METFORMIN

 

ACTIONS AND USES: Metformin is a preferred oral antidiabetic drug for managing type 2 DM because of its effectiveness and safety. It is used alone or in combination with other antidiabetic medications or insulin. It is approved for use in children age 10 or above. It is available as regular-release tablets, solution, and sustained-release forms. Metformin reduces fasting and postprandial glucose levels by decreasing the hepatic production of glucose by the process of gluconeogenesis and reducing insulin resistance. It does not promote insulin release from the pancreas. A major advantage of the drug is that it does not cause hypoglycemia. The drug's actions do not depend on stimulating insulin release, so it is able to lower glucose levels in patients who no longer secrete insulin. In addition to lowering blood glucose levels, it lowers triglyceride and total and low-density lipoprotein (LDL) cholesterol levels, and it promotes weight loss. Metformin reduces insulin resistance, which in turn lowers insulin and androgen levels, thus restoring normal menstrual cycles and ovulation.

ADMINISTRATION ALERTS: Sustained-release tablets must be swallowed whole and not crushed or chewed. Fasting blood glucose levels should be obtained every 3 months, and the dose adjusted accordingly. Discontinue the medication immediately if signs of acidosis are present. Pregnancy category B.

PHARMACOKINETICS: Onset Peak Duration Less than 1 h 1–3 h (regular release); 4–8 h (extended release) 12 h (regular release); 24 h (extended release)

ADVERSE EFFECTS: The most common adverse effects are GI related and include nausea, vomiting, abdominal discomfort, metallic taste, diarrhea, and anorexia. It may also cause headache, dizziness, agitation, and fatigue. Unlike the sulfonylureas, metformin rarely causes hypoglycemia or weight gain.

Warning: Lactic acidosis is a rare, though potentially fatal, adverse effect. The risk for lactic acidosis is increased in patients with renal insufficiency or any condition that puts them at risk for increased lactic acid production, such as liver disease, severe infection, excessive alcohol intake, shock, or hypoxemia.

RELATED;

1. DIABETES MELLITUS

2. INSULIN

3.  PATHOPHYSIOLOGY OF DIABETES

4.  PHARMACOLOGY AND THERAPEUTICS

MEGALOBLASTIC ANEMIA

 

INTRODUCTION: In the anemias caused by deficiencies of vitamin B12 or folic acid, identical bone marrow and peripheral blood changes occur because both vitamins are essential for normal DNA synthesis. DNA,the genetic material

PATHOPHYSIOLOGY:

Folic Acid Deficiency: Folic acid is stored as compounds referred to as folates. The folate stores in the body are much smaller than those of vitamin B12, and they are quickly depleted when the dietary intake of folate is deficient (within 4 months). Folate deficiency occurs in people who rarely eat uncooked vegetables. Alcohol increases folic acid requirements; folic acid requirements are also increased in patients with chronic hemolytic anemias and in women who are pregnant. Some patients with malabsorptive diseases of the small bowel may not absorb folic acid normally.

Vitamin B12 Deficiency: A deficiency of vitamin B12 can occur in several ways. Inadequate dietary intake is rare but can develop in strict vegetarians who consume no meat or dairy products. Faulty absorption from the GI tract is more common, as with conditions such as Crohn’s disease or after ileal resection or gastrectomy. Another cause is the absence of intrinsic factor. A deficiency may also occur if disease involving the ileum or pancreas impairs absorption. The body normally has large stores of vitamin B12, so years may pass before the deficiency results in anemia.

Clinical Manifestations: Symptoms of folic acid and vitamin B12 deficiencies are similar, and the two anemias may coexist. Symptoms are progressive, although the course of illness may be marked by spontaneous partial remissions and exacerbations. Gradual development of signs of anemia (weakness, listlessness, and fatigue). Possible development of a smooth, sore, red tongue and mild diarrhea (pernicious anemia). Mild jaundice, vitiligo, and premature graying. Confusion may occur; more often, paresthesias in the extremities and difficulty keeping balance; loss of position sense. Lack of neurologic manifestations with folic acid deficiency alone. Without treatment, patients die, usually as a result of heart failure secondary to anemia.

ASSESSMENT AND DIAGNOSTIC FINDINGS: Schilling test (primary diagnostic tool): Complete blood cell count (Hgb value as low as 4 to 5 g/dL, WBC count 2,000 to 3,000 mm3 , platelet count fewer than 50,000 mm3 ; very high MCV, usually exceeding 110 m3 ). Serum levels of folate and vitamin B12 (folic acid deficiency and deficient vitamin B12)

MEDICAL MANAGEMENT: Folic Acid Deficiency: Increase intake of folic acid in patient’s diet and administer 1 mg folic acid daily. Administer IM folic acid for malabsorption syndromes. Prescribe additional supplements as necessary, because the amount in multivitamins may be inadequate to fully replace deficient body stores. Prescribe folic acid for patients with alcoholism as long as they continue to consume alcohol.

