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BENIGN PROSTATIC HYPERTROPHY(BPH)
- -Benign enlargement of prostate resulting in obstruction of urethra.
- -Overgrowth of epithelial cells (mechanical)
- -Overgrowth of smooth muscle cells (dynamic)
- Symptoms: hesitancy, urgency, frequency, dysuria, dribbling, smaller stream, post-void residual, nocturia, straining
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BPH tx
- Treatment options:
- -Medications (moderate), surgery(severe cases), “watchful waiting”(minimal ss)
- Treatment goal: Relieve symptoms
- Two main classes: many pt take both
- **Alpha-1 Adrenergic Antagonists (blockers)- for dynamic
- **5-alpha Reductase Inhibitors-for mechanical
- -Recommended drug regimen: combination of drugs
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Alpha-1 Adrenergic Antagonists- mech of action, examples
- -Mechanism of action: relax smooth muscle of the prostatic urethra and bladder neck (trigone and sphincter) by blocking alpha 1 receptors.
- -Improvement in symptoms is rapid
- Examples:
- Terazosin (Hytrin®) and Doxazosin (Cardura®)
- -Block alpha receptors in blood vessels;vasodilation-decrease BP
- Alfuzosin (Uroxatral®) and Tamsulosin (Flomax®)
- -Selective for alpha receptors in prostrate, can raise BP
- Azosin-A1 blocker
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Alpha-1 Adrenergic Antagonists- ADR
- -Nasal congestion (vasodilation)
- -Retrograde ejaculation (relaxation of smooth muscle in bladder neck)
- -Hypotension, dizziness, fainting, nasal congestion for Hytrin® and Cardura®
- -These drugs often tried before finasteride (Proscar®) because less incidence of sexual side effects; however combination therapy more effective.
- *DO NOT CAUSE DECREASE IN PSA LEVELS (like Proscar®)
- Drug Interactions- Nitrates, Phosphodiesterase 5 inhibitor (viagra, levitra, cialis), BP meds
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5-Alpha Reductase Inhibitors- mech of action, ADR, examples
- -Example: finasteride (Proscar®)
- -Mechanism of action:
- -Promotes regression of prostatic tissue by inhibiting 5-alpha reductase, the enzyme that converts testosterone to DHT.
- -Effects seen in 6-12 months.
- -ADR’s:
- -sexual dysfunction (5-10%) <libedo, <ejaculation
- -gynecomastia
- -decreases prostate specific antigen (PSA) levels
- -Contraindicated with pregnancy- cat x use precaution-absorbed through skin & inhaled
- -Note: also marketed under brand name Propecia® for male-pattern baldness
- -Other example: Dutasteride (Avodart®)-long half life; more complete reduction in DHT
- if PSA doesnt go down, more likely cancer
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Erectile Dysfunction
- -Erectile dysfunction- impotence
- -Defined as a persistent inability to achieve or sustain an erection
- -Associated with chronic illnesses such as DM, HTN, depression
- -Risk increases with age
- -Treatment include drugs and implants
- -Phosphodiesterase 5 (PDE5) Inhibitors
- -Sildenafil (Viagra)
- **Used for pulmonary HTN-Revatio
- -Vardenafil (Levitra)
- -Talalafil (Cialis)
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Erectile dysfunction ADR/interactions
- -Sildenafil (Viagra)
- -Relaxes penile and arterial and trabecular smooth muscle (>cyclic GMP)
- -Drug interactions
- -Nitrates (GMP)- biggest drug drug interactions
- -Alpha 1 blockers
- -Grapefruit juice
- -Most common is headache, flushing
- -hypotension may occur especially in men taking nitrates and alpha blockers
- -Ischemic optic neuropathy, sudden hearing loss
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Bethanechol- use, ADR, caution
- Urinary retention
- -Activates muscarinic receptors
- -Used for urinary retention
- Adverse effects
- -Heart-Bradycardia
- -Gland-Increased sweating, salivation, bronchial secretions, gastric acid secretions
- Caution:
- -Asthma, peptic ulcer, GI/GU obstructions
- Contraction in lung (constriction)
- GI (increased musccle tone)
- Bladder (contraction of detrusor)
- Vascular (relaxation, vasodilation, hypotension)
- Eye (pupil constrctiona nd ciliary contraction)
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URINARY INCONTINENCE
“Overactive Bladder”- cause, tx, drug, mech of action, ADRs
- Cause: most frequently due to involuntary contraction of the bladder muscle. Very common in elderly.
