This document discusses diuretics, including their pharmacology, indications, types, dosing, and adverse effects. It covers the main classes of diuretics - thiazides, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. Key points include thiazide diuretics being first-line for hypertension, loop diuretics being used for more severe edema, and factors like renal function and food affecting diuretic dosing and efficacy. Adverse effects include electrolyte disturbances, hypotension, and renal impairment.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
The kidneys lie on the posterior abdominal wall, one on each side of the vertebral column, behind the peritoneum and below the diaphragm
The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule
Continuing from the glomerular capsule the remainder of the nephron is about 3 cm long and is described in three parts:
the proximal convoluted tubule
the medullary loop (loop of Henle)
the distal convoluted tubule, leading into a collecting duct
High efficacy diuretics (Inhibitors of Na-+K+-2Cl¯ cotransport)
Sulphamoyl derivatives : Furosemide, Bumetanide, Torasemide
2. Medium efficacy diuretics (Inhibitors of Na+-Cl¯ symport)
Benzothiadiazines (thiazides) Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide
Thiazide like (related heterocyclics) Chlorthalidone, Metolazone, Xipamide, Indapamide, Clopamide
3. Weak or adjunctive diuretics
(a) Carbonic anhydrase inhibitors : Acetazolamide
(b) Potassium sparing diuretics
Aldosterone antagonist: Spironolactone, Eplerenone
Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride.
(c) Osmotic diuretics :Mannitol, Isosorbide, Glycerol
the above presentation contain the history of the thyroid disorder, including the definition of thyrotoxicosis, and its two main cause that are graves' disease and another toxic nodular goiter and the classification of drugs that are used in hyperthyroidism i.e. hormone sythesis inhibitor, hormone release inhibitors, destroy thyroid tissue, and inhibit ionic trapping with it's example including the adverse effect and side effect and marketted preparation of the same and the agents which cause hypothyroidism and the agents which are used to prescribe in the pregnancy
Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.
Myocardial Infarction Treatment
Classes of drugs used in the treatment of myocardial infarction
Vasodilators
General Pharmacology
Cardiac depressant drugs
Antiarrhythmics
Anti-thrombotics
Thrombolytics
Analgesics
General Mechanisms of Action
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
The kidneys lie on the posterior abdominal wall, one on each side of the vertebral column, behind the peritoneum and below the diaphragm
The nephron consists of a tubule closed at one end, the other end opening into a collecting tubule
Continuing from the glomerular capsule the remainder of the nephron is about 3 cm long and is described in three parts:
the proximal convoluted tubule
the medullary loop (loop of Henle)
the distal convoluted tubule, leading into a collecting duct
High efficacy diuretics (Inhibitors of Na-+K+-2Cl¯ cotransport)
Sulphamoyl derivatives : Furosemide, Bumetanide, Torasemide
2. Medium efficacy diuretics (Inhibitors of Na+-Cl¯ symport)
Benzothiadiazines (thiazides) Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide
Thiazide like (related heterocyclics) Chlorthalidone, Metolazone, Xipamide, Indapamide, Clopamide
3. Weak or adjunctive diuretics
(a) Carbonic anhydrase inhibitors : Acetazolamide
(b) Potassium sparing diuretics
Aldosterone antagonist: Spironolactone, Eplerenone
Inhibitors of renal epithelial Na+ channel: Triamterene, Amiloride.
(c) Osmotic diuretics :Mannitol, Isosorbide, Glycerol
the above presentation contain the history of the thyroid disorder, including the definition of thyrotoxicosis, and its two main cause that are graves' disease and another toxic nodular goiter and the classification of drugs that are used in hyperthyroidism i.e. hormone sythesis inhibitor, hormone release inhibitors, destroy thyroid tissue, and inhibit ionic trapping with it's example including the adverse effect and side effect and marketted preparation of the same and the agents which cause hypothyroidism and the agents which are used to prescribe in the pregnancy
Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.
