1. Diuretics

2. Outline
1. Sites of drug action 2. Osmotic diuretics 3. Carbonic anhydrase inhibitors 4. Thiazide diuretics 5. Loop diuretics 6. Potassium-sparing diuretics

3. Definitions Diuretics: substance that promotes the excretion of urine
caffeine, yerba mate, nettles, cranberry juice, alcohol
Natriuretic: substance that promotes the renal excretion of Na+

4. Renal Physiology renal epithelial transport tubular reabsorption
proximal tubule
loop of Henle
thick ascending limb
distal convoluted tubule
collecting tubule
tubular secretion
collecting tubules

5. Summary: Sites of Action

6. Osmotic Diuretics
Do not interact with receptors or directly block renal transport
activity dependent on development of osmotic pressure
Mannitol (prototype)
Urea
Glycerol
Isosorbide

7. Mechanism of Action osmotic diuretics are not reabsorbed
increases osmotic pressure specifically in the proximal tubule and loop of Henle
prevents passive reabsorption of H2O
osmotic force solute in lumen > osmotic force of reabsorbed Na+
increased H2O and Na+ excretion

8. Therapeutic Uses Mannitol
drug of choice: non-toxic, freely filtered, non-reabsorbable and non-metabolized
administered prophylatically for acute renal failure secondary to trauma, CVS disease, surgery or nephrotoxic drugs
short-term treatment of acute glaucoma
infused to lower intracranial pressure
Urea, glycerol and isosorbide are less efficient
can penetrate cell membranes

9. Side Effects increased extracellular fluid volume cardiac failure
pulmonary edema
hypernatremia
hyperkalemia secondary to diabetes or impaired renal function
headache, nausea, vomiting

10. Carbonic Anhydrase Inhibitors
limited uses as diuretics
Acetazolamide
prototype carbonic anhydrase inhibitor
developed from sulfanilamide (caused metabolic acidosis and alkaline urine)

11. Mechanism of Action
inhibits carbonic anhydrase in renal proximal tubule cells
carbonic anhydrase catalyzes formation of HCO3- and H+ from H2O and CO2
inhibition of carbonic anhydrase decreases [H+] in tubule lumen
less H+ for for Na+/H+ exchange
increased lumen Na+, increased H2O retention

12. Therapeutic Uses used to treat chronic open-angle glaucoma
aqueous humor has high [HCO3-]
acute mountain sickness
prevention and treatment
metabolic alkalosis
sometimes epilepsy
mostly used in combination with other diuretics in resistant patients

13. Side Effects rapid tolerance
increased HCO3- excretion causes metabolic acidosis
drowsiness
fatigue
CNS depression
paresthesia (pins and needles under skin)
nephrolithiasis (renal stones)
K+ wasting

14. Thiazide Diuretics active in distal convoluted tubule
Chlorothiazide (prototype)
Hydrochlorothiazide
Chlorthalidone
Metolazone

15. Mechanism of Action
inhibit Na+ and Cl- transporter in distal convoluted tubules
increased Na+ and Cl- excretion
weak inhibitors of carbonic anhydrase, increased HCO3- excretion
increased K+/Mg2+ excretion
decrease Ca2+ excretion

16. Therapeutic Uses hypertension congestive heart failure
hypercalciuria: prevent excess Ca2+ excretion to form stones in ducts
osteoperosis
nephrogenic diabetes insipidus
treatment of Li+ toxicity

17. Pharmacokinetics orally administered poor absorption
onset of action in ~ 1 hour
wide range of T 1/2 amongst different thiazides, longer then loop diuretics
free drug enters tubules by filtration and by organic acid secretion

18. Side Effects hypokalemia increased Na+ exchange in CCD
volume-contraction induced aldosterone release
hyponatremia
hyperglycemia
diminished insulin secretion
elevated plasma lipids
hyperuricemia
hypercalcemia

19. Loop Diuretics active in “loop” of Henle Furosemide (prototype)
Bumetanide
Torsemide
Ethacrynic acid

20. Mechanism of Action enter proximal tubule via organic acid transporter
inhibits apical Na-K-2Cl transporter in thick ascending loop of henle
competes with Cl- binding site
enhances passive Mg2+ and Ca2+ excretion
increased K+ and H+ excretion in CCD
inhibits reabsorption of ~25% of glomerular filtrate

