Urologic Pharmacology UTI’S AND BEYOND!

Urologic Pharmacology UTI’S AND BEYOND!
J. Alison Hanson, MD Southwest Urology Associates Albuquerque, NM UTI= Urinary Tract Infection

UTIs and Beyond ACUTE UTI RECURRENT UTI, PROSTATITIS OR IS IT:
CYSTITIS, OAB, LUTS? I am going to discuss those pts with recurrent symptoms. They need a culture to document whether this is actually an infection or not, and the best drug to use for treatment. Sometimes this reveals No growth, and they need to be evaluated for other causes for their symptoms. Cystitis= Bladder irritation, increased sensitivity of the bladder, often due to infection, dietary and/or bowel factors, neurologic issues or other causes: bacterial cystitis=UTI; Radiation cystitis; chemotherapy cystitis; interstitial cystitis) OAB= OverActive Bladder LUTS= Lower Urinary Tract Symptoms BOO=Bladder Outlet Obstruction

UTI, PROSTATITIS, CYSTITIS, LUTS SYMPTOMS
More frequent need to urinate; up at night Often intense urge to urinate, though little comes out; +/- incontinence Pain or pressure in your back, rectum or lower abdomen Cloudy, dark, bloody, or strange-smelling urine Pain, burning feeling when you urinate Many believe they mainly have nocturia, but when they do a voiding diary, also have daytime frequency. It doesn’t bother them as much because they are already up…. May complain of pain with urination, decreased force of stream.

UTI, PROSTATITIS, CYSTITIS, LUTS
Pink or red urine: red-tinted foods, (beets, rhubarb, blackberries…) Need UA to evaluate for hematuria. Some foods make urine smell … unique, like asparagus: breaks down into volatile acids like asparagusic acid. Other foods that can stink: salmon, curry, coffee, garlic, Brussels sprouts… Sometimes foods actually cause changes in color: Blue-green urine: may result from medications: vitamins, laxatives, some chemotherapy and other drugs, including amitriptyline, indomethacin (Indocin) and propofol (Diprivan). Bright yellow or orange urine: indicates a lot of vitamin C, carrots, beets, or other foods, also some medication: include rifampin; the anti-inflammatory drug sulfasalazine (Azulfidine); phenazopyridine (Pyridium), a drug that numbs urinary tract discomfort; some laxatives; and certain chemotherapy drugs Dark orange or brown: Eating large amounts of fava beans, rhubarb or aloe can cause dark brown urine. Medications including the antimalarial drugs chloroquine and primaquine, antibiotics metronidazole (Flagyl) and nitrofurantoin, laxatives containing cascara or senna, and methocarbamol — a muscle relaxant. Some liver and kidney disorders; urinary tract infections. Pink or red urine: red-tinted food, such as beets, rhubarb, and blackberries. Need to evaluate with UA for hematuria. Bloody urine may occur from urinary tract infections, enlarged prostate, cancerous and noncancerous tumors, kidney cysts, long-distance running, and kidney or bladder stones. Cloudy urine has been found to suggest the presence of phosphates, which can be a precursor to kidney stones. In women with vaginitis (such as yeast vaginitis or sexually transmitted infections like gonorrhea), the vaginal discharge, if present, may sometimes contaminate the urine sample, making the urine appear cloudy. Odors: high blood ketone levels from a low-carb diet or fasting, and from diabetes (ketoacidosis): a sweet, acetone-like odor in the urine can be detected. Cloudy urine with odor can also be a sign of dehydration, and may smell like ammonia Sit up straight and arch back to void – eliminates much of the “vaginal washout” and much post void dribbling.

The presence of pyuria (leukocytes ≥10 /mm3) is NOT sufficient for diagnosis of UTI. In urine samples from asymptomatic elderly women; 60 % of samples with pyuria had no bacteriuria. Need urine culture and sensitivity if recurrent UTI to document and treat with appropriate drug

