An analgesic is any medicine intended to relieve pain. Over-the-counter analgesics—that is,...
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PAIN KILLERS AND YOUR KIDNEY..
An analgesic is any medicine intended to relieve pain. Over-the-counter analgesics—that is, painkillers available without a prescription—include aspirin,
An analgesic is any medicine intended to relieve pain.
Over-the-counter analgesicsthat is, painkillers available without a
prescriptioninclude aspirin, acetaminophen, ibuprofen, naproxen
sodium, and others. These drugs present no danger for most people
when taken in the recommended dosage. But some conditions make
taking even these common painkillers dangerous for the
kidneys.
Slide 3
Also, taking one of these drugs regularly over a long period of
time may increase the risk for kidney problems. Most drugs that can
cause kidney damage are excreted only through the kidneys. That is,
they are not broken down by the liver, as alcohol is, or passed out
of the body through the digestive tract.
Slide 4
CLASSIFICATION I) TYPE-I (BASED ON DEGREE OF ANALGESIA) MILD
MODERATE STRONG acetylsalicylic acid codeine ** morphine **
(aspirin or ASA) pentazocine ** (Talwin) hydromorphone **
(Dilaudid) acetaminophen oxycodone ** methadone** (Tylenol, Datril,
etc) NSAIDs meperidine ** propoxyphene ** hydrocodone ** (Darvon) *
= prescription ** = prescription and a controlled substance
(potential for abuse exists)
Mode of action Most NSAIDs act as non-selective inhibitors of
the enzyme cyclooxygenase, inhibiting both the cyclooxygenase-1
(COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. Cyclooxygenase
catalyzes the formation of prostaglandins and thromboxane from
arachidonic acid (itself derived from the cellular phospholipid
bilayer by phospholipase A2). Prostaglandins act as messenger
molecules in the process of inflammation.
Slide 9
Biosynthesis of PGs phospholipid (in cell wall lipid)
-------(phospholipase A2) arachidonic acid PGsynthase cox1 &2
Prostaglandins leukotrine Prostacyclin thromboxane
Slide 10
Pharmacokinetics Most NSAIDs are weak acids, They are absorbed
well from the stomach and intestinal mucosa. They are highly
protein-bound inplasma (typically >95%), usually to albumin.
Most NSAIDs are metabolized in the liver to inactive metabolites
which are typically excreted in the urine. Ibuprofen and diclofenac
have short half-lives (2-3 hours). Some NSAIDs (typically oxicams
have very long half-lives (e.g. 20-60 hours)
Slide 11
Adverse effects of NSAIDS The two main adverse drug reactions
associated with NSAIDs relate to gastrointestinal (GI) effects and
renal effects of the agents. These effects are dose-dependent, and
in many cases severe enough to pose the risk of ulcer perforation,
upper gastrointestinal bleeding, and death, limiting the use of
NSAID therapy.
Slide 12
COMMONLY USED ANALGESICS ASPIRIN IBUPROFEN MEPHENAMIC ACID
DICLOFENAC ACETAMINOPHEN CELECOXIB NIMESULIDE MORPHINE SULPHATE
OTHER OPIOIDS
Slide 13
ASPIRIN For mild to moderate pain, not for visceral pain THE
THREE MAJOR EFFECTS OF THE SALICYLATES a. analgesic b. antipyretic
"pyrexis" Greek for "heat", therefore, antipyretic = c.
anti-inflammatory
Slide 14
IBUPROFEN ADVERSE EFFECT: 1)Gastric discomfort, Nausea,Vomiting
2)CNS side effects 3)Rashes, Itching, Hypersensitivity USES: 1)Most
common drug in dental treatment 2)Musculoskeletal pain
DICLOFENAC ADVERSE EFFECTS: 1)Mild-epigastric pain, nausea,
headache 2)Gastric ulceration USES: 1)Toothache 2)Rheumatoid and
osteoarthritis 3)Post-traumatic and post-operative inflammatory
condition
Slide 17
ACETAMINOPHEN(PARACETAMOL) OTHER NAMES FOR ACETAMINOPHEN
INCLUDE: TYLENOL, DATRIL, PANADOL, MAPAP, APAP Actions of
acetaminophen a. analgesic and anti-pyretic ONLY NO
ANTI-INFLAMMATORY ACTION b. no effect on platelets c. no effect on
ulceration or GI bleeding at therapeutic doses COMPLETELY SAFE,
RIGHT? WRONG! a. overdosage causes IRREVERSIBLE kidney and liver
damage b. death from overdosage not immediate c. some damage
possible even at chronic therapeutic doses d. OVERDOSES TREATED
WITH ACETYLCYSTEINE (Mucomyst)
Slide 18
MORPHINE SULPHATE 1) Opioid receptors-this receptor is the site
of action for morphine, its congeners, and the narcotic antagonists
2) Elevates pain threshold and alters pain perception 3) Other
General Effects: a. respiratory depression, even in small doses b.