Myocardial Infarction Treatment
Classes of drugs used in the treatment of myocardial infarction
Vasodilators
General Pharmacology
Cardiac depressant drugs
Antiarrhythmics
Anti-thrombotics
Thrombolytics
Analgesics
General Mechanisms of Action
Presentación sobre las características principales, incidicaciones, dosis y efectos adversos de este medicamento.
Realizado por Paula Duque, residente de psiquiatría UdeA
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
hypertensive drugs in various conditions.pptxSunandaMohan
Electrolyte imbalance
Metabolic: hyperglycemia, hyperlipidemia, hyperuricemia.
Erectile dysfunction
Not effective in chronic renal disease.
More effective in elderly: also in patients with isolated systolic hypertension.
Long acting, used once a day
No tolerance and no fluid retention
Reduce calcium excretion, preferred in osteoporosis (especially older women).
Hydrochlorothiazide is one commonly used thiazide and consider as 1st choice.
the main problem with thiazide is hypokalemia and this can be avoided by K+ supplementation or using K+ sparing diuretics.
However, ACEI/ARBs should not combined with K+ sparing diuretics which cause dangerous hyperkaliemia in some pt.
Indications: HT, especially co-existing with:-
DM,
Nephropathy,
Left Ventricular Hypertrophy (LVF),
Chronic Heart Failure (CHF),
Angina,
Post Myocardial Infarction (MI) cases.
ADRs: Dry persistent cough, Fetal malformations, granulocytopenia, proteinuria (Rare).
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Contraindicated in CHF, Pulmonary diseases (Bronchial asthma/COPD), Peripheral vascular disease and Variant angina.
Cardioprotective – especially helpful to prevent sudden cardiac death if given Post MI, along with ACEIs.
Hypoglycemic episodes – (1 selective less risky)
Absence of SEs like Postural Hypotension, GIT effects etc
Efficacy as monotherapy ~30-40%. Always combined with other drugs
Slow onset (1-3 weeks), well sustained action
Gradual in BP in hypertensives only.
Mech : Initially, TPR increases due to -blockade
Later TPR decreases – resistance vessels adapt to chronically decreased CO
Both systolic & diastolic BP reduced.
Also, ↓ release of NA from sympathetic nerve endings, ↓ Renin release from kidney (1).
Almost obsolete drugs
Reserpine – R.serpentina roots. Indigenous. Inhibits tpt of NA into storage granules depletion. Slow onset (2-3 wks). Also CA & 5HT depletion in brain depression, antipsychotic effect & Parkinsonism like symptoms. Not preferred as anti-HT drug now.
Guanethidine – Displaces NA from storage granules, release of NA from nerve terminals & NA reuptake inhibited depletion. Obsolete drug.
Latest guidelines (JNC8, NICE 2011): Consider:-
Age / Race: Younger patients (↑ renin) respond better to ACEIs/ARBs. Blacks & aged respond better to CCBs. Diuretics alternatives to CCBs.
If monotherapy ineffective – ACEIs/ARBs + CCBs/Diuretics.
ACEIs/ARBs + CCBs + Diuretics – 3rd step
If all fails – resistant HT – add a aldosterone antagonist or beta-blocker with vasodilator action.
BP > 140/90 in pregnancy can be risky
CKD, Diabetes & Chronic HT are risk factors for Pre-eclampsia
Aspirin
Chlorthalidone for poorly controlled hypertension in chronic kidney diseasesShadab Ahmad
Given the central role of volume excess in the pathogenesis of hypertension in CKD, and the low cost of thiazide diuretics, there is a need to study the use of these drugs to lower BP among patients with uncontrolled hypertension and moderately advanced CKD.
presentation regarding investigations and treatment of heart failure in pediatrics, including the management of an emergency , and includes brief description about even drugs used
Scope: This subject is intended to impart the fundamental knowledge on various aspects
(classification, mechanism of action, therapeutic effects, clinical uses, side effects and
contraindications) of drugs acting on different systems of body and in addition,emphasis
on the basic concepts of bioassay. Objectives: Upon completion of this course the student should be able to
1. Understand the mechanism of drug action and its relevance in the treatment of
different diseases
2. Demonstrate isolation of different organs/tissues from the laboratory animals by
simulated experiments
3. Demonstrate the various receptor actions using isolated tissue preparation
2. Objectives
• Understand the basic pharmacology of the different diuretic agents
• Evaluate what diuretic class is appropriate for the clinical vignette of a patient.
