July 28th, 2010 by admin

Overview of insulin secretion

An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. They usually work by lowering the glucose levels in the blood. There are different types of anti-diabetic drugs, and their use depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Insulin, exenatide, and pramlintide are the only non-oral antidiabetic drugs. Insulin is the mainstay of treatment in Type I diabetes, in which insulin production is impaired. In Type II diabetes, Insulin is used when oral medication has become ineffective. Exenatide and pramlintide are new injectable medications approved in 2005 in the US by the FDA to treat Diabetes mellitus type 2.

Sulfonylureas

Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the K_ATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The “second-generation” drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.

• First-generation agents
  • tolbutamide (Orinase)
    acetohexamide (Dymelor)
    tolazamide (Tolinase)
    chlorpropamide (Diabinese)
• Second-generation agents
  • glipizide (Glucotrol)
    glyburide (Diabeta, Micronase, Glynase)
    glimepiride (Amaryl)
    gliclazide (Diamicron)

Meglitinides

Meglitinides are related to sulfonylureas and of often called “short-acting secretagogues.” The amplification of insulin release is shorter and more intense, and they are taken with meals to boost the insulin response to each meal.

• repaglinide (Prandin) – The max dosage is 16mg/day. Take this drug 0 to 30 minutes prior before eating a meal. If a meal is skipped, then the medication should also be skipped.
• nateglinide (Starlix) – The max dosage is 360 mg/day, usually 120 mg three times a day (TID). It also follows the same recommendations as repaglinide.

Adverse reactions include weight gain and hypoglycemia.

Biguanides

Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers.

• metformin (Glucophage)
• Phenformin (DBI): used in 1960-1980s, withdrawn due to lactic acidosis risk.

Metformin should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.

Thiazolidinediones

Thiazolidinediones, also known as “glitazones,” bind to PPARγ, a type of nuclear regulatory protein involved in transcription of numerous genes regulating glucose and fat metabolism. They act as “insulin sensitizers” without increasing insulin secretion.

• rosiglitazone (Avandia)
  pioglitazone (Actos)
  troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.

Alpha glucosidase inhibitors

Alpha glucosidase inhibitors are “diabetes pills” but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.

• miglitol (Glyset)
  acarbose (Precose/Glucobay)

These medications are rarely used in the United States because of the severity of their side effects (flatulence and bloating). They are more commonly prescribed in Europe.

Incretin mimetic

Exenatide (also Exendin-4, marketed as Byetta) is the first of a new class of medications approved for the treatment of type 2 diabetes. It is to be used in conjunction with oral medications such as metformin and/or a sulfonylurea to improve glucose control. The medication is injected twice per day using a specially designed pen. The typical human response is both an improvement of the release of internal insulin by the pancreas and suppression of pancreas glucagon release, behaviors more typical of individuals without blood sugar control problems. In the presence of exenatide, these responses are greater when the blood sugar is elevated.

DPP-4 inhibitors

• Dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, sitagliptin) increase blood concentration of GLP-1 (glucagon-like peptide-1).

Amylin analogue

• Pramlintide.

Experimental agents

Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research. Others are undergoing phase I/II studies.

• PPARα/γ ligands (muraglitazar and tesaglitazar) – development stopped due to adverse risk profile
• SGLT (sodium-dependent glucose transporter 1) inhibitors increase urinary glucose.
• FBPase (fructose 1,6-bisphosphatase) inhibitors decrease gluconeogenesis in liver.

Insulin by mouth

The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. Unlike all the oral drugs described in this article, insulin is a protein. Protein hormones, like meat proteins, are digested in the stomach and gut. One alternative delivery method is by inhalation. In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin.

However, the potential market for an oral form of insulin is enormous and many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.[1]

Herbal extracts

The first registred use of anti-diabetic drugs was as herbal extracts used by indians in the Amazon Basin for the treatment of type 2 diabetes, and today promoted as vegetable insulin although not formally an insulin analog.[1] The major recent development was done in Brazil around Myrcia sphaerocarpa and other Myrcia species.

“Many countries, especially in the developing world, have a long history of the use of herbal remedies in diabetes (…) STZ diabetic rats were also used to test Myrcia Uniflora extracts (…) “^[2].

The usual treatment is with concentrated (root) Myrcia extracts, commercialized in a 4 US dollar per kilogram packed rocks (~100 times cheaper than equivalent artificial drugs), named “Pedra hume de kaá”. Phytochemical analysis of the Myrcia extracts reported kinds of flavanone glucosides (myrciacitrins) and acetophenone glucosides (myrciaphenones), and inhibitory activities on aldose reductase and alpha-glucosidase.^[3]

A recent review article presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000 and states that “Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager.”^[4]

References

• Lebovitz HE. Therapy for Diabetes Mellitus and Related Disorders. 4th edition. Alexandria:American Diabetes Association, 2004.
• Holland, Norman & Adams, Michael Patrick. Core Concepts in Pharmacology. Pearson Education, Inc. New Jersey. 2003.

