A 100 mg Rimadyl pill around 19 mm (0.75 in) wide and 8.6 mm (0.34 in) solid, sold in america
Carprofen, marketed less than many brands worldwide, is a nonsteroidal anti-inflammatory medication (NSAID) that veterinarians prescribe mainly because a supportive tréatment for various circumstances in pets. It offers day-to-dáy treatment for discomfort and inflammation from different types of joint pain along with post-operative discomfort. Carprofen reduces inflammation by inhibition of COX-1 and COX-2; its specificity for COX-2 differs from species to species.
1 Use in dogs
2 Adverse effects
3 Human use
4 Equine use
5 Brands and dosage forms for veterinary use
Use in canines
Most dogs respond very well to carprofen usé, but like aIl NSAIDs, it might cause gastrointestinal, kidney and liver complications in some patients.
After introduction, significant anecdotal reviews of sudden animaI deaths fróm its use arosé. To time[when?], the FDA provides received a lot more than 6,000 adverse reaction reports about the medication (manufactured by Pfizer). As a total result, the FDA réquested that Pfizer recommend consumers within their advertising that loss of life is a possible side-effect. Pfizer refused and pulled their advertising; nevertheless, they now include loss of life as a possible side-effect on the medication label. Plans require a “Dear Doctor” letter to recommend veterinarians, and a security sheet mounted on pill packages.
Adverse effects include:
Loss of appetite
Increase in thirst
Increase in urination
Exhaustion and/or lethargy (drowsiness)
Loss of coordination
Liver dysfunction: jaundicé (yellowing of éyes)
Blood or dark tar-like materials in urine or stools
Staggering, stumbling, wéakness or partial paraIysis, complete paralysis.
Change in pores and skin (redness, scabs, or scratching)
Change in behavior (such as for example decreased or incréased activity level, séizure or aggression).
Ramifications of overdose include ulcer and gastritis formation.
In healthy canines given carprofen, simply no perioperative undesireable effects on the heart have already been reported at suggested dosages.  Perioperative administration of carprofen to cats didn’t effect postoperative respiratory price nor heartrate.
Carprofen shouldn’t be administered with steroids concurrently, as this can trigger ulcers in the tummy. Dogs should be removed carprofen for three complete times before ingesting a steroid (such as for example prednisolone). Carprofen shouldn’t be given simultaneously with other styles of medicines such as additional NSAIDs (aspirin, etodoIac, deracoxib, meloxicam, tepoxaIin) or steroids such as for example dexamethasone, triamcinolone, prednisone or cortisone.
Carprofen can be used with caution within the guidance of a veterinarian in canines with liver or kidney disease, dehydration, bleeding déficits, or other health issues. It isn’t recommended for make use of in canines with bleeding disorders (such as for example Von WiIlebrand’s disease), ás safety is not established in canines with these disorders. It has not been established whether carprofen can be utilized in pregnant dogs safely, dogs utilized for breeding purposés, or in Iactating feminine dogs.
Several laboratory research and medical trials have already been conducted to determine the safety óf using Carprofen. Clinical studies were conducted in almost 300 dogs, via different breeds. The canines had been treated with RimadyI at the suggested dose for 14 days. Regarding to these scholarly studies, the medication was clinically weIl tolerated and thé treated canines did not have a larger incidence of effects in comparison with the control group.
Several factors that may donate to the high incidénce of adverse reviews received for carprofen by the guts for Veterinary Medication in the late 1990s. Included in these are:
The kind of drug;
Duration of use. As the unwanted effects from carprofen are recognized to occur within a brief time period after administration, it really is thought that long-term use could possibly lead to an increased risk for advérse reactions[citation néeded];
Senior dog use. Old dogs are more susceptible to side effects due to carprofen generally.
Carprofen was found in humans for a decade almost, starting in 1988. It had been utilized for the same circumstances as in canines, viz., joint inflammation and pain. Unwanted effects tended to become mild, usually comprising nausea or gastro-intestinal discomfort and diarrhea. Carprofen was available just by préscription in 150 to 600 mg dosages. Dosage over 250 mg was limited to relieving pain after serious trauma, such as for example post-surgery infIammation. 150 mg doses were typically used to alleviate the discomfort of arthritis, whiIe 200 mg doses were typically recommended in cases of serious arthritis or serious inflammation pain. The medication orally was taken. Pfizer voluntarily taken out it from the marketplace for human make use of on commercial grounds.
