Hello friends. In this PPT I am talking about diuretics. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
3. Diuretics
• Diuretics (natriuretics) are drugs which cause a net
loss of Na+ and water in urine
• COLT Pee (Site of action)
1. Carbonic anhydrase inhibitors (PCT)
2. Osmotic diuretics (LOH)
3. Loop diuretics (TAL of LOH)
4. Thiazides (DT)
5. Potassium Sparing diuretics (CT)
4.
5. Loop diuretic (Furosemide)
• Its maximal natriuretic effect is much greater than
that of other classes
• It is active even in patients with relatively severe
renal failure
• The major site of action is the thick AscLH
(therefore called loop diuretics) where it inhibits
Na+- K+-2Cl¯ cotransport
• Furosemide ↑ Ca2+ excretion (contrast thiazides
which reduce it) as well as Mg2+ excretion
6.
7.
8. • Diuresis is delayed whereas release of PGs is
immediate action
I.v. Furosemide causes prompt ↑ in systemic venous
capacitance (venodilation) due to ↑ PGs
↓
↓ LV filling pressure (↓ preload)
↓
Shifting of fluid from pulmonary to sytemic
circulation
↓
Immediate relief in dyspnoea (Quick relief in LVF and
pulmonary edema)
9. Bumetanide
• 40 times more potent than Furosemide
• Induces very rapid diuresis
• Highly effective in pulmonary edema.
• Site of action and duration of action are similar to
furosemide
• Hyperuricaemia, K+ loss, glucose intolerance and
ototoxicity are claimed to be less marked, but it
may rarely cause myopathy
10. Uses
1. Edema Diuretics are used irrespective of
etiology of edema—cardiac, hepatic or renal. The
high ceiling diuretics are preferred in CHF for
rapid mobilization of edema fluid. They are the
diuretics of choice for nephrotic and other forms
of resistant edema
2. Acute pulmonary edema (acute LVF, following MI)
I.v. Furosemide or its congeners produces
prompt relief. This is due to vasodilator action
that precedes the saluretic action.
11. 3. Cerebral edema Though osmotic diuretics are
preferred, Furosemide may be given i.m.
4. Hypertension High ceiling diuretics are
indicated only in the presence of renal insufficiency,
CHF, or in resistant cases and in hypertensive
emergencies; otherwise thiazides are preferred
12. Thiazides
• Medium efficacy diuretics
• Site of action Cortical diluting segment or the
early DT
• Inhibit Na+Cl¯ symport at the luminal membrane
• Moderately efficacious diuretics, because nearly
90% of the glomerular filtrate has already been
reabsorbed before it reaches their site of action
• Thiazides have a flat dose response curve
13.
14. • The extrarenal actions of thiazides consist of
a slowly developing fall in BP in hypertensives
and elevation of blood sugar in some patients due
to decreased insulin release which probably is a
consequence of hypokalaemia
15. Indications
1. Edema Thiazides may be used for mild-to
moderate cases
• For mobilization of edema fluid more efficacious
diuretics are preferred, but thiazides may be
considered for maintenance therapy
• They act best in cardiac edema; are less effective in
hepatic or renal edema
• They are powerless in the presence of renal failure
• Cirrhotics often develop refractoriness to thiazides
due to development of secondary
hyperaldosteronism
16. 2. Hypertension Thiazides and related diuretics,
especially Chlorthalidone are one of the 1st line drugs
3. Diabetes insipidus Thiazides decrease positive
free water clearance and are the only drugs effective
in nephrogenic diabetes insipidus
• However, they reduce urine volume in pituitary
origin cases as well
17.
18. Adverse Effects
1. Hypokalaemia This is the most significant
problem.
• It is rare at low doses, but may be of grave
consequence when brisk diuresis is induced or on
prolonged therapy.
• The usual manifestations are weakness, fatigue,
muscle cramps.
19. • Cardiac arrhythmias are the serious complications.
• It can be prevented and treated by:
(a) High dietary K+ intake or
(b) Supplements of KCl (24–72 mEq/day) or
(c) Concurrent use of K+ sparing diuretics.
