Manual of Medical Treatment in Urology Ismaila A Mungadi, Hyacinth N Mbibu, Ehab Eltahawy, Abdullahi Abdulwahab-Ahmed
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1BENIGN UROLOGICAL DISEASES
Medical Treatment of Pain
Ismaila A Mungadi, Stella A Eguma, Abdullahi Abdulwahab-Ahmed
Antimicrobial Therapy
Ismaila A Mungadi, Hamidu M Liman, Aliu Abdulhameed
Medical Management of Erectile Dysfunction
Samy Heshmat, Ehab Eltahawy
Medical Treatment of Urinary Incontinence
Ayman Mahdy, Ismaila A Mungadi
Benign Prostatic Hyperplasia
Ismaila A Mungadi, Olayiwola B Shittu, Abdullahi Abdulwahab-Ahmed
Medical Treatment of Urolithiasis
Ehab Eltahawy, Ismaila A Mungadi
Miscellaneous Use of Drugs
(Late) Hyacinth N Mbibu, Ismaila A Mungadi
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Medical Treatment of PainCHAPTER 1

Ismaila A Mungadi,
Stella A Eguma,
Abdullahi Abdulwahab-Ahmed
 
INTRODUCTION
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.1,2
Urologic pain may be local, originating from the organ itself or be referred from surrounding diseased organs. Due to common innervations, urologic pain is often referred to other sites, and so gastroenteric and gynecological pain may indeed signify urologic pathology.
Pain in the urinary tract may result from distension, inflammation, carcinoma, ischemia, or infection of the urinary tract. The severity of pain varies depending on the onset of the cause of pain. Noxious stimuli from the urinary tract are transmitted via A-delta and C fibers to the spinal cord through the dorsal roots. There, they synapse on neurons within the dorsal horn of the spinal cord segment that they entered and also on neurons one to two segments above and below their segment of entry. The secondary neurons ascend through the spinothalamic tract through the medulla and synapse on neurons in the thalamus. Some neurons also synapse in the medulla's reticular formation. Nerves from the thalamus then relay the signal to the somatosensory cortex where the stimulus is interpreted as pain (Fig. 1.1).
In addition, when tissue is damaged or there is a noxious pathological stimulus, second messenger systems are activated resulting in the release of inflammatory mediators (bradykinin, histamine, prostaglandins, serotonin) at the site of injury, and this results in pain produced by tissue damage or by pathological processes.
The management of most urologic pains should proceed according to the analgesic ladder proposed by the World Health Organization (WHO) (Fig. 1.2).3 This is applicable to cancer pain and management of prostatitis and chronic pelvic pain syndromes. The starting dosage should be individualized paying attention to patient age, preexisting diseases and other risk factors.
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Fig. 1.1: Pain pathway
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Fig. 1.2: WHO analgesic ladder
 
PAIN ASSESSMENT
For effective management, pain should be measured. This facilitates assessment of efficacy of medical treatment and allows comparison of treatment modalities employed. Various grading systems exist. There is no absolute measurement of the degree of pain. Pain is subjective. Numerical rating scales ask patients to judge their pain intensity on a scale from 0 (no pain at all) to 10 (unimaginable pain). Other assessment scales include visual analog scales (VAS), numeric pain intensity scale, verbal rating scale, and pain faces scale (used for children over 5 years), and the McGill Pain Questionnaire.
 
Visual Analogue Scale
A visual analogue scale is a measurement instrument that tries to measure the amount of pain that a patient feels across a continuum from none to an extreme amount of pain. It is usually a horizontal line, 100 mm in length and 5marked with “no pain” at one end and “very severe pain” at the other end. The patient marks on the line the point that they feel represents their perception of their pain. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks.
No pain__________________________________ Very severe pain
 
RENAL AND URETERIC COLIC
Renal and ureteric colic results from increased pressure and tension in the renal pelvis and ureter secondary to obstruction. Renal inflammation leads to increased accumulation of pain mediators that can also increase blood flow and enhance urine production thus exacerbating the pain. Both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are effective. NSAIDs also reduce renal blood flow and urine production thus reducing pressure and tension proximal to obstruction. Drugs with ureteric spasmolytic effect may be used as adjuvants in the treatment of ureteric colic. Drugs that may have adjuvant role in ureteric colic but are not in routine clinical practice include muscarinic agonists, desmopressin, nitrites, and calcium channel blockers. The use of alpha-adrenergic blockers (e.g. Tamsulosin) or calcium channel blockers (e.g. Nifedipine) may reduce pain and improve spontaneous passage of ureteric stones.4
 