Recurrent UTI: ≥2 documented UTIs/ 6 months or ≥3/year. Recurrent UTIs are common in young, healthy women with normal urinary tracts. Chronic prostatitis: = recurrent UTIs entering the prostate gland. May exist years before symptoms, which can fluctuate. Diagnosis often challenging; difficult to culture. Recurrent episodes with documented NEGATIVE culture is an example of cystitis: irritated bladder. Interventions to calm the bladder and improve bowel function (probiotics, fiber, stool softners, etc) and decreasing irritants in the diet often help. Frequently, antibiotic prophylaxis for a few months also helps to return them to normal. Continued post coital (sex) prophylaxis is often indicated if that is a risk factor. Repeated cultures within a month suggests a bowel wall (diverticulitis) infection. The bladder has nowhere to hide bacteria. Often the urine is sterile if checked post treatment, because the recurrence isn’t actually from the bladder. May need to treat longer or use different antibiotics(not nitrofurantoin – poor tissue levels) How big diverticulitis to be seen on CT? NSAID: NonSteroidal AntiInflammatory Drugs: Ibuprofen, Naproxen, etc. ProstatitisTreatment: antibiotics for 4 to 12 weeks, warm baths, NSAIDs for pain. Sometimes suppressive antibiotic prophylaxis. May result in chronic pelvic pain syndrome

UTI, PROSTATITIS, CYSTITIS, LUTS RISK FACTORS
Sex: infrequent, new/multiple partners Spermicide use (vaginal irritation) Family history of UTIs (?irritation, sensitive) Increased susceptibility to vaginal colonization with uropathogens Cystitis, incontinence (Bladder, vaginal irritation) CONSTIPATION; diverticulosis/itis; other bowel issues.

Some women more prone to infections with sexual activity; loss of estrogen after menopause may make urinary tract more vulnerable to infection. DIET: foods that are direct irritants can cause cystitis symptoms and increase the incidence of UTI. Diet Irritants: The worst offenders: tomatoes/tomato products, including spaghetti sauce and tomato paste coffee and tea, both caffeinated and decaffeinated alcoholic beverages Carbonated beverages, sparkling water Tobacco Also: spicy foods, such as those containing hot peppers or curry citrus fruits and juices, such as orange, tangerine, and grapefruit Chocolate Apples Grapes vinegar

RECURRENT UTI, PROSTATITIS ANTIBIOTICS
Commonly recommended include: Amoxicillin/clavulanate (Augmentin) Trimethoprim/sulfamethoxazole (TMP/SMX)(Bactrim, Septra) Nitrofurantoin (Macrodantin, Macrobid) Ciprofloxacin(Cipro)Levofloxacin(Levaquin) Cephalexin (Keflex); other cephalosporins Most UTIs (75-95%) are caused by a Escherichia coli (E. coli). Other Enterobacteriaceae types of bacteria also occur, and others at a significantly lower rate. Proteus and Klebsiella, and Pseudomonas may be associated with stone disease or other urologic problems. Different treatments may be recommended in different areas of the country based on regional patterns of drug resistance. Other cephalosporins like cefpodoxime, cefdinir, or cefaclor High rates of antibiotic resistance are seen with both ampicillin and amoxicillin for E. coli, although amoxicillin/clavulanate (Augmentin) may still be an option. increasing rates of resistance include sulfamethoxazole-trimethoprim (Bactrim DS, Septra DS) and the fluoroquinolones. Resistance rates for the oral cephalosporins and Augmentin are still usually less than 10 percent.

KNOW YOUR DRUGS Amoxicillin/clavulanate
mechanism of action: bactericidal; inhibits cell wall mucopeptide synthesis / inhibits beta-lactamases renal dosing use immediate-release form: CrCl 10-30: q12h; CrCl <10: q24h hepatic impairment: caution advised Monitoring Parameters: baseline Cr; if prolonged tx: Cr, CBC, LFTs periodically The clavulanic acid prevents bacteria from destroying the antibiotic amoxicillin. The clavulanic acidis known as a beta-lactamase inhibitor. amoxicillin/clavulanate (Augmentin) All PCNs: increased tendency for yeast inf. Contraindications: include allergies to PCNs, Cephalosporins, mononucleosis, live typhoid vaccine caution if hypersens. to multiple allergens, caution if asthma or hx, caution if ALL caution if HIV infection, caution if recent abx-assoc. colitis hx, caution if seizure disorder caution if renal impairment, caution if hepatic impairment, caution if PKU (phenylalanine-containing forms All oral contraceptives… Warfarin, methotrexate, +

Common Side effects: include diarrhea, vomiting, nausea, thrush, yeast, skin rash. All antimicrobial agents: antibiotic-associated diarrhea due to Clostridium difficile infection—may lead to pseudomembranous colitis—may occur during or after treatment.

