Medical
Pain Killers
An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. Analgesic drugs include the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, and synthetic drugs with narcotic properties such as tramadol. Other classes of drugs not normally considered analgesics are used to treat neuropathic pain syndromes; these include tricyclic antidepressants and anticonvulsants.
NSAIDs such as aspirin, naproxen, and ibuprofen not only relieve pain but also reduce fever and inflammation. Narcotic analgesics such as opiates and opioids largely work through specific opioid receptors in the central nervous system and alter the perception of pain (nociception). They are used to alleviate pain not relieved by the NSAIDs.
Tetrahydrocannabinol and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic properties.
Other analgesic agents include Ketamine (an NMDA receptor antagonist), Clonidine and other alpha-2 receptor agonists and Mexiletine and other local anaesthetic analogues.
Analgesics are frequently used in combination, such as the paracetamol (acetaminophen) and codeine preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as pseudoephedrine for sinus-related preparations, or with antihistamine drugs for allergy sufferers.
Safety
When used appropriately, narcotic analgesics are safe and effective, carrying relatively little risk of addiction. In the United States in recent years, however, there has been a wave of new addictions to prescription painkillers such as Oxycontin and Vicodin. The U.S. Government is now taking steps to reverse this epidemic, which it has blamed on easy access to prescription drugs over the Internet.
Side effects of analgesic use may include ulceration and gastric irritation (with NSAIDs), as well as reduced digestive function (a side effect of opioids).
Anti-Inflammatory Drugs
Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. The term "non-steroidal" is used to distinguish these drugs from steroids, which (amongst a broad range of other effects) have a similar eicosanoid depressing anti-inflammatory action. NSAIDs are sometimes also referred to as non-steroidal anti-inflammatory agents/analgesics (NSAIAs). The most prominent members of this group of drugs are aspirin and ibuprofen. Paracetamol, or acetaminophen, has little anti-inflammatory activity, and is not an NSAID.
Beginning in 1829, with the isolation of salicylic acid from the folk remedy willow bark, NSAIDs have become an important part of the pharmaceutical treatment of pain (at low doses) and inflammation (at higher doses). Part of the popularity of NSAIDs is that, unlike opioids, they do not produce sedation, respiratory depression, or addiction. NSAIDs, however, are not without their own problems. Certain NSAIDs have become accepted as relatively safe, resulting in the rescheduling of these agents, e.g. ibuprofen, to allow availability over-the-counter.
Adverse Reactions
The widespread use of NSAIDs has meant that the adverse effects of these relatively safe drugs have become increasingly prevalent. The two main adverse drug reactions (ADRs) associated with NSAIDs relate to gastrointestinal (GI) effects and renal effects of the agents.
GI effects or Adverse Drug Reactions (ADRs)
Common gastrointestinal adverse reactions iinclude:
nausea
dyspepsia (constant pain in the stomach)
ulceration/bleeding
diarrhoea
Risk of ulceration increases with duration of therapy, and with higher doses. In attempting to minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time, a practice which studies show is not often followed.
There are also some differences in the propensity of individual agents to cause gastrointestinal ADRs. Ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.
Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations which are claimed to reduce the incidence of gastrointestinal ADRs. Similarly, there is a belief that rectal formulations may reduce gastrointestinal ADRs. However, in consideration of the mechanism of such ADRs and indeed in clinical practice, these formulations have not been shown to have a reduced risk of GI ulceration.
Commonly, gastrointestinal adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g. omeprazole; or the prostaglandin analogue misoprostol. Misoprostol is itself associated with a high incidence of gastrointestinal ADRs (diarrhoea). While these techniques may be effective, they prove to be expensive for maintenance therapy.
Renal (Kidney) Adverse Drug Reactions (ADRs)
NSAIDs are also associated with a relatively high incidence of renal ADRs. The mechanism of these renal ADRs is probably due to changes in renal haemodynamics (bloodflow), ordinarily mediated by prostaglandins, which are affected by NSAIDs.
Common ADRs associated with altered renal function include:
Salt and fluid retention
Hypertension
These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor and a diuretic - the so-called "triple whammy" effect.