Footnotes

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia.

July 8th, 2010 by admin

An anesthetic (or anaesthetic, see spelling differences) is a drug that causes anesthesia—reversible loss of sensation. These drugs are generally administered to facilitate surgery. A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia, although others are used commonly by all disciplines. Anesthetics are categorized in to two classes: general anesthetics, which cause a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body while maintaining consciousness. Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects, however, adverse effects may also be increased.

A wide variety of drugs are used in modern anaesthetic practice. Many are rarely used outside of anaesthesia, although others are used commonly by all disciplines. Some of the prominent ones include:

• local anaesthetics
• general anaesthetics
  • inhalational anaesthetics
    • volatile anaesthetics
      • desflurane
        sevoflurane
        isoflurane
        halothane
        enflurane
        methoxyflurane
    • nitrous oxide
    • xenon
  • intravenous anaesthetics
    • propofol
      etomidate
    • barbiturates
      • methohexital
        thiopentone/thiopental
    • benzodiazepines
      • midazolam
      • diazepam
    • ketamine
• analgesics
  • opioids
    • morphine
    • fentanyl
    • alfentanil
      sufentanil
      remifentanil
    • methadone
    • meperidine / pethidine
  • NSAIDs
• muscle relaxants
  • depolarising muscle relaxants
    • succinylcholine, also known as suxamethonium
  • nondepolarising (curare-like) muscle relaxants
    • atracurium
      cisatracurium
      vecuronium
      rocuronium
      mivacurium
      tubocurarine (see mislabelled article “turbocurnanine” under “search.” Can this article be placed correctly under tubocurarine also?)
      pancuronium bromide
• vasoconstrictors, also known as vasopressors
  • phenylephrine
  • ephedrine
  • metaraminol
• antiemetics: phenothiazines, e.g.: prochlorperazine, promethazine, cyclizine;
• butyrophenones, e.g.: droperidol; antihistamines, e.g.: dimenhydrinate (old); newer agents: ondansetron and tropisetron, and granisetron; steroids, e.g.: dexamethasone; and lastly, metoclopramide (variable efficacy).

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia.

July 5th, 2010 by admin

An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). This derives from Greek an-, “without”, and -algia, “pain”. Analgesic drugs act in various ways on the peripheral and central nervous system; they include paracetamol (acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others. Some other classes of drugs not normally considered analgesics are used to treat neuropathic pain syndromes; these include tricyclic antidepressants and anticonvulsants.

The major classes

Paracetamol and NSAIDs

The exact mechanism of action of paracetamol is uncertain, but it appears to be acting centrally. Aspirin and the NSAIDs inhibit cyclooxygenase, leading to a decrease in prostaglandin production; this improves pain and also inflammation (in contrast to paracetamol and the opioids).

Paracetamol has few side effects, but dosing is limited by possible hepatotoxicity (potential for liver damage). NSAIDs may predispose to peptic ulcers, renal failure, allergic reactions, and hearing loss. They may also increase the risk of hemorrhage by affecting platelet function. The use of certain NSAIDs in children under 16 suffering from viral illness may contribute to Reye’s syndrome.

COX-2 inhibitors

These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested that most of the adverse effects of NSAIDs were mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as rofecoxib and celecoxib) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular. However post-launch data indicated increased risk of cardiac and cerebrovascular events with these drugs, and rofecoxib was subsequently withdrawn from the market. The role for this class of drug is currently hotly debated.

Opiates and morphinomimetics

Morphine, the archetypal opioid, and various other substances (e.g. pethidine, oxycodone, hydrocodone, diamorphine) all exert a similar influence on the cerebral opioid receptor system. Tramadol and buprenorphine are thought to be partial agonists of the opioid receptors. Dosing of all opioids may be limited by opioid toxicity (confusion, myoclonic jerks and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.

Opioids, while very effective analgesics, may have some unpleasant side-effects. Up to 1 in 3 patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics). Pruritus (itching) may require switching to a different opioid. Constipation occurs in almost all patients on opioids, and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-prescribed.

When used appropriately, opioids and similar narcotic analgesics are safe and effective, carrying relatively little risk of addiction. Occasionally, gradual tapering of the dose is required to avoid withdrawal symptoms.

Specific agents

In patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic antidepressants, especially amitriptyline, have been shown to improve pain in what appears to be a central manner. The exact mechanism of carbamazepine, gabapentin and pregabalin is similarly unclear, but these anticonvulsants are used to treat neuropathic pain with modest success.

Specific forms and uses

Combinations

Analgesics are frequently used in combination, such as the paracetamol 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.

The use of paracetamol concurrently with opiates has been shown to have beneficial synergistic effects and it is generally recommended that they are prescribed together.

Topical or systemic

Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel; capsaicin also is used topically. Lidocaine and steroids may be injected into painful joints for longer-term pain relief. Lidocaine is also used for painful mouth sores and to numb areas for dental work and minor medical procedures.

