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RationaleRecent recognition of the need to improve pain management in cats has led to the investigation of the pharmacokinetics and efficacy of opioid analgesic drugs in this species. The results of these studies may be difficult to interpret because the effect of these drugs varies with dose, route of administration and the method used to assess them. As equipotency of different opioids is not known, it is hard to compare their effects. Animals do not verbalise the pain they feel and, in cats, it may be more difficult to recognise signs of pain in comparison with other species such as dogs.AimThis article reviews the use of opioid analgesics in cats. It must be remembered that not all drugs are licensed for use in cats, and that marketing authorisations vary between different countries.IntroductionIn recent years research into pain assessment and management in cats has increased. This interest and focus may have been in response to reports that cats have been undertreated for pain in comparison with other species.Advances in knowledge have led to internationally recognised veterinary bodies issuing guidelines on pain management in cats, including those very recently from the American Animal Hospital Association and the American Association of Feline Practitioners.In 2014, the World Small Animal Veterinary Association also published guidelines on the recognition, assessment and treatment of pain. Tramadol for PetsPain assessment in catsPain assessment and quantification in animals is challenging because pain is a subjective sensory and emotional experience and animals are unable to verbalise their suffering. The most reliable way to assess pain in cats is thought to be through a combination of behavioural observations and interaction with the animal.Various scales have been created to try to quantify pain in cats. For example, the Colorado State University Veterinary Medical Center has designed a feline acute pain scale,whereby psychological and behavioural components are evaluated in conjunction with the cat’s response to palpation of the site of surgery and its body tension. In many studies the visual analogue scale (VAS) is used: an assessor marks a point on a 100 mm line that best correlates with the cat’s pain intensity; VAS is based on visual observation and ‘0’ is considered no pain, while ‘100’ is considered the worst pain imaginable. The so-called dynamic interactive visual analogue scale (DIVAS) also includes interaction with the cat, such as palpation of the wound. Recently, a multidimensional composite scale for assessing postoperative pain in cats has been validated.This tool combines evaluations of postoperative psychomotor changes, reaction to palpation of the wound area and vocal expression of pain, together with appetite and arterial blood pressure. It is important to remember that increased arterial blood pressure can be a sign of stress, fear and anxiety, and not necessarily pain. Another method with the potential to assess pain in cats is the evaluation of facial expressions.Limitations of pain assessment using the aforementioned methods include the subjective nature of the evaluation and the difficulties in recognising behavioural clues that may be indicative of pain, particularly in a hospital environment. However, use of a pain scale has the advantages that it focuses the attention of members of staff on pain and also means that an individual cat’s response to analgesic administration can be assessed and monitored.Nociceptive threshold testing has been used to assess the antinociceptive effects of analgesic drugs in a more objective way. In cats, mechanical, thermal and electrical threshold testing has been employed in experimental settings to evaluate the effects of opioids.For each of these techniques a baseline nociceptive threshold is measured, an analgesic is then administered and the thresholds are measured again at specific time points. An increase in the threshold is usually accepted as evidence of a drug’s anti-nociceptive effect. Nociceptive threshold testing does have a number of limitations,including the lack of evaluation of the emotional components of pain. Despite these limitations it is a useful tool for identifying drugs and dosages for further evaluation in clinical cases. In a clinical setting, mechanical nociceptive testing has also been used, in conjunction with subjective assessments of pain, in cats undergoing surgery.There are numerous publications investigating the effects of drugs on the minimum alveolar concentration (MAC) of inhalant anaesthetics in cats. However, this is not an effective way to evaluate the analgesic effects of opioidsSince it only indicates the immobilising potency of the inhalation anaesthetic at the spinal cord level, while pain also involves supraspinal pathways. Several opioids, including morphine, buprenorphine, methadone, butorphanol, hydromorphone, fentanyl, alfentanil, remifentanil and tramadol, have been proven to decrease, to different degrees, the MAC of inhalant anaesthetics, but the effects were not always clinically relevant and were not as profound as have been reported in other species, including dogs.Thus, a significant reduction in volatile anaesthetic concentration after opioid administration should not be expected in