• Be able to recall the correct dosing of diuretic agents for treating hypertension
and edema.
• Apply pharmacokinetic parameters to convert doses from oral loop diuretics to
IV loop diuretics.
• Apply pharmacokinetic parameters to convert doses between the various IV loop
diuretics.
• Recognize the adverse effects of diuretics in patients at UTMC.
3. Introduction and Pharmacology
• What are diuretics?
• Medications to reduce blood pressure and edema.
• Most inhibit electrolyte transporters in the nephron.
• Some have osmotic effects
• Can be hazardous or C/I in certain patients
• AKI
• Dehydration
• Electrolyte disturbances
• Oliguria and anuria
4. Indications for Diuretics
• HTN (Thiazide/K sparing diuretics, some loops)
• Chronic or acute edema (Thiazides, Loops)
• Hypercalcemia (Loops), prevention of Kidney stones/osteoporosis (Thiazides)
• AKI, acute closed angle glaucoma, brain edema, drug overdose (Osmotic)
• Altitude sickness, Hypercapnic COPD (CA inhibitors)
⬇
5. Types of Diuretics
• Thiazide diuretics-inhibit sodium and chloride reabsorption in the distal tubule
• Hydrochlorothiazide (Microzide)
• Chlorthalidone (Thalitone)
• Metolazone (Mykrox)
• Loop diuretics-inhibit chloride reabsorption in the thick ascending loop of Henle
• Furosemide (Lasix)
• Bumetanide (Bumex)
• Torsemide (Demadex)
• Ethacrynic acid (Edecrin)
6. Types of Diuretics continued
• Potassium sparing diuretics – Work on the DCT to
increase Na excretion and decrease K secretion.
• Amiloride (Midamor)
• Triamterene (Dyrenium)
• Aldosterone antagonists – Block aldosterone’s action in RAAS
system, preventing fluid retention.
• Spironolactone (Aldactone)
• Eplerenone (Inspra)
7. Types of Diuretics continued
• Osmotic diuretics
• Mannitol (Resectisol)- Initially increases plasma volume and
blood pressue followed by osmotic diuresis
• Carbonic anhydrase inhibitor
• Acetazolamide (Diamox)
9. HTN -ALLHAT
• In patients with hypertension, what is the efficacy and safety of alpha
blockers, calcium channel blockers, ACE inhibitors, or thiazide diuretics
in lowering the incidence of CV events?
• No difference in primary outcome between CCBs, ACEI, or thiazides.
• Thiazides shown to have stroke benefit. (ALLHAT)
• Chlorthalidone had 15% less incidence of stroke than Lisinopril arm
• Alpha blocker arm stopped early due to increased CHF.
• Thiazides became the first line agent for treatment of HTN
JAMA 2002: 288-2981-97.
10. JAMA. 2014 Feb 5;311(5):507-20. doi: 10.1001/jama.2013.284427.
11. Dosing – HTN
• HCTZ: 12.5-50 mg/day – 1st line therapy
• Chlorthalidone: 12.5-25 mg/day – 1st line therapy
• Metolazone: 2.5-5 mg/day
• Amiloride: 5-10 mg/day
• Eplerenone: 50-100 mg/day
• Triamterene: 50-100 mg/day
• Spironolactone: 25-50 mg/day
• Furosemide: 40 mg twice daily – Loops may be used in ESRD with resistant HTN
• Torsemide: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks
Consider in resistant HTN or HTN w/HF (EF <35-40%)
12. Dosing - Edema
• For edema, there is no target dose, each patient is different
• Each patient has a different renal threshold for diuresis
• Start with double the patient’s home dose and double that dose until
diuresis occurs.
• Once patient has achieved diuresis, there is no further efficacy from
higher doses.
• Treatment of edema confers a symptomatic benefit only.
