Renal/Uro pharm Flashcards
(40 cards)
1
Q
Diuretic
A
Any substance that increases urine volume
- Inhibitors of renal ion transporters
- Decreases the reabsorption of sodium at different sites of the nephron
- Increase in urine flow is secondary to increase in sodium excretion
- Kidneys adjust the excretion of sodium and water to maintain extracellular fluid (ECF)
- In pathophysiologic states, this balance is altered
Used for:
- Diseases causing edema: CHF, Cirrhosis, nephrotic syndrome, renal failure
- HTN
- Nephrolithiasis
- Hypercalcemia (loop diuretics)
- Diabetes insipidus
2
Q
Natriuretic
A
Any substance increasing renal sodium excretion (same function as diuretci)
3
Q
Acetazolamide
A
Carbonic anhydrase inhibitor
Site of action: proximal tubule
MOA:
- Inhibits carbonic anhydrase
- Decreases sodium bicarbonate reabsorption
- Cause bicarbonate diuresis (up to 85%) that may lead to metabolic acidosis
- Over time (several days), effectiveness decreases–> soon increase Na reabsorption (thus reversing diuresis)
Use: metabolic alkalosis (alkalinizes urine)
- Induces hyperchloremic metabolic acidosis after excessive use of other diuretics
- Prophylax acute mountain sickness (decreases CSF formation, pH–> increase minute ventilation–> decrease symptoms)
- Glaucoma (decreases rate of aqueous humor formation–> decreased IOP)
AEs:
- Metabolic acidosis
- Phosphaturia, hypercalciuria (can cause calcium stone formation)
- Potassium wasting
- Toxicity: drowsiness/fatigue (CNS carbonic anhydrase inhibition), parasthesis, avoid in liver disease (increases ammonia–> hepatic encephalopathy)
4
Q
Dichlorphenamide
A
Carbonic anhydrase inhibitor
Site of action: proximal tubule
MOA:
- Inhibits carbonic anhydrase
- Decreases sodium bicarbonate reabsorption
- Cause bicarbonate diuresis (up to 85%) that may lead to metabolic acidosis
- Over time (several days), effectiveness decreases–> soon increase Na reabsorption (thus reversing diuresis)
Use: metabolic alkalosis (alkalinizes urine)
- Induces hyperchloremic metabolic acidosis after excessive use of other diuretics
- Prophylax acute mountain sickness (decreases CSF formation, pH–> increase minute ventilation–> decrease symptoms)
- Glaucoma- topical use (decreases rate of aqueous humor formation–> decreased IOP)
AEs:
- Metabolic acidosis
- Phosphaturia, hypercalciuria (can cause calcium stone formation)
- Potassium wasting
- Toxicity: drowsiness/fatigue (CNS carbonic anhydrase inhibition), parasthesis, avoid in liver disease (increases ammonia–> hepatic encephalopathy)
5
Q
Methazolamide
A
Carbonic anhydrase inhibitor
Site of action: proximal tubule
MOA:
- Inhibits carbonic anhydrase
- Decreases sodium bicarbonate reabsorption
- Cause bicarbonate diuresis (up to 85%) that may lead to metabolic acidosis
- Over time (several days), effectiveness decreases–> soon increase Na reabsorption (thus reversing diuresis)
Use: metabolic alkalosis (alkalinizes urine)
- Induces hyperchloremic metabolic acidosis after excessive use of other diuretics
- Prophylax acute mountain sickness (decreases CSF formation, pH–> increase minute ventilation–> decrease symptoms)
- Glaucoma (decreases rate of aqueous humor formation–> decreased IOP)
AEs:
- Metabolic acidosis
- Phosphaturia, hypercalciuria (can cause calcium stone formation)
- Potassium wasting
- Toxicity: drowsiness/fatigue (CNS carbonic anhydrase inhibition), parasthesis, avoid in liver disease (increases ammonia–> hepatic encephalopathy)
6
Q
Furosemide
A
Loop diuretic
Site of action: cortical and medullary TAL of loop of Henle
MOA: inhibits Na+-K+-2Cl- transporter
Clinical:
- Rapid onset of action (first line in pulmonary edema)
- Stimulates prostaglandin synthesis in lung, kidneys (NSAIDs–> decreased prostaglandins–> decreased diuresis)
