(True/False) the SAR for diuretics is clearly defined.
False, not much is known about how they bind at the site of action
What is a spiro functional group?
2 rings attached at one carbon
Sulfamylbenzoic acid derivatives such as furosemide are reserved but rarely used (other drugs are available) for__________________________________.
hypertensive patients with significant impaired renal function
(True/False) Pyridylsulfonylurea derivatives can be used for treatment of hypertension.
True
What are Sulfamylbenzoic acids generally used to treat?
Severe heart failure, pulmonary edema, acute renal failure and poisoning
How do Sulfamylbenzoic acids treat Poisoning?
Causes forced diuresis of the poison
What negative side effect can result from fast IV infusions with large doses of Furosemide (sometimes also seen with oral doses)?
Ototoxicity
Why might Ototoxicity result from a fast IV infusion of Furosemide?
Interaction of the anionic -COOH group with cationic ear fluid, may involve 8th cranial nerve
What are symptoms of ototoxicty due to Furosemide?
Tinnitus, Vertigo and Decreased auditory acuity
If a patient has a history of Furosemide induced ototoxicity, what alternative drug should they be given?
Bumex
Does Bumex cause Ototoxicity?
No
The pyridylsulfonylurea derivative is less or more likely to cause hyperkalemia than Sulfamylbenzoic acids?
Less
Does the pyridylsulfonylurea derivative cause ototoxicity?
No
(True/False) Sulfamyl group may cause problems with hypersensitivity and may result in cross allergy with other structures with a sulfonamide group.
True
Does Ethacrynic acid cause Ototoxicity?
Yes (greater incidence)
Why is Ethacrynic acid rarely used?
Greater incidence of ototoxicity and GI side effects
If a patient in acute renal failure is allergic to sulfonamides, would you suggest they take furosemide, ethacrynic acid or bumetanide?
Ethacrynic acid
What supplementation is often be given with loop diuretics?
K
A patient comes in complaining of Malaise, fatigue, cramps and arrhythmias. They have been taking Bumex. What issue do you suspect?
Hypokalemia
What type of diuretics are prescribed most as initial monotherapy for the treatment of hypertension because of high efficacy, low side effects and low cost?
Thiazide diuretics
How long will it take for Thiazide diuretics results to appear?
2 weeks.
Thiazide or Loop diuretics are more potent?
Loop diuretics
Thiazide diuretics are ineffective below what Creatinine Clearance rate?
< 35ml/min
If a patient has a CrCl of < 35ml/min, would you use a Thiazide or Loop Diuretic?
Loop, Thiazides are ineffective at this low CrCl
Are Thiazides effective in African Americans?
Yes, most effective
A patient has edema due to moderate Heart Failure, is a Thiazide diuretic a good choice?
Yes
Which Thiazide diuretics are the most efficacious?
All about equal, with similar maximal responses
Would you supplement with K when using a Thiazide diuretic?
Yes
Aldactazide (hydrochlorothiazide (HCTZ) /spironolactone), Dyazide (HCTZ/triamterene), Maxzide (HCTZ/triamterene) and Moduretic (HCTZ/amiloride) are all formulated for what reason?
To obtain maximal diuresis while minimizing hypokalemia
A patient comes into the pharmacy complaining of muscle irritability, a coarse hand tremor and GI effects. They also seem somewhat confused. They have been taking Lithium, and Hydrochlorothiazide. What do you suspect?
Lithium toxicity due to increased reabsorption of the drug by HCTZ
A patient has been taking Lithium and just received a prescription for HCTZ. What would you recommend to the doctor?
Reduce the dose of Lithium as HCTZ will increase its reabsorption
Would you expect the onset of action to be faster for an aldosterone antagonist or pteridine analog?
Pteridine analog
Why are aldosterone antagonists slower acting than pteridine analogs?
Pteridine analogs act directly and aldosterone antagonists are heavily metabolized by the liver and are dependent on aldosterone conc.
Aldosterone antagonist can result in decreased libido and gynecomastia (True/False).
True, due to steroid like structure
What conditions cause high amounts of aldosterone, making spirolactone the drug of choice for treatment?
Hyperaldosteronism and Hepatic cirrhosis
What is the major side effect of K sparing diuretics?
Hyperkalemia
A patient is complaining of Fatigue, Muscle weakness, Bradycardia and has an abnormal EKG. What might be the issue?
Hyperkalemia
What drugs used incombination with K sparing diuretics can enhance the risk of hyperkalemia?