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PARA LA CONSTITUCIÓN DEL BANCO COMUNAL FONDO SOCIAL
Parkinson’s disease is associated with decreased dopamine in the substantia nigra and corpus striatum, and effects are typically tremor, muscle rigidity and hypokinesis (reduced voluntary movement). Levodopa is considered first-line treatment but is, unfortunately, extensively metabolised into dopamine peripherally preventing it passing through the blood-brain barrier and thus (i) requires a very high dose to spare enough levodopa to become centrally active and (ii) results in peripheral side effects. These problems are overcome by combining levo- dopa with an agent called carbidopa or benserazide that helps prevent its peripheral conversion which reduces the equipotent dose of levodopa to be reduced tenfold. Levo- dopa is short-acting and so side effects revolve around rapid alteration of symptoms ranging from dyskinesis and hypokinesis to rigidity fairly rapidly. These effects usually progress over time but more instant side effects include nausea and vomiting, and postural hypotension. Other treatment options increasing in popularity include dopamine receptor agonists, such as pergolide, ropinerole and pramipexole.
Anxiolytic and hypnotic drugs are widely used to reduce anxiety, muscle tone, aggression, convulsions and to help sedate patients. Benzodiazepines such as diazepam, temazepam, nitrazepam, etc. act on γ-aminobutyric acid (GABAA) receptors enhancing the effect of this inhibitory amino acid in the central nervous system. This relaxant effect helps to break the anxiety (for example dental pro- cedures, flying, phobias, etc.) and sustained muscle con- traction/increased tone (e.g. cerebral palsy, acute back pain, etc.). They are typically well absorbed orally and peak plasma concentration occurs within the hour. Side effects include drowsiness and poor coordination, so the patient is advised not to drive.
Antibiotics
The side effects of most antibiotics are nausea and vomit- ing, gastrointestinal upset and skin irritation. However, if you notice that a patient is taking an aminoglycoside they may require a closer eye than normal. As with any antibi- otic, you will want to know exactly why they are having them from an infection-control perspective.
Tramadol is extensively used in the community for many musculoskeletal conditions.
Non-steroidal anti-inflammatory drugs (NSAIDs) provide symptomatic relief from mild-to-moderate pain associated with inflammation. The oldest form is aspirin, which has been in use since the late nineteenth century, and the most common is ibuprofen. They typically act by the inhibition of the COX enzyme and thus the production of prostaglandin and thromboxanes, which are pro- inflammatory. There are three identified isoforms of COX (1, 2 and, more recently, 3) although the third (also known as brain COX) may well not actually func- tionally exist in humans. COX-1 is primarily involved, although not exclusively, in the normal functions of the human body: homeostasis, gastric protection, regula- tion of renal blood flow and initiation of childbirth. COX-2, among other things, is responsible for producing pro-inflammatory mediators. Research in recent years has shown that a COX-2-selective NSAID gives rise to throm- botic events in those at risk and so most NSAIDs available have little or no selectivity between the two COX isoforms. Therefore, the side effects are considerable and the patient’s past-medical history needs to be accounted for if they are taking NSAIDs. The inhibition of prostaglan- dins at the hypothalamus ‘resets’ the normal body tem- perature which will have been affected by a bacterial infection, thus producing an antipyretic effect.
Gastrointestinal disturbances are the most often cited side effect of the NSAIDs, which are as a result of COX-1 inhibition. COX-1 products are responsible for the inhibi- tion of acid into the stomach and maintenance of the cytoprotective layer which protects the stomach lining from the acidic gastric juices. Inhibition of COX-1 is det- rimental to these essential components and, as such, the stomach lining is under threat. The prostanoids responsi- ble for renal blood flow are also a product of COX-1, specifically PGE2 which dilates the vessels. Healthy indi- viduals are at little risk but older patients, infants and those with existing renal insufficiency are at particular risk; therefore, NSAIDs with COX-1 inhibition (such as ibuprofen) are contra-indicated. Approximately 5–10% of patients with asthma will have a reaction to NSAIDs.
While aspirin and ibuprofen are the most common, readily-available NSAIDs from pharmacies, there is a whole range of NSAIDs, each with varying degrees of COX-1 : 2 ratio and potency, etc. As a general rule, those ending in ‘-fen’ are more weakly COX-1 selective and those ending in ‘-coxib’ are COX-2 selective.
Paracetamol (aka acetaminophen in the USA) is one of the most common analgesic drugs in the world. It can be taken for mild-to-moderate pain and fever, and, although classed as a NSAID, it lacks anti-inflammatory action and associated gastric irritation. The action is largely unknown as its action on COX-1 and 2 is limited: taken orally, it is well-absorbed with a half-life of approximately three hours. Between 5% and 15% of paracetamol In the event of an overdose, naloxone, an opioid antago-
nist, will block the receptors and rapidly reduce the effects. Unfortunate consequences of prolonged use include tolerance, whereby a higher dose is indicated for an equi-analgesic effect, and dependence, whereby with- drawal produces significant adverse physiological effects, such as irritability, weight loss, shaking, etc. In essence, morphine-like drugs are of vast importance but also a considerable danger to the patient – care must always be exercised when using them. Common opioids are listed below.
Morphine is reasonably fast-acting, is metabolised into a more potent form and has a half-life of approximately four hours. Usually given i.v., orally as a tablet or syrup, or transdermal patch. Commonly used in the community and in acute settings.
Diamorphine (heroin) is used clinically, especially intra- nasally for children in significant pain. Much faster- acting than morphine and is metabolised into morphine. Typically only used within hospitals. It has a high lipid solubility which allows a much faster ‘rush’ compared with morphine, but when taken orally its effects are largely similar.
Methadone is commonly used for heroin addicts as it can be much safer and has a much longer half-life (greater than 24 hours). The side effect profile is as above but with less euphoria.
Pethidine (aka meperidine in the USA) is given orally or by i.m. injection, usually by midwives during childbirth as, in contrast to morphine, it causes restlessness rather than sedation and therefore dose not reduce the uterine contraction force. With a shorter acting half-life (2–4 hours), pethidine is better controlled with little chance of accumulation.
Buprenorphine is a partial agonist and is given as a sub- lingual tablet or as an injection as the first-pass metabo- lism is so extensive it is rendered inactive orally. It is slow-acting with a predictable 12-hour half-life and less respiratory depression than morphine, hence its common usage in the community.
Fentanyl is delivered by epidural and transdermal patch. It has a short-acting half-life (2 hours) and is highly potent. Remifentanil (a variant form) is becoming increas- ingly popular as it is faster-acting and is associated with more rapid recovery.
Codeine/dihydrocodeine is used for mild pain and is available to buy from pharmacies. It is a prodrug (it is metabolised into morphine) and taken as a syrup or tablets commonly combined with paracetamol. It is approximately a fifth as potent as morphine but more readily taken up when taken orally. Codeine is also used as an antitussive (suppresses coughs) in children.
Tramadol is taken orally or i.v. It is generally well absorbed and has a predictable half-life of 4–6 hours. Although it has a weak opioid action, it also has a centrally- acting action which inhibits the uptake of noradrenaline.
Pharmacology