the clinical setting.When discussing opioids, opioid receptors and comparisons between different opioid drugs, some concepts should be made clear. Affinity refers to how avidly a drug binds to a receptor, efficacy indicates the magnitude of the effect produced by the drug–receptor interaction, and potency indicates the quantity of drug needed to produce a maximal effect.Opioids and catsOpioids play an important role in the clinical management of pain in cats. Ideally, analgesics should be administered before noxious stimulation (preventive analgesia) with the aim of preventing sensitisation of the central nervous system, which could lead to the development of hyperalgesia. A multimodal approach is also recommended; this involves the concurrent administration of different classes of analgesics, such as opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics and α-adrenoreceptor agonists, with the aim of decreasing the doses and thus the side effects of individual agents, while improving the control of pain in the animal.In cases of acute pain, opioids are effective and versatile analgesics, with wide therapeutic margins and relatively minor side effects in cats.Their effects can also be antagonised if required. Historically there was a reluctance to administer opioids to cats due to concerns over the potential excitatory effects reported by Wikler in 1944.However, ‘morphine mania’ was elicited at doses 100-fold higher (15 mg/kg) than those used in the clinical setting.Sufentanil and alfentanil administration in cats is associated with an increase in sympathetic outflow and central stimulatory effects,but a study investigating morphine administered to cats at clinical (0.3 mg/kg) and supraclinical (0.6–2.4 mg/kg) doses reported no excitement.At clinically used doses the behavioural effects of opioids include euphoria, manifesting as purring, rubbing, rolling and kneading with the forepaws.

When should you see your doctor?When the pain in the neck persists for more than three days or reappears.When you suffer from neck pain after a fall or accident.When neck pain extends into the arms and legs.For more info visit this article.What the symptoms revealFollowing one's instincts is perfectly normal.But if you let your chin sag on your chest when you sit or when you are standing or walking, you will surely feel neck pain.If you move your shoulders sagging and your chin is straight in front of you, your head is not balanced properly on your neck.This forces the ligaments and other soft tissues of the neck to support an average of 35 kilograms of incorrectly distributed weight: a bad way to use one's head."We think that the big problem with the neck and spine is that the joints are kept in an extreme position for a long time and that abnormal pressure eventually leads to pain," says Wayne Rath, physio-therapist, co-director of the Summit Physiotherapy Center and a renowned lecturer at the McKenzie International Institute in Syracuse, New York, and an Assistant Clinical Professor in the Physiotherapy Department at Thomas Jefferson University in Philadelphia.The various structures of your neck can cause pain.The rupture of an intervertebral disc, a donut-shaped rubber pad, located between the vertebrae, can cause difficulty.There may also be problems with the muscles, joints or ligaments of the neck.They can all be painful during an injury.The whiplash, a very common injury, occurs when someone hits your car from behind.The neck slams sharply from front to back.The gradual degeneration of any neck structure, whether due to aging or excess, can also cause neck pain.Relief of symptomsNeck pain can often seem intolerable to you.However, be aware that these pains will respond as well to the suggested pain treatment for the lower back.There are, however, several specific remedies that can provide rapid relief to neck pain.Wear a necklace."Some people have found that cervical collars (minerves) sold in medical supply stores and most pharmacies can provide temporary relief by immobilizing the neck," advises Philip Paul Tygiel,physiotherapist and consultant for the Back Problems Clinic at the University of Arizona Medical Center, Tucson."It's not a good idea, though, to immobilize your neck for long periods of time," he says.Wearing a cervical collar for more than two days can weaken the neck muscles, and make you more susceptible to other injuries.If the pain persists for more than three days, consult a physiotherapist or doctor.Wait a minute."Studies have shown that about 80 to 90% of people who have neck pain and choose to do nothing notice that the pain subsides after two to three days," Wayne Rath reports.Straighten up. "Poor posture includes not only how to sit or stand, but how you stand as you move, sit, stand, lean, lift, play golf, etc. It's finally how you hold your body while you're active or inactive, "says Wayne Rath. In addition, poor posture when sitting is the biggest culprit."Imagine that your head is a golf ball that rests on a tee.What would happen if this tee was inserted at a 30 degree angle?Then notice how people place their necks, "says Wayne Rath.Ask yourself what keeps their head from falling.Think of all the muscles and ligaments to which this pressure is inflicted.To maintain good posture, sit upright, clear your chest, lower your chin a little