Rarely, cholestatic jaundice (cholestatic hepatitis liver toxicity) may occur several weeks after treatment, takes weeks to resolve: more frequent in men, older, long courses of treatment All aminopenicillins, possible associated Stevens–Johnson syndrome/toxic epidermal necrolysis; very rare Stevens-Johnson syndrome is a rare, serious disorder of your skin and mucous membranes. It's usually a reaction to a medication or an infection. Often, Stevens-Johnson syndrome begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters. Then the top layer of the affected skin dies and sheds. Stevens-Johnson syndrome is a medical emergency that usually requires hospitalization. Treatment focuses on eliminating the underlying cause, controlling symptoms and minimizing complications. Recovery after Stevens-Johnson syndrome can take weeks to months, depending on the severity of your condition. If it was caused by a medication, you'll need to permanently avoid that drug and others closely related to it. If you are of Asian descent, consider genetic testing before taking certain drugs. If you are of Chinese, Southeast Asian or Indian descent, talk with your doctor before taking carbamazepine (Carbatrol, Tegretol). This drug is useful to treat epilepsy, bipolar disorder and other conditions. But people with a gene called HLA-B 1502 have an increased risk of Stevens-Johnson syndrome if they take this drug. The Food and Drug Administration recommends people of Asian ancestry undergo genetic testing before taking carbamazepine.

KNOW YOUR DRUGS BACTRIM
Absorption: Increases with food Mechanism of action: TMP + SMX sequentially inhibit bacterial synthesis of tetrahydrofolic acid (THF). Reduced THF inhibits thymidine synthesis, which inhibits DNA synthesis. BACTRIM blocks two consecutive steps in the biosynthesis of DNA and proteins essential to many bacteria Among enteric gram-negative bacteria, resistance to Bactrim and other antibiotics is most often due to acquisition of plasmids with genes that encode drug resistant enzymes. These plasmids often carry genes that also confer resistance to other classes of antimicrobials. Maximal synergistic action occurs when microorganisms are susceptible to both component drugs. However, bacteria that are resistant to one drug component, but remain fully susceptible to the other drug, can still be inhibited by the combination. ●TMP-SMX is effective against a wide variety of aerobic gram-positive and gram-negative bacteria, and some protozoa. Both trimethoprim and sulfamethoxazole distribute to sputum and vaginal fluid; pass the placental barrier and are excreted in breast milk; trimethoprim also distributes to bronchial secretions. Bioavailability of TMP-SMX is approximately 85 percent for both compounds; absorption of TMP-SMX is not affected by food or other medications

KNOW YOUR DRUGS BACTRIM
common adverse reactions involve GI tract (nausea, vomiting) and skin (rash and pruritus) Renal dose adjustment: dosing should be altered if creatinine clearance <30 mL/minute. Other side effects that can occur include: ●Renal tubular acidosis ●Hepatitis ●Hypoglycemia ●Hyponatremia ●Hemolysis in glucose-6-phosphate dehydrogenase deficiency Severe rare reactions include neutropenia, anaphylaxis, and uncommon severe dermatologic reactions such as Stevens-Johnson syndrome Nephrotoxicity is uncommon; however, TMP is known to decrease the tubular secretion of creatinine. This can lead to an increase in serum creatinine that is not reflective of a true reduction in glomerular filtration rate. Alter dose: decrease amount of dose and or frequency TMP-SMX should be avoided during certain stages of pregnancy. ●TMP-SMX can interact with a variety of drugs that may require adjustment of therapy and/or more frequent monitoring

KNOW YOUR DRUGS NITROFURANTOIN
Absorption: Increases with food Mechanism of Action: inactivates/alters bacterial ribosomal proteins: inhibition of protein synthesis, aerobic energy metabolism, DNA, RNA, and cell wall synthesis. Nitrofurantoin is bactericidal in urine Long-term exposure to nitrofurantoin has been associated with pulmonary reactions, chronic hepatitis, and neuropathy. These toxicities are rare but patients should be warned about them. In general, nitrofurantoin use should be avoided in patients with CrCl<30 mL/minute in whom efficacy may be decreased and the risk for toxicity may be greater. Can cause reaction with ETOH ( also? some cephalosporins, Bactrim) like Flagyl: Disulfiram-ethanol reaction: Head, neck, and chest flushing - Histamine-induced vasodilation Throbbing headaches Nausea, vomiting (may be refractory), diarrhea, and abdominal pain Weakness, dizziness, confusion, and anxiety Vertigo and ataxia Orthostatic hypotension - Hypotensive flushing reaction with warm extremities Diaphoresis Palpitations and dysrhythmias Pruritus Refractory cyanosis (eg, methemoglobinemia) Antibiotics: Metronidazole, Cephalosporins (with nMTT side chain) Cefoperazone, Cefotetan, Cefmetazole Nitrofurantoin Oral hypoglycemics: Sulfonylureas Industrial agents: Carbon disulfide, Hydrogen sulfide Mushrooms: Coprinus atramentarius Clitocybe clavipes