21. Therapeutic Uses edema: cardiac, pulmonary or renal
chronic renal failure or nephrosis
hypertension
hypercalcemia
acute and chronic hyperkalemia

22. Pharmacokinetics orally administered, rapid absorption
rapid onset of action
bound to plasma proteins: displaced by warfarin, and clofibrate
increase toxicity of cephalosporin antibiotics and lithium
additive toxicity with other ototoxic drugs
inhibitors of organic acid ion transport decrease potency (i.e. probenecid, NSAID’s)

23. Side Effects hypokalemia hyperuricemia metabolic alkalosis
hyponatremia
ototoxicity
Mg2+ depletion

24. K+ sparing diuretics three groups steroid aldosterone antagonists
spironolactone, eplerenone
Pteridines
triamterene
Pyrazinoylguanidines
amiloride

25. Mechanism of Action K+ sparing diuretics function in CCD
decrease Na+ transport in collecting tubule
Spironolactone
competitive antagonist for mineralocorticoid receptor
prevents aldosterone stimulated increases in Na+ transporter expression
Triamterene/Amiloride
organic bases
secreted into lumen by proximal tubule cells
inhibit apical Na+ channel

26. Therapeutic Uses
primary hyperaldosteronism (adrenal adenoma, bilateral adrenal hyperplasia)
congestive heart failure
cirrhosis
nephrotic syndrome
in conjunction with K+ wasting diuretics

27. Pharmacokinetics Spironolactone orally administered
aldactazide: spironolactone/thiazide combo
Amiloride
oral administration, 50% effective
not metabolized
not bound to plasma proteins
Triamterine
60% bound to plasma proteins
liver metabolism, active metabolites

28. Side Effects hyperkalemia: monitor plasma [K+]
spironolactone: gynecomastia
triamterene: megaloblastic anemia in cirrhosis patients
amiloride: increase in blood urea nitrogen, glucose intolerance in diabetes mellitus

29. Antibiotics

30. Antibiotics Sulfonamides Penicillins Cephalosporins Tetracyclines
Aminoglycosides
Quinolones
Macrolides

31. What are Antibiotics? Antibiotics = “against life”
Antibiotics are molecules that stop microbes, both bacteria and fungi, from growing or kill them outright.
Antibiotics can be either natural products or synthetic chemicals.

32. Antibiotics Medications used to treat bacterial infections
Ideally, before beginning antibiotic therapy, the suspected areas of infection should be cultured to identify the causative organism and potential antibiotic susceptibilities.

33. Antibiotics
Empiric therapy: treatment of an infection before specific culture information has been reported or obtained
Prophylactic therapy: treatment with antibiotics to prevent an infection, as in intra-abdominal surgery

34. Antibiotics Bactericidal: kill bacteria
Bacteriostatic: inhibit growth of susceptible bacteria.

37. Antibiotics can be categorized based on their target specificity:
narrow-spectrum" antibiotics target particular types of bacteria, such as Gram-negative or Gram-positive bacteria.
broad-spectrum antibiotics affect a wide range of bacteria.

38. Primary Modes of Action

39. Bacteriocidal
A bacteriocide is a substance that kills the bacteria of choice and, preferably, nothing else.
Microbe death is usually achieved by disruption of the bacterial cell membrane leading to lysis.

40. Bacterial Antibiotics
Antibiotics were created at a time when previously untreatable infections such as tuberculosis, gonorrhea, and syphilis could be almost incredibly treated.
Bacteria have been successful because they are capable of adapting to changes in their environment.
Penicillin is the best-known antibiotic, which is used to treat bacterial infections, such as syphilis, gonorrhea, meningitis, and anthrax.

41. Antibiotics: Penicillins
First introduced in the 1940s
Bactericidal: inhibit cell wall synthesis
Kill a wide variety of bacteria
Also called “beta-lactams”

42. Penicillins: Side Effects
Common side effects:
nausea, vomiting, diarrhea, abdominal pain
Other side effects are less common

43. Antibiotics: Cephalosporins
Semisynthetic derivatives from a fungus
Structurally and pharmacologically related to penicillins
Bactericidal action
Broad spectrum
Divided into groups according to their antimicrobial activity

44. Cephalosporins: Side Effects
similar to penicillins

45. Antibiotics: Tetracyclines
Natural and semi-synthetic
Obtained from cultures of Streptomyces
Bacteriostatic—inhibit bacterial growth
Inhibit protein synthesis
Stop many essential functions of the bacteria