MEDICAL MANAGEMENT: Vitamin B12 Deficiency: Provide vitamin B12 replacement: Vegetarians can prevent or treat deficiency with oral supplements with vitamins or fortified soy milk; when the deficiency is due to the more common defect in absorption or the absence of intrinsic factor, replacement is by monthly IM injections of vitamin B12. A small amount of an oral dose of vitamin B12 can be absorbed by passive diffusion, even in the absence of intrinsic factor, but large doses (2 mg/day) are required if vitamin B12 is to be replaced orally. To prevent recurrence of pernicious anemia, vitamin B12 therapy must be continued for life.

RELATED;

1.  CONDITIONS OF ANEMIA  

2.  COMPOSITION OF BLOOD

3.  MEDICAL CONDITIONS

REFERENCES

OPIOID ANALGESICS

 

Introduction: Successful treatment of pain is a challenging task that begins with careful attempts to assess the source and magnitude of the pain. The amount of pain experienced by the patient is often measured by means of a pain Numeric Rating Scale (NRS) or less frequently by marking a line on a Visual Analog Scale (VAS) with word descriptors ranging from no pain (0) to excruciating pain (10). In either case, values indicate the magnitude of pain as: mild (1–3), moderate (4–6), or severe (7–10).  For a patient in severe pain, the administration of an opioid analgesic is usually considered a primary part of the overall management plan. Determining the route of administration, duration of drug action, ceiling effect also known as maximal intrinsic activity, duration of therapy, potential for adverse effects, and the patient’s past experience with opioids all should be addressed.  Use of opioid drugs in acute situations may be contrasted with their use in chronic pain management, in which a multitude of other factors must be considered, including the development of tolerance to and physical dependence on opioid analgesics.

Clinical Use of Opioid Analgesics:  1)  Analgesia: Severe, constant pain is usually relieved with opioid analgesics with high intrinsic activity. This includes the pain associated with cancer and other terminal illnesses. Such conditions may require continuous use of potent opioid analgesics and are associated with some degree of tolerance and dependence. Opioid analgesics are also often used during obstetric labor. Because opioids cross the placental barrier and reach the fetus, however care must be taken to minimize neonatal depression. If it occurs, immediate injection of the antagonist naloxone will reverse the depression.  

2)  Acute Pulmonary Edema: The relief produced by intravenous morphine in dyspnea from pulmonary edema associated with left ventricular heart failure is remarkable. Proposed mechanisms include reduced anxiety and reduced cardiac preloa and afterload. However, if respiratory depression is a problem, furosemide may be preferred for the treatment of pulmonary edema. On the other hand, morphine can be particularly useful when treating painful myocardial ischemia with pulmonary edema.  

3) Cough: Suppression of cough can be obtained at doses lower than those needed for analgesia. However, in recent years the use of opioid analgesics to allay cough has diminished largely because a number of effective synthetic compounds have been developed that are neither analgesic nor addictive.  

4)  Diarrhea: Diarrhea from almost any cause can be controlled with the opioid analgesics, but if diarrhea is associated with infection such use must not substitute for appropriate chemotherapy. Crude opium preparations were used in the past to control diarrhea, but now synthetic surrogates with more selective gastrointestinal effects and few or no CNS effects, such as diphenoxylate or loperamide, are used.  

5)  Shivering: Although all opioid agonists have some propensity to reduce shivering, meperidine is reported to have the most pronounced anti-shivering properties. Meperidine apparently blocks shivering mainly through an action on subtypes of the α2 adrenoceptor.  

6)  Applications in Anesthesia: The opioids are frequently used as premedicant drugs before anesthesia and surgery because of their sedative, anxiolytic, and analgesic properties. They are also used intra-operatively both as adjuncts to other anesthetic agents and, in high doses, as a primary component of the anesthetic regimen . Opioids are most commonly used in cardiovascular surgery and other types of high-risk surgery in which a primary goal is to minimize cardiovascular depression. In such situations, mechanical respiratory assistance must be provided.

RELATED; 

1.  CORTICOSTEROIDS  

2.  CHRONIC INFLAMMATION

3.  MORPHINE

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

ARTEMISININ & ITS DERIVATIVES

INTRODUCTION: Artemisinin is a sesquiterpene lactone endoperoxide, the active component of an herbal medicine that has been used as an antipyretic in China for over 2000 years. Artemisinin is insoluble and can only be used orally. However, analogs have been synthesized to increase solubility and improve antimalarial efficacy. The most important of these analogs are artesunate which is water-soluble and is useful for oral, intravenous, intramuscular, and rectal administration. The other one is artemether which is lipid-soluble and useful for oral, intramuscular, and rectal administration, and dihydroartemisinin which is water-soluble and useful for oral administration.