- Treatment: behavioral therapy and medications (often called “antispasmodics”)
- The drugs:
- -Oxybutynin (Ditropan®)
- -Tolterodine (Detrol®)
- -Solifenacin (VESIcare)
- -Mechanism of action: block muscarinic receptors of bladder muscle (detrusor) to prevent bladder contraction
- -ADR’s”: anticholinergic side effects
- Dry mouth, blurred vision, photophobia, hyperthermia, CNS-confusion , dizziness, AMS, psychosis, hot dry flushed skin
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furosemide (Lasix®)
Others: ethacrynic acid (Edecrin®), bumetanide (Bumex®), torsemide (Demadex®)
- Loop diuretics- most powerful D
- -Most effective diuretics
- -Site of action: loop of Henle (kidney)
- -Mechanism of action: blocks Na and chloride reabsorption>increased osmotic pressure>increased H20 excretion
- Main uses:
- -Hypertension
- -Edema (cardiac, pulmonary, renal, hepatic)used more for edema than HTN
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Loop diuretics- ADRs, Allergy, drug interactions
- ADR’s:
- -dehydration
- -hypotension
- -hypokalemia
- -ototoxicity (reversible)
- -hyperglycemia
- dry mucus membranes, skin turger, confusion (monitor BP)
- -contraindicated in pregnancy
- -Allergy: avoid if history of sulfonamide allergy
- Drug interactions:
- -digoxin- increases toxicity
- -aminoglycosides- also ototoxic
- -antihypertensives
- -Work well even with renal impairment (even w/ Cr clearance <30)
- usually on K+ supp, can cause hearing loss
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DIURETICS- uses, classifications
- Promote “diuresis”- movement of fluids and electrolytes out of body.
- Two major uses:
- -Hypertension
- -Edema
- Classification:
- -Loop diuretics
- -Thiazide diuretics
- -Osmotic diuretics
- -Potassium-sparing diuretics
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hydrochlorothiazide (HydroDIURIL®)- mech of action, uses, allergy
- Thiazide Diuretics
- -Generic names end with “-thiazide”
- -Much less diuresis compared to “Loops”
- -Mechanism of action: same as “Loops” but at the distal convoluted tubule of kidney; dilate blood vessels
- Major uses:
- -**Hypertension
- -Edema due to mild to moderate CHF
- -Allergy: derived from sulfonamides
- -Do NOT work well in renal impairment (do not use if cr clear <30)
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hydrochlorothiazide- ADRs, Drug interaction
- ADR’s:
- -Dehydration
- -Hypokalemia
- -Hyperglycemia
- -Contraindicated in pregnancy
- Drug interactions:
- -Digoxin- can increase toxicity
- -Antihypertensives
- -NSAIDs+dehyd=kidney failure
- -Lithium+dehyd=>lith level
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Metolazone (Zaroxolyn)
- Related drugs (non-thiazide)
- act like thiazide
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spironolactone (Aldactone®)- mech of action, main use
- Potassium-sparing Diuretics
- -Amount of diuresis is low
- Mechanism of action: Blocks action of aldosterone at kidney collecting duct
- -Aldosterone promotes Na uptake and K secretion
- Main uses:
- -With other diuretics for its K-sparing properties
- -Hypertension (alone, not a first choice)
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spironolactone (Aldactone®)- ADRs, drug interactions, other examples
- ADR’s:
- -hyperkalemia (EKG, arrythmias, palpations)
- -many endocrine effects because structurally similar to hormones (gynocomastia)
- Drug interactions:
- -potassium supplements
- -drugs that cause hyperkalemia (ie. ACE inhibitors, ARBs)
- Other examples:
- -Triamterene (Dyrenium®) and Amiloride (Midamor®)
- -Both block sodium-potassium exchange in distal nephron
- -May cause hyperkalemia
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omannitol (Osmitrol®)-mech of action, main use, ADRs
- Osmotic Diuretics
- Mechanism of action: creates an osmotic force within lumen of proximal convoluted tubule of kidney which pulls water into lumen of tubule.
- -Causes no significant effect on excretion of electrolytes (sodium, chloride, potassium)
- Main uses:
- -Preserve urine flow in impending renal failure
- -Reduce intracranial pressure
- typically only used in ICU
- ADR’s:
- -Can cause edema! Discontinue if signs of pulmonary edema or if renal failure develops.
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Electrolytes-Potassium
- -Most abundant intracellular cation
- -Helps with nerve conduction and acid-base balance, maintain electrical muscle activity
- -Hypokalemia-cramps, arrhythmias, insulin
- -Potassium salts usually SR- less N/V/D
- -Administer IV slowly
- -Assess renal function and EKG changes
- -Hyperkalemia-tissue trauma, acidosis , elevated T waves, PR prolonged, cardiac arrest
- -Hyperkalemia S/S-Confusion, weakness or heaviness of legs, numbness, tingling of hands, feet, lips
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Electrolytes- Magnesium
- Hypomagnesemia
- -Caused by diarrhea, hemodialysis, chronic alcholism, others
- Treatment
- -Po magnesium gluconate or hydroxide (diarrhea)
- -IV magnesium sulfate (no diarrhea
- -Caution with replacement in renal insuffiency can cause kidney failure
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