In rarer instances NSAIDs may also cause more severe renal conditions, such as:
Interstitial nephritis
Nephrotic syndrome
Acute renal failure
Anti-Depressant Drugs
An antidepressant is a medication used primarily in the treatment of clinical depression. Some examples of antidepressants on the market today are Prozac, Zoloft, Effexor, and Celexa. They also are not thought to produce tolerance, although sudden withdrawal may produce adverse effects. Antidepressants create little if any immediate change in mood and require between several days and several weeks to take effect.
Some antidepressants, notably the tricyclics, are commonly used off-label in the treatment of neuropathic pain, whether or not the patient is depressed. Smaller doses are generally used for this purpose, and they often take effect more quickly.
Many antidepressants also are used for the treatment of anxiety disorders, and tricyclic antidepressants are used in the treatment of chronic pain disorders such as Chronic Functional Abdominal Pain (CFAP), Myofacial Pain Syndrome, and post-herpetic neuralgia.
Antidepressants do not seem to have all of the same addictive qualities as other substances such as nicotine, caffeine, cocaine, or other stimulants. There is still controversy on the definition of addiction. Some argue that antidepressants do not meet the general requirements for the common established view. While some antidepressants may cause dependence and withdrawal they do not seem to cause uncontrollable urges to increase the dose due to euphoria or pleasure. For example if some SSRI medications are suddenly discontinued they may produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). When the decision is made to stop taking some antidepressants it is common practice to “wean” off of them by slowly decreasing the dose over a period of several weeks.
It is generally not a good idea of taking antidepressants without prescription. Selection of antidepressant and dosage suitable for the certain case and certain person is a lengthy and complicated process, requiring knowledge of a professional. Unqualified approach can only make things worse. Certain antidepressants can initially make a depression worse, or can induce anxiety, or can make a patient aggressive, dysphoric or acutely suicidal. In certain cases, an antidepressant can induce a switch from depression to mania or to accelerate and shorten a cycle (promote rapid-cycling pattern) or hypomania, or induce a development of psychosis (or just a re-activation of latent psychosis) in a patient which depression wasn't psychotic before an antidepressant.
History
Like many psychiatric drugs, antidepressants were discovered by accident. The first antidepressants, imipramine, a tricyclic, and iproniazid, a monoamine oxidase inhibitor, were discovered in the 1950s. These drugs were found to have the side effect of improving the patients' mood. However, the newer SSRI antidepressants were early examples of rational drug design.
How they are believed to work
The therapeutic effects are believed to be related to an effect on neurotransmitters, particularly by inhibiting the monoamine transporter proteins of serotonin and norepinephrine. Selective serotonin reuptake inhibitors (SSRIs) specifically prevent the reuptake of serotonin (thereby increasing the level of serotonin in synapses of the brain), whereas earlier monoamine oxidase inhibitors (MAOIs) blocked the destruction of neurotransmitters by enzymes which normally break them down. Tricyclic antidepressants (TCAs) prevent the reuptake of various neurotransmitters, including serotonin, norepinephrine, and dopamine. Although these drugs are clearly effective in treating depression, the current theory still leaves unanswered questions. For example, concentrations in the blood build to therapeutic levels in only a few days and begin affecting neurotransmitter activity immediately. Changes in mood, however, often take four weeks or more to appear. One explanation holds that the "down-regulation" of neurotransmitter receptors—an apparent consequence of excess signaling and a process that takes several weeks—is actually the mechanism responsible for the alleviation of depressive symptoms. Another theory, based on recent research published by the National Institutes of Health in the United States, suggests that antidepressants may derive their effects by promoting neurogenesis in the hippocampus.
Side effects
Antidepressants can often cause side effects, and an inability to tolerate these is the most common cause of discontinuing the medication. Sexual dysfunction is a very common side effect, especially with the SSRI's. One exception to this is Wellbutrin (bupropion), which in many cases results in a moderately increased libido. Some clinicians have found that adding Wellbutrin to a regimen of SSRI medications can sometimes alleviate some degree of sexual dysfunction. However, the mechanism of action for Wellbutrin appears to be unique and quite different from other mood elevators, among these being a stimulant-like effect and concurrent insomnia, especially in the first few weeks of use. Moreover, some patients, as seen with most psycho-active drugs, cannot tolerate it all.