NITROFURANTOIN does NOT achieve adequate tissue levels in prostate or kidney Achieves high concentration in urine; concentration variable in impaired renal function. The manufacturer contraindicates use in CrCl <60 mL/minute; however, limited data suggest nitrofurantoin is safe and effective for short-term treatment of uncomplicated UTI in patients with decreased renal function (Oplinger 2013; Santos 2016; Singh 2015). The Beers Criteria recommends avoiding use in geriatric patients ≥65 years with a CrCl <30 mL/minute (Beers Criteria [AGS 2015]). Use caution in patients with G6PD deficiency; may be at increased risk for hemolytic anemia.

Identified as potentially inappropriate medication 65+ yrs (independent of diagnosis or condition) due to potential pulmonary toxicity, hepatotoxicity, peripheral neuropathy, particularly if taken long-term; “safer alternatives exist”. Avoid with CrCl <30 mL/min or for long-term suppressive therapy (Beers Criteria AGS 2015). “For more than 20 years, the Beers Criteria have led to decreased reliance on potentially inappropriate medications and a deeper appreciation for medication safety as a facet of high-quality care for older adults,” notes AGS President Steven R. Counsell, MD, AGSF. “Our 2015 update extends the legacy of the late Mark Beers, MD—who led creation of the first list in Our 2015 update was developed after a review of the latest evidence, and we have created new companion tools intended to help older people, health professionals, and other stakeholders appreciate the AGS Beers Criteria as a resource, not a replacement, for sound clinical judgment on a case-by-case basis,”

Pharmacy Quality Alliance (PQA): when cumulative day supply is greater than 90 days, identified as high-risk medication in patients 65+ on the PQA’s, Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans The American Geriatrics Society (AGS) Oct 2015 released its second updated and expanded Beers Criteria—lists of potentially inappropriate medications for older adults who are not receiving hospice or palliative care, and one of the most frequently cited reference tools in the field of geriatrics. The Society also unveiled a suite of new companion resources—including a list of alternative therapies for potentially inappropriate medications and more detailed guidance on best practices for implementing AGS recommendations—all published online in the Journal of the American Geriatrics Society and available for free from GeriatricsCareOnline.org

KNOW YOUR DRUGS KEFLEX Inhibits bacterial cell wall synthesis, binding to penicillin-binding proteins:. Bacteria eventually lyse due to activity of cell wall autolytic enzymes while cell wall assembly is arrested Absorption: Increases with food Inhibits bacterial cell wall synthesis, binding to penicillin-binding proteins: inhibits final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to activity of cell wall autolytic enzymes while cell wall assembly is arrested

KNOW YOUR DRUGS KEFLEX Adverse Reactions: >10%: GI: Diarrhea, duration dependent No Hepatic dosing needed Renal dosing: CrCl <30mls/min Treats GU infections, including acute prostatitis, caused by E. coli, P. mirabilis, Klebsiella pneumo. (good tissue levels) 1% to 10%: CV: Local thrombophlebitis (2%) GI: Nausea and vomiting (3% to 7%), unpleasant taste (5%) Genitourinary: Vaginitis (≤5%) Hematologic: Decreased hematocrit, decreased hemoglobin (≤10%), eosinophilia (1-7%) Hepatic: Increased serumtransaminases, & serum alkaline phosphatase (2%) Immunologic: Jarisch-Herxheimer reaction (6%) Jarisch–Herxheimer reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. The antibiotics are so successful at killing a lot of bacterial cells that now the contents of those burst cells provoke some irritation and must be cleared. Jarisch–Herxheimer reactions are usually not life-threatening. Often they last only a few hours.] It resembles bacterial sepsis and can occur after initiation of antibacterials Typically, the death of these bacteria and the associated release of endotoxins or lipoproteins occurs faster than the body can remove the substances. It usually manifests within a few hours of the as fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia (muscle pain), exacerbation of skin lesions and anxiety. The intensity of the reaction indicates the severity of inflammation. Reaction commonly occurs within two hours of drug administration, but is usually self-limiting.

KNOW YOUR DRUGS CIPRO, LEVAQUIN
Mechanism of Action: Inhibits DNA-gyrase in susceptible organisms; inhibits relaxation of supercoiled DNA, promotes breakage of double-stranded DNA Absorption: OK with food except large amounts of Calcium RESISTENCE: the A subunit of DNA gyrase is a target of resistence to ciprofloxacin and other quinolones. Ciprofloxacin resistance appears to occur both by mutation in this target and by alteration of drug permeation through the outer membrane of the cell.