drowsiness, mental clouding, inability to concentrate c.
constipation --opioids used to treat diarrhea --camphorated
tincture of opium PAREGORIC --diphenoxylate (mixed with atropine,
it is called LOMOTIL) d. physical dependence e. constriction of
pupils f. effect on urinary tract a. increase in urethral tone
--constriction, causing urinary retention --consider KIDNEY STONE
patients! b. increase in bladder tone --increased urge to urinate
(but! the urethra is constricted, making urination difficult...what
a dilemma) g. tolerance possible 4) Uses: a. analgesic/pre-op b.
has antitussive properties, but not used for this
Slide 19
OTHER OPIOIDS 1. Semisynthetics --minor alterations in the
structure of the morphine molecule, usually altering comparative
potency a. hydromorphone (Dilaudid) --5x potency of morphine (1-3mg
SQ) b. oxymorphone--10x potency (1mg SQ) 2. Synthetics a.
meperidine (Demerol) i. 1/10 potency of morphine, 50-100mg IM, PO
ii. fewer side effects, less constipation b. methadone i. 5-10mg
po, IM ii. less euphoria iii. some withdrawal symptoms iv. use for
heroin addiction c. fentanyl citrate (Sublimaze) --short acting;
surgical use only in injection form TECHNOLOGY TAKES OVER, HOWEVER!
NOW AVAILABLE IN THE NEW IMPROVED TOPICAL PATCH FORM! DURAGESIC! it
delivers analgesic in micrograms per hour, hence the dosages of
25mcg, 50mcg, 75mcg, 100mcg one patch is good for 3 days (72 hours)
d. alfentanyl (Alfenta) --also short acting, and also reserved for
surgical use
Slide 20
TRAMADOL Tramadol 50, 100 and 150 mg provided significantly
more analgesia than placebo as determined by single-patient data
meta-analysis, and also has been shown by single- patient data
meta-analysis to have analgesic efficacy equal to that of aspirin
650 mg plus codeine 60 mg Unlike aspirin, acetaminophen and
codeine, which have an analgesic duration of approximately four
hours, tramadol provides analgesia for five to six hours after
dental surgery. Also, tramadol successfully managed pain for
patients with chronic periodontitis, chronic pulpitis and
alveolitis.
Slide 21
DRUG NAMETRADE NAMECOMBINATIONDOSAGE ASPIRIN1)ASPIRIN
2)COLSPIRIN 3)DISPRIN 4)LOPRIN 5)ECOSPIRIN BIOSPIRIN: Lysine
acetylsalicylate+gly sine 75-300;mg 1tab x 3times a day
IBUPROFEN1)BRUFEN 2)EMFLAM 3)IBUGESIC 4)IBUSYNTH COMBIFLAM:
IBUPROFEN + PARACETAMOL 400-600mg 1tab x 3times a day DICLOFENAC
SODIUM 1)VOVERON 2)DICLONAC 3)MOVINAC 4)DICLOMAX VOLTAFLAM:
DICLOFENAC+ POTASSIUM 50-75mg 1tab x 3times a day 75mg inj./im.
NIMESULIDE1)NIMULIDE 2)NIMEGESIC 3)NIMODOL 50-100mg 1tab x 3times a
day
Slide 22
DRUG NAMETRADE NAMECOMBINATIONDOSAGE PARACETAMOL1)CROCIN
2)METACIN 3)PARACIN 4)CALPOL DICLOGEM: PARACETAMOL+ DICLOFENAC
250-1000mg 1tab x 3times a day pentazocinZOCIN30-60mg Inj/im
TRAMADOLACTAMON50mg oral FENTANYLDUROGESIC25mg/1hr transdermal
Slide 23
Slide 24
Analgesic use has been associated with two different forms of
kidney damage: acute renal failure a type of chronic kidney disease
called analgesic nephropathy.
Slide 25
Acute Kidney Failure Here is acute kidney failure which can
happen suddenly by the use of over-the-counter pain killers. This
includes aspirin, Advil and Aleve. These patients in pain were
often dehydrated or hadn't taken a sufficient amount of fluids
throughout the days they were taking the pain-relieving
medicines.medicines This also happened in heavy alcohol users,
lupus patients, older folks and those who already have kidney
disease whether they knew it or not.
