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However, if the noxious insult was severe, or if a focus of ongoing inflammation persists, then pain will persist as is the case in dogs with chronic inflammatory diseases such as arthritis, otitis, gingivitis, dermatitis and back pain. Neuropathic pain is defined as pain caused or initiated by a primary lesion, injury or dysfunction in the peripheral nervous system or central nervous system. There follows a plethora of changes in the peripheral nervous system, spinal cord, brainstem and brain as damaged nerves fire spontaneously and develop hyper-responsivity to both inflammatory and normally innocuous stimuli. Prevention of neuropathic pain is frequently accomplished by appropriate selection and duration of administration of analgesic(s). Post-surgical pain: persistent pain after surgery remains a problem in humans, particularly following major surgery, with a minority of these patients experiencing severe chronic pain, often neuropathic in nature. The risk of persistent post-surgical pain in dogs and cats has not been quantified; however, it is likely to occur. The analgesic protocol should be re-assessed by careful examination and observation to ensure there is no new underlying problem causing pain. Chronic pain: there is no direct link between the duration or intensity of injury which transforms acute transient pain into chronic pain. However, as with neuropathic pain, appropriate management of acute pain is essential to prevent establishment of chronic pain. As noted, the pain information processing systems display plasticity, driven by peripheral and central sensitization. This plasticity can be reversible, as is commonly the case in acute inflammatory pain; or it can be long-lasting which is associated with changes expressed in the phenotype of the nociceptive cells and their expression of proteins involved in pain processing. Cats that have been injured or undergone surgery should be monitored closely and pain must be treated promptly to prevent it from escalating. The degree of trauma dictates the intensity and duration of the inflammatory response but treatment may be required for several days. Feral cats require preemptive administration of analgesics based on the severity of the proposed surgical procedure rather than based on their behaviour; in addition, interactive pain assessment is not possible in this population. Some cats may not display clear overt behaviour indicative of pain, especially in the presence of human beings, other animals or in stressful situations. Cats should not be awakened to check their pain status; rest and sleep are good signs of comfort but one should ensure the cat is resting or sleeping in a normal posture (relaxed, curled up). In some cases cats will remain very still because they are afraid or it is too painful to move, and some cats feign sleep when stressed. Following abdominal surgery a hunched position and/or a tense abdomen is indicative of pain. Abnormal gait or shifting of weight and sitting or lying in abnormal positions may reflect discomfort and protection of an injured area. Comfortable cats should display normal facial expressions, postures and movement after successful analgesic therapy. Behavioural changes associated with acute pain in cats: reduced activity, loss of appetite, quietness, hiding, hissing and growling (vocalization), excessive licking of a specific area of the body (usually involving surgical wounds), guarding behaviour, cessation of grooming, tail flicking and aggression may be observed. Illustrations of normal postures and facial expressions and those that may be indicative of pain.
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Based on the blood pressure response or Candesartan side effects, the dosage may be increased or decreased. With each change in dosage, it may take several weeks to see the full effects of Candesartan on lowering blood pressure. Journal of Applied Pharmaceutical Science 01 (10); 2011: 12-17 Most people require a final dose of Candesartan 2 mg to 32 mg either as one daily dose or two smaller doses. Overdosage No lethality was observed in acute toxicity studies in mice, rats, and dogs given single oral doses of up to 2000 mg/kg of Candesartan cilexetil. In mice given single oral doses of the primary metabolite, Candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg. The most likely manifestation of overdosage with Candesartan cilexetil would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. When pregnancy is detected, Candesartan should be discontinued as soon as possible. Some of these Candesartan interactions include: Diuretics When using Candesartan with a diuretic, the blood pressure may decrease too much. In order to decrease the chances of this interaction, healthcare provider may change the dosages of either medicine, start with on a lower dose of Candesartan, and monitor the more closely. Diuretics like torsemide, furosemide & hydrochlorothiazide interact with Candesartan. Potassium-sparing diuretics, such as spironolactone, triamterene & amiloride, have also shown interactions. Potassium Supplements If using a potassium supplement with Candesartan, the levels of potassium in the blood may become too high. Lithium Using a lithium preparation with Candesartan can pose a serious problem due to interaction. Candesartan reduces the blood pressure and is an effective antihypertensive agent in patients with mild to moderate hypertension. The drug also reduces blood pressure when used as monotherapy in patients with severe hypertension or when used adjunctively in patients with resistant hypertension. Importantly, Candesartan is safer, more tolerable and as effective as other commonly used antihypertensive agents. The drug therefore represents a useful therapeutic option in the management of patients with hypertension and congestive heart failure will be particularly useful in patients not responding to , or intolerant of, anti-hypertensive agents from other drug classes. Pharmacokinetic-pharmacodynamic interactions of Candesartan Cilexetil and losartan. Pharmacokinetics and pharmacodynamics of Candesartan cilexetil in patients with normal to severely impaired renal function. The combination could cause blood pressure to increase or may Journal of Applied Pharmaceutical Science 01 (10); 2011: 12-17 Etinger M. Pharmacokinetics of Candesartan after single and repeated doses of Candesartan cilexetil in young and elderly healthy volunteers. Synthesis and biological activity of potential prodrugs of benzimidazole-7-carboxylic acids.