CHRONIC PELVIC PAIN SYNDROME (CPPS)
This chronic nonbacterial prostatitis is one of the most difficult conditions to treat. It presents with genitourinary pain in the absence of identifiable uropathogenic bacteria. Pain is localized to the perineum, penis, or suprapubic area. This may be associated with testicular, perineal, anal, suprapubic, and rectal pain. There may be discomfort when sitting, post bowel movement pain, low back pain, or ejaculatory pain. Urinary frequency, urgency, hesitancy, burning, frequent night-time urination, and post-orgasm discomfort (often the next day) may occur. There may be related dyssynergic voiding and intraprostatic ductal reflux. A feeling of anxiety, depression, and helplessness often sets in.
There is no standardized evidence-based drug therapy for CPPS. At present a combination of antibiotics, anti-inflammatory drugs, adrenergic blockers, muscle relaxants, antidepressants, benzodiazepine, and finasteride can be tried. Also sitz baths and biofeedback techniques may offer some relief. When the pain is exacerbated by ingestion of certain substances like alcohol, caffeine, and some foodstuff, dietary restriction is recommended. Adrenergic blockers are more appropriate in patients with urodynamic evidence of outflow obstruction. Pentosan polysulphate may be tried in patients with interstitial cystitis–like symptoms.5
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INTERSTITIAL CYSTITIS
Interstitial cystitis is a chronic pelvic pain syndrome that affects men and women of all cultures, socioeconomic backgrounds, and ages. The pathology reveals a damaged urinary tract endothelium. The etiology is unknown; however, sensory nervous system abnormalities, autoimmunity, and increased urothelial permeability are the main theories of causation of interstitial cystitis. The pain of interstitial cystitis is worsened with bladder filling and improved with urination. Certain foods or drink may worsen the pain.
There may be pain with sexual intercourse, and discomfort and difficulty while driving, travelling, or working.
Treatment of interstitial cystitis pain is also empirical. Therapy is typically multimodal, including the use of a bladder coating, an antihistamine to help control mast cell activity, and a low dose antidepressant to fight neurogenic inflammation. Intravesical instillation of pentosan polysulfate sodium,5 dimethylsulphoxide, and BTX-A may help in nonoral medication responders. The use of a variety of traditional pain medications, including opiates and synthetic opioids such as tramadol, is often necessary to treat the varying degrees of pain.
 
UROLOGICAL CANCER PAIN
Cancer-related pain can be very incapacitating. The aim of drug therapy is to palliate the symptoms and improve the quality of life. The recommendation of the WHO expert committee on cancer pain relief has been validated. The committee recommends round-the-clock and oral therapy whenever possible. Treatment should progress according to the analgesic ladder (Fig. 1.2) and be tailored toward individual needs.
Adjuvant therapy varies depending on the cancer, the stage, and site of involvement and the type of metastasis. Bone metastasis in patients with prostatic cancer may require treatment with calcitonin, biphosphonate (pamidronate, ibandronate, zoledronic acid), or corticosteroids in addition of conventional analgesics.
Neuropathic pain may respond to tricyclic antidepressant and anticonvulsants (Carbamazepine, Phenytoin, Valproate, Clonazepam, Gabapentin) in addition to analgesics. Visceral pain may be alleviated with Octereotide or Oxybutinin.
 
POSTOPERATIVE ANALGESIA
A clear understanding of postoperative pain is essential for effective control. Postoperative pain is a type of acute pain and is a manifestation of autonomic, psychological, and behavioral responses to surgical trauma that result in an unpleasant, sensory, and emotional experience. Following surgery, the 7trauma triggers neurohumoral responses to facilitate healing as well as release of local response mediators that lead to pain. Treatment of pain is essential because inadequately managed pain may exacerbate patient discomfort and dissatisfaction, prolong hospital stay, prompt undue medical expense, and result in poor surgical outcome.
The goal for postoperative pain management is to reduce or eliminate pain and discomfort with a minimum of side effects at low cost.
Analgesia should be started promptly and given regularly. A stepwise approach is advocated depending on the severity of pain. If oral dosing has to be delayed, then initial intravenous, epidural, or intrathecal route may be resorted to. Rectal, buccal, or sublingual route, where appropriate, can be very valuable and these routes avoid first-pass metabolism. Local anesthetics provide effective relief and can be used topically; by infiltration, by wound irrigation or nerve blockade.
NSAIDs are particularly effective in postoperative pain because the associated inflammation sensitizes pain fibers. In our experience, a combination of paracetamol and a nonsteroidal anti-inflammatory drugs will control majority of postoperative pains, except in severe cases. This is also effective for most day-care surgery.
 