46. Tetracyclines: Therapeutic Uses
Wide spectrum:
gram-negative, gram-positive, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease
Demeclocycline is also used to treat SIADH, and pleural and pericardial effusions

47. Tetracyclines: Side Effects
May also cause:
Vaginal moniliasis
Gastric upset
Enterocolitis
Maculopapular rash

48. Antibiotics: Aminoglycosides
gentamicin (Garamycin)
kanamycin
neomycin
streptomycin
tobramycin
amikacin (Amikin)
netilmicin

49. Aminoglycosides Natural and semi-synthetic Produced from Streptomyces
Poor oral absorption; no PO forms
Very potent antibiotics with serious toxicities
Bactericidal
Kill mostly gram-negative; some gram-positive also

50. Aminoglycosides: Side Effects
Ototoxicity and nephrotoxicity are the most significant
Headache
Paresthesia
Neuromuscular blockade
Dizziness
Vertigo
Skin rash
Fever
Superinfections

51. Antibiotics: Quinolones
ciprofloxacin (Cipro)
enoxacin (Penetrex)
lomefloxacin (Maxaquin)
norfloxacin (Noroxin)
ofloxacin (Floxin)

52. Quinolones: Side Effects
Body System Effects
CNS headache, dizziness, fatigue, depression, restlessness
GI nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies

53. Quinolones: Side Effects
Body System Effects
Integumentary rash, pruritus, urticaria, flushing, photosensitivity (with lomefloxacin)
Other fever, chills, blurred vision, tinnitus

54. Antibiotics: Nursing Implications
Before beginning therapy, assess drug allergies; hepatic, liver, and cardiac function; and other lab studies.
Be sure to obtain thorough patient health history, including immune status.
Assess for conditions that may be contraindications to antibiotic use, or that may indicate cautious use.
Assess for potential drug interactions.

55. Antibiotics: Nursing Implications
It is ESSENTIAL to obtain cultures from appropriate sites BEFORE beginning antibiotic therapay
Patients should be instructed to take antibiotics exactly as prescribed and for the length of time prescribed; they should not stop taking the medication early when they feel better.
Assess for signs and symptoms of superinfection: fever, perineal itching, cough, lethargy, or any unusual discharge.

56. Antibiotics: Nursing Implications
Each class of antibiotics has specific side effects and drug interactions that must be carefully assessed and monitored.
The most common side effects of antibiotics are nausea, vomiting, and diarrhea.
All oral antibiotics are absorbed better if taken with at least 6 to 8 ounces of water.

57. Antibiotics: Nursing Implications
Sulfonamides
Should be taken with at least 2400 mL of fluid per day, unless contraindicated.
Due to photosensitivity, avoid sunlight and tanning beds.
These agents reduce the effectiveness of oral contraceptives.

58. Antibiotics: Nursing Implications
Penicillins
Any patient taking a penicillin should be carefully monitored for an allergic reaction for at least 30 minutes after its administration.
The effectiveness of oral penicillins is decreased when taken with caffeine, citrus fruit, cola beverages, fruit juices, or tomato juice.

59. Antibiotics: Nursing Implications
Cephalosporins
Orally administered forms should be given with food to decrease GI upset, even though this will delay absorption.
Some of these agents may cause an Antabuse-like reaction when taken with alcohol.

60. Antibiotics: Nursing Implications
Tetracyclines
Milk products, iron preparations, antacids, and other dairy products should be avoided because of the chelation and drug-binding that occurs.
All medications should be taken with 6 to 8 ounces of fluid, preferably water.
Due to photosensitivity, avoid sunlight and tanning beds.

61. Antibiotics: Nursing Implications
Aminoglycosides
Monitor peak and trough blood levels of these agents to prevent nephrotoxicity and ototoxicity.
Symptoms of ototoxicity include dizziness, tinnitus, and hearing loss.
Symptoms of nephrotoxicity include urinary casts, proteinuria, and increased BUN and serum creatinine levels.

62. Antibiotics: Nursing Implications
Quinolones
Should be taken with at least 3 L of fluid per day, unless otherwise specified

63. Antibiotics: Nursing Implications
Macrolides
These agents are highly protein-bound and will cause severe interactions with other protein-bound drugs.
The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many agents are taken after a meal or snack.

64. Antibiotics: Nursing Implications
Monitor for therapeutic effects:
Disappearance of fever, lethargy, drainage, and redness

65. Question?