Last Updated on Tuesday, 21 January 2014 12:13
(Highly Prevalent but Underdaignosed Problem)
Overactive Bladder(OAB) is a symptom syndrome of Urgency(With or Without Urge incontinence), Frequency and Nocturia. This term on be if there is no proven injection or other obvious pathology.
in US & Europian countries prevalence of OAB is above 16.5% in population and increases markedly with age in both men and women. In asian population the incidence of OAB is much higher 53% and treatment rate is very low-only 21% get treated. When compared with western world.
OAB is as common as Arthritis and Sinusitis and Much more prevalent than Heart Disease, High Cholesterol, Asthama, Chronic Bronchitis, Diabetes.
Impact of OAB on Quality of Life:
There is limitation and in some patients cessation of Physical activity. These patients have increased Abscentism from work and have low productivity affecting Occupational Aspect of life. They tend to avoid Sexual Contact and Intimacy affecting their Sexual life. On psychological front there is guilt, depression, loss of self esteem and fear of being burden to the family. They restrict social interactions, mixing and limit and pkn their travel, activity around toilet accecibility. On domestic front they need special garments, bedcovers, sleeping arrangements near toilet etc.
Co-Morbidity with OAD:
Hospitalization in women increases by 30% and men by 50%. There is significantly increased frequency of UTI(Urinary Tract Infection) and Skin lesions in introital region and private parts. There is increased risk of fall by 35% and fractures by 45%. In menopausal women there is 50% increase in fracture neck femur. Overall 60% of patients suffer from depression.
Pathophysiology of OAB:
This is illunderstood or partly understood. There is increased afferent activity of impulses going to Brain from Detrussor Muscle of Bladder. Normally there is tonic inhibition in Suprapontine region. There excess impulses which in OAB is impaired and decreases. Hence there is increased contraction mediating transmitter i.e. Acetylcholine, which works on Cholinergic receptors in Bladder.
Also in OAB there is increased sensitivity of Cholinergic receptors in Detussor to tevis contraction mediating transmitter Acetylcholine.
Due to this there are Uninhibited detrussor contractions & Urgency, Frequency and Nocturia.
77% of OAB patients never receive any kind of therapy. Many patients consider it part of Normal Aging. Many feel too embarrassed to discuss with doctor and have impression that treatment is unlikely to help. Approach to OAB management is twofolds
- Nonpharmacological or Behavioral Therapy
this essentially involves asking patient to keep voiding diary, Monitor fluid and dietary intake, have timed voiding. Patient is asked to avoid items which are likely to irritate bladder like Coffee, Tea, Colas, Citrus Fruits and Juices, Sodas, Alcohol and Spices. He is advised to have more of bladder friendly Fluids and Solids like Water, Apple juice, Cranberry juice, Grape juice, Pear, Banana etc He is asked to add more time between the toilet visit and train bladder. Pelvic Floor Exercises(Kegal’s Exercises) are highly effective which strengthen the muscles controlling micturation.
Drug therapy is currently the mainstay in managing OAB. Various pharmacological agents being used are
- Estrogens(Post menopausal females)
Amongst these Antimuscarinic agents are Gold standard and highly effective.
Antimuscarinic agents, currently available are
The selectivity of the drug for M2 and M3 muscarinic receptors in bladder vary and needless to say it has effect on Muscarinic receptors present all over the body in various organs. Thses receptors are present in various places in body like 1. Ciliary body(Iris), 2. Lachrymal gland, 3. Salivary gland, 4. Heart, 5. Stomach, 6. Colon, 7. Bladder, 8. CNS(Central Nervous System). Hence these agents affect function of these organs and this causes
- Dry mouth
- Cognitive impairment
- Blurring of Vision
However Judicious use of these agents with close monitoring of patients they give extremely rewarding results.