Although recent drugs may have fewer side effects, patients sometimes report severe side effects associated with their discontinuation, particularly with Paroxetine. Additionally, a certain percentage of patients do not respond to antidepressant drugs. Another advantage of some newer antidepressants is they can show effects within as few as five days, whereas most take four to six weeks to show a change in mood. However, some studies show that these medication might be even more likely to result in moderate to severe sexual dysfunction. However, there are medications in trials that appear to show an improved profile in regards to sexual dysfunction and other key side effects.
MAO inhibitors can produce a lethal hypertensive reaction if taken with foods that contain the amino acid tyramine, such as cheese and wine. Likewise, lethal reactions to both prescription and over the counter medications have occurred. Any patient currently undergoing therapy with an MAO inhibiting medication should be monitored closely by the prescribing physician and always consulted before taking an over the counter or prescribed medication. Such patients should also inform emergency room personnel and information should be kept with one's identification indicating the fact that the holder is on MAO inhibiting medications. Some doctors even suggest the use of a medical alert ID bracelet.
Antidepressants often make the mania component of bipolar disorder worse, and should be used with great care in the treatment of that disorder, usually in conjunction with mood stabilisers. Their use should be monitored by a psychiatrist, but in countries such as Britain, New Zealand and the United States, primary care physicians are able to prescribe antidepressants without consulting a psychiatrist.
In particular, it has been noted that the most dangerous period for suicide in a patient with depression is immediately after treatment has commenced, as antidepressants may reduce the symptoms of depression such as psychomotor retardation or lack of motivation before mood starts to improve. Although this appears to be a paradox, studies indicate the suicidal ideation is a relatively common component of the initial phases of antidepressant therapy, and it may be even more prevalent in younger patients such as pre-adolescents and teenagers. It is strongly recommended that other family members and loved ones monitor the young patient's behavior, especially in the first eight weeks of therapy, for any signs of suicidal ideation or behaviors.
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Classes of antidepressant
monoamine oxidase inhibitors (MAOIs)
tricyclic antidepressants
selective serotonin reuptake inhibitors (SSRIs)
serotonin-norepinephrine reuptake inhibitors (SNRIs)
selective noradrenaline reuptake inhibitors (NARIs)
novel antidepressants
tetracyclic antidepressants
Despite controversy, alternative treatments for depression such as the herbal remedy St John's wort and the amino acid derivative SAM-e have also gained popularity in recent years, although their effectiveness varies. Clinical trials have shown SAM-e to be as effective as standard antidepressant medication, with many fewer side effects. In contrast, a recent study showed St. John’s Wort to be no more effective than a placebo in case of a severe depression. (Hypericum Depression Trial Study Group, 2002) Most studies conclude that St. John’s Wort is usually as effective against depressions as other modern medication. Tryptophan dietary supplements, although banned in many countries, have also been used as natural antidepressants.
Anti-Convulsant Drugs
The anti-convulsants, sometimes also called anti-epileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. Many typical anticonvulsants work by blocking voltage-sensitive sodium channels in the brain. They include Barbiturates, which are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. Some also are used as anticonvulsants.
They also include the Benzodiazepines, whcih are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant properties. They are believed to act on the GABA receptor GABAA, the activation of which dampens higher neuronal activity. They began to be widely prescribed for stress-related ailments in the 1960s and 1970s. Benzodiazepines are often used for short-term relief of severe, disabling anxiety. Long-term use can be problematic due to the development of tolerance and dependency. These drugs are preferred to the use of barbiturates because they have a lower abuse potential and relatively lower adverse reactions and interactions. However, drowsiness, ataxia, confusion, vertigo, impaired judgement, and a number of other effects are still common.
Two very important Anti-convulsant drugs used in neurosurgery are Phenytoin and Carbamazepine. See further information about them here.
Phenytoin
Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK) is a commonly used antiepileptic or antiseizure drug. It can be injected or taken orally. It was first synthesized in 1908, but is was not until 1938 that scientists discovered phenytoin's usefulness for controlling seizures, without the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilisation, although it has never been approved for those purposes by the USA FDA. It is used especially to prevent tonic-clonic (grand mal) epileptic seizures, and complex partial seizures (psychomotor seizures). It may be used alone or with phenobarbital or other anti-convulsants.
Dose
The dosing of phenytoin is very patient specific. It may be given once, twice, or three times daily. Doses are often adjusted to find the optimal dose, based on measurement of blood levels. Taking phenytoin with food may reduce some of the side effects. Elderly patients, debilitated persons, and patients with certain kidney or liver diseases may need lower doses. The suspension should not be given at the same time as tube feedings.