13. Renal Threshold
• Patient’s with worse renal function
will have high thresholds,
requiring higher doses.
• Thiazides may not work in ESRD,
loop diuretics will be more
efficacious.
• CrCl <30, thiazides will not work at
all.
• Other strategies if refractory
• thiazide+loop
• inotrope+loop
• Last line therapies
J Am Coll Cardiol. 2012;59(24):2145-2153.
14. Dosing - Edema
• Furosemide: 20-80 mg PO qday-bid,
20-200 mg IV per dose. Max 600 mg daily.
• Can repeat in 1-2 hours
• Bumetanide: 0.5-5 mg PO qday-bid,
0.5 mg-1 mg IV per dose. Max 10 mg daily
• Can repeat in 4-5 hours for up to 2
doses
• CIVI
• 1 mg IV load then 0.5-2
mg/hour; repeat loading dose
before increasing infusion rate
• Torsemide: 10-100 mg PO qday-bid,
10-20 mg IV per dose. Max 200 mg daily.
• Can repeat every 2 hours
• Ethacrynic Acid 50-200 mg PO qday,
0.5-1 mg/kg IV per dose. Max 100
mg/dose
• Can repeat in 8-12 hours, usually
only one dose is given
• Mannitol: 0.25-1 g/kg dose q6-8 hours
(cerebral) keep serum osmol <320
15. Pharmacokinetics – Loop diuretics
Drug IV Potency Bioavailability Oral: IV Metabolism Affected
by Food?
Furosemide 40 50% 2:1 Renal Yes, ⬇
Torsemide 20 ~100% 1:1 Hepatic No
Bumetanide 1 ~100% 1:1 Hepatic Yes, ⬇
*NSAIDs and food can diminish diuretic effects
16. Sulfa allergy?
• All common loop diuretics, acetazolamide, and thiazides have a
sulfonamide group in them.
• However, very few patients have a true type one allergic reaction to
the sulfonamide moiety.
• Most patients have allergy to sulfates or sulfites, which would not prevent a
patient from receiving these medications.
• “What loop diuretic can be used in a true type 1 allergy to
sulfonamides?”
17. Practice Question #1
• HS is a 67 yo WM with CC of SOB secondary to pulmonary edema.
Pt’s BP is 136/80 with HR of 80. SCr is 1.8, K+: 4.3, all other labs
within normal. PMH includes HFrEF (35%), HTN, HLD, GERD,
and T2DM. NKDA.
• TBW: 89 kg, was 82 kg last week. IBW: 50 kg. BMI: 35.
• His home dose of Lasix is 40 mg qday with food. The decision is
made to initiate IV Bumetanide for inpatient diuresis.
• What dose of IV bumetanide is appropriate?
18. Practice Question #1 Answer
• Home dose: furosemide 40 mg po qday with food
• Food decreases absorption
• Assessment of renal threshold. Warm/wet HF exacerbation.
Give 2-2.5 times his home dose to manage (DOSE trial)
• 40 mg po x 2: 80 mg
• Convert 80 mg PO furosemide to IV furosemide
• 80 mg PO= 40 mg IV push qday
• Convert IV furosemide to IV bumetanide
• 40 mg IV furosemide qday = 1 mg IV bumetanide qday
19. Practice Question #2
• You give HS the appropriate diuretic dose, but his I/O are still
positive at 1030:500 with no resolution of pulmonary edema.
Renal function still reduced but stable with SCr 1.82. Albumin 1.8.
BP 128/76 and HR: 80. What are appropriate interventions for HS
to improve his diuresis? (Multiple correct answers)
20. Practice Question #2 Answer
• Option 1: Add a Thiazide or Thiazide like diuretic before next dose of
bumetanide (if po). If using IV chlorthalidone, give at same time.
• Option 2: Add Dobutamine (if patient goes from warm and wet to cold
and wet with hypoperfusion)
• Option 3: Transition patient to dialysis if you feel kidney function is
heading towards ESRD and above interventions will not be effective.
(clinical judgement)
• Option 4: Administer 6.25 mg Albumin 5% with next dose of bumetanide
• Controversial, last line.
