L 4/5 Diuretics 1/2 Flashcards
Hypervolemia can lead to both hypertension and heart failure as it effects both preload and after load what can be used to fix this and what other negative systemic effect can it help in instances of increased sodium levels.
Diuretics can promote water loss via natriuresis to help fix hypervolemic situations as well as reduce Edema
1) Diuretics in High blood pressure and hypertension work by:
2) diuretics in Heart failure work by
1) By promoting diuresis and natriuresis diuretics can help decrease hypervolemia and hypernatremia decreasing preload
2) In heart failure can reduce edema and congestion
Acetozolamid, Dichlorphenamide and Methazolamid are:
1) examples of what drugs
2) Adverse effects
3) How do they work
(1 and 2 are what you really need)
1) are examples of Carbonic Anhydrase drugs and affect:
CA Type IV in the lumen and CA Type II in the cytoplasm
“Just remember that these drugs inhibit type 4 outside the cell and type 2 inside the cell”
2) Sulfonamide like alllergic reactions causing skin toxicity
(background of how it works)
3) These drugs lead to excretion of excess water by preventing H+ generation and Na+ reabsorption. With a lack of ion gradient the NHE (Na+ H+ exchange protein) will not function as an Antiporter between H+ and Na+ and Sodium will not traverse into the cell. Since water chases salt, if Na is not reabsorbed then the water will follow it through the tubules and be excreted.
**
1) What is an example of an Osmotic Diuretic discussed in lecture
2) where does the drug work in nephron
3) Mechanism
4) Lethality towards heart failure patients and Kidney disease
5) generic Adverse effects
1) Mannitol ; promotes urine output
2) is a Loop of Henle Diuretic; synonymous to osmotic diuretic
3) Mannitol itself acts as an osmole agent like glucose and essentially stays in the lumen and increases the osmolarity of the environment and draws fluid from the renal cells
4) Bc mannitol is non specific it leads to excretion of Na+ k+ ca+ etc… which can be extremely lethal to Heart failure, and pulmonary congestion patients and kidney/liver disease.
5) Hyponatremia, nausea vomiting
Furosemide, Bumetanide, Ethacrynic Acid, and Torsemide
1) work as what and where
2) Known as Ceiling diuretics… WHY?
3) MOA (redundant)
4) Main Adverse effects highlighted
1) these are: Na+ K+ 2CL- symport inhibitor loop diuretics which work in the Thick Ascending Limb (TAL)
2) Known as Ceiling Diuretics for their efficacy to dispel all 3 ions (sometimes too well)
3) These Na+ K+ 2CL- inhibitors bind at the symporter in the TAL
4a) RAAS pathway activation due to sympathetic reflex:
(explanation) Basically the next position in the nephron after the TAL is the Distal tubule which contains the Macula Densa. Remember Macula Densa is responsible for sensing osmo-irregularity and it basically freaks out and triggers baroreceptor and JGA -> RAAS activation
4b) Ototoxicity irregularity of ions causes conductance issues in ear and you get tinnitus; the Ringing shit that happens in ur ear randomly
2 things he mentioned which may be questions or part of a question
(redundant but important)
1a) When asked which has the ability to stimulate the RAAS/ sympathetic reflex it should always be
1b) Sympathetic reflex will not be triggered by ________ bc they act on the distal tubule after the macula densa
1a) Always Loop Diuretics
1b) Thiazide diuretics will not trigger RAAS
1) Which drugs work on the Distal convoluted tubule and what do they work on
2) what is unique about the epithelia in Distal tubule
3) How do they effect RAAs, Renin and GFR
4) Lethal drug drug interaction
1) Thiazide diuretics work here to block the Na+/Cl- costransporter
Hydrochlorothiazide, Chlorthalidone, Chloorothiazide, Indapamide and Metolazone
2) Epithelium is tight with litte water permeability
3) Minimal effect on GFR, Renin, RAAs because they act past the site of the macula densa
-This differentiates them from other loop diuretics
4) Thiazides and Quindine can lead to tachycardia and ventricle fibrillation -> death
What are some adverse effects on Ion concentration in blood caused by K+ sparring diuretics
Hyperkalemia and HYPOnatremia
Remember they get traded under NORMAL circumstances where Na+ is usually absorbed and k+ is excreted
Loop and Thiazide Diuretics can lead to ion incidences such as _______which is why we give K+ sparring
HYPOkalemia
Triamteren and Amiloride :
1)are examples of what type of drugs,
2) and act on what?
3) Adverse (this one actually highlighted so know this)
1) K+ sparring Drugs
2) act DIRECTLY ON THE ENAC CHANNEL ItSELF they spare K+
In distal convoluted tubule and collecting duct
3) **Hyperkalemia especially in the presence of Trimethoprim, NSAIDS and ACE inhibiters
“Do not give RAAS/ACE/AT1 drugs with K+ sparring… Big No No”
Spironolactone and Eplerenone :
1)are examples of what type of drugs,
2) and act on what? (primary mech)
3) they promote what as a secondary mechanism
4) AE
5) He said to know this specifically about Eplerenone
1) K+ sparring drugs
2) ACT AS MINERALOCORTICOID RECEPTOR ANTAGONIST to decrease aldosterone induced expression of ENAC channel protein
-So less ENAC channels transcribed=less channels
3) Promote ENAC degradation by preventing aldosterone mediated NEDD inhibition by SGK1
4) Hyperkalemia and spironolactone can cause sex hormone issues
5) Eplerenone is MR SPECIFIC ANTAGONIST; with reduced non specific effects
(im assuming in comparison to spirinolactione)
1) Nesiritide is an example of what type of drug:
2) what does it inhibit and
3) what is it an analogue to (endogenous natriietic
1) Nesitiride is an example of a Non-specific Cation Channel/Natriuretic Peptide
2) it works as a recombinant peptide to inhibit CNG channels by activating cGMP and PKG
(just know CNG part)
3) it mimics BNP a natural analogue of body
I really gotta shit rn
1)What Is Desmopressin
2) what is it activating
3) how is it compared to its natural analogue
4) Clinical indications for use
1) Desmopressin is a vasopressin selective V2 Agonist
2) activates V2 receptor to stimulate AQP2
3) it is 3000x more powerful than AVP analogue
4) used in Diabetes insidious and Nocturia
Mozavaptan, Tolvapatan and Lixivaptan —– Conivaptan
1) what type of drugs (specific/non-specific)
2) used for what treatment
3) Two of these drugs come with a black box warning, describe them
1) these are Vasopressin Receptor Antagonist (opposite of Desmopressin)
- Moza, Tolva and Lixi are V2 specific Antagonist
- Conivaptan is a V1a/V2 antagonist or non-specific
2) treatment of Hypervolemic Hyponatremia usually due to SIADH SYNDROME
-SIADH is a HYPER AVP syndrome which increases blood volume -> preload increases and can lead to heart failure and hypertension
3) Tolvaptan and Mozavaptan have blackbox bc they cause demyelination disorder because they fix the Na+ levels too fast sometimes (must be admin in hospital setting)