Carprofen could be administered intravenously to horses. An individual dose has been proven to lessen prostaglandin E2 creation and inflammatory exudate for 15 hours, although there is less influence on eicosanoid production in comparison with the effects made by NSAIDs such as for example phenylbutazone or fIunixin. Prostaglandin E2 and inflammatory exudate are also reduced and leukotriene B4 is inhibited. Carprofen may also be given orally, but intramuscular use may make muscle damage.
Brands and dosagé forms for véterinary make use of
It really is marketed under many brands including: Acticarp, Austiofén, Bomazeal, Canidryl, CarporaI, Carprieve , Carprocow, CarprodoIor, Carprodyl, Carprofelican, Carprofén, Carprofène, Carproféno, Carprofenum, Carprogesic, CarprosoI, Carprotab, Carprox, Cómforion, Dolagis, Dolocarp, DoIox, Eurofen, Kelaprofen, Librévia, Norocarp, Norodyl, Nóvocox, Prolet, Reproval, RimadyI, Rimifin, Rofeniflex, Rycárfa, Scanodyl, Tergive, Vétprofen, and Xelcor.
Veterinary dosage fórms include 25 mg, 75 mg, and 100 mg tablets, and 50 mg per mL injectable form.
^ a b Drugs.october 4 com International brands for Carprofen Web page accessed, 2017
^ a b c Carprofen/Rimadyl (Carprofen) prescribing instructions
^ “Update On RimadyI, FDA’s Middle for Veterinary Medication, December 1, 1999”.
^ “AN ASSESSMENT of Symptoms of a Possibly Life-threatening A reaction to Rimadyl”. Retrieved 2010-05-20.
^ “Dog Owner INFORMATION REGARDING Rimadyl (carprofen)”. Retrieved 2010-05-20.
^ “Generic Pet Rimadyl Online”. Retrieved 2010-05-20.
^ Boström, lM; Nyman, GC; Lórd, PE; Häggström, J; Jones, BE; BohIin, HP (Might 2002). “Ramifications of carprofen on renaI function and outcomes of serum biochemical and hematologic analyses in anesthetized canines that experienced low blood circulation pressure during anesthesia”. Américan journal of véterinary study. 63 (5): 712-21. doi:10.2460/ajvr.2002.63.712. PMID 12013473.
^ Frendin, JH; Bóström, IM; Kámpa, N; EkseIl, P; Häggström, JU; Nymán, GC (December 2006). “Ramifications of carprofen on renaI function during médetomidine-propofol-isoflurane anésthesia in canines”. American journal of veterinary study. 67 (12): 1967-73. doi:10.2460/ajvr.67.12.1967. PMID 17144795.
^ Höglund, 0dd V; Dyall, Bárbara; Gräsman, Victória; Edner, Anna; 0lsson, Ulf; HögIund, Katja (22 November 2017). “Aftereffect of non-steroidal anti-inflammatory medicines on postoperative respiratory and heartrate in cats put through ovariohysterectomy”. Journal of Feline Medication and Surgery: 1098612X1774229. doi:10.1177/1098612X17742290.
^ “Rimadyl (Carprofen)”. Retrieved 2010-05-20.
^ “Rimadyl [package insert]. NY, NY: Pfizer Animal Wellness, 2007” (PDF). Retrieved 2014-08-13.
^ a b Committée for Veterinary MedicinaI Items: Carprofen, European Company for the EvaIuation of Medicinal Próducts
^ McIlwraith CW, Frisbié DD, Káwcak CE. NonsteroidaI Anti-Inflammatory Medicines. Proc. AAEP 2001 (47): 182-187.
^ Lees, P; McKellar, Q; Might, SA; Ludwig, B (Might 1994). “Pharmacodynamics and pharmacokinetics of carprofen in the equine”. Equine veterinary journaI. 26 (3): 203-8. doi:10.1111/j.2042-3306.1994.tb04370.x. PMID 8542839.
