Pharmacology Flashcards
What is terlipressin and it’s mechanism of action?
It’s a synthetic analogue of vasopressin. It causes splanchnic vasoconstriction resulting in a reduction in portal pressures
What are the indications for terlipressin?
Acute variceal bleeding and HRS
What are the indications for loop diuretics?
Salt and fluid overload states such as pulmonary oedema, peripheral oedema and cirrhosis
What is the mechanism of action of loop diuretics?
- They block the na/k/2cl symport in the thick ascending loop of Henle which prevents reabsorption of the filtered sodium ultimately leading to na and water loss
- They cause venodilatation through prostaglandin synthesis causing a reduction in cardiac preloads with consequent relief of dyspnoea in those with APO before diuresis occurs
What is the mechanism of action of thiazide diuretics?
The inhibit na and Cl reabsorption through inhibition of the na/cl symport
Their site of action is the ascending loop of Henle and the DCT
What are the 2 types of potassium sparing diuretics?
Aldosterone antagonists e.g. spironolactone and eplerenone
Those acting independently from aldosterone e.g. amiloride
How does spironolactone work?
It’s an aldosterone antagonist that inhibits an reabsorption a day K loss through the blockade of aldosterone receptors in the DCT
How do carbonic anhydrate inhibitors work?
Acts in the PCT
Carbonic anhydrase is found in the luminal and basolateral membranes of the PCT
It catalyses the interconversion between co2 and water leading to the formation of bicarbonate and hydrogen ions
The na/h exchanger in the pct is responsible for na reabsorption in exchange for hydrogen ions which with bicarbonate to form h2co3. CA causes this to disassociate to h20 and co2.
By inhibiting CA and reducing hydrogen ion concentration, carbonic anhydrase inhibitors reduce na reabsorption
Impaired neutralisation of luminal bicarbonate leads to alkaline urine and increased Cl re absorption resulting in hyperchloraemic metabolic acidosis
What are the indications for carbonic anhydrase inhibitors?
Glaucoma
AMS
Selected cases of metabolic alkalosis
How do osmotic diuretics work?
These are pharmacologically inert substances that stay within the tubular lumen to remain osmotically active
This results in retained sodium and water within the tubule
Contrary to other diuretic agents mannitol results in a greater degree of diuretics that naturesis and thus lead to hypernatraemia
Why might vitamin c and thiamine be useful in sepsis?
- Vitamin C is a Co-factor for catecholamine synthesis. It is also anti-inflammatory, limits endothelial injury, is immunomodulatory, and promotes the antibacterial action of a range of leukocytes
- Vitamin C levels drop during sepsis
- high dose vitamin c can generate oxalate which can deposit in the kidneys - this is an effect which can be ameliorated by thiamine, which is often deficient during sepsis
Why might hydrocortisone be useful during sepsis?
- anti-inflammatory
- restores vascular reactivity to catecholamines
- improves endothelial barrier function
Describe the VICTAS trial
RCT trying to determine if the combination of vitamin c, thiamine and hydrocortisone were effective in patients with sepsis
Intervention group received 1.5g vitamin c, 100mg thiamine and 50mg hydrocortisone every 6 hours for up to 96 hours
Trial stopped early after additional funding was declined
501 patients enrolled
No difference in the primary outcome of vasopressin and ventilator free days, 30day mortality, 180 day mortality, iculos, hlos, rrt
Issues - 32% patients in the control group received open labelled hydrocortisone
The outcome of this trial is similar to most other rcts looking at vitamin c and thiamine in sepsis. In 2016 there was a single centred retrospective study that reported a big improvement in mortality with vitamin c, but this has never been found to be reproducible.
The LOVIT trial due out in 2022 is awaited.
What is in pabrinex?
Ampoule 1 - 250mg thiamine (b1), 4mg riboflavin (b2), 50mg pyridoxine (b6)
Ampoule 2 - ascorbic acid 500mg, nicotinamide 160mg (b3), glucose 1000mg