22. Clinical Pearls
• Triamterene has a BBW for hyperkalemia
• Septra’s trimethoprim component is structurally similar to triamterene
• Metolazone is preferred in ESRD to enhance loop diuretic effects in
refractory edema. It has a once daily dosing frequency.
• Hypotension from diuretics can lead to falls, especially in the
elderly
23. Important Take Home Points
• For edema, diuretics confer a symptomatic benefit only
• There are no target doses for diuretics
• There are goal BP ranges for HTN
• Thiazides are a first line treatment for HTN and have low efficacy w/CrCl<30
• Monitor electrolytes, renal function, and hydration status.
• NSAIDs and food can reduce loop diuretic efficacy.
• Loop diuretics have different potencies and require dose conversion.
24. References
• ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: The Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel
blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288 : 2981 –2997, 2002,
JAMA. 2002;288(23):2981-2997. doi:10.1001/jama.288.23.2981.
• DiPiro, Joseph; Talbert, Robert L.; Yee, Gary; Wells, Barbara; Posey, L. Michael (2014-02-26). Pharmacotherapy A Pathophysiologic Approach 9/E
(Pharmacotherapy : a Pathophysiologic Approach)
• Felker G, Mentz RJ. Diuretics and Ultrafiltration in Acute Decompensated Heart Failure. J Am Coll Cardiol. 2012;59(24):2145-2153.
doi:10.1016/j.jacc.2011.10.910.
• http://pharmacologycorner.com/video-animation-on-renal-physiology-and-diuretics-mechanism-of-action/
• Ohtani T, Felker GM, McNulty SE, LeWinter MM, Braunwald E, Redfield MM. Plasma Renin Activity (PRA) Predicts Diuretic Resis- tance in Acute
Heart Failure Patients: An Ancillary Study of the Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF). J Card Fail
2011;17:S25–6.
• Lexi-Comp, Inc. (Lexi-Drugs® ). Lexi-Comp, Inc.; January 29, 2015.
• James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey
LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the
panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20. doi: 10.1001/jama.2013.284427. Erratum in: JAMA.
2014 May 7;311(17):1809. PubMed PMID: 24352797.
Primarily affect sodium transport. Na=water
Affect sodium at different sites!
some have osmotic effects by increasing osmolality of the filtrate, drawing more fluid in.
Obstructive uropathy, don’t want to give in patients with no urine output, MONITOR I/O’s
Read up on Hypercapnic COPD and altitude sickness!
Sometimes can use loops for hyperkalemia (not really)
Read up on hypercalciuria
Thiazides can treat kidney stones Data from a randomized, double-blind, placebo-controlled study supports the use of hydrochlorothiazide for the prevention of recurrent calcium nephrolithiasis (Laerum 1984). Additional trials may be necessary to further define the role of hydrochlorothiazide in the treatment of this condition.
Based on the American Urologic Association (AUA) guidelines for the medical management of kidney stones, hydrochlorothiazide is effective and recommended for the prevention of recurrent calcium stones in patients with high or relatively high urine calcium concentrations.
THINK ABOUT IT, THIS MAKES SENSE. In kidney stones, calcium deposits are in the FILTRATE, thiazides decrease calcium in the filtrate and increase it in the blood, which helps osteoporosis.
Na+/2Cl−/K+ cotransporter- loops
Thiazide diuretics such as hydrochlorothiazide block sodium reabsorption in the distal convoluted tubule (approximately 5% to 8% of filtered sodium).
Chlorothiazide is the only thiazide diuretic that can be given intravenously (500 to 1000 mg once or twice daily)
Metolazone is actually a thiazide like diuretic. These drugs are called benzothiadiazides, or thiazides for short. Chemically, metolazone is not a substituted benzothiadiazine, and therefore is not technically a thiazide. However, since metolazone, as well as other drugs like indapamide, act on the same target as thiazides and behave in a similar pharmacologic fashion, they are considered "thiazide-like diuretics".
Additional C/I for Potassium sparing. acute renal insufficiency; significant impairment of renal excretory function; hyperkalemia; Addison’s disease
eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) OR K+ >5 for initiation
Discontinue if serum potassium >5.5 or serum creatinine >4 mg/dL.
Avoid routine triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone.
Instruct patients with heart failure to discontinue use during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).
-worsening hyperkalemia or renal dysfunction
Bring up the fact that they studied chlorthalidone and not HCTZ. MR.FIT saw a nonsignificant trend of worse outcomes with HCTZ and then included chlorthalidone.
Chlorthalidone was the actual drug studied in the ALLHAT study. We do not have HARD data for HCTZ, and it was trending poorly in Mr. FIT. Can’t go into detail in that one today.
Can do aldosterone antags if EF <40% IF they have T2DM or symptomatic HF while already on an ACEI and BB. If not, wait until <35%.
Resistant HTN= combination of at least three antihypertensive medications of different classes, optimally dosed and usually includ- ing a diuretic AND the patient is ADHERENT to them! No white coat HTN either
chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed.
-Unlike thiazides, loop diuretics maintain their effectiveness in the presence of impaired renal function, although higher doses may be necessary to obtain adequate delivery of the drug to the site of action
-loop diuretics are highly bound to plasma proteins, they are not highly filtered at the glomerulus.
Adding ALBUMIN to Bumex…Few patients with severe hypoalbuminemia (plasma albumin <2.0 g/dL) have been studied. It is possible that infusion of furosemide or other loop diuretic plus albumin would be effective in patients with refractory edema and severe hypoalbuminemia. However, if attempted, sodium excretion should be monitored after addition of albumin infusions, and infusions should be discontinued if they do not result in a net increase in sodium excretion. General issues related to the management of edema in patients with nephrotic syndrome are discussed in detail elsewhere.
Administer 6.25 mg Albumin 5% with next dose of bumetanide
--They reach the tubular lumen by active transport via the organic acid transport pathway. Competitors for this pathway (probenecid or organic by-products of uremia) can inhibit delivery of loop diuretics to their site of action and decrease effectiveness.
-Loop diuretics also induce a prostaglandin-mediated increase in renal blood flow, which contributes to their natriuretic effect.
-Coadministration of NSAIDs blocks this prostaglandin-mediated effect and can diminish diuretic efficacy.
-Excessive dietary sodium intake may also reduce the efficacy of loop diuretics.
You can also use Hydrochlorothiazide for Edema Oral: 25 to 100 mg daily in 1 to 2 divided doses; may administer intermittently on alternate days or on 3 to 5 days each week.
Furosemide Continuous IV infusion (ACCF/AHA [Yancy, 2013]); Brater, 1998; Howard, 2001): Initial: IV bolus dose 40-100 mg over 1-2 minutes, followed by continuous IV infusion rate of 10-40 mg/hour; repeat loading dose before increasing infusion rate. Note: With lower baseline CrCl (eg, CrCl <25 mL/minute), the upper end of the initial infusion dosage range should be considered. If urine output is <1 mL/kg/hour, double as necessary to a maximum of 80-160 mg/hour (Howard, 2001; Schuller, 1997). The risk associated with higher infusion rates (80-160 mg/hour) must be weighed against alternative strategies.
Average duration of effect for oral intake is ~ 6 hours for all agents, Bumex is the shortest, Torsemide is the longest
Bumetanide 1 mg = furosemide 40 mg = torsemide 20 mg = ethacrynic acid 50 mg
Half life and expected duration of action can be increased in renal or hepatic dysfunction
Furosemide also comes as a sublingual tablet as well
Bumex and Cirrhosis: Use caution in patients with cirrhosis; initiate bumetanide therapy with conservative dosing and close monitoring of electrolytes; avoid sudden changes in fluid and electrolyte balance and acid/base status which may lead to hepatic encephalopathy.
Answer: Ethacrynic acid, less potent than furosemide (50:1 bumex) Has high potential for ottotoxicity
Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
The nonsulfonamide diuretic ethacrynic acid may be used in patients who are allergic to sulfonamide-based diuretics, but is not considered a first-line agent because it may be more ototoxic than the sulfonamide diuretics in high doses and its relative insolubility makes it difficult to administer intravenously.