Psychotropic agents

Tetrahydrocannabinol and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic properties, although the use of cannabis derivatives is illegal in many countries. Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other α2-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues.

Addiction

In the United States in recent years, however, there has been a wave of new addictions to prescription narcotics such as oxycodone (OxyContin) and hydrocodone (Vicodin, Lortab etc.) when available in pure formulations as opposed to combined with other medications (as in Percocet which contains both oxycodone and acetaminophen/paracetamol).

References

• Cancer pain relief and palliative care. Report of a WHO expert committee [World Health Organization Technical Report Series, 804] . Geneva, Switzerland: World Health Organization; 1990. pp. 1-75. ISBN 92-4-120804-X.
• Bandolier pain site (Oxford pain group)

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July 1st, 2010 by admin

Bas-relief at Angkor Wat, Cambodia, c. 1150, depicting a demon inducing an abortion by pounding the abdomen of a pregnant woman with a pestle.

An abortifacient is a substance that induces abortion.

History

The ancient Greek colony of Cyrene at one time had an economy based almost entirely on the production and export of Silphium, a powerful abortifacient in the parsley family. Silphium figured so prominently in the wealth of Cyrene that the plant appeared on the obverse and reverse of coins minted there. Silphium, which was native only to that part of Libya, was overharvested by the Greeks and was effectively driven to extinction.

As the Catholic Church gained control of European society, women who dispensed abortifacient herbs found themselves classified as witches and were often persecuted. ^[1]

Present time

Herbal abortifacients

Many herbs sold “over the counter” today, including Wild carrot, Black cohosh, Pennyroyal, Nutmeg, and Mugwort, are themselves abortifacients. Typically the labeling will contraindicate use by pregnant women, but will not contain an explanation for this contraindication. There are naturally occurring abortifacients like green Papaya and Common Rue though there does not seem to be any available data on their efficacy.

King’s American Dispensatory of 1898 recommended a mixture of brewer’s yeast and pennyroyal tea as “a safe and certain abortive”

Pharmaceutical abortifacients

The methods of operation of prescription drugs used as abortifacients are better understood than those of traditional herbal remedies, but they have been controversial since the 1980s. The most prominent of these is Mifepristone (also known as “RU-486″ and marketed under the brand name “Mifeprex”), which is used in conjunction with Misoprostol (an anti-ulcer drug marketed under the name “Cytotec”). Mifepristone has been approved for inducing abortions in many Western countries since the late 1990s, while this use of Misoprostol is off-label.

Misoprostol alone is sometimes used for self-induced abortion in Latin American countries where legal abortion is not available, and by some immigrants from these countries in the United States who cannot afford a legal abortion.

Pre-implantation labeling controversy

There is controversy as to whether a woman is pregnant at the time of fertilization, or at the implantation of the blastocyst in the uterine lining. Some agents have a proposed back-up effect of preventing implantation and thus destroying the blastocyst, although their primary effect is to prevent fertilization. American federal and British laws mark the beginning of pregnancy at implantation; thus, these agents are labeled as contraceptives, rather than abortifacients. They are generally not effective if taken after implantation.^[2] Labeling of these agents as abortifacient is most ardently supported by those opposed to abortion, ^[3] usually due to their belief that human life begins at fertilization. The following agents may prevent implantation of a blastocyst, although, in most cases, they merely prevent fertilization:^[4]

• Hormonal contraceptives
  • Combined estrogen & progesterone:
    • Combined oral contraceptive pill (“The Pill”)*
      Contraceptive patch
      Contraceptive vaginal ring
      Lunelle (monthly injection)
  • Progesterone used alone:
    • Progesterone only pill (POP)*
      Depo Provera (injection every three months)
      Implants (such as Norplant or Implanon)
      IntraUterine System (“IUS”)
• Intrauterine device (“IUD”)*
• Some herbal contraceptives may work primarily by preventing implantation

(*) These methods may also be used as Emergency contraception. POPs are also packaged for use as emergency contraception under the brand name “Plan B”.

References

1. ^ Kramer, Heinrich, & Sprenger, Jacob. (1487). Malleus Maleficarum. (Montague Summers, Trans.). Retrieved June 3, 2006.
2. ^ Vivian M. Dickerson (June 2005). Emergency Contraception: Out of Sight, Out of Mind? (PDF). Advanced Studies in Medicine, Vol. 5, No. 6 pp. 283-284. Johns Hopkins University, School of Medicine. Retrieved on 2006-08-03.
3. ^ Finn, J.T. (2005-04-23). “Birth Control” Pills cause early Abortions. Pro-Life America — Facts on Abortion. prolife.com. Retrieved on 2006-08-25.
4. ^ Abortion Facts. Center for Bio-Ethical Reform. Retrieved on 2006-08-03.

Links

• SisterZeus on Pregnancy Termination
• Signs of pregnancy

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia.