Trachte drugs Flashcards
What are the major loop diuretics?
Lasix (furosemide)
Bumetanide
Ethacrynic acid
If you have a sulfa allergy can you take Lasix?
No
What should you take if you have a sulfa allergy for a loop diuretic?
Bumetanide
What is a common side effect of long term Loop diuretic use? what should you give to compensate?
Hypomagnesium (We are blocking NKCC here which makes the interstium very positive and paracellularly pushes 20% of Mg through)
Give Mg2+
Hypocalcemia is rare
What does low salt in the interstium lead to?
Increase in Cox 2
-Which increases prostaglandins, increases RPF and GFR, which potentiates the drug
What are loop diuretics good to treat?
- Pulmonary edema
- Edema
- Hyperkale
- Acute renal failure
- Anion overdoes with Bromide, flouride and iodide
- Acute HF
- Ascites
What are the 5 common AE of loop diuretics?
- Hypokale (Na gets exchanged for K in the collecting duct)
- Hearing loss
- Lasix (allergy can lead to Acute interstitial nephritis)
- Hyperurecemia
- Contraction Alkalosis
What stimulates ADH secretion?
Increased osmolarity
Decreased volume
Why would we get hyperuricemia in loop diuretic pts?
Cauese hypovolumic state
- induces ADH secretion
- Cause upregulation of UT1 which leads to increase absorption of Urea!
What causes contract alkalosis in pts whom are on a loop diuretic?
Multifold:
- Increase in RAAS–> increase aldosterone which upregulates K+/H+ anti-porter in the alpha intercalated cell in the collecting duct
- Increased RAAS–> increased AgII leads to increase in Na+/H+ anti-porter in the PCT
both lead to increased H+ in the filtrate. Leading to an alkalosis.
What are the major Thiazide diuretics? What is their MOA?
- Chlorithalidone
- Hydrochlorothiazide
- Metalazone
- block NCC channel in DCT
What are some of the major uses of thiazides?
- HTN–> 1st line
- HF–> adjunctive treatment with 1st line Loopers
- Nephrolithiasis by Hypercalcemia
- Nephrogenic diabetes insipidus
- Osteoporosis
How do thiazides lead to hypercalemia?
There is an Na/Ca antiporter on the basolateral side of the endothelial cells. This is driven by concentration gradients.
- Since Thiazides block Na into cell this increase the pump
- Ca is going out of the cell and Na is coming in
- Increasing the pump thus decreases the intracellular Ca which leads to a greater conc. gradient
- Ca flows faster down the TRPV5 channel into the cell
- leads to hypercalcemia
- treats calcium related stones
Can one with a sulfa allergy take thiazides?
No
What are some major AE of Thiazides?
- Hyperglycemia
- Hyperuricemia
- Hypokale
- Hyperlipidemia–> 5-15% increase in LDL’s
- Hyponatremia
- allergic rxns
- Contraction alkalosis
- Lithium pt monitored
What causes the hyperglycemia in Thiazide use?
- There are potassium pumps on Beta-Cells in the pancreas
- When these are closed–> leads to more positive membrane potential inside cell which depolarizes and causes Calcium channels to open
- Calcium rushes and cause insulin vesicle release
- Sulfonyureas inhibit Potassium pumps
- Increases K+ intracellular
What are the 2 mechanisms of Potassium sparing diuretics?
- Inhibit aldosterone receptors
2. Inhibit Na exchange for K and H in the cortical collecting duct
What are the aldosterone inhibitors?
- Spironolactone (aldactone
2. Eplerenone (inspra)
What are the Na exchange inhibitors potassium sparring diuretics?
- Amiloride (Midamor)
2. Triamterene (Dyrenium)
What is Amiloride used to treat
Li+ induced nephrogenic diabetes insipitus
What is the MOA of Potassium sparing diuretics?
Blocks absorption of Na in the collecting duct for the exchange of K+
Where does aldosterone bind and what are its affects?
Intracellular SRE
- Increase K+ excretion
- Increase Na+ resorption
- Increase H+ excretion
- Upregulates Na/K ATPase of basolateral membrane
What is the MOA of Elperenone?
Mineralcorticol receptor antagonist
what is the MOA of Amlodipine?
inhibits ENAC thus decreases Na resorption
What is the MOA of Triamterene?
Blocks ENAC
What is the MOA of spironolactone?
Antagonist of the mineralcorticoid receptor
- blocks 17 alpha-hydroxylase which is the enzyme used to make testosterone from cholesterol
what are potassium sparing diuretics used for?
- HF
- Prevents myocardial remodeling
- Liddle’s syndrome
- Hyperaldosteronism 1st and 2nd degree
If spironolactone blocks 17 a-hydroxylase what are some of its SE’s?
- Gynecomastia
- Impotence and decrease libido
- Polycystic ovarian syndrome
What are the general AE’s of K sparing diuretics?
- Hyperkale
- Hyperchloremic metabolic acidosis
- Gynecomastia
- Acute renal failure
- Kidney stones
- Type 4 renal tubular acidosis
What is the synthetic version of vasopressin? What is it used for?
Desmopressin
- Diabetes insipidus
- Bedwetting
What is Desmopressins MOA?
G protein coupled receptor in the collecting duct that recruits Aquaporins
- Leads to downstream induction of CREB-P a transcription factor that promotes the mRNA transcription and protein translation of Aquaporins
What is Covaptan?
Non-selective ADH antagonist that can be used to treat syndromes of inappropriate ADH secretion
What is Demococycline?
a tetracycline- 30s inhibitor
- however has some ADH antagonistic affects
What class drug is Mannitol and how does it work?
Osmotic diuretic
- Its not reabsorbed and keeps filtrate osmolality high which keeps water in the tubule
What is Mannitol used to treat?
Intracranial pressure
Increased intraocular pressure
What are some AE’s of Mannitol?
- Pulmonary edema
- Extracellular volume expansion
- Dehydration, hyperkale and hypernatremia
- Hyponatremia with renal impairment
Above what level will glucose start spilling into the urine?
240 mg/dL
What is the MOA of SGLT-2 blockers?
Block glucose resorption in the PCT
What can SGLT-2 blockers be used for?
- Treat DM
2. Weight loss
What are some AE’s of SGLT-2 blockers?
- Ketoacidosis
- UTI’s
- Yeast infections
- Hypoglycemia
What are some examples of SGLT-2 blockers?
- Canigliflozin (Invokana)
- Dapagliflozin (Farziga)
- Gliflozin
increases flow and some zin to urine