but straighten your head so that your ears are directly above your shoulders and not in front of them.If you have recurrent neck pain, ask your doctor to assess your posture and, if necessary, refer you to someone who can help you correct your bad posture.Control your cough."Take care not to hurt your neck when you cough and sneeze constantly and strongly.Try to maintain good posture or even tilt your head and neck a little backwards in such a situation, "recommends Wayne Rath.Use your hands.Hold the phone in your hands rather than holding it between your ear and shoulder, which can cause pressure on the soft tissues of the neck and muscles of the upper back."Better yet, get a headset or a hands-free system," advises Hubert Rosomoff, DMS, physician, medical director of the Rehabilitation Center at the University of Miami in Miami Beach.When you hold the phone between your ear and shoulder, you change your posture and force the neck and head into an abnormal position, he adds.It's really to be avoided. "Get a briefcase. Rather than bend the trunk and neck to read the texts you enter on the computer, get a briefcase that you place at the height of the screen."It's probably one of the best tools a person can have," says Annie Pivarski, a San Francisco back care consultant.The pillows.Poor pillows can be a common cause of neck pain.But rather than following someone else's advice, get a comfortable pillow for yourself.Any pillow that provides support to the neck ligaments can be very helpful.Avoid especially the pillows that push your head towards your chest.Get a cervical roll. "You will find in most medical supply stores a roll that you place under your neck while you sleep. This tool reduces pressure on the neck joints, "says Wayne Rath.Exercises that help prevent neck painWe all know that exercise strengthens muscles and increases flexibility."Even light neck exercises can help lubricate and promote nutrients in this area," says Paul Tygiel.Here are some good exercises to perform.Bending of the head.Move your head up and down, slowly tilting your chin towards the chest and slowly raising it to the normal position.Repeat ten times.Then, tilt your head slowly from left to right then return to the normal position.Repeat ten times.Then turn your head from side to side and return to the normal position.Repeat ten times as well.Do these exercises only in an area without pain.(Do not worry if you hear creaks.)"Most people, in normal daily activities, do not exercise the joints of their neck every day, so these exercises are a good therapy," reports Philip Tygiel.Make pressure.Place the palm of your hand behind your neck and apply some light pressure while resisting your head.Hold and count to 10. Repeat but put the palm of your hand on your forehead.Then do the exercise by placing the palm of your right hand against the right side of your head and continue to resist this pressure.Repeat on the left side.Do these exercises once a day.Avoid rotations. "Performing rotations of the head, as some people do to relax the neck muscles, can actually cause more damage than good. Avoid this exercise, "warns Philip Tygiel.

Yes, some do. It's rather well-known in the medical community that genetics play a role in the way some medications work for different people. Because I believe that a variety of people may be interested in the answer to this question, I will use both layman's and more scientific explanations here.A quick overview for anyone who needs it: because I'll be talking about genetics in this answer, I just want to clarify some terms for persons reading who may not be familiar with scientific jargon.Nucleotide: this is the "building block" of DNA. You can think of it as a link in a chain, perhaps, and when a lot of nucleotides are linked together they can form strands of genetic information, called genes.Wild-type: this is a fancy word that indicates the "normal" form of a gene that usually occurs in people.SNP: stands for "single nucleotide polymorphism". Pronounced "snip" when reading, this is the term for when a change happens to one single building block of the gene. It could be that the wrong information was inserted, the correct information was left out, or some other possible situations. Whatever the cause, this can result in a different DNA sequence and potentially an altered gene functionality from the wild-type. I will refer to the SNPs occasionally by naming the gene or specific area of the SNP, usually by a combination of letters/numbers/asterisks. This system just serves to indicate the specific sequencing area within the gene that the SNP is located.Now that's out of the way, I'll first address your question on a surface level: do medical drugs, including vaccines, work differently for different ethnic groups? The answer is yes, we do know of medications that work differently in different ethnic groups.CodeineA prominent example of a medication working differently in specific ethnic groups is that of codeine. Codeine is a popular opioid medication used to treat minor-moderate pain via action at opioid receptors in the central nervous system. Codeine, however, is not an active drug in and of itself; that is, it actual codeine molecule doesn't work to reduce pain. In the body, codeine is partially metabolized to morphine, and the action of the morphine is