2. Acute saline depletion Overenthusiastic use of
diuretics, particularly high ceiling ones, may cause
dehydration and marked fall in BP
20. 3. Dilutional hyponatraemia
• Occurs in CHF patients when vigorous diuresis is
induced with high ceiling agents, rarely with
thiazides.
• Kidney tends to retain water, though it is unable to
retain salt due to the diuretic; e.c.f. gets diluted,
hyponatraemia occurs and edema persists despite
natriuresis.
21. • Patients feel very thirsty.
• Treatment of this distortion of fluid-electrolyte
balance is difficult:
1. Withhold diuretics
2. Restrict water intake
3. Give glucocorticoid which enhances excretion of
water load.
4. If hypokalaemia is present, its correction helps
22. 4. GIT and CNS disturbances Nausea, vomiting and
diarrhoea may occur with any diuretic.
• Headache, giddiness, weakness, paresthesias,
impotence are occasional complaints
5. Hearing loss Occurs rarely, only with high ceiling
diuretics
6. Allergic manifestations Rashes, photosensitivity
occur, especially in patients hypersensitive to
sulfonamides.
23. 7. Brisk diuresis induced in cirrhotics may precipitate
mental disturbances and hepatic coma
8. Hyperuricaemia Long-term use of higher dose
thiazides in hypertension has caused rise in blood
urate level but is rare now due to use of lower doses
24. 9. Hyperglycaemia and hyperlipidemia Have
occurred in the use of diuretics as antihypertensive.
These metabolic changes are minimal with low dose
thiazides now recommended.
10. Magnesium depletion It may develop after
prolonged use of thiazides as well as loop diuretics
25. Interactions
1. Thiazides and high ceiling diuretics potentiate all
other antihypertensives
2. Hypokalaemia induced by these diuretics
enhances digitalis toxicity
3. Loop diuretics can enhance ototoxicity and
nephrotoxicity of aminoglycoside
4. Indomethacin and other NSAIDs diminish the
action of diuretics by inhibiting PG synthesis in
the kidney
26. 5. Probenecid competitively inhibits tubular
secretion of furosemide and thiazides: decreases
their action
6. Serum lithium level rises due to enhanced
reabsorption of Li+ in PT
27. Carbonic Anhydrase Inhibitors
• In the proximal tubule, carbonic anhydrase
catalyzes the reversible conversion of hydrogen ion
and bicarbonate to carbon dioxide and water,
thereby enabling the reabsorption of sodium
bicarbonate
• This process is inhibited by carbonic anhydrase
inhibitors such as acetazolamide
28.
29. Uses (GAME)
1. Glaucoma Adjuvant to other ocular
hypotensives
2. To alkalinise urine for urinary tract infection or
to promote excretion of certain acidic drugs
3. Acute Mountain sickness Symptomatic relief
as well as prophylaxis. Benefit occurs probably
due to reduced CSF formation and lowering of
brain pH
4. Epilepsy (catamenial)
30. Adverse Effects
• Acidosis, hypokalaemia, drowsiness, paresthesias,
fatigue, abdominal discomfort
• Hypersensitivity reactions—fever, rashes
• Bone marrow depression is rare but serious
• Contraindicated in liver disease may precipitate
hepatic coma by interfering with urinary
elimination of NH3 (due to alkaline urine)
31. Potassium sparing diuretics
• Aldosterone antagonists and renal epithelial Na+
channel inhibitors indirectly conserve K+ while
inducing mild natriuresis potassium sparing
diuretics
• In the collecting duct, sodium enters the principal
cells through sodium channels
• Sodium is then transferred into the interstitial fluid
by the sodium pump, while potassium is pumped in
the opposite direction and then moves through
potassium channels into the tubular fluid
32. • Aldosterone stimulates these processes by
increasing the synthesis of messenger RNA that
encodes for sodium channel and sodium pump
proteins
• The potassium-sparing diuretics exert their effects
via two mechanisms:
1. Amiloride and Triamterene inhibit the entrance of
sodium into the principal cells
2. Spironolactone blocks the mineralocorticoid
receptor and thereby inhibits sodium
reabsorption and potassium secretion
33.