OUTLINE OF PHARMACOTHERAPY6,7
 
Nonopioids
 
Paracetamol (Acetaminophen)
Mechanism: Centrally acting antipyretic and analgesic. Precise mechanism unknown.
Indication: Mild to moderate pain.
Side effects: Hypersensitivity, hepatotoxicity, renal damage, contact dermatitis (injectable).
Precaution: Renal and hepatic impairment.
Interactions: Coumarins (enhances coumarins), cholestyramine (reduces absorption of paracetamol), metoclopramide, and domperidone (enhances absorption of paracetamol).
Dosage: 0.5–1 g four times a day, children 90 mg/kg/day in divided doses.
Preparations: Oral, injectable (proparacetamol)
 
Nonsteroidal Anti-inflammatory Drugs
Mechanism: Inhibit prostaglandin synthesis at therapeutic doses.
Indication: Mild to moderate inflammatory and postoperative pain. Renal and ureteric colic.
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Shared side effects: Gastrointestinal symptoms including ulceration, hemorrhage, perforation, renal impairment, fluid retention, hypersensitivity, headaches, premature closure of ductus arteriosus, and inhibition of labor.
Contraindications: Active peptic ulcer, hypersensitivity, renal impairment, pregnancy.
Precaution: Allergic disorders, coagulation defects.
Interactions: Angiotensin-converting enzyme inhibitor (ACE; antagonism), other NSAIDs (increased side effects), antacids (absorption reduced), anticoagulants (enhanced anticoagulant activity) antihypertensive (enhanced hypertensive effects), diuretic (increased risk of nephrotoxicity). Other drugs that may interact with NSAIDs are antidepressants, cardiac glycosides, methotrexate, nitrates, phenytoin, sulphonylureas, corticosteroids, lithium, rifampicin, ketoconazole, haloperidol, zidovudine, biphosphates, cyclosporins, estrogens, progestogens, and uricosuric drugs.
 
Ibuprofen
Dosage:1.2 g/day to 1.8 g/day in divided doses
Preparation: Oral.
 
Diclofenac
Usually as an intermediate release diclofenac potassium (Cataflam) or slow release diclofenac sodium (Voltaren)
Dosage: 75–150 mg daily in 2–3 divided doses.
Preparation: Oral, rectal, IM
 
Tenoxica
Dosage: 20 mg daily.
Preparation: Oral, IM, IV
 
Piroxicam
Dosage: 10–20 mg as single or divided doses.
Preparation: Oral, IM
 
Selective Cyclooxygenase-2 (Cox2) Inhibitors
These drugs have less gastrointestinal side-effects profile. Cox1 inhibits prostaglandin synthesis in the gut and platelets while Cox2 inhibit prostanoid mediators of pain, inflammation, fever, and ovulation. Other profiles are similar to NSAIDs.
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Celecoxib
Dosage: 200–400 mg as single or two divided doses
Preparation: Oral
 
Etodolac
Dosage: 600 mg as single or two divided doses
Preparation: Oral
 
Panecoxib
Dosage: 20–40 mg, 6–12 hourly (start 40 mg)
Preparation: IM/IV
 
Opioids
 
Morphine
Mechanism: Opioid receptor agonist
Indication: Moderate to severe pain, postoperative analgesia, standard against which all other opioids are measured.
Side effects: Nausea, vomiting, constipation, palpitation, hypotension, respiratory depression, drowsiness, difficult micturation, allergy, dependence, miosis.
Contraindication: Paralytic ileus, raised intracranial pressure or head injury, respiratory depression, acute alcoholism, pheochromocytoma, ureteric, and biliary colic.
Interaction: Alcohol, amitriptyline, chlorpromazine clomipramine, benzodiazepines, fluphenazine, haloperidol, metochlopramide ritonavir, cimetidine, ciprofloxacin, MAOIs.
Dosage: Acute pain, by IM or SC injection 10 mg 4 hourly if necessary.
Chronic pain, oral or SC 5–20 mg every 4 hours
(oral dose: IV dose conversion 2:1 to 3:1)
Other routes: IV, rectal.
 