- CHF (decrease ECF volume)
- Excretion of: K+, Mg+2 and Ca+2 (Ca reabsorbed later in DCT, but can be used in hypercalcemia)
- Blocks reabsorption of bromide, fluoride, iodide (poisoning)
- Used 2nd line or with thiazide diuretics for HTN
- Edema of nephrotic syndrome (refractory to other diuretics)
Side effects:
- hypokalemia, hypomagnesemia
- hyperuricemia (gouty attack)
- hypochloremic metabolic alkalosis (increased excretion of H+)
- Dose-related irreversible hearing loss (alters membranous labyrinth in inner ear)
- Cross-reactivity with sulfonamide allergy
- Dehydration
- Increased LDL, triglycerides, decreased HDL
7
Q
Bumetanide
A
Loop diuretic
8
Q
Torsemide
A
Loop diuretic
9
Q
Ethacrynic acid
A
Loop diuretic
10
Q
Hydrochlorothiazide
A
Thiazide diuretics
Site of action: distal convoluted tubule
MOA: inhibits luminal co-transport of Na, Cl
- Contraction of ECF volume–> decrease in CO–> decrease peripheral vascular resistance
Clinical use:
- Augment production of vasodilatory prostaglandins (NSAID interaction)
- Use in HTN, mild CHF
- Edema due to liver/renal disease
- Only moderately efficacious in decreasing Na+ reabsorption (most reabsorbed before DCT)
- Increased K, H excretion
- Decreased renal Ca+2 excretion (good with urinary stone treatment)
Conditions:
- Nephrogenic DI: paradoxical decrease in urine output
AEs:
- Avoid in low GFR
- “Ceiling diuretics”: increasing dose does not promote further diuresis
- hypokalemia, hypomagnesemia
- hyperuricemia (gouty attack)
- hypochloremic metabolic alkalosis
- Sulfa allergy interaction: photosensitivity, generalized dermatitis (rare)
- Hyperglycemia (impair pancreatic insulin release, tissue utilization of glucose)
- Hyperlipidemia
11
Q
Chlorothalidone
A
Thiazide diuretics
12
Q
Metolazone
A
Thiazide diuretics
13
Q
Spironolactone, eplerenone
A
Potassium-sparing diuretic
MOA: competitive antagonist of aldosterone receptors on collecting tubule (Na-H exchanger)
SIte of action:
- Cortical collecting tubule
Clinical:
- Most effective in primary/secondary hyperaldosteronism (Conn syndrome) - prevents binding of aldosterone to its receptor
- Secondary hyperaldosteronism seen in: CHF, hepatic cirrhosis, nephrotic syndrome
- Ascites
- HTN
- Loop/thiazide-induced hypokalemia
AEs:
- Hyperkalemia (if not on another diuretic)
- Hyperchloremic metabolic acidosis= blocks collecting duct Na-H exchange (aldosterone receptor)–> can’t excrete H+
- Endocrine abnormalities: gynecomastia, hirsutism, impotence, benign prostatic hyperplasia, menstrual irregularities
14
Q
Triamterene, amiloride
A
Postassium-sparing diuretic
MOA: interferes with Na+ influx thru epithelial Na ion channels in luminal membrane (Na-H exchanger in collecting duct)
- K+ secretion coupled with Na+ entry (therefore spare K+ secretion by blocking Na entry)
Clinical use:
- HTN
- Loop/thiazide-induced hypokalemia
AEs:
- Hyperkalemia (if not on another diuretic)
- Hyperchloremic metabolic acidosis= blocks collecting duct Na-H exchange (aldosterone receptor)–> can’t excrete H+
15
Q
Eplerenone
A
Spironolactone with greater selectivity to mineralocorticoid receptor
- Less activity on androgen, progesterone receptors (decreased side effects)
- Blocks fibrosis/inflammation caused by aldosterone–> slows albuminuria in diabetes
16
Q
Mannitol
A
Osmotic diuretic
Not reabsorbed, causing water to be retained initially, then diuresis
Site of action:
- Proximal tubule: decreased Na reabsorption by osmotic gradient–> increased urine volume
- Descending loop of Henle: increased medullary blood flow, inhibit reabsorption of water
- Collecting duct: opposes action of ADH
Clinical:
- Prevents acute renal failure after severe trauma, complicated surgical procedures (hemolysis, rhabdomyolysis)