- · OAB is highly prevalent condition but is Underdiagnosed
- · As our population grows, ages, incidence will rise
- · It affects both males and females
- · OAB has large impact on patient’s Quality of life
- · Patients perceive great benefit with Therapy and improvement in Quality of life is significant
Last Updated on Sunday, 27 February 2011 18:40
The two kidneys lie at the back of the body cavity, one on either side of the spinal column, with their upper portions behind the lower ribs. Each Kidney is 10 - 12.5cm (4 - 5 inches) long & contains about 1 million nephrons. Each nephron is a filtering unit made up of a filter, called glomerulus, attached to a long collecting tube. There is a constant flow of blood through the kidneys which is filtered by these nephrons.
Last Updated on Sunday, 27 February 2011 18:42
- Diabetes is the commonest cause of CRF in both, the developed and the developing countries comprising 25% of all cases.
- Another 25% develop ESRD due to chronic glomerulonephritis.
- 10 percentage of patients develop ESRD due to hypertension, another lifestyle disease which is correctable.
- Some other correctable causes are allopathic drugs especially pain killers, which are consumed for trivial reasons as they are easily available OTC drugs.
- In addition Ayurvedic products, especially those containing heavy metals in the form of BHASMAS, are an important cause of CKD.
- Indian subcontinent is in the stone belt and stones not treated in time can lead to kidney failure if stone disease is involving both sides.
Last Updated on Sunday, 27 February 2011 18:26
HOW TO PRESCRIBE DRUGS IN A CKD PATIENT
How does CKD affect drug handling?
Accumulation of drugs normally excreted. Eg- antibiotics
Accumulation of active drug metabolites. Eg- acyclovir, chloramphenicol
Changes in drug distribution – protein binding and volume of distribution. Eg- diazepam
Decreased metabolism of drugs in failing kidneys. Eg- insulin
Drug interactions. Eg- NSAIDs & aminoglycosides.
Important questions to ask before writing a prescription in a case of CKD:
Will this drug be effective in renal failure?
Will it hurt the already failing kidneys and worsen renal failure – type A?
Will it or its toxic products accumulate in the body because of renal dysfunction-type B?
4. If drug is type A or B, why not find another safer substitute drug?
5. Will renal failure modify the pharmacokinetics of this drug Eg- iron tablets
6. Is the liver function normal eg- in ceftriaxone?
7. If I must use an unsafe (type A or B) drug, how should I modify the drug prescription?
Drugs ineffective in renal failure:
Thiazide diuretics when GFR<30 ml/min
These drugs only work after being filtered in the glomerulus.
How do you detect worsening of renal function?
Increase in urea/creatinine
Sodium & water retention
Hypoglycemia in diabetic
Increase in urea alone – steroids, tetracycline
Increase in urea and creatinine - NSAIDs, ACE inhibitor, ARBs, aminoglycoside, diuretics in excess, radiocontrast agents.
Sodium & water retention - steroids, NSAIDs
Hyperkalemia – NSAIDs, ACE-I, ARB, kesol, spironolactone, tetracycline, K sparing diuretics.
Metabolic acidosis – Metformin in diabetics (creat>1.4 ), acetazolamide, NSAIDs
Hyperuricemia – diuretics
Bleeding – aspirin, clopidogrel, warfarin, heparin.
Hypoglycemia in diabetics – Long acting insulins,
All oral hypoglycemics except acarbose, glipizide and gliclazide, pioglitazone, repaglinide.
Drugs that accumulate in renal failure:
Antibiotics – aminoglycoside, vancomycin, tetracyclines, most cephalosporins, carbapenems
Antivirals – acyclovir, gancyclovir, indinavir, zidovudine
Anti TB – INH, ehthambutol, PZA
Antifungals – amphotericin, fluconazole.
Cardiac – digoxin, antiarrythmics
Hypoglycemic agents – insulin, sulfonylureas
Opioids – morphine, codeine, meperidine
Sedatives – barbiturates, benzodiazepenes
Others – allopurinol, fibrates, aluminium
How to adjust doses:
COCKROFT GAULT FORMULA
GFR = (140 – age) X Ideal body wt
72 x S. creat
Multiply by 0.85 for females
Schwartz formula in children
Reduce the dose according to GFR.