CHEMISTRY & PHARMACOKINETICS: Artemisinin and its analogs are rapidly absorbed, with peak plasma levels occurring in 1–2 hours and half-lives of 1–3 hours after oral administration. Artemisinin, artesunate, and artemether are rapidly metabolized to the active metabolite dihydroartemisinin. Drug levels appear to decrease after a number of days of therapy.

Artemether-lumefantrine (Coartem, Lumartem, Combiat, Riamet): Co-formulated; first-line therapy in many countries; approved in the USA

Artesunate-amodiaquine (ASAQ, Arsucam, Coarsucam): Co-formulated; first-line therapy in many African countries

Artesunate-mefloquine: Co-formulated; first-line therapy in parts of Southeast Asia and South America.

Dihydroartemisinin-piperaquine (Artekin, Duocotecxin): Co-formulated; first-line therapy in some countries in Southeast Asia

Artesunate-sulfadoxine-pyrimethamine: First-line therapy in some countries, but efficacy lower than other regimens in most areas.

CLINICAL USES: Artemisinin-based combination therapy is now the standard for treatment of uncomplicated falciparum malaria in nearly all areas endemic for falciparum malaria. These regimens were developed because the short plasma half-lives of the artemisinins led to unacceptably high recrudescence rates after short-course therapy, which were reversed by inclusion of longer-acting drugs. Combination therapy also helps to protect against the selection of artemisinin resistance. However, with completion of dosing after 3 days, the artemisinin components are rapidly eliminated, and so selection of resistance to partner drugs is of concern. The WHO recommends five artemisinin-based combinations for the treatment of uncomplicated falciparum malaria. One of these, artesunate-sulfadoxine-pyrimethamine is not recommended in many areas owing to unacceptable levels of resistance to sulfadoxine-pyrimethamine, but it is the first-line therapy in some countries in Asia, South America, and North Africa. The other four recommended regimens are now all available as combination formulations, although manufacturing standards may vary. Artesunate-mefloquine is highly effective in Southeast Asia, where resistance to many antimalarials is common; it is the first-line therapy in some countries in Southeast Asia and South America. This regimen is less practical for other areas, particularly Africa, because of its relatively high cost and poor tolerability. Either artesunate-amodiaquine or artemether-lumefantrine is now the standard treatment for uncomplicated falciparum malaria in most countries in Africa and some additional endemic countries on other continents. Dihydroartemisinin-piperaquine is a newer regimen that has shown excellent efficacy; it is the first-line therapy for falciparum malaria in Vietnam. T he relative efficacy and safety of artemisinin-based combination therapies are now under active investigation. In general, the leading regimens are highly efficacious, safe, and well tolerated, and they are the new standard of care for the treatment of uncomplicated falciparum malaria. Artemisinins are also proving to have outstanding efficacy in the treatment of complicated falciparum malaria. Large randomized trials and meta-analyses have shown that intramuscular artemether has an efficacy equivalent to that of quinine and that intravenous artesunate is superior to intravenous quinine in terms of parasite clearance time and—most important—patient survival. Intravenous artesunate also has a superior side-effect profile compared with that of intravenous quinine or quinidine. Thus, intravenous artesunate will likely replace quinine as the standard of care for the treatment of severe falciparum malaria, although it is not yet widely available in most areas. Artesunate and artemether have also been effective in the treatment of severe malaria when administered rectally, offering a valuable treatment modality when parenteral therapy is not available.

ADVERSE EFFECTS & CAUTIONS: Artemisinins are generally very well tolerated. The most commonly reported adverse effects are nausea, vomiting, diarrhea, and dizziness, and these may often be due to underlying malaria rather than the medications. Rare serious toxicities include neutropenia, anemia, hemolysis, elevated liver enzymes, and allergic reactions. Irreversible neurotoxicity has been seen in animals, but only after doses much higher than those used to treat malaria. Artemisinins have been embryotoxic in animal studies, but rates of congenital abnormalities, stillbirths, and abortions were not elevated, compared with those of controls, in women who received artemisinins during pregnancy. Based on this information and the significant risk of malaria during pregnancy, the WHO recommends artemisininbased combination therapies for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy, intravenous artesunate or quinine for the treatment of severe malaria during the first trimester, and intravenous artesunate for treatment of severe malaria during the second and third trimesters.

RELATED;

1.  PENICILLINS  

2.  AZITHROMYCIN

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

FETAL DIAGNOSIS

INTRODUCTION: Several procedures are currently available to determine certain kinds of abnormalities in a fetus or to monitor development.  We should once again remember that the human gestation age goes 40 weeks from the days of the last normal menstruations period.  And although for some people this period may be less or slightly more, the fetus is always monitored with non invasive procedures to make sure that it's life is not in danger and any concerns diagnosed are addressed right away.

ULTRASOUND (OR FETAL ULTRASONOGRAPHY): This is a non-invasive procedure; high-frequency sound waves are transmitted through the abdominal wall into the uterus. The reflected sound waves are converted into an image called a sonogram. This method is used to confirm multiple pregnancies, fetal age or position, or to detect fetal abnormalities such as heart defects or malformations of other organs. Ultrasound may also be used to determine the thickness of the fetal neck, which is an indicator of Down syndrome.

AMNIOCENTESIS: This procedure is usually performed at 16 to 18 weeks of gestation. A hypodermic needle is inserted through the wall of the abdomen into the amniotic sac, and about 10 to 20 mL of amniotic fluid is removed. Within this fluid are fetal cells, which can be cultured so that their chromosomes may be examined. Through such examination and biochemical tests, a number of genetic diseases or chromosome abnormalities may be detected. Because women over the age of 35 years are believed to have a greater chance of having a child with Down syndrome, amniocentesis is often recommended for this age group. A family history of certain genetic diseases is another reason a pregnant woman may wish to have this procedure.

CHORIONIC VILLUS SAMPLING (CVS): In this procedure, a biopsy catheter is inserted through the vagina and cervix to collect a small portion of the chorionic villi. These cells are derived from the fetus but are not part of the fetus itself. The information obtained is the same as that for amniocentesis, but CVS may be performed earlier in pregnancy, at about 8 weeks. Although there is a risk that the procedure may cause a miscarriage, CVS is considered comparable in safety to amniocentesis. It is important to remember that no invasive procedure is without risks.

MATERNAL BLOOD TESTS: Alpha-fetoprotein (AFP) is produced by the fetus and is found in maternal circulation. The level reaches a peak between 12 and 15 weeks of gestation, and should then decrease. If AFP is still high after 16 to 18 weeks, there is a 95% chance that the fetus has spina bifida or anencephaly, malformations of the central nervous system. Maternal blood levels of pregnancy-associated plasma protein A (PAPP-A) and beta hCG can be measured during the first trimester. These tests, in conjunction with ultrasound, can reliably detect Down syndrome.

RELATED;

1. DRUG USE AND PREGNANCY  

2. HEMMOLYTIC DISEASE OF THE NEW BORN

3.  NORMAL LABOR AND VARGINAL DELIVERY

REFERENCES

CATEGORIES OF DRUGS IN RELATION TO PREGNANCY

 

INTRODUCTION:  Drug use during pregnancy is one of the most important threats to worry about in order to ensure the safety of the mother and the baby.  In the first place although the mother may have less or no effect, our fear rotates around the growing fetus that may take in the drug via the placenta and develop fetal malformations.

1.  RISK CATEGORY A

INTERPRETATION: Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy.

EXAMPLE OF DRUGS: Prenatal multivitamins, insulin, thyroxine, folic acid.

2.  RISK CATEGORY B

INTERPRETATION: Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women.

OR

Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate risk to the fetus in any trimester.

EXAMPLE OF DRUGS: Penicillins, cephalosporins, azithromycin, acetaminophen, ibuprofen in the first and second trimesters.

3.  RISK CATEGORY C

INTERPRETATION: Animal studies have shown an adverse effect and there are no adequate and well controlled studies in pregnant women.

OR

No animal studies have been conducted and there are no adequate and well controlled studies in pregnant women.

EXAMPLE OF DRUGS: Most prescription medicines; antimicrobials such as clarithromycin, fluoroquinolones, and Bactrim; selective serotonin reuptake inhibitors (SSRIs); corticosteroids; and most antihypertensives.

4.  RISK CATEGORY D

INTERPRETATION: Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective.

EXAMPLE OF DRUGS: Alcohol, ACE inhibitors, angiotensin receptor blockers (ARBs) in the second and third trimesters, gentamicin, carbamazepine, cyclophosphamide, lithium carbonate, methimazole, mitomycin, nicotine, nonsteroidal antiinflammatory drugs (NSAIDs) in the third trimester, phenytoin, propylthiouracil, streptomycin, tetracyclines, valproic acid.

5.  RISK CATEGORY X

INTERPRETATION: Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant. There is no indication for use in pregnancy.

EXAMPLE OF DRUGS: Clomiphene, fluorouracil, isotretinoin, leuprolide, menotropins, methotrexate, misoprostol, nafarelin, oral contraceptives, raloxifene, ribavirin, statins, temazepam, testosterone and thalidomide, and warfarin.

RELATED;

1.  HEMORRHAGIC DISEASE OF THE NEW BORN  

2.  ENDOMETRIOSIS

3.  OBSTETRICS AND GYNECOLOGY

REFERENCES

JAUNDICE

 

Objectives this article:  By the end of this article, the learner will be able to; 

1.  understand the cause of the yellow color that appear in mucous membranes.

2.  Explain the role of the liver in elimination of bilirubin

INTRODUCTION: Jaundice is not a disease, but rather a sign caused by excessive accumulation of bilirubin in the blood. Because one of the liver’s many functions is the excretion of bilirubin, jaundice may be a sign of liver disease such as hepatitis or cirrhosis. Hepatitis

This may be called hepatic jaundice, because the problem is with the liver. Other types of jaundice are prehepatic jaundice and posthepatic jaundice: The name of each tells us where the problem is. Recall that bilirubin is the waste product formed from the heme portion of the hemoglobin of old RBCs. Hemoglobin: The human red blood cells

PATHOPHYSIOLOGY: Prehepatic jaundice means that the problem is “before” the liver; that is, hemolysis of RBCs is taking place at a more rapid rate. Rapid hemolysis is characteristic of sickle cell anemia, malaria, and Rh disease of the newborn; these are hemolytic anemias. Sickle cell anaemia: Rh disease of the newborn

As excessive numbers of RBCs are destroyed, bilirubin is formed at a faster rate than the liver can excrete it. The bilirubin that the liver cannot excrete remains in the blood and causes jaundice. Another name for this type is hemolytic jaundice.

Posthepatic jaundice means that the problem is “after” the liver. The liver excretes bilirubin into bile, which is stored in the gallbladder and then moved to the small intestine. If the bile ducts are obstructed, perhaps by gallstones or inflammation of the gallbladder, bile cannot pass to the small intestine and backs up in the liver. Bilirubin may then be reabsorbed back into the blood and cause jaundice. Another name for this type is obstructive jaundice.

RELATED;

1.  THE CYTOCHROME P450 ENZYME SYSTEM  

2.  CATALASE

3.  FUNCTIONS OF THE LIVER

4.  MEDICAL CONDITIONS

REFERENCES

SULFONAMIDES

 

INTRODUCTION: Sulfonamides with varying physical, chemical, pharmacologic, and antibacterial properties are produced by attaching substituents to the amido group (–SO₂–NH–R) or the amino group (–NH₂ ) of the sulfanilamide nucleus. Sulfonamides tend to be much more soluble at alkaline than at acid pH. Most can be prepared as sodium salts, which are used for intravenous administration.

MECHANISM OF ACTION & ANTIMICROBIAL ACTIVITY: Sulfonamide-susceptible organisms, unlike mammals, cannot use exogenous folate but must synthesize it from PABA. This pathway is thus essential for production of purines and nucleic acid synthesis. Nucleic acids  As structural analogs of PABA, sulfonamides inhibit dihydropteroate synthase and thus folate production.

SPECTRUM OF ACTIVITY: Sulfonamides inhibit both gram-positive and gram-negative bacteria, Nocardia sp, Chlamydia trachomatis, and some protozoa. Some enteric bacteria, such as Escherichia coli, Klebsiella pneumoniae, Salmonella, Shigella, and Enterobacter sp are also inhibited. It is interesting to note however that rickettsiae are not inhibited by sulfonamides but are instead stimulated in their growth. The activity is poor against anaerobes. Pseudomonas aeruginosa is intrinsically resistant to sulfonamide antibiotics. Bacteriology: Antibiotics  Combination of a sulfonamide with an inhibitor of dihydrofolate reductase (trimethoprim or pyrimethamine) provides synergistic activity because of sequential inhibition of folate synthesis.

RESISTANCE: Mammalian cells and some bacterial cells lack the enzymes required for folate synthesis from PABA and depend on exogenous sources of folate; therefore, they are not susceptible to sulfonamides. Sulfonamide resistance may occur as a result of mutations that; (1) cause overproduction of PABA, (2) cause production of a folic acid-synthesizing enzyme that has low affinity for sulfonamides, or (3) impaired permeability to the sulfonamide.

CLINICAL USES: Sulfonamides are infrequently used as single agents. Many strains of formerly susceptible species, including meningococci, pneumococci, streptococci, staphylococci, and gonococci, are now resistant. Antimicrobial drug resistance  The fixed-drug combination of trimethoprim-sulfamethoxazole is the drug of choice for infections such as Pneumocystis jiroveci (formerly P. carinii) pneumonia, toxoplasmosis, nocardiosis, and occasionally other bacterial infections.

ORAL ABSORBABLE AGENTS: Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents used almost exclusively to treat urinary tract infections. The usual adult dosage is 1 g of sulfisoxazole four times daily or 1 g of sulfamethoxazole two or three times daily. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade. The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. Sulfadoxine is the only long-acting sulfonamide currently available in many countries including sub Saharan Africa, and only as a combination formulation with pyrimethamine (Fansidar), a second-line agent in the treatment of malaria.

ORAL NONABSORBABLE AGENTS: Sulfasalazine (salicylazosulfapyridine) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease.

TOPICAL AGENTS: Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma. Another sulfonamide, mafenide acetate, is used topically but can be absorbed from burn sites. The drug and its primary metabolite inhibit carbonic anhydrase and can cause metabolic acidosis, a side effect that limits its usefulness. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds.

ADVERSE REACTIONS: All sulfonamides, including antimicrobial sulfas, diuretics, diazoxide, and the sulfonylurea hypoglycemic agents, have been considered to be partially cross-allergenic. The most common adverse effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea, and difficulties referable to the urinary tract. Other unwanted effects include stomatitis, conjunctivitis, arthritis, hematopoietic disturbances, hepatitis, and, rarely, polyarteritis nodosa and psychosis.

RELATED;

1.  Artemisinin and its derivatives

2.  Antibiotics

3.  Metronidazole

4.  Pharmacology and therapeutics

REFERENCES

ALLERGY

 

INTRODUCTION: An allergy is a hypersensitivity to a particular foreign antigen, called an allergen. Allergens include plant pollens, foods, chemicals in cosmetics, antibiotics such as penicillin, dust, and mold spores. Such allergens are not themselves harmful. Most people, for example, can inhale pollen, eat peanuts, or take penicillin with no ill effects.

HYPERSENSITIVITY: Hypersensitivity means that the immune system overresponds to the allergen, and produces tissue damage by doing so. Allergic responses are characterized by the production of IgE antibodies, which bond to mast cells. Mast cells are specialized connective tissue cells and are numerous in the connective tissue of the skin and mucous membranes.

INFLAMMATORY MEDIATORS: Chemicals in mast cells include histamine and leukotrienes, which are released by the bonding of IgE antibodies or when tissue damage occurs. These chemicals contribute to the process of inflammation by increasing the permeability of capillaries and venules. Tissue fluid collects and more WBCs are brought to the damaged area. In an allergic reaction, the effects of inflammatory chemicals create symptoms such as watery eyes and runny nose (hay fever) or the more serious wheezing and difficult breathing that characterize asthma. Several medications are available to counteract these effects.

ANAPHYLACTIC SHOCK: Anaphylactic shock is an extreme allergic response that may be elicited by exposure to penicillin or insect venoms. On the first exposure, the person becomes highly sensitized to the foreign antigen. On the second exposure, histamine is released from mast cells throughout the body and causes a drastic decrease in blood volume. The resulting drop in blood pressure may be fatal in only a few minutes. People who know they are allergic to bee stings, for example, may obtain a self-contained syringe of epinephrine to carry with them. Epinephrine can delay the progression of anaphylactic shock long enough for the person to seek medical attention.

RELATED;

1.  IMMUNOGLOBULINS  

2.  IMMUNISATION

3.  MEDICAL CONDITIONS

REFERENCES

ISONIAZID (INH)

 

Therapeutic Class: Antituberculosis drug

Pharmacologic Class: Mycolic acid inhibitor

Actions and uses: Isoniazid is a first-line drug for the treatment of M. tuberculosis because decades of experience have shown it to have a superior safety profile and to be the most effective, single drug for the infection. The drug acts by inhibiting the synthesis of mycolic acids, which are essential components of mycobacterial cell walls. It is bacteriocidal for actively growing organisms but bacteriostatic for dormant mycobacteria. It is selective for M. tuberculosis. Isoniazid may be used alone for chemoprophylaxis, or in combination with other antituberculosis drugs for treating active disease. Approximately 10% of patients will develop resistance to isoniazid during long-term therapy.

Administration alerts: Give on an empty stomach, 1 hour after or 2 hours before meals. For IM administration, administer deep IM, and rotate sites. The drug is pregnancy category C.

Adverse effects: The most common adverse effects of isoniazid are numbness of the hands and feet, rash, and fever. Neurotoxicity is a concern during therapy, and patients may exhibit paresthesia of the feet and hands, convulsions, optic neuritis, dizziness, coma, memory loss, and various psychoses.

Warning: Although rare, hepatotoxicity is a serious and sometimes fatal adverse effect; thus, the patient should be monitored carefully for jaundice, fatigue, elevated hepatic enzymes, or loss of appetite. Liver enzyme tests are usually performed monthly during therapy to identify early hepatotoxicity. Hepatotoxicity usually appears in the first 1 to 3 months of therapy but may occur at any time during treatment. Older adults and those with daily alcohol consumption are at greater risk of developing hepatotoxicity.

Contraindications: Isoniazid is contraindicated in patients with hypersensitivity to the drug and in patients with severe hepatic impairment.

Interactions: Drug–Drug: Aluminum-containing antacids should not be administered concurrently because they can decrease the absorption of isoniazid. When disulfiram is taken with INH, lack of coordination or psychotic reactions may result. Drinking alcohol with INH increases the risk of hepatotoxicity. Isoniazid may increase serum levels of phenytoin and carbamazepine.

Treatment of Overdose: Isoniazid overdose may be fatal. Treatment is mostly symptomatic. Pyridoxine (vitamin B6) may be infused in a dose equal to that of the isoniazid overdose to prevent seizures and to correct metabolic acidosis. The dose may be repeated several times until the patient regains consciousness

RELATED;

1. DRUG USE IN RELATION TO PREGNANCY  

2. TUBERCULOSIS

3.  ETHAMBUTOR

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

HISTAMINE H2 RECEPTOR BLOCKERS

 

INTRODUCTION: Histamine has two types of receptors: H1 and H2. Activation of H1 receptors produces the classic symptoms of inflammation and allergy, whereas the H2 receptors are responsible for increasing acid secretion in the stomach. The H2-receptor antagonists are effective at suppressing the volume and acidity of parietal cell secretions. Duodenal ulcers usually heal in 6 to 8 weeks, and gastric ulcers may require up to 12 weeks of therapy. All of the H2-receptor antagonists are available OTC for the short-term (2 weeks) treatment of GERD.

Prototype Drug: Ranitidine

Therapeutic Class: Antiulcer drug

Pharmacologic Class: H2-receptor antagonist

ACTIONS AND USES: Ranitidine acts by blocking H2 receptors in the stomach to decrease acid production. It has a higher potency than cimetidine, which allows it to be administered once daily, usually at bedtime. Adequate healing of the ulcer takes approximately 4 to 8 weeks, although those at high risk for PUD may continue on drug maintenance for prolonged periods to prevent recurrence. Gastric ulcers require longer therapy for healing to occur. Intravenous (IV) and intramuscular (IM) forms are available for the treatment of acute, stress-induced bleeding ulcers. Ranitidine is available in a dissolving tablet form for treating GERD in children and infants older than 1 month of age. 

ADMINISTRATION ALERT: Administer after meals and monitor liver and renal function.

Pregnancy category B (Read about drug use in relation to pregnancy)

ADVERSE EFFECTS: Adverse effects are uncommon and mild. Ranitidine does not cross the blood–brain barrier to any appreciable extent, so it does not cause the confusion and

CNS depression observed with cimetidine. Although rare, severe reductions in the number of red and white blood cells and platelets are possible; thus, periodic blood counts may be performed. High doses may result in impotence or loss of libido in men.

Contraindications: Contraindications include hypersensitivity to H2-receptor antagonists, acute porphyria, and OTC administration in children less than 12years of age.

INTERACTIONS: Drug–Drug: Ranitidine has fewer drug–drug interactions than cimetidine. Ranitidine may reduce the absorption of cefpodoxime, ketoconazole, and itraconazole. Antacids should not be given within 1 hour of H2-receptor antagonists because the effectiveness may be decreased due to reduced absorption. Smoking decreases the effectiveness of ranitidine.

Lab Tests: Ranitidine may increase the values of serum creatinine, AST, ALT, LDH, alkaline phosphatase, and bilirubin. It may produce false positives for urine protein.

Herbal/Food: Absorption of vitamin B12 depends on an acidic environment; thus, deficiency may occur. Iron is also better absorbed in an acidic environment.

RELATED;

1. PROTON PUMP INHIBITORS  

2. ANTIBIOTICS  

3. PEPTIC ULCER DISEASE

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

CANDIDIASIS

INTRODUCTION:  This is a fungal infection that is common especially in immunocompromised patients.  Usually fungi microbes are not a big burden in immunocompetent individuals and if the do infect an individual, in most cases they will be asymptomatic.  The commonest of these fungal species is Candida albicans.  Other important species include; Candida tropicalis, C. pseudotropicalis, C. brumptii, C. parapsilosis, C. guilliermondii, C. krusei.  

MORPHOLOGY AND REPRODUCTION:  The thallus of Candida consists of yeast cells and pseudohyphae. They reproduce by budding, ferment a number of sugars and assimilate nitrogen.  Microscopic examination of pathological material shows round or oval yeast cells in the process of budding and often exhibiting pseudohyphae.

PATHOGENESIS:  Under normal conditions this fungus is not pathogenic. Many factors predispose to pathogenic effect and these include the following;

1.  Impaired immune defences,

2. Pregnancy

3. Spontaneous hormonal

4. Menopause changes

5. Premature birth

6. Use of Corticosteroids

7. Immunosuppression

8. Long-term antibiotic therapy

9. Oral contraceptives

10. Diabetes mellitus

11. Pre-existing lesions of skin

CLINICAL FEATURES:  A variety of infections are caused by Candida species though it is an opportunistic fungus.  In addition to general predisposing factors, following local conditions also predispose to this infection: Chemical, mechanical or biological irritants, Reduced salivation, Digestive disorders, Remnants of milk left fermenting in the mouth of infants.

LABORATORY DIAGNOSIS:  Collection of Infected Material Skin or nail scrapings, mucous patches from the mouth, vagina or anus, sputum, blood, CSF or faeces may be collected for diagnosis in the laboratory. The material should be collected in sterile containers or as smears on slides.

TREATMENT:  Predisposing factors should be eliminated. The affected area should be kept dry.  Topical application of nystatin and systemic treatment with Amphotericin B, oral ketoconazole and fluconazole is effective.

 

RELATED;

1.  INTRODUCTION TO FUNGI

2.  AMPHOTERICIN B

3.  OPPORTUNISTIC MYCOSES

REFERENCES

ANTIBACTERIAL PROPERTIES OF GOLDENSEAL

 

INTRODUCTION:  Goldenseal (Hydrastis canadensis) was once a common plant found in woods in the eastern and midwestern United States. Native Americans used the root for a variety of medicinal applications, including skin diseases, ulcers, and gonorrhea. Recent uses include the treatment of colds and other respiratory tract infections, infectious diarrhea, eye infections, vaginitis, wounds, canker sores, and cancer.

Goldenseal was once reported to mask the appearance of drugs in the urine of patients wanting to hide drug abuse but this claim has since been proved false. The roots and leaves of goldenseal are dried and are available as capsules, tablets, salves, and tinctures. Two of the active ingredients in goldenseal are berberine and hydrastine, which are reported to have antibacterial properties.

When used topically or locally, goldenseal is claimed to be of value in treating bacterial and fungal skin infections and oral conditions such as gingivitis and thrush. As an eyewash, it can soothe inflamed eyes. Considered safe for most people, it is contraindicated in pregnancy and hypertension. Hypertension: Pregnancy and drug use

RELATED;

1.  GINSENG FOR CARDIOVASCULAR DISEASE  

2.  GARLIC FOR CARDIOVASCUAR DISEASE

REFERENCES

THROMBOCYTOPENIA

 

INTRODUCTION: Thrombocytopenia which is a condition of low platelet count, is the most common cause of abnormal bleeding.

PATHOPHYSIOLOGY: Thrombocytopenia can result from decreased production of platelets within the bone marrow or from increased destruction or consumption of platelets.

CAUSES: Causes include failure of production as a result of hematologic malignancies, myelodysplastic syndromes, metastatic involvement of bone marrow from solid tumors, certain anemias, toxins, medications, infections, alcohol, and chemotherapy; increased destruction as a result of idiopathic thrombocytopenia purpura, lupus erythematosus, malignant lymphoma, chronic lymphocytic leukemia, medications, infections, and sequestration; and increased utilization, such as results from disseminated intravascular coagulopathy (DIC).

CLINICAL MANIFESTATIONS: With platelet count below 50,000/mm³ : bleeding and petechiae. With platelet count below 20,000/mm³ : petechiae, along with nasal and gingival bleeding, excessive menstrual bleeding, and excessive bleeding after surgery or dental extractions. With platelet count below 5,000/mm³: spontaneous, potentially fatal central nervous system hemorrhage or gastrointestinal hemorrhage.

ASSESSMENT AND DIAGNOSTIC FINDINGS: Bone marrow aspiration and biopsy, if platelet deficiency is secondary to decreased production. Increased megakaryocytes (the cells from which platelets originate) and normal or even increased platelet production in bone marrow, when platelet destruction is the cause.

MEDICAL MANAGEMENT: The management of secondary thrombocytopenia is usually treatment of the underlying disease. Platelet transfusions are used to raise platelet count and stop bleeding or prevent spontaneous hemorrhage if platelet production is impaired; if excessive platelet destruction is the cause, the patient is treated as indicated for idiopathic thrombocytopenia purpura.

For some patients a splenectomy can be therapeutic, although it may not be an option for other patients for example, patients in whom the enlarged spleen is due to portal hypertension related to cirrhosis.

RELATED;

1. BLOOD PLATELETS

2. THE COAGULATION CASCADE

3. BLEEDING DISORDERS

4.  MEDICAL CONDITIONS

REFERENCES