Drug Interactions
There are many potential drug interactions with phenytoin. Phenytoin can increase the metabolism (elimination) of many drugs, reducing their concentrations in the body. Drugs that may be affected include: digoxin, carbamazepine, clonazepam, corticosteroids (e.g. prednisone), cyclosporine, disopyramide, doxycycline, estrogens, felodipine, levodopa, lidocaine, methadone, mexiletine, oral contraceptives, paroxetine, quinidine, tacrolimus, theophylline, phenobarbital, and warfarin. Phenytoin can interact with these drugs not only when it is added to therapy but also when it is discontinued. In the latter case, the concentration of the other drugs may increase.
Phenytoin's metabolism may be affected by other drugs. Drugs that can reduce the amount of phenytoin in the body include rifampin and phenobarbital. Drugs that increase phenytoin concentrations include amiodarone, chloramphenicol, cimetidine, disulfiram, fluconazole, fluoxetine, isoniazid (INH), omeprazole, and paroxetine. Thus, measuring levels of phenytoin in the blood may be necessary when patients begin or discontinue other medications.
The oral absorption of phenytoin can be reduced by any of the following: antacids containing magnesium, calcium carbonate, or aluminum; calcium salts; or enteral feeding products (tube feedings). Separating the administration of phenytoin and enteral feeding products, antacids, or calcium salts by at least 2 hours will help avoid this interaction.
Adverse Reactions
Many varied adverse effects can occur during phenytoin therapy including dizziness, drowsiness, difficulty focusing (vision), unsteady gate, tiredness, abnormal involuntary movements, nausea, vomiting, constipation, abdominal pain, and loss of appetite. Children and young adults can develop overgrowth of the gums during long-term therapy which requires regular treatment by a dentist. Good oral hygiene and gum massage may reduce the risk. Rashes can occur in between 1 in 20 and 1 in 10 persons; some may be severe. Additionally, darkening coloration of the skin may develop (more commonly in women). Phenytoin can produce unusual growth of hair in some patients. This reaction most commonly affects the arms and legs but can also affect the trunk and face; it may be irreversible.
Various lymph node reactions have been reported with phenytoin therapy. Lymph nodes may swell up, sometimes painfully. Phenytoin cause serum glucose to rise. Thus, blood sugar should be monitored closely when phenytoin is administered to patients with diabetes. Phenytoin can potentially injure the liver although this is an uncommon occurrence. Phenytoin can cause the platelet or white blood cell counts to drop, increasing the risk of bleeding or infection, respectively. Phenytoin also can cause anemia. Because it interferes with vitamin D metabolism, phenytoin can cause weakening of the bones (osteomalacia). Phenytoin can cause sexual dysfunction including decreased libido, impotence, and priapism (painful, prolonged erections).
Carbamazepine
Carbamazepine is an anti-seizure medication, and mood stabilising drug, used primarily in the treatment of epilepsy and bipolar disorder; but also used to treat schizophrenia and trigeminal neuralgia, a painful nerve condition of the face. Recurrent seizures (epilepsy) are divided into two main categories according to how much of the brain is involved, partial and generalized epilepsy (which includes petit mal, grand mal, and myoclonic epilepsy). Seizures are called "simple" if there is no loss of consciousness and "complex" if there is. Medicines that inhibit seizures are called anti-convulsants. Carbamazepine works as an anti-convulsant for partial and grand mal seizures by reducing or blocking certain responses in the brain. It is also used for treating trigeminal neuralgia. One dosage form, Equetro, has been approved for treating bipolar disorder.
Carbamazepine is used in the treatment of simple and complex partial seizures and in generalized seizures of the grand mal type.a. Equetrol is used to treat bipolar disorder.
Dose
Carbamazepine may be taken with or without food. Carbamazepine is excreted by the kidney and metabolized by the liver and dosages may need to be lowered in patients with liver or kidney dysfunction. Drug blood levels of carbamazepine can be followed.
Drug Interactions
Carbamazepine interacts with multiple drugs and caution should be used in combining other medicines with it. Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin, or primidone. Warfarin, phenytoin, theophylline, and valproic acid are more rapidly metabolized with carbamazepine, while carbamazepine levels are elevated when taken with erythromycin, cimetidine, propoxyphene, and calcium channel blockers. Carbamazepine also increases the metabolism (destruction) of the hormones in birth control pills and can reduce the effectiveness of birth control pills. Unexpected pregnancies have occurred in patients taking both carbamazepine and birth control pills.