^ Lees, P; Ewins, CP; Taylor, JB; Sedgwick, Advertisement (1987). “Serum thromboxane in the equine and its own inhibition by aspirin, phenylbutazone and flunixin”. The British veterinary journal. 143 (5): 462-76. doi:10.1016/0007-1935(87)90024-8. PMID 3119142.
^ McKellar, QA; Bógan, JA; von FeIlenberg, RL; Ludwig, B; CawIey, GD (July 1991). “Pharmacokinetic, biochemical and tolerance research on carprofen in the equine”. Equine veterinary journaI. 23 (4): 280-4. doi:10.1111/j.2042-3306.1991.tb03718.x. PMID 1915228.
^ Carprofen (Veterinary-Systemic) AMERICA Pharmacopeial Convention, 2007
Prostaglandin F2α (dinoprost)
Prostacyclin (prostaglandin We2, epoprostenol)
Prostaglandin E1 (alprostadil)
Agonists: Carbocyclic thromboxane A2
Pinane thromboxane A2
Precursors: Linoleic acid
γ-Linolenic acid (gamolenic acid)
Leukotriene signaling modulators
Nuclear receptor modulators
Bullous pemphigoid is an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the epidermis and dermis skin layers. It is classified as a type II hypersensitivity reaction, with the formation of anti-hemidesmosome antibodies.
Clinically, the earliest lesions may appear urticarial (like hives), but could also appear dermatitic, targetoid, lichenoid, nodular, or even without visible rash (essential pruritus). Tense bullae eventually erupt, most commonly at the inner thighs and upper arms, but the trunk and extremities are frequently both involved. Any part of the skin surface can be involved. Oral lesions are present in a minority of cases. The disease may be acute, but typically will wax and wane. Several other skin diseases may have similar symptoms. However, milia are more common with epidermolysis bullosa acquisita, because of the deeper antigenic targets. A more ring-like configuration, with a central depression or centrally collapsed bullae may indicate linear IgA disease. Nikolsky’s sign is negative unlike pemphigus vulgaris where it is positive.
In most cases of bullous pemphigoid, no clear precipitating factors are identified. Potential precipitating events that have been reported include exposure to ultraviolet light and radiation therapy. Onset of bullous pemphigoid has also been associated with certain drugs, including furosemide, nonsteroidal anti-inflammatory agents, DPP-4 inhibitors, captopril, penicillamine, and antibiotics.
The bullae are formed by an immune reaction, initiated by the formation of IgG autoantibodies targeting Dystonin, also called Bullous Pemphigoid Antigen 1, and/or type XVII collagen, also called Bullous Pemphigoid Antigen 2, which is a component of hemidesmosomes. A different form of dystonin is associated with neuropathy. Following antibody targeting, a cascade of immunomodulators results in a variable surge of immune cells, including neutrophils, lymphocytes and eosinophils coming to the affected area. Unclear events subsequently result in a separation along the dermoepidermal junction and eventually stretch bullae.
A photo of legs covered in popped blisters caused by bullous pempigoid. The blisters cover his entire body, but subject preferred to stay clothed.
Diagnosis is based on two biopsies of the skin, one submitted for routine H&E staining and one for immunofluorescence studies.
Treatments include class I topical steroids (clobetasol, halobetasol, etc.) which in some studies have proven to be equally effective as systemic, or pill, therapy and somewhat safer. However, in difficult-to-manage or widespread cases, systemic prednisone and powerful steroid-free immunosuppressant medications, such as methotrexate, azathioprine or mycophenolate mofetil, may be appropriate. Some of these medications have the potential for severe adverse effects such as kidney and liver damage, increased susceptibility to infections, and bone marrow suppression. Antibiotics such as tetracycline or erythromycin may also control the disease, particularly in patients who cannot use corticosteroids. The anti-CD20 monoclonal antibody rituximab has been found to be effective in treating some otherwise refractory cases of bullous pemphigoid. A 2010 meta-analysis of 10 randomized controlled trials showed that oral steroids and potent topical steroids are effective treatments though their use may be limited by side-effects, while lower doses of topical steroids are safe and effective for treatment of moderate bullous pemphigoid.