- Toxin excretion
- Reduces intracranial, intraocular pressure–> fluid (not Na) leaves cells
- Does not increase Na excretion (only water)
- Must be given IV (only effects colon if given orally)
AEs:
- Rapidly distributes to ECF–> extracts water from cells
- Causes acute increase in ECF/hyponatremia (can’t use in CHF, pulmonary edema)
- N/V, headache
- Severe dehydration, hypernatremia
- Hyperkalemia
17
Q
Conivaptan
A
Antidiuretic hormone antagonist
MOA: inhibits effects of ADH
Site of action: collecting duct
Clinical use:
- Hypervolemic, euvolemic hyponatremia not corrected by fluid restriction
- SIADH (with failure of water restriction)
- CHF, cirrhosis (diminished circulating blood volume)–> increased ADH
- Conivaptan= IV
AEs:
- Severe hypernatremia
- Too rapid correction can cause seizures/death
18
Q
Tolvaptan
A
Antidiuretic hormone antagonist
Can be administered PO
19
Q
Edema and diuretics
A
NaCl reabsorption too high in many disease states leading to:
- Water retention
- increased blood volume
- Expansion of ECF compartment
20
Q
CHF and diuretics
A
Diuretic of choice: Loop diuretic
CO continues to deteriorate–> kidney retains sodium, water
- Water leaks from vasculature–> interstitial–> pulmonary edema
Diuretics:
- Improve exercise tolerance, quality of life
- Reduce fluid retention symptoms
- Reduce hospitalizations
Do not:
- alter disease progression
Clinical:
- Change in body weight is sensitive marker of fluid retention due to CHF
21
Q
Kidney disease and diuretics
A
Cause retention of sodium, water
- Milder renal insufficiency, diuretics beneficial
- Need larger doses as GFR declines (risk hearing loss)
- Continuous infusion dosing best
Does not:
- reverse clinical disease, help with renal function
- minimally beneficial in severe insufficiency
- avoid acetazolamide (worsening acidosis) and potassium-sparing diuretics (hyperkalemia)
22
Q
Diuretic resistance in renal failure
A
- Excessive sodium intake
- Inadequate diuretic dose
- Reduced oral bioavailability (double dose IV to oral)
- Nephrotic syndrome: glomerulus allows plasma protein loss–> decreased osmotic pressure and increased aldosterone–> edema/Na/water retention
- Reduced renal blood flow:
- NSAIDs, ACE-I, Vasodilators
- Hypotension (Intravascular volume expansion, vasopressors)
- Intravascular depletion (volume expansion) - Heart failure
- Nephrotic adaptation
- Cirrhosis (tx: paracentesis)
- Acute tubular necrosis
- Some patients with resistance respond to continuous infusions
23
Q
Cirrhosis and diuretics
A
Liver disease–> obstructed portal blood flow–> increased portal pressure
- Decreased plasma protein synthesis–> decreased oncotic pressure
- Both cause fluid to leave portal vascular system–> collects in abdomen
Mechanism for Na retention:
- diminished renal perfusion
- Diminished plasma volume (+ ascites)
- Diminished oncotic pressure (low albumin)
- Primary sodium retention (elevated aldosterone)
24
Q
HTN and diuretics
A
Thiazide= first line
Enhance other anti-hypertensives
25
Nephrolithiasis and diuretics
Thiazide diuretics: enhance calcium reabsorption (decrease urinary calcium concentration)
2/3 kidney stones have calcium phosphate or oxalate crystals (hypercalcuria)
26
Drug treatments for BPH
1. Alpha antagonists (-zosin)
- Old= terazosin, dexazosin (need to be titrated to avoid hypotension)
- Newer formulas target Alpha-1 receptors
- Decreased risk of postural hypotension
2. 5-alpha reductase inhibitors
- May take 6-12 months for maximal effect
27
Alpha-1 antagonists: AEs
- Postural hypotension (dizziness)
- Nasal congestion
- Headache
- Asthenia (weakness)
- Abnormal (retrograde) ejaculation)
- Erectile dysfunction (can cause or improve)