Tissue concentrations often EXCEED serum concentrations especially in kidneys, gallbladder, liver, lungs, gynecological tissue, and prostate IV and po levels similar

ALERT: US Boxed Warning Serious adverse reactions: Fluoroquinolones associated with disabling, potentially irreversible serious adverse reactions that have occurred together including: tendon rupture, CNS effects, peripheral neuropathy, tendinitis.

Discontinue immediately, avoid use in patients who have any serious adverse reactions; reserve use for patients who have no alternative treatment options for the following indications: acute exacerbation of chronic bronchitis, acute sinusitis, and acute uncomplicated cystitis. (UTI) especially in the Achilles' tendon of the heel. This can happen during treatment or up to several months after you stop. Tendon problems may be more likely to occur if you are over 60, if you take steroid medication, or if you have had a kidney, heart, or lung transplant.

Exacerbation of myasthenia gravis: monitored closely for signs/symptoms of disordered glucose regulation. Altered cardiac conduction: may prolong QTc interval; avoid use in patients with a history of or at risk for QTc prolongation Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis. Caution in: tendon problems, bone problems, arthritis or other joint problems diabetes (especially if use insulin or oral diabetes medication); Bradycardia or other heart rhythm disorder (on meds for this) personal or family history of long QT syndrome; liver or kidney disease; history of epilepsy or other seizure disorder; nerve disorder; low levels of potassium(hypokalemia); blood thinner (warfarin, Coumadin, Jantoven)

KNOW YOUR DRUGS ESTROGEN
Patients treated with estrogen cream had an increase in the prevalence of lactobacilli and decrease in E. coli vaginal colonization. Topical estrogen normalizes the vaginal flora and greatly reduces the risk of UTI in postmenopausal women. . In a randomized trial of 93 postmenopausal women with a history of recurrent UTI, topically applied intravaginal estriol cream (0.5 mg estriol nightly for two weeks then twice weekly for eight months) significantly reduced the incidence of UTI compared with placebo (0.5 versus 5.9 episodes/ patient/year) Some women are more prone to these infections following sexual activity. Also, the loss of estrogen after menopause makes the urinary tract more vulnerable to infection. -I recommend a small (lentil or kernel of corn sized) dab into vagina q day….

UTI, PROSTATITIS PROBIOTICS
May prevent vaginal uropathogen colonization by: Steric hindrance: block potential attachment sites. Producing hydrogen peroxide, microbicidal to E. coli and other uropathogens Maintenance of a low pH Inducing anti-inflammatory cytokine responses in epithelial cells

UTI, PROSTATITIS PROPHYLAXIS
Prophylaxis is highly effective in reducing recurrent UTI, decreasing recurrences by up to 95 % compared with placebo. Prophylaxis has been advocated for two or more symptomatic UTIs within six months or three or more over 12 months. Continuous prophylaxis, postcoital (after sex) prophylaxis, and intermittent self-treatment (which is not really a prophylaxis method) have all been demonstrated to be effective in the management of recurrent uncomplicated cystitis. The choice of approach depends upon the frequency and pattern of recurrences. Recommend low dose Keflex 250mg, Trimethoprim 100mg, Nitrofurantoin mg for 6-12 months if significant recurrence rate.

UTI, PROSTATITIS CONSTIPATION
Increase fiber intake: 14 grams of fiber for every 1,000 calories in your daily diet, about 35 gms/day. Exercise most days of the week Physical activity increases muscle activity of intestines. Park further away, take the stairs. Adding fiber to your diet increases the weight of your stool and speeds its passage through your intestines. Slowly begin to eat more fresh fruits and vegetables each day. Choose whole-grain breads and cereals. Start slowly to avoid bloating and gas. Laxatives: Several types of laxatives exist. Each works somewhat differently to make it easier to have a bowel movement. The following are available over the counter: Fiber supplements. Fiber supplements add bulk to your stool. These include psyllium (Metamucil, Konsyl), calcium polycarbophil (FiberCon) and methylcellulose fiber (Citrucel). Stimulants. Stimulants including Correctol, bisacodyl (Ducodyl), Dulcolax and senna-sennosides oral (Senokot) cause your intestines to contract. Osmotics. Osmotic laxatives help fluids move through the colon. Includes oral magnesium hydroxide (Phillips Milk of Magnesia), magnesium citrate, lactulose (Kristalose), polyethylene glycol (Miralax). In addition, polyethylene glycol (PEG) (Golytely, Nulytely) is available by prescription. Lubricants. Lubricants such as mineral oil enable stool to move through your colon more easily. Stool softeners. Stool softeners such as docusate sodium (Colace) and docusate calcium (Surfak) moisten the stool by drawing water from the intestines. Enemas and suppositories. Sodium phosphate (Fleet), soapsuds or tap water enemas can be useful to soften stool and produce a bowel movement. Glycerin or bisacodyl suppositories also can soften stool.

UTI, PROSTATITIS, CYSTITIS, LUTS SYMPTOMS
More frequent need to urinate; up at night Often intense urge to urinate, though little comes out; +/- incontinence Pain or pressure in your back, rectum or lower abdomen Cloudy, dark, bloody, or strange-smelling urine Pain, burning feeling when you urinate

CYSTITIS, OAB, LUTS Overactive bladder affects millions of adults, with profound personal and economic costs. Diet, behavioral changes, & anticholinergic drugs can improve voiding symptoms.

CYSTITIS, LUTS Lifestyle and Diet Adjustments: Kegel exercises, diet and fluid intake changes, scheduled voiding, weight loss, urinary pads or adult diapers oral medications: anticholinergics, beta-3 adrenergic agonist Procedures: Botox, PTNS, Interstim WHERE ARE YOU ON THE OAB TREATMENT PATHWAY? A medical professional confirmed OAB: symptoms of urgency, frequency and/or leakage. Lifestyle and Dietary Adjustments: Kegel exercises, dietary and fluid intake adjustments, scheduled voiding, weight loss… Disposables: pads or pantyliners, urinary pads or adult diapers, catheters Medications: Over-the-counter treatments: oral medications or transdermal patch; Prescription treatments: oral medications such as anticholinergics, beta-3 adrenergic agonist. Procedures: Botox: In-office procedure through a cystoscope. Treatment is repeated every 4-9 months. Possible retention. Percutaneous Tibial Nerve Stimulation: Electrode nerve stimulation. Initially every week for 12 weeks, then once a month x 4 weeks for maintenance. Sacral Neuromodulation Surgically implanted device, battery typically replaced every 5-9 years.

KNOW YOUR DRUGS ANTICHOLINERGICS
hyoscyamine (Levsinex) oxybutynin (Ditropan, Oxytrol, Gelnique) tolterodine (Detrol) fesoterodine (Toviaz) solifenacin (Vesicare) darifenacin (Enablex) Oxybutinin IR: 4-6 hrs, high side effect profile ER (extended release) or XL (Xtra long): 24 hrs lower SE profile Some anticholinergics are derived from plants of the deadly nightshade family called Solanaceae. Burning the roots, stems, and seeds of these plants releases the anticholinergics. Inhalation of the smoke has been used for hundreds of years to treat obstructive airway disease. Anticholinergics can treat a variety of conditions, including urinary incontinence, chronic obstructive pulmonary disorder, and certain types of poisoning. They also help block involuntary muscle movements associated with certain diseases. Sometimes, they’re used before surgery to help maintain body functions during anesthesia.

Anticholinergic drugs have anti-muscarinic properties: increase bladder capacity, decrease urgency. Systematic reviews prove these drugs are better than placebo in decreasing the # of incontinent episodes, # voids/24hr. Efficacy increases over 4 weeks. Anticholinergics are classified according to the receptors that are affected: Antimuscarinic agents operate on the muscarinic acetylcholine receptors. The majority of anticholinergic drugs are antimuscarinics. Receptors from the nerve endings to the muscles in the wall (Detrussor muscle) of the bladder. Blocking Ach slows down the action potential, decreasing the “trigger point” thus allowing longer filling and decreasing frequency. Antinicotinic agents operate on the nicotinic acetylcholine receptors. The majority of these are non-depolarising skeletal muscle relaxants for surgical use that are structurally related to curare.

Side effects may significantly limit use: dry mouth, constipation drowsiness, decreased cognitive function, blurred vision. About 80% of patients discontinue treatment after a year. Caution/contraindications: Antihistamines, phenothiazines, MAOI's and TCA's Provider Impications: Assess for: Urine retention, arrow angle glaucoma, recent MI, tachycardia, allergies, hiatal hernia and GI/GU obstruction(s). Sensitivity to light and dry mouth may occur. High risk of heat stroke in geriatric patients, so limit higher temperatures, physical exertion, and/or exercise, and stress fluid and salt intake Ask about the following conditions: Urinary hesitancy and/or constipation, palpitations, tremors, confusion, sedation or amnesia, excessive dry mouth and fever

KNOW YOUR DRUGS BETA 3 AGONIST
MIRABEGRON (MYRBETRIQ): β3 adrenergic receptors are identified in urothelium and detrusor muscle. Activation leads to muscle relaxation and an increase in bladder capacity. metabolized in liver, a substrate for/by cytochrome CYP2D6

KNOW YOUR DRUGS BETA 3 AGONIST
MIRABEGRON (MYRBETRIQ) ADVERSE EFFECTS >10%: Elevated BP, predominantly in patients with preexisting hypertension (7-11%) Mirabegron is metabolized in the liver. Importantly, mirabegron acts as a substrate for and is metabolized by cytochrome P450 3A4 (CYP3A4) and 2D6 (CYP2D6) Mirabegron increases pulse rate and blood pressure from baseline; however, these increases are minor and comparable to those seen with tolterodine. Mirabegron activates the β3 adrenergic receptor in the detrusor muscle in the bladder, which leads to muscle relaxation and an increase in bladder capacity. SIDE EFFECTS INCLUDE: common cold symptoms (nasopharyngitis) urinary tract infection constipation diarrhea dizziness headache Mirabegron increases pulse rate and blood pressure from baseline; however, these increases are minor and comparable to those seen with tolterodine. Most of the side effects are at rate seen with placebo.

LUTS: Lower Urinary Tract Symptoms BOO: Bladder Outlet Obstruction
PVR?

KNOW YOUR DRUGS ALPHA BLOCKERS
Terasozin(Hytrin) Doxazosin(Cardura) Tamsulosin(Flomax) Alfuzosin(Uroxatral) Silodosin(Rapaflo) α1 adrenergic receptor antagonists: relax bladder neck muscle fibers and the prostate Tamsulosin; : Higher risk of allergic reaction in those with sulfa allergies Adverse effects Ophthalmologic: Patients are prone to a complication known as floppy iris syndrome during cataract surgery, if the Doctor is aware of previous/current alpha blocker use, different stabilizing drops are utilized. Severe hypotension. Cardiac Contraindications: Hypotension, mechanical heart failure (valvular, pulmonary embolism, pericarditis), congestive heart failure. Tamsulosin has also affected sexual function in men. It can cause males to experience retrograde ejaculation.In males, retrograde ejaculation occurs when the fluid to be ejaculated, which would normally exit the body via the urethra, is redirected to the urinary bladder. Normally, the bladder sphincter contracts and the ejaculate goes to the urethra, the area of least pressure. In retrograde ejaculation, this sphincter does not function properly. This side effect can be mitigated by exercising the sphincter muscle; this is done by practicing a pumping action during ejaculation and urination - some semen fluid can then be ejaculated.

Contraindications: caution in severe renal, liver insufficiency; patients with known QT prolongation, or medications known to prolong the QT interval. Tamsulosin; : Higher risk of allergic reaction in those with sulfa allergies Adverse effects Ophthalmologic: Patients are prone to a complication known as floppy iris syndrome during cataract surgery, if the Doctor is aware of previous/current alpha blocker use, different stabilizing drops are utilized. Severe hypotension. Cardiac Contraindications: Hypotension, mechanical heart failure (valvular, pulmonary embolism, pericarditis), congestive heart failure. Tamsulosin has also affected sexual function in men. It can cause males to experience retrograde ejaculation.In males, retrograde ejaculation occurs when the fluid to be ejaculated, which would normally exit the body via the urethra, is redirected to the urinary bladder. Normally, the bladder sphincter contracts and the ejaculate goes to the urethra, the area of least pressure. In retrograde ejaculation, this sphincter does not function properly. This side effect can be mitigated by exercising the sphincter muscle; this is done by practicing a pumping action during ejaculation and urination - some semen fluid can then be ejaculated.

The most common side effects: dizziness (due to postural hypotension), upper respiratory tract infection, headache, fatigue, retrograde ejaculation and abdominal disturbances. Tamsulosin; : Higher risk of allergic reaction in those with sulfa allergies Adverse effects Ophthalmologic: Patients are prone to a complication known as floppy iris syndrome during cataract surgery, if the Doctor is aware of previous/current alpha blocker use, different stabilizing drops are utilized. Severe hypotension. Cardiac Contraindications: Hypotension, mechanical heart failure (valvular, pulmonary embolism, pericarditis), congestive heart failure. Tamsulosin has also affected sexual function in men. It can cause males to experience retrograde ejaculation. In males, retrograde ejaculation occurs when the fluid to be ejaculated, which would normally exit the body via the urethra, is redirected to the urinary bladder. Normally, the bladder sphincter contracts and the ejaculate goes to the urethra, the area of least pressure. In retrograde ejaculation, this sphincter does not function properly. This side effect can be mitigated by exercising the sphincter muscle; this is done by practicing a pumping action during ejaculation and urination - some semen fluid can then be ejaculated.

KNOW YOUR DRUGS 5 ALPHA REDUCTASE INHIBITORS
Finasteride (PROSCAR), Dutasteride (AVODART) Inhibits 5α-reductase: prevents testosterone conversion to dihydrotestosterone (DHT), decreasing serum DHT levels by 65–70% , and prostate DHT levels by 85–90%. This reduces prostate volume, improves LUTS and may reduce risk of prostate cancer. Reduces androgen activity in the scalp and is also used to treat male and female pattern baldness. MINOXIDIL Reduces epididymal weight, decreases motility and normal morphology of spermatozoa in the epididymis. Prevents the formation of neurosteroids, these may contribute to reduction of GABAA activity, implicated in depression, anxiety, and sexual dysfunction. The drug can be absorbed through the skin. If the film coating of the tablet has been broken or the tablet crushed, it should not be handled by a woman who is pregnant or planning to become pregnant. Exposing a developing male infant to Finasteride/Dutasteride can result in abnormalities of the genitals. They should not be used in women, especially during pregnancy or breast-feeding. It may harm an unborn or breast-feeding baby. Do not donate blood while taking this medication and for at least 6 months after stopping it to prevent the possibility of the blood being given to a pregnant woman.

KNOW YOUR DRUGS 5 ALPHA REDUCTASE INHIBITORS
Adverse effects: sexual dysfunction, including erectile dysfunction, loss of libido,(lower sexual desire), reduced ejaculate (3- 16% of men.) Effects may persist even after discontinuation in a subset of men. Other general side effects include headache and GI distress.

KNOW YOUR DRUGS TADALAFIL (CIALIS)
Originally developed to treat (ED), also relieves BPH symptoms. FDA approved in 2011 for both BPH and ED at 5 mg/day Increases levels of cGMP: Increases blood flow to penis, relaxes muscle cells in bladder and prostate. May be how it eases the symptoms of BPH. Rarely: sudden loss of vision or hearing after taking Cialis and other drugs in its class. cyclic guanosine monophosphate

KNOW YOUR DRUGS TADALAFIL (CIALIS)
Adverse effects: nausea, diarrhea, headache, stuffy nose, indigestion, back pain, muscle pain, flushing of the face; can potentiate the hypotensive effects of alpha-blockers. Nitrates: CIALIS is contraindicated if using any form of organic nitrate, regularly or intermittently: could cause a sudden, unsafe drop in blood pressure. Consuming significant amounts of alcohol also increases this risk. Guanylate Cyclase (GC) Stimulators: CIALIS is contraindicated in patients using a GC stimulator, such as riociguat. PDE5 inhibitors, including CIALIS, may potentiate the hypotensive effects of GC stimulators Potential Drug Interactions: can potentiate the hypotensive effects of alpha-blockers, antihypertensives or substantial amounts of alcohol (≥5 units). not recommended in combination with alpha-blockers for treatment of benign prostatic hyperplasia (BPH) symptoms because efficacy of the combination has not been adequately studied and due to the risk of blood pressure lowering. Caution is advised when CIALIS is used as a treatment for ED in men taking alpha-blockers. CIALIS for once daily use provides continuous plasma tadalafil levels. Potent inhibitors of CYP3A4: For patients taking potent inhibitors of CYP3A4, the lowest dose should be used: for use as needed: 10 mg no more than once every 72 hours. for once daily use:recommended dose is 2.5 mg

IMPORTANT SAFETY TIPS Properly discard medication when expired or no longer needed. Do not flush medications down the toilet or pour them into a drain. Consult your pharmacist for more details about how to safely discard medications. Before having surgery, tell your doctor or dentist about ALL the products you take (including prescription drugs, nonprescription drugs, and herbal products.)

Urologic Pharmacology UTI’S AND BEYOND!

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Urologic Pharmacology UTI’S AND BEYOND!

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Presentation on theme: "Urologic Pharmacology UTI’S AND BEYOND!"— Presentation transcript:

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