IgA-mediated pemphigoid can often be difficult to treat even with usually effective medications such as rituximab.
Bullous pemphigoid may be self-resolving in a period ranging from several months to many years even without treatment. Poor general health related to old age is associated with a poorer prognosis.
Very rarely seen in children, bullous pemphigoid most commonly occurs in people 70 years of age and older. Estimated frequency is seven to 14 cases per million per year, but has been reported to be as high as 472 cases per million per year in Scottish men older than 85. At least one study indicates the incidence might be increasing in the United Kingdom. Some sources report it affects men twice as frequently as women, while others report no difference between the sexes.
Many mammals can be afflicted, including dogs, cats, pigs, and horses, as well as humans. It is very rare in dogs; on average, three cases are diagnosed around the world each year.
Animal models of bullous pemphigoid have been developed using transgenic techniques to produce mice lacking the genes for the two known autoantigens, dystonin and collagen XVII.
see also fibrous proteins
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Non-Hodgkin lymphoma (NHL) is cancer of the lymph tissue. Lymph tissue is found in the lymph nodes, spleen, and other organs of the immune system. White blood cells called lymphocytes are found in lymph tissue. They help prevent infections. Most l…
Drug allergies are a group of symptoms caused by an allergic reaction to a drug (medication).
Amlodipine, sold under the brand name Norvasc among others, is a medication used to treat high blood pressure and coronary artery disease. While not typically recommended in heart failure, amlodipine may be used if other medications are not sufficient for high blood pressure or heart-related chest pain. Amlodipine is taken by mouth and has an effect for at least a day.
Common side effects include swelling, feeling tired, abdominal pain, and nausea. Serious side effects may include low blood pressure or a heart attack. Whether use is safe during pregnancy or breastfeeding is unclear. Doses should be decreased in people with liver problems and in elderly individuals. Amlodipine is a long-acting calcium channel blocker of the dihydropyridine (DHP) type. It works partly by increasing the size of arteries.
Amlodipine was first patented in 1986 with commercial sale beginning in 1990. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. Wholesale cost in the developing world is US$0.003 to 0.066 per day for a typical dose as of 2015. In the United States, a month’s supply costs less than $25.
Amlodipine is used in the management of hypertension and coronary artery disease in people with either stable angina (where chest pain occurs mostly after physical or emotional stress) or vasospastic angina (where it occurs in cycles) and without heart failure. It can be used as either monotherapy or combination therapy for the management of hypertension or coronary artery disease. Amlodipine can be administered to adults and children 6–17 years of age.
Amlodipine can be given as a combination therapy with a variety of medications:
The only absolute contraindication to amlodipine is an allergy to amlodipine or any other dihydropyridines.
Other situations occur, however, where amlodipine generally should not be used. In patients with cardiogenic shock, where the heart’s ventricles are not able to pump enough blood, calcium channel blockers exacerbate the situation by preventing the flow of calcium ions into cardiac cells, which is required for the heart to pump. While use in patients with aortic stenosis (narrowing of the aorta where it meets the left ventricle) since it does not inhibit the ventricle’s function is generally safe, it can still cause collapse in cases of severe stenosis. In unstable angina (excluding variant angina), amlodipine can cause a reflex increase in cardiac contractility (how hard the ventricles squeeze) and heart rate, which together increase the demand for oxygen by the heart itself. Patients with severe hypotension can have their low blood pressure exacerbated, and patients in heart failure can get pulmonary edema. Those with impaired liver function are unable to metabolize amlodipine to its full extent, giving it a longer half-life.
Amlodipine’s safety in pregnancy has not been established, although reproductive toxicity at high doses is known. Whether amlodipine enters the milk of breastfeeding mothers is also unknown.
Some common dose-dependent side effects of amolodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing. Peripheral edema (fluid accumulation in the tissues) occurs at rate of 10.8% at a 10-mg dose (versus 0.6% for placebos), and is three times more likely in women than in men. It causes more dilation in the arterioles and precapillary vessels than the postcapillary vessels and venules. The increased dilation allows for more blood, which is unable to push through to the relatively constricted postcapillary venules and vessels; the pressure causes much of the plasma to move into the interstitial space. Amlodipine-association edema can be avoided by adding ACE inhibitors or angiontensin II receptor antagonist. Of the other dose-dependent side effects, palpitations (4.5% at 10 mg vs. 0.6% in placebos) and flushing (2.6% vs. 0%) occurred more often in women; dizziness (3.4% vs. 1.5%) had no sex bias.