Adverse Reactions
Serious side effects include dangerously low red and white blood cell counts. Severe skin reactions can occur as well as serious liver abnormalities, such as hepatitis, resulting in jaundice. Low sodium levels and thyroid abnormalities have been described. Minor more common side effects include dizziness, unsteadiness, nausea, and vomiting.
Anti-Biotic Drugs
An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of "antimicrobials", a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term originally described only those formulations derived from living organisms, but is now applied also to synthetic antimicrobials, such as the sulfonamides. Antibiotics are small molecules with a molecular weight less than 2000 and they are not enzymes.
Unlike previous treatments for infections, which included poisons such as strychnine, antibiotics were labelled "magic bullets": drugs which targeted disease without harming the host. Antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual antibiotics vary widely in their effectiveness on various types of bacteria. Some specific antibiotics (called "narrow-spectrum antibiotics") target either gram-negative or gram-positive bacteria, and others are more wide-spectrum antibiotics. The effectiveness of individual antibiotics varies with the location of the infection and the ability of the antibiotic to reach this site. Oral antibiotics are the simplest approach when effective, with intravenous antibiotics reserved for more serious cases. Antibiotics may sometimes be administered topically, as with eyedrops or ointments.
Side effects
Side effects range from slight headache to a major allergic reaction. One of the more common side effects is diarrhea, which results from the antibiotic disrupting the balance of intestinal flora, the "good bacteria" that dwell inside the human digestive system. Other side effects can result from interaction between the antibiotic and other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.
Antibiotic misuse
Common forms of antibiotic misuse include taking an inappropriate antibiotic, in particular the use of antibacterials for viral infections like the common cold, and failure to take the entire prescribed course of the antibiotic, usually because the patient feels better before the infecting organism is completely eradicated. In addition to treatment failure, these practices can result in antibiotic resistance.
In the United States, a vast quantity of antibiotics is routinely included as low doses in the diet of healthy farm animals, as this practice has been proved to make animals grow faster. Opponents of this practice, however, point out the likelihood that it also leads to antibiotic resistance, frequently in bacteria that are known to also infect humans, although there has been little or no evidence as yet of such transfer of antibiotic resistance actually occurring.
Antibiotic resistance
One side effect of misusing antibiotics is the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms which survived the original treatment. This survival often results from an inheritable resistance to the compound, which was infrequent in the original population but is now much more frequent in the descendants thus selected entirely from those originally infrequent resistant organisms.
Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic. In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the normal, low cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads inexorably to the rise of resistance to those drugs, and a never-ending ever-spiraling race to discover new and different antibiotics ensues, just to keep us from losing ground in the battle against infection. The fear is that we will eventually fail to keep up in this race, and the time when people did not fear life-threatening bacterial infections will be just a memory of a golden era.
Another example of selection is Staphylococcus aureus, which could be treated successfully with penicillin in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistant to nafcillin, leaving only a narrow selection of drugs such as vancomycin useful for treatment. The situation is worsened by the fact that genes coding for antibiotic resistance can be transferred between bacteria, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used widely as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.
Beyond antibiotics
Unfortunately, the comparative ease of finding compounds which safely cured bacterial infections proved much harder to duplicate with respect to fungal and viral infections. Antibiotic research led to great strides in our knowledge of basic biochemistry and to the current biological revolution; but in the process it was discovered that the susceptibility of bacteria to many compounds which are safe to humans is based upon significant differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. In contrast, despite the seemingly huge differences between fungi and humans, the basic biochemistries of the fungal cell and the mammalian cell are much more similar; so much so that there are few therapeutic opportunities for compounds to attack a fungal cell which will not harm a human cell. Similarly, we know now that viruses represent an incredibly minimal intracellular parasite, being stripped down to a few genes worth of DNA or RNA and the minimal molecular equipment needed to enter a cell and actually take over the machinery of the cell to produce new viruses. Thus, the great bulk of viral metabolic biochemistry is not merely similar to human biochemistry, it actually is human biochemistry, and the possible targets of antiviral compounds are restricted to the relatively very few components of the actual virus itself.
