrotic oedema
• Primary hyperaldosteronism (Conn’s syndrome)
• Resistant essential hypertension

Question 10

where is the CA enzyme present

Answer 10

renal tubules, gastric mucosa, pancreas, eye brain and RBC

Question 11

systemic CA inhibitor

Answer 11

acetazolamide

Question 12

describe the action of CA inhibitors in the proximal tubule

Answer 12

• increase the excretion of bicarbonate with Na, K and water by blocking CA
• results in an alkaline diuresis, hypokalaemia and metabolci acidosis

Question 13

what is the use of CA inhibitors in acute mountain sickness

Answer 13

• prophylaxis and treatment
• Prevents the respiratory alkalosis caused by inhibiting the formation of CO₂

Question 14

why would one want to alkalinze the urine

Answer 14

to excrete acidic drugs eg salicylates (poisoning) and barbituates

Question 15

what drugs can be use to alklinize the urine

Answer 15

CA inhibitors

Question 16

what are the adverse effetcs of using CA inhibitors to alkalinize the urine

Answer 16

can cause dysuria or UTI

Question 17

how is mannitol given

Answer 17

10-20% solution IV - there is no oral form

Question 18

action of mannitol

Answer 18

Pharmacologically inert substances, that are filtered in the glomerulus but not reabsorbed by the nephron. To cause a diuresis they must constitute an appreciable fraction of the osmolality of the tubular fluid.

Within the nephron, their main effort is exerted on the parts of the nephron that are permeable to water: the proximal tubule, the descending limb of loop of Henle, and (in the presence of ADH) the collecting ducts. Passive water reabsorption is reduced by the presence of non-reabsorbable solute within the tubule – consequently a larger volume of fluid remains in the proximal tubule. This has the secondary effect of reducing Na⁺ reabsorption.

Question 19

what is the use of mannitol in raised ICP/IOP eg acute angle closure glaucoma

Answer 19

• increased plasma osmolality by the addition of a solite that doesnt enter these compartments, water effluxes out down its concentration gradient

Question 20

what is the action of V₂ receptor in the kidney

Answer 20

Question 21

what receptors does ADH bind to

Answer 21

V 1 2 and 3

Question 22

V1 receptor action

Answer 22

• vasoconstriction of smooth muscles, particularly cardiac muscles
• very high concentrations of ADH are needed for this to happen eg in severe hypovolemic states

Question 23

desmopressin

Answer 23

• ADH analogue
• longer durationof action and more potent
• several routes available, including nasal spray

Question 24

second line ADH analogue

Answer 24

terlipressin

Question 25

clinical uses of ADH analogues

Answer 25

* Neurogenic diabetes insipidus * Desmopressin * Nocturnal enuresis in children (\>10 years) * Oral/intranasal desmopressin * Control variceal bleeding in portal hypertension – vasoconstrictory activity * Vasopressin infusion/Terlipressin

Question 26

vaptans

Answer 26

competitive antagonists of ADH receptors

Question 27

action of vaptans

Answer 27

* Electrolyte free aquaresis * Reducing urine osmolality * Raise serum Sodium

Question 28

clinical indications for vaptans

Answer 28

conditions of excess ADH to correct hyponatraemia * SIADH * CHF * cirrhosis

Question 29

conivaptan

Answer 29

non selective V1/V2 antagonists IV only

Question 30

what receptor is Tovlaptan selective to

Answer 30

V2 oral

Question 31

what effect do vaptans have on thirst

Answer 31

increase it

Question 32

formation of PG

Answer 32

* PGs are formed from the fatty acid arachidonic acid (in membrane phospholipids) by COX 1 and 2 * The PGs that are important in the kidneys are PGE₁ ad PGI₂.

Question 33

action of PG in the renal system

Answer 33

* *In the renal system, cause **vasodilation and natriuresis**. Are necessary to increase renal blood flow and GFR (in angiotensin induced vasoconstriction in volume depleted states).* * PG synthesis is low under basal conditions, however when vasoconstrictors (e.g. angiotensin II and noradrenaline) are release, they cause compensatory vasodilation in the kidney. * Exert a diuretic effect – increased water, Sodium and potassium excretion * Increase potassium secretion mainly by stimulating secretion of renin and activating RAAS * Also acts as a counter-regulatory factor and decreases Sodium reabsorption via inhibition of triple co transporter in the thick ascending Loop of Henle

Question 34

triple whammy combination

Answer 34

do not give **ACEi/ARB + diuretic + NSAID** – detrimental to renal function, leading to sodium retention, oedema, blunted diuretic and antihypertensive effects of drug

Question 35

action of NSAIDs in heart failure etc

Answer 35

* NSAIDs increase blood pressure in patients treated for hypertension by impairing PG mediated vasodilatation and salt excretion * They exacerbate salt and water retention in patients with heart failure

Question 36

digoxin mechanism

Answer 36

* increases intracellular Ca stores: inhibiting NaK ATPase - increases intracellular Na and activates Na Ca exchanger. this increases the force of myocardial contraction * stimulates vagal nerve (acts via ACh) - acts on SA and AVN to slow heart rate and slow AVN conduction

Question 37

signs of digoxin toxicity

Answer 37

nausea, yellow vision, bradycardia, lethargic and tired, hypotension, vomiting, arrhythmia

Question 38

digoxin toxicity

Answer 38

* has a very narrow therapeutic window * at toxic concentrations, causes ectopic beats which can lead to arrhythmias * bradycardia etc due to excessive CNX stimulation

Question 39

what effect does renal failure have on the excretion of drugs

Answer 39

those that are excreted renally will have a longer half life

Question 40

renal failure and digoxin toxicity

Answer 40

* longer half life due to renal excretion * if patient is on diuretics these cause hypokalaemia, meaning that digoxin doesnt have to compete with K for binding at NaK ATPase so it is upregulated * increased risk of toxicity