CrCL w/ IBW is <30
HF exacerbations in patient’s with ESRD are usually admitted as inpatient. Inpatient management is IV loop therapy.
His renal threshold will be very high, bumex is appropriate
HF increases threshold
With renal insufficiency, as seen in >50% of ADHF patients (15), organic anions compete with receptor sites for tubular transporters (16) and further increase dose requirements.
DOSE trial randomized 308 ADHF patients to IV furo- semide given as twice-daily boluses or continuous infusion and to either a low dose (IV dose numerically equivalent to the patient’s oral dose) or a high dose (2.5 times oral dose given intravenously) strategy. There was no significant difference in either of the co-primary endpoints of global assessment of symptoms
There was no significant difference in either of the co-primary endpoints of global assessment of symptoms
the higher dose group had fewer serious adverse events and no evidence of worse 60-day outcomes. Taken as a whole, the data suggest that higher doses of diuretics are likely to be more efficacious in relieving congestion than a low-dose strategy,
Thiazides or thiazide like diuretics may be added before loop diuretics
Positive inotropes may be added to loop diuretics to promote renal perfusion
Decreases threshold for diuresis.
Sodium reabsorption can be blocked in the distal tubule by the concurrent administration of a thiazide diuretic [4,31-33]. The distal tubule reabsorbs about 75 to 80 percent of the sodium delivered out of the loop of Henle. Administration of a loop diuretic increases distal sodium delivery and therefore sodium reabsorption in the distal tubule, an effect mediated in part by increased activity of the thiazide-sensitive sodium-chloride cotransporter in the luminal membrane of the distal tubule cells
Loop diuretics are highly (≥95 percent) protein bound. As a result, they primarily enter the tubular lumen by secretion in the proximal tubule, not by glomerular filtration.
Patients who do not respond to usual loop diuretic therapy may be resistant because of decreased diuretic secretion into the tubular lumen. As examples, decreased renal perfusion in heart failure (due to the reduced cardiac output) and cirrhosis (due to renal vasoconstriction) and competitive inhibition of tubular secretion in renal failure may contribute to impaired diuretic secretion
Patients with nephrotic syndrome may also be unresponsive to diuretics because of decreased tubular secretion. Because loop diuretics are highly protein bound, hypoalbuminemia associated with the nephrotic syndrome may reduce the delivery of diuretic to the renal tubule. In addition, filtered albumin in nephrotic patients may bind loop diuretics in the tubular lumen, thereby interfering with their function. HOWEVER THIS STUDY WAS DONE IN RATS
However, a subsequent study in patients with nephrotic syndrome (mean plasma albumin 3.0 g/dL) found that a mixture of loop diuretic and albumin (60 mg of furosemide infused in 200 mL of a 20 percent albumin solution) produced only a modest increase in sodium excretion compared with furosemide alone without an increase in the rate of furosemide excretion Coadministration of HA potentiates the action of FU in patients with the nephrotic syndrome, but only modestly. This effect is mediated by changes in renal hemodynamics. Increase in sodium excretion was due to the salt in the bag, no increase in sodium excretion!
Few patients with severe hypoalbuminemia (plasma albumin <2.0 g/dL) with refractory edema have been studied. It MAY work in these patients but no evidence.
Ototoxicity: Bumetanide-induced ototoxicity (usually transient) may occur with rapid IV administration, renal impairment, excessive doses, and concurrent use of other ototoxins (eg, aminoglycosides). In the setting of ESRD or hepatic disease (depends on agent)
Electrolyte disturbances can manifest as mental status change, cardiac arrythmias
MAKE SURE TO REPLENISH ELECTROLYTES Patients can be given potassium for supplementation to offset hypokalemia from loop diuretics.
Thiazides can help in osteoporosis but also worsen gout.
which is why Septra can also cause hyperkalemia
Ensure patient has urine output after administration
-If not, dose may need to be increased or investigate AKI/urinary blockage