Steroids
In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
Synthetic drugs with corticosteroid-like effect are used in a variety of conditions, ranging from brain tumours to skin diseases. Dexamethasone and its derivatives are almost pure glucocorticoids, while prednisolone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef®) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia.
Synthetic glucocorticoids are used in the treatment of joint pain or inflammation (arthritis), dermatitis, allergic reactions, asthma, hepatitis, lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin or inflammatory bowel disease are available.
Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension (abnormally high blood pressure), hypokalemia (low potassium levels in the blood), hypernatremia (high sodium levels in the blood) without causing peripheral edema, and metabolic alkalosis.
Dexamethasone
Dexamethasone is a synthetic adrenal corticosteroid. Corticosteroids are natural substances produced by the adrenal glands located adjacent to the kidneys. Corticosteroids have potent anti-inflammatory properties, and are used in a wide variety of inflammatory conditions such as arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. There are numerous preparations of corticosteroids, including oral tablets, capsules, liquids, topical creams and gels, inhalers and eye drops, and injectable and intravenous solutions. Dexamethasone that is prescribed in oral tablet form is addressed in this article.
Dose
Dosage requirements of corticosteroids vary among individuals and diseases being treated. In general, the lowest possible effective dose is used. Corticosteroids given in multiple doses throughout the day are more effective, but also more toxic, than if the same total dose is given once daily, or every other day. Should be taken with food.
Drug Interactions
Prolonged use of dexamethasone can depress the ability of the body's adrenal glands to produce corticosteroids. Abruptly stopping dexamethasone in these individuals can cause symptoms of corticosteroid insufficiency, with accompanying nausea, vomiting and even shock. Therefore, withdrawal of dexamethasone is usually accomplished by gradual tapering. Gradually tapering dexamethasone not only minimizes the symptoms of corticosteroid insufficiency, it also reduces the risk of an abrupt flare of the disease under treatment.
Dexamethasone and other corticosteroids can mask signs of infection and impair the body's natural immune response to infection. Patients on corticosteroids are more susceptible to infections, and can develop more serious infections than healthy individuals. For instance, chicken pox and measles viruses can produce serious and even fatal illnesses in patients on high doses of dexamethasone. Live virus vaccines, such as small pox vaccine, should be avoided in patients taking high doses of dexamethasone, since even vaccine viruses may cause disease in these patients. Some infectious organisms, such as tuberculosis (TB) and malaria, can remain dormant in a patient for years. Dexamethasone and other corticosteroids can reactivate dormant infections in these patients and cause serious illnesses. Patients with dormant tuberculosis may require anti- TB medications while undergoing prolonged corticosteroid treatment.
By interfering with the patient's immune response, dexamethasone can impede the effectiveness of vaccinations. Dexamethasone can also interfere with the tuberculin (TB) skin test and cause false negative results in patients with dormant tuberculosis infection.
Dexamethasone impairs calcium absorption and new bone formation. Patients on prolonged treatment with dexamethasone and other corticosteroids can develop osteoporosis and an increased risk of bone fractures. Supplemental calcium and vitamin D are encouraged to slow this process of bone thinning. In rare individuals, destruction of large joints can occur while undergoing treatment with dexamethasone or other corticosteroids. These patients experience severe pain in the involved joints, and can require joint replacements. The reason behind such destruction is not clear.
Adverse Reactions
Dexamethasone side effects depend on the dose, the duration and the frequency of administration. Short courses of dexamethasone are usually well tolerated with few and mild side effects. Long term, high doses of dexamethasone will usually produce predictable, and potentially serious side effects. Whenever possible, the lowest effective doses of dexamethasone should be used for the shortest possible length of time to minimize side effects. Alternate day dosing can also help reduce side effects.
Side effects of dexamethasone and other corticosteroids range from mild annoyances to serious irreversible bodily damages. Side effects include fluid retention, weight gain, high blood pressure, potassium loss, headache, muscle weakness, puffiness of and hair growth on the face, thinning and easy bruising of skin, glaucoma, cataracts, peptic ulceration, worsening of diabetes, irregular menses, growth retardation in children, convulsions, and psychic disturbances. Psychic disturbances can include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior. The bone and joint complications of corticosteroids are discussed above in DRUG INTERACTIONS.