what causes the analgesic effects.Image credit: Diclofenac does not interact with codeine metabolism in vivo: A study in healthy volunteersIn order to "activate" codeine to morphine and get the painkilling effects, an enzyme located in the liver has to act on the codeine and metabolize it to morphine. This enzyme is part of a major liver enzyme family called Cytochrome P450. Many enzymes in this family are largely responsible for metabolism of drugs in the body. In the specific case of codeine, the CYP 2D6 enzyme is responsible for processing codeine into morphine. In the average individual, approximately 10% of the codeine is converted to morphine, and the rest is inactivated before it can be made into codeine.However, this CYP 2D6 enzyme is susceptible to genetic variation. Variance of the gene responsible for encoding CYP 2D6 activity on chromosome 22 can result in normal (CYP2D6*1), increased (*2), none (*3, *4, *5), or decreased (*9, *10, *17) activity of the enzyme. With respect to codeine, this variance in enzyme activity can produce variance in how well the CYP 2D6 enzyme works to metabolize morphine to codeine. Logically, a person with normal CYP 2D6 enzyme function will metabolize an average amount of the codeine to morphine (about 10%, as mentioned above). Someone with reduced enzyme activity will convert less codeine to morphine, and someone with no enzyme activity will not convert any. Conversely, someone with increased enzyme activity will change more codeine to morphine than is usual.This has implications for both efficacy and safety of the drug. You may have heard of people who report that codeine doesn't really work for them. This may in fact be true. Persons with the lower/nonexistent enzyme function will have less morphine present in their body, and therefore reduced/no analgesic effects. These patients will report that their pain is not effectively controlled. The persons who have the increased enzyme function will have more morphine acting in their body, and will likely have higher than average analgesic effects. This sounds like a good thing, but this can be very dangerous. Opioid analgesics can strongly affect patients who aren't used to their effects, and so the increased morphine can cause a lot of side effects for these "ultra-rapid" metabolisers. They may experience drowsiness, constipation, etc. There have even been deaths associated with ultra-rapid metabolisers having massive circulating concentrations of morphine in their blood.Genetic testing is available to determine what type of metabolizer a patient is, but it is uncommonly used. However, if we do know a patient's genetic status with regard to CYP 2D6, we can tailor therapy accordingly. For "average" metabolisers (also referred to as extensive metabolisers), we can give codeine at standard doses. For persons with reduced/non-functional enzyme activity, we generally avoid codeine use, and would prescribe other analgesics that are not dependent on CYP 2D6 function. For ultra-rapid metabolisers, we also avoid codeine use due to the risk of toxicity, and would likely prescribe something else.So how does ethnicity play into all this? Well, it just so happens that different ethnic groups have different incidence patterns of the metaboliser types. In Caucasian populations, the incidence of poor metabolisers is about 6-10%. This is lower in other ethnic groups, with Asians having about a 2% incidence of poor metabolisers. It may also be higher in other ethnic groups, such as with African-American populations. Persons of African and Middle Eastern background may also have a higher chance of being an ultra-rapid metaboliser than someone who is Caucasian.Further reading on codeine polymorphisms; rest of answer follows below:[Table, Table 1. CYP2D6 phenotypes and recommendations for codeine therapy]CPIC Dosing Guideline for codeine and CYP2D6CYP2D6CodeineAlthough we have a rough idea of the percentages of persons in different ethnic groups who display different metaboliser phenotypes, this doesn't really help healthcare practitioners. Since there is a chance of any patient fitting any metaboliser type, no matter how common they are in their ethnicity, we have to assume that they could be any type of metaboliser. So, unless they've had genetic testing done, we have to counsel each patient taking codeine to closely monitor for both efficacy and side effects.I hope by now you've realized that the answer to this question is not so much about ethnicity as it is about genetics, as this is what more commonly affects how some drugs vary in their efficacy across populations. Codeine is not the only example of this; many drugs are affected by SNPs or other polymorphisms that can alter their efficacy or safety in persons using them.Another example of this is the drug clopidogrel (brand name Plavix). It is an anticoagulant drug that blocks P2Y12 receptors on platelets, preventing their activation by ADP released when platelets degranulate. Like codeine, clopidogrel is a prodrug, which means it needs to be metabolized in the body before it can become fully active.Image credit: CLOPIDOGRELIn this case, the responsible enzyme is CYP 2C19, of the same enzyme family that CYP 2D6. Within the gene that encodes CYP 2C19, there is the potential for a SNP to occur that can cause genetic variance. A *1 variant encodes for a normal copy of the enzyme, and a *17 variant encodes for a higher metabolism copy of the enzyme. All other variants encode a defective copy of the enzyme. Since each person has 2 copies of the genes for the CYP 2C19 enzyme, there are 4 possible phenotypes:*1,*1: normal metabolizer (two copies of the normal gene)*17, *17 or *1: ultra-rapid metabolizer (one copy of higher metabolism gene either with another copy of the high metabolism gene or a normal gene)def, *17 or *1: intermediate metabolizer (one copy of a defective gene with a copy of a functional gene)def, def: poor metaboliser (no functional copies of gene)Like was described above with codeine, the metaboliser classification of the patient can affect how much active drug their body can produce. In the case of clopidogrel, the normal and ultra-rapid metabolizers are usually okay to take the normal dose. However, intermediate and poor metabolizers may not make enough active metabolite from clopidogrel for the anticoagulant effect to be great enough, and are therefore at an increased risk for developing blood clots.If, from genetic testing, we know a patient is an intermediate or poor metabolizer, we can instead prescribe a related drug, prasugrel, which works the same way but does not need the conversion by CYP 2C19 to function. But, as I mentioned above, most patients don't have genetic testing done in order to know what type of metabolizer they are. Since its estimated that up to 25% of patients don't respond to clopidogrel due to genetics, there have been assessment tools created to help evaluate patients for their risk of clopidogrel treatment failure, such as the PREDICT score.In addition to the CYP 2C19 variances, another genetic polymorphism can also affect clopidogrel. P-gp, a protein that resides in the wall of the intestine, can act to pump clopidogrel out of the bloodstream and back into the gut, where it will then be excreted rather than utilized by the body. In the gene that codes for the P-gp protein, there is the potential for a SNP: ABCB1 3435 C>T. This SNP causes P-gp to be more active. If a person has 2 copies of the overactive gene, P-gp will pump an excess amount of clopidogrel into the intestine, where it can't be utilized as needed. Persons with 2 copies of the overactive gene may be at a higher risk for blood clots as the full dose of clopidogrel isn't being used.Further reading on clopidogrel, answer continues below:PREDICT score allows personalized antiplatelet therapyThe Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score.ClopidogrelCYP2C19There are many more examples of drugs being affected by genetic polymorphisms that I won't discuss in detail here, but some more examples include:Irinotecan (chemotherapy agent)Tamoxifen (chemotherapy agent)Methotrexate (chemotherapy agent)Warfarin (anticoagulant)Azathioprine (immunosuppressant)Gefitinib (chemotherapy agent)Additionally, you had asked about vaccines as well. It does appear that their effectiveness may also be determined (at least partially) by genetic variation amongst individuals. A meta-analysis published 2014 in the journal Vaccine by an Italian group shows some data that may indicate that efficacy of vaccines could be affected by genetic polymorphisms (if you would like to read more on the subject of scientific studies: Leah Pritchett's answer to What is the valuable difference between medical observational studies (like meta analysis, cohort studies, etc.) and interventional studies (clinical trials)?). The link is here, but I think it may be behind a paywall: (Libraries : University of Manitoba). I haven't had a chance to thoroughly read and assess the meta-analysis, but a quick skim through it shows that their meta-analysis may have indicated a link between human leukocyte antigen (HLA) genetic polymorphisms and responsiveness to vaccines. Essentially, this means that there has been research done that may indicate a link between genetic variance in the DNA encoding key parts of the immune system and how well patients respond to vaccines. There appears to be both patients who hyperrespond to vaccines, as well as patients who under-respond. If the link can be more strongly established, it may explain why there can be so much variance in the blood antibody levels (which indicate immunity) between two people who got the same vaccine at the same time. If this link were proven, it may also help guide healthcare professionals to make more informed decisions about how often some patients need "booster" vaccinations.After all this, you may be wondering why we don't just start genotyping everyone for this kind of stuff as soon as they're admitted to the hospital. The problem lies in money: the special equipment and personnel to run genetic tests don't come cheap! So doing these tests is likely not cost-effective for many hospitals. Also, we sometimes already have a cheaper way of doing things that can help guide therapy. We can measure blood antibody titres to help evaluate vaccine efficacy, and we can measure how thin the blood is if a patient is on warfarin. These more routine, cheaper tests already help us decide on therapy for our patients, and do not drain healthcare resources.I hope this lengthy answer helped! Feel free to comment or message me if you have any persisting questions/need clarification.