Dihydrocodeine (DITC)
Mechanism: Weak opioid receptor agonist
Dosage: 30–60 mg every 4–6 hours.
 
Tramadol
Mechanism: Weak opioid agonist, serotonin, and noradrenaline re-uptake inhibitor.
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Comparative side effects: Causes less sedation, constipation, nausea respiratory depression, and less potential for abuse as with other opioids.
Dosage: 50 –100 mg, 6 hourly.
Preparation: IM, IV, oral
 
Pentazocine
Mechanism: Mixed opioid agonist/antagonist
Indication: Moderate to severe pain
Distinctive side effects: Atrial and pulmonary hypertension, increased myocardial workload. Other side effects include nausea, vomiting, constipation, palpitation, hypotension, respiratory depression, drowsiness, difficult micturition, allergy, dependence, miosis.
Dosage: 30–60 mg, 6 hourly
Preparation: oral, IV, IM, rectal
 
Pethidine
Mechanism: Powerful opioid agonist, but less potent then morphine
Side effects: Metabolized to nor-pethidine that accumulates in renal dysfunction causing coma and convulsions. Other side effects are similar to those of morphine.
Dosage: 50–100 mg IM, IV or SC 2–3 hourly
Preparation: IV, IM, SC, oral.
 
Local Anesthetics
Mechanism: Block sodium channels reversibly
Indications: Topical infiltration, wound irrigation, nerve block, epidural and intrathecal blocks.
Side effects: Inebriation feeling, sedation, circum oral paresthesia, twitching, hypersensitivity, convulsions and cardiovascular collapse.
Contraindication/Precaution: IV injection, injection into inflamed tissues, traumatized urethra, in combination with adrenaline in appendages, heart block, hypovolemia.
Lignocaine (Lidocaine, xylocaine)
Onset: 5–10 minutes
Duration: 30–150 minutes
Dosage: Maximum 4 mg/kg plain, 7 mg/kg with adrenaline.
Preparation: Injection, plain and with adrenaline, gel, ointment, heavy (5% in glucose).
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Prilocaine
Safe for IV regional block
Dosage: Maximum 400 mg
Distinctive side effects: Methemoglobinemia and cyanosis (treatment: 1% methylene blue at 1 mg/kg IV)
Preparation: Injection
 
Bupivacaine
Onset: 15–20 minutes
Duration: 4 hours
Dosage: 2 mg/kg/4 hours maximum
Distinctive side effects: Myocardial depression, ventricular fibrillation.
Distinctive contraindication: Biers block
Preparations: Injection with and without adrenaline for nerve blocks, infusion (for Continuous epidural infusion), heavy (0.5% in glucose).
 
Adjuvants
Adjuvants or “coanalgesics” are employed in the management of neuropathic, visceral, and bone pain. Examples of drugs used as adjuvants in the treatment of pain are as follows.
 
Tricyclic antidepressants
 
Amitriptyline
Dosage: 10–25 mg 8 hourly
 
Gabapentin
Dosage: 100–300 mg daily
 
Corticosteroids
 
Biphosphonate
Octereotide
Finasteride, dutasteride
Spasmolytic drugs e.g.1 adrenergic antagonist, antimuscarinic agents (e.g. Oxybutinin hydrochloride).
Nitrite
Pentosan Polysulfate
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REFERENCES
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  1. Cancer pain relief: with a guide to opioid availability, 2nd edn. WHO;  Geneva.  1996.
  1. Singh A, Alter HJ, Littlepage A. A systematic review of medical literature to facilitate passage of ureteric stones. Ann Emerg Med. 2007;50:552–63.
  1. Hwang P, Auclair B, Beechinor D, Dement M, Einarson TR. Efficacy of pentason polysulfate in the treatment of interstitial cystitis: a meta-analysis. Urology. 1997;50:39–43.
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  1. Burke A, Smyth EM, Fitzgerald GA. Analgesic-antipyretic agents; pharmacology of gout. In: Brunton LL, Lazo JS, Parker KL (Eds). Goodman and Gilman: The pharmacological basis of therapeutics, 11th edn., McGraw-Hill;  New York,  NY: 2006:671–716.