Formula for radiocontrast
DOSE = 1 X Usual dose
Eg. If S.Creatinine is 3.0, Maximum Dose of radiocontrast allowed is one-third of usual dose.
What to do when contraindicated drugs have to be used:
Take informed consent
Documentation of renal function
Prepriscription investigation – renal artery doppler before prescribing RAAS blockers
Reduce doses as per GFR
Avoid dehydration – this applies to most nephrotoxic drugs esp. Radiocontrast agents, nsaids, acyclovir, lithium, methotrexate, cisplatin
Use once daily dosing – aminoglycosides
Avoid concomitant use of diuretics when prescribing NSAIDs, aminoglycosides
Pre and post prescription antidote – acetylcysteine for radiocontrast agents
Take special care in certain situations :
-while other nephrotoxic agents are being used.
Last Updated on Sunday, 27 February 2011 18:45
DRUGS AND THE KIDNEY: WHAT’S NEW TODAY?
Drugs & kidney interaction:
Excretion of drugs:
Kidney is a route of removal in healthy state.
In disease of kidneys drugs accumulate in the kidneys.
Doses of drugs must be adjusted in renal failure.
Drugs produce renal injury:
Avoid in certain situation.
Apply strategies to protect when unavoidable.
37% of all acute renal failure (ARF) seen in major tertiary referral hospital is Drug induced or Drug aggravated
Drugs reported to cause alteration of renal function:
-Antineoplastic and/or immunocompressive agents like Cis-platinum, Methotrexate, Interferon, Cyclosporin
Radio-opaque contrast agents like Diatrizoate meglumine, Diatrizoate sodium, Iodipamide.
Analgesics like Salicyclates, Aminopyrine, Phenylbutazone, Indomethacin, Ibuprofen, Naproxen, Fenoprufen, Tolimetin, Phenacetin.
Diuretics like Mannitol, Thiazides, Frusemide.
Anaesthetic agents like Chloroform, ethyl chloride, Halothane, Fluroxene, Cyclopropane.
Anti-hypertensive like Hydralazine, Propanolol, Nifedepine, Captopril.
Role of FDA / Others
High Risk Doctors:
Radiologists / Angiographers
Ayurvedic / Homeopathic
Knowledge of Pharmacokinetics
Recognition of high risk situations / increased vigilance
Product insert / PDR
Continuing medical education programs
Prescription review in hospitals
Fear of legal actions
Renal Susceptibility to Drug Toxicity:
High renal blood flow
Renal tubule cells – high metabolism
Renal enzymes blocked by -8H groups
High concentration of drugs in medulla (counter current renal multiplier)
High concentration of urine in tubules
Urinary PH changes render drugs insoluble
Largest surface area of vascular endothelium
Tubular transport ionic mechanisms
Large tubular epithelial surface.
Clinical Syndromes of Drug Induced Renal disease:
- Pre – renal azotemia - Sterile pyuria
- Acute renal failure - Fanconi syndrome
- Hypertension - Renal tubular acidosis
- Acute nephritis - Renal salt wasting
- Nephrotic syndrome - Isolated proteinuria
- Chronic renal failure - Hyperkalemia
Hypercalcemia induced ARF
Drugs Producing Acute Renal Failure:
Nephrotoxic nephropathy - Aminoglycosides
Dose dependent toxicity - Cephalosporins,tetracyclines,amphotericin, Colistin,radiocontrast agents
Allergic nephritis - Methicillin,rifampicin,penicillin,cephalosporin, sulfa ; NSAID`s ; allopurinol,diuretics
Drugs causing hemolysis - esp. in G6PD deficiency
Drugs causing hypercalcemia – Vit.D intoxication
Poisons - Lead, mercury, cadmium,bismuth, gold
Agents masquarading as drugs - Glycols, carbontetrachloride, tetrachloroethylene
Radio Contrast Renal Failure:
Pre existing renal insufficiency
History of ARF due to dye in past
Large contrast load
Congestive Heart failure
Pre existing CKD
Low EF/ dehydration
Concomitant undiagnosed RAS
Other nephrotoxic drugs
Higher doses of contrast
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