34. Uses of Spironolactone
1. To counteract K+ loss due to thiazide and loop
diuretics
2. Edema Useful in cirrhotic and nephrotic
edema in which aldosterone levels are generally
high
• Spironolactone is frequently added to a
thiazide/loop diuretic in the treatment of ascites
due to cirrhosis of liver
35. 3. Hypertension: Used as adjuvant to thiazide to
prevent hypokalemia, it may slightly add to their
antihypertensive action
• More importantly, it may have the potential to
attenuate hypertension related renal fibrosis and
ventricular/vascular hypertrophy
4. CHF As additional drug to conventional therapy
in moderate to severe CHF; can retard disease
progression and lower mortality
36. Interactions
1. Given together with K+ supplements— dangerous
hyperkalaemia can occur
2. Aspirin blocks Spironolactone action by inhibiting
tubular secretion of its active metabolite
canrenone
3. More pronounced hyperkalaemia can occur in
patients receiving ACE inhibitors/ARBs
4. Spironolactone increases plasma digoxin
concentration
37. Adverse effects
• Side effects Drowsiness, mental confusion,
epigastric distress and loose motions
• Spironolactone interacts with progestin and
androgen receptors as well
• In addition, it may enhance testosterone clearance
or its peripheral conversion to estradiol, producing
dose and duration of treatment related hormonal
side effects like gynaecomastia, erectile dysfunction
or loss of libido in men, and breast tenderness or
menstrual irregularities in women
• Most serious is hyperkalaemia that may occur,
especially if renal function is inadequate
38. Eplerenone
• It is a newer and more selective aldosterone
antagonist which has much lower affinity for other
steroidal receptors
• Less likely to produce hormonal disturbances like
gynaecomastia, impotence, menstrual
irregularities, etc.
• This feature makes it particularly suitable for
longterm use in the therapy of hypertension and
chronic CHF
• Risk of hyperkalaemia and g.i. side effects are like
spironolactone
39. Osmotic diuretics (Mannitol)
• Acts on Loop of Henle
• Mannitol appears to limit tubular water and
electrolyte reabsorption by
1. Retains water isoosmotically in PT—dilutes
luminal fluid which opposes NaCl reabsorption
2. Inhibits transport processes in the thick AscLH by
an unknown mechanism Largest contributor to
the diuresis
40. 3. Expands extracellular fluid volume (because it
does not enter cells, Mannitol draws water from the
intracellular compartment)—increases g.f.r. and
inhibits renin release.
41. Uses
1. Increased intracranial or intraocular tension
(acute congestive glaucoma, head injury, stroke,
etc.): by osmotic action it encourages movement
of water from brain parenchyma, CSF and
aqueous humour. It is also used before and after
ocular/brain surgery to prevent acute rise in
intraocular/intracranial pressure
2. To maintain GFR and urine flow in impending
acute renal failure e.g. in shock, severe trauma,
cardiac surgery, haemolytic reactions
Hinweis der Redaktion
Osmolarity is affected by changes in water content, as well as temperature and pressure. In contrast, osmolality is independent of temperature and pressure. 2[Na+] + [Glucose]/18 + [ BUN ]/2.8[7] where [Glucose] and [BUN] are measured in mg/dL. 285-295 milli-osmoles per kilogram. 1 mole nacl = 23 + 35 = 58gm
The clearance of a drug is the theoretical volume of plasma from which the drug is completely removed in unit time. CL = Rate of elimination/C
Thiazide diuretics have a paradoxical effect in diabetes insipidus (↓ free water clearance).
Inh. PDE enz. & ↑ 3,5-cAMP ↑ memb. Perm. Of CD & DT
↓ ECF vol. & hyponatremia Stim. Na & H2O reabs. From PT ↓ delivery to DT ↓ urine o.
ADH inc. memb. Permeab. Of CT by inc. 3,5-cAMP
Dilutional hyponatremia, also known as water intoxication, it is a potentially life-threatening condition which occurs when a person consumes too much water without an adequate intake of electrolytes.
Paresthesia (or paraesthesia) is an abnormal dermal sensation (e.g., a tingling, pricking, chilling, burning, or numb sensation on the skin) with no apparent physical cause. The manifestation of a paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes.
Catamenial epilepsy is a gender-specific type of epilepsy in which seizure frequency intensifies during certain phases of the menstrual cycle.