Slide 26
"Extremely large doses of aspirin and paracetamol can cause
acute renal failure, usually when taken as a suicide attempt. Acute
kidney failure usually occurs when the blood supply to the kidneys
is suddenly interrupted or when the kidneys become overloaded with
toxins
Slide 27
MICROSCOPIC VIEW
Slide 28
DIAGNOSIS : Diagnosis of kidney failure is confirmed by : blood
tests measuring the buildup of waste products in the blood - BUN,
creatinine, and GFR.creatinine This is the rate with which blood is
filtered through the kidneys and can be calculated based upon the
creatinine level, age, race, and gender. Abnormal fliud levels in
the body. Abnormal levels on phosphate,calcium,potassium in urine
and blood.
Slide 29
Analgesic nephropathy This can occur after taking any kind of
painkiller regularly for many years. This kind of chronic kidney
disease can cause kidney failure.disease The kidney patient will
then have to go on dialysis and wait for a kidney transplant.
Slide 30
Prolonged or frequent use of two common over-the- counter pain
medicines increases a person's chances of developing irreversible
kidney failure. Adults who take the equivalent of more than two
tablets of ibuprofen a day for seven years have roughly nine times
the risk of kidney failure seen in people who take about two
tablets a week.
Slide 31
Similar consumption of acetaminophen, the most popular
painkiller in the United States, increases the risk of kidney
failure about twofold.
Slide 32
MICROSCOPIC VIEW
Slide 33
TREATMENT If you have been taking analgesics regularly to
control chronic pain, you may be advised to find new ways to treat
your pain: behavior modification or relaxation techniques. change
your diet,depending on how much your kidney function has declined
limit the fluids you drink, take medications to avoid anemia and
bone problems caused by kidney disease. Your doctor will monitor
your kidney function with regular urine and blood tests.
Slide 34
If serious pain requires the use of a pain killer, make sure
not to over medicate yourself consult your physician if you begin
experiencing any symptoms associated with kidney failure such as
extreme fatigue, itching, headaches, weight loss, appetite loss or
nausea.
Slide 35
RENAL PAPILLARY NECROSIS One of the most common and most
preventable etiologic factors is the use of analgesics. Etiology
Generally, any condition associated with ischemia predisposes an
individual to papillary necrosis. Important general considerations
include shock, massive fluid sequestration (eg, as in
pancreatitis), dehydration, hypovolemia, and hypoxia.
Slide 36
A useful mnemonic device for the conditions associated with
renal papillary necrosis is POSTCARDS, which stands for the
following: Pyelonephritis Obstruction of the urinary tract Sickle
cell hemoglobinopathies, including sickle cell trait Tuberculosis
Cirrhosis of the liver, chronic alcoholism Analgesic abuse Renal
transplant rejection, radiation Diabetes mellitus Systemic
vasculitis
Slide 37
In this figure, the multifactorial nature of renal papillary
necrosis is represented by 5 of the disease's most frequently
associated conditions: infection, obstruction, diabetes mellitus,
analgesic abuse, and sickle cell disease. Each circle represents a
condition. Note how the conditions overlap; the red areas show the
coexistence of 2 conditions, and the black areas represent 3
coexistent conditions. Multiple conditions exhibit synergism and,
therefore, worsen both the severity of the disease and the
prognosis.
Slide 38
Renal papillary necrosis (RPN) is characterized by coagulative
necrosis of the renal medullary pyramids and papillae brought on by
several associated conditions and toxins that exhibit synergism
toward the development of ischemia. The clinical course of renal
papillary necrosis varies depending on the degree of vascular
impairment, the presence of associated causal factors, the overall
health of the patient, the presence of bilateral involvement, and,
specifically, the number of affected papillae.
Slide 39
Renal papillary necrosis can lead to secondary infection of
desquamated necrotic foci, deposition of calculi, and/or separation
and eventual sloughing of papillae, with impending acute urinary
tract obstruction.urinary tract obstruction Multiple sloughed
papillae can obstruct their respective calyces or can congregate
and embolize to more distal sites (eg, ureteropelvic junction,
ureter, ureterovesical junction). Previously undiagnosed congenital
anomalies (eg, partial ureteropelvic junction obstruction) can
provide a narrowed area where the sloughed papilla can nest and
obstruct.ureteropelvic junction obstruction
Slide 40
Renal papillary necrosis is potentially disastrous and, in the
presence of bilateral involvement or an obstructed solitary kidney,
may lead to renal failure. The infectious sequelae of renal
papillary necrosis are more serious if the patient has multiple
medical problems, particularly diabetes mellitus.