- Avoid with planned cataract surgery (Floppy Iris Syndrome)
28
5-alpha reductase inhibitors
Testosterone converted to 5-DHT in prostate by 5-alpha reductase
- 5DHT contributes to BPH
- Blocking 5-alpha reductase--> decreased DHT--> decreased BPH
Type 2= seen primarily in genitals vs Type 1 (liver and skin)
29
Finasteride
Inhibits Type II 5-AR
Side effects:
- Decreased libido
- Ejaculatory disorder
- Erectile dysfunction
- Breast tenderness
- Gynecomastia
30
Dutasteride
Inhibits Type I and II 5-AR
Side effects:
- Decreased libido
- Ejaculatory disorder
- Erectile dysfunction
- Breast tenderness
- Gynecomastia
31
Comparison of 5-alpha reductase inhibitors vs alpha-1 blockers
5-AR inhibitors:
- Symptom improvement from ~6 months
- increased flow from 1 month
- Effects on symptoms and flow demonstrated to 10 yr
- Reduce prostate volume
- Reduce the risk of AUR (acute urinary retention)
- Reduce the risk of surgery
- Decrease PSA (< 1 month
Alpha-1 blockers;
- increased flow from < 1 month
- Effect on symptoms and flow > 12 months not well established
- Do not reduce prostate volume
- Do not prevent AUR and surgery (Delay??)
32
Treatment of Erectile Dysfunction
Phosphodiesterase-5 inhibitors:
- Prevent break down of cGMP
Lifestyle modifications:
- Smoking cessation
- Limit/avoid EtOH
- Diet
- Exercise
Medication-induced
- Anti-HTN
- SSRIs
- Hormonal agents
- H2-receptor antagonists
33
Oral PDE5 inhibitors
Sildenafil
Tadalafil
Vardenafil
AEs:
1. Contraindicated with nitrates
- Can potentiate vasodilation and hypotension associated with NO
- Several early deaths in elderly men with concomittant heart disease on nitrates
2. Caution in vascular disease, coronary disease, vascular risk factors (cardiac eval)
3. Any recent MI, arrhytmias, obstructive hypertrophic cardiomyopathy
34
Second-line therapy for ED
1. MUSE: Medicated uretheral suppository for erection
- Administers local alprostadil (PGE-1) to enhance erection
- Useful in non-responsive patients or patients on nitrates
* * PGE-1= stimulates adenylyl cyclase--> increased cGMP
2. Intracavernosal injection (PDE-inhibitors: alprostadil, papaverine)
- More reliable, instant predictable erection
- Fewer AEs, contraindications
* Phentolamine= alpha-blocker
35
Muscarinic receptors in bladder
Normal contraction mediated by activation of muscarinic receptors in detrusor muscles (Ach binding):
- M3 receptor= primary mediator of bladder contraction
- M2= more prevalent
36
Fesoterodine
Derofenisine
Tolteradine
Solifenacin
MOA:
1. Antimuscarinic action
- Inhibits binding of acetylcholine to cholinergic receptor and suppresses bladder contractions
2. Antispasmodic
- Allows detrusor smooth-muscle relaxation to control overactive bladder and urge urinary incontinence
Effects on Urinary Bladder= Motor and sensory
- Increase bladder capacity
- Reduce urinary frequency
- Diminsh urinary incontinence episodes resulting from involuntary bladder contractions
AEs:
- Dry mouth
- Headache
- Constipation
- Diarrhea
- Pain
- Dyspepsia
37
Oxybutynin
Tertiary amine, antimuscarinic agent
| HIgher rates of AEs than tropsium
38
Tropsium
Quarternary amine
| Less likely to cross BBB- better for use in older patients with concern of interfering with cognitive function
39
Mirabegron
Beta-3 adrenergic agonist
| - Relaxes bladder detrusor muscle
40
Testosterone replacement
```
ROA:
Oral androgens not used in US
- Difficulty with achieving consistent levels
- Hepatotoxicity
Injectable agents
Transdermal/topical agents
Buccal preparations
Long acting implants
```
Used to treat symptoms of hypogonadism:
- ED, low libido, depression, fatigue, anemia
Diagnosis both clinical and serological
- Should have endocrine eval before T replacement
* * Need to be careful in prostate cancer