Common but not dose-related side effects are fatigue (4.5% vs. 2.8% with a placebo), nausea (2.9% vs. 1.9%), abdominal pain (1.6% vs. 0.3%), and somnolence (1.4% vs. 0.6%). Side effects occurring less than 1% of the time include: blood disorders, impotence, depression, peripheral neuropathy, insomnia, tachycardia, gingival enlargement, hepatitis, and jaundice.
See also: Calcium channel blocker toxicity
Although rare, amlodipine overdose toxicity can result in widening of blood vessels, severe low blood pressure, and fast heart rate. Toxicity is generally managed with fluid replacement monitoring ECG results, vital signs, respiratory system function, glucose levels, kidney function, electrolyte levels, and urine output.Vasopressors are also administered when low blood pressure is not alleviated by fluid resuscitation.
Several drugs interact with amlodipine to increase its levels in the body. CYP3A inhibitors, by nature of inhibiting the enzyme that metabolizes amlodipine, CYP3A4, are one such class of drugs. Others include the calcium-channel blocker diltiazem, the antibiotic clarithromycin, and possibly some antifungals. Amlodipine causes several drugs to increase in levels, including cyclosporine, simvastatin, and tacrolimus (the increase in the last one being more likely in people with CYP3A5*3 genetic polymorphisms). When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases. Giving amlodipine with Viagra increases the risk of hypotension.
Amlodipine is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells. Amlodipine inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries.
Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Among the two stereoisomers [R(+), S(–)], the (–) isomer has been reported to be more active than the (+) isomer. Serum calcium concentration is not affected by amlodipine. And it specifically inhibits the currents of L-type Cav1.3 channels in the zona glomerulosa of the adrenal gland.
The mechanisms by which amlodipine relieves angina are:
Amlodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.
Amlodipine and one of its major metabolites: The nitrogen-containing ring is oxidized, and two of the side chains are hydrolyzed.
Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug. Amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%; the half-life of amlodipine is about 30 h to 50 h, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing. Its long half-life and high bioavailability are largely in part of its high pKa (8.6); it is ionized at physiological pH, and thus can strongly attract proteins. It is slowly metabolized in the liver by CYP3A4, with its amine group being oxidized and its side ester chain being hydrolyzed, resulting in an inactive pyridine metabolite. Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. However, renal impairment does not significantly influence amlodipine elimination.
Pfizer’s patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007. A number of generic versions are available. In the United Kingdom, tablets of amlodipine from different suppliers may contain different salts. The strength of the tablets is expressed in terms of amlodipine base, i.e., without the salts. Tablets containing different salts are therefore considered interchangeable. The efficacy and tolerability of a fixed-dose combination of amlodipine and perindopril, an angiotensin converting enzyme inhibitor, have recently been confirmed in a prospective, observational, multicentre trial of 1250 hypertensive patients.
The medical form comes as besylate, mesylate or maleate.
Amlodipine is most often used to treat systemic hypertension in cats and dogs. In cats, it is the first line of treatment due to its efficacy and few side effects. Systemic hypertension in cats is usually secondary to another abnormality, such as chronic kidney disease, and so amlodipine is most often administered to cats with kidney disease. While amlodipine is used in dogs with systemic hypertension, it is not as efficacious. Amlodipine is also used to treat congestive heart failure due to mitral valve regurgitation in dogs. By decreasing resistance to forward flow in the systemic circulation it results in a decrease in regurgitant flow into the left atrium. Similarly, it can be used on dogs and cats with left-to-right shunting lesions such as ventricular septal defect to reduce the shunt. Side effects are rare in cats. In dogs, the primary side effect is gingival hyperplasia.
See also: Receptor/signaling modulators • Transient receptor potential channel modulators
Mineralocorticoids and antimineralocorticoids
Glucocorticoid receptor modulators
List of corticosteroids
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