Slide 41
Renal papillary necrosis is considered a sequela of ischemia
occurring in the renal papillae and the medulla. Various insults
generate this ischemia, one of which may be infection. The boggy
inflammatory interstitium of the pyelonephritic kidney compresses
the medullary vasculature and, thus, predisposes the patient to
ischemia and renal papillary necrosis. This vasculature can become
compressed, attenuated, or impaired from several other associated
diseases, most notably diabetes mellitus, urinary tract
obstruction, and analgesic nephropathy. Therefore, renal papillary
necrosis is a distinct clinical and pathophysiological entity
primarily caused by ischemia that can develop without
pyelonephritis or urinary tract infection and is likely a focus for
infectious complications. Renal papillary necrosis has a
well-documented association with several diseases that predispose a
patient to ischemia.
Slide 42
One of the most common and most preventable etiologic factors
is the use of analgesics. A classic factor is phenacetin, with its
highly toxic metabolite, p-phenetidin. Recently, however, the
rising popularity of nonsteroidal anti-inflammatory drugs (NSAIDs),
particularly those that inhibit cyclooxygenases (ie, COX-1, COX-2)
has led to a relatively high frequency of adverse events in
patients at risk for renal papillary necrosis.
Slide 43
In healthy individuals in whom renal arterial blood flow is not
compromised, NSAIDs have little effect unless they are used in
excess. This is mostly true because the kidney is not relying on
the vasodilatory effects of prostaglandin to supply adequate
perfusion. However, in patients who are predisposed to renal
hypoperfusion, local prostaglandin synthesis protects the glomeruli
and tubules from ischemia. The inhibition of prostaglandin
synthesis by NSAIDs that inhibit COX- 1 and, as recently reported,
COX-2, removes this protective mechanism and predisposes the kidney
to further renal hypoperfusion and, ultimately, ischemia. An
extremely important precaution is to strictly monitor patients with
prior renal disease or any of the above-mentioned etiologic
conditions when prescribing NSAIDs.
Slide 44
Additionally, note that a short course of NSAIDs has caused
papillary necrosis and nonoliguric renal failure in otherwise
healthy individuals as young as age 17 years. A case such as this
may be an anomaly, but caution is warranted when prescribing
NSAIDs, and adequate hydration is recommended. These precautions
should also be extended to patients receiving specific COX-2
inhibitors. Touted as being safer than COX-1 inhibitors because
they spare the gastrointestinal tract, COX-2 inhibitors have been
shown to significantly decrease renal medullary prostaglandin
levels. Therefore, care should be exercised when administering even
the COX-2 inhibitors to patients with a predisposition to renal
disease or renal papillary necrosis, and otherwise healthy patients
should maintain adequate hydration and avoid physiologic stress
while on these medications.
Slide 45
Recently, multiple publications have described
indinavir-induced renal papillary necrosis. In one study, diagnosis
was delayed as the initial symptoms were attributed to suspected
urinary tuberculosis. These studies demonstrate the necessity of
renal function monitoring during HIV treatment above that of
calculus monitoring. 7,8
Slide 46
Pathophysiology Renal papillary necrosis is classified as focal
(ie, involving only the tip of the papilla) or diffuse (ie,
involving the whole papilla and areas of the medulla), depending
primarily on the patient's degree of impaired vasculature. Renal
papillary necrosis may simply affect a single papilla, or the
entire kidney may be grossly involved. Once again, renal papillary
necrosis is more often a bilateral process; many of the
predisposing factors are systemic. Renal papillary necrosis never
involves the entire medulla; the disease is always strictly limited
to the inner, more distal zone of the medulla and the papilla.
Slide 47
Researchers recognize 2 pathologic forms of renal papillary
necrosisthe medullary form and the papillary form. The pathogenic
form is dictated by the degree of vascular impairment. The
medullary form is characterized by intact fornices, discrete
grain-sized necrotic areas, and later defects in the papillae.
Clinicians often observe sinus tracts extruding from irregular
medullary cavities. In the papillary form, the calyceal fornices
and the entire papillary surface are destroyed, demarcated, and
sequestered. If these fornices and papillary surfaces are not
sloughed, they reepithelialize and acquire a smoother
appearance.
Slide 48
Patients with medullary ischemia develop decreased glomerular
filtration rates, salt wasting, an impaired ability to concentrate,
and polyuria because the vasa rectae supply the medulla and serve
the countercurrent exchange mechanism.
Slide 49
The pathologic findings on a cut section include gray-white to
yellow necrosis that resembles infection on the tips or distal two
thirds of the pyramids. Microscopically, the tissue shows
characteristic coagulative infarct necrosis, with preserved tubule
outlines. The leukocytic response is limited to the junctions
between preserved and destroyed tissue. After the acute phase,
scars that can be observed on the cortical surface as fibrous
depressions replace the inflammatory foci. This pyelonephritic scar
is usually associated with inflammation, fibrosis, and a
deformation of the underlying calyces and pelvis.
