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

IMPETIGO

 

INTRODUCTION:  Impetigo is a superficial infection of the skin caused by staphylococci, streptococci, or multiple bacteria. Exposed areas of the body, face, hands, neck, and extremities are most frequently involved. Impetigo is contagious and may spread to other parts of the skin or to other members of the family who touch the patient or who use towels or combs that are soiled with the exudate of the lesion. Impetigo is seen in people of all ages. It is particularly common among children living in poor hygienic conditions. Chronic health problems, poor hygiene, and malnutrition may predispose adults to impetigo.

CLINICAL MANIFESTATIONS: Lesions begin as small, red macules that become discrete, thin-walled vesicles that rupture and become covered with a honey-yellow crust. These crusts, when removed, reveal smooth, red, moist surfaces on which new crusts develop. If the scalp is involved, the hair is matted, distinguishing the condition from ringworm.  Bullous impetigo, a deep-seated infection of the skin caused by Staphylococcus aureus, is characterized by the formation of bullae from original vesicles. The bullae rupture, leaving a raw, red area.

MEDICAL MANAGEMENT:  Pharmacologic Therapy: Systemic antibiotic therapy is the usual treatment for impetigo. It reduces contagious spread, treats deep infection, and prevents acute glomerulonephritis (kidney infection). Agents for nonbullous impetigo: benzathine penicillin, oral penicillin, or erythromycin. Topical antibacterial therapy is the usual treatment for disease that is limited to a small area. The topical preparation is applied to lesions several times daily for 1 week. Lesions are soaked or washed with soap solution to remove central site of bacterial growth and to give the topical antibiotic an opportunity to reach the infected site.

RELATED;

1.  STREPTOCOCCUS

2.  STAPHYLOCOCCUS

3.  SEBORRHEIC DERMATITIS

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

DRUG ABSORPTION

 

Introduction: Absorption is a process involving the movement of a substance from its site of administration, across body membranes, to circulating fluids. Drugs may be absorbed across the skin and associated mucous membranes, or they may move across membranes that line the gastrointestinal (GI) or respiratory tract. Most drugs, with the exception of a few topical medications, intestinal anti-infectives, and some radiologic contrast agents, must be absorbed to produce an effect. Absorption is the primary pharmacokinetic factor determining the length of time it takes a drug to produce its effect. Pharmacokinetics

In order for a drug to be absorbed it must dissolve. The rate of dissolution determines how quickly the drug disintegrates and disperses into simpler forms; therefore, drug formulation is an important factor of bioavailability. Bioavailability

In general, the more rapid the dissolution, the faster the drug absorption and the faster the onset of drug action. For example, famotidine administered as an orally disintegrating tablet dissolves within seconds and after being swallowed is delivered to the stomach where it blocks acid secretion from the stomach, thereby treating conditions of excessive acid secretion. Pepticulcer disease: Histamine H2 receptor blockers

At the other extreme some drugs have shown good clinical response as slowly dissolving drugs such as liothyronine sodium (T3) and thyroxine (T4) administered for resolution of hypothyroid symptoms. In some instances it is advantageous for a drug to disperse rapidly. In other cases, it is better for the drug to be released slowly where the effects are more prolonged for positive therapeutic benefit. Absorption is conditional on many factors. Drugs in elixir or syrup formulations are absorbed faster than tablets or capsules. Drugs administered in high doses are generally absorbed more quickly and have a more rapid onset of action than those given in low concentrations. The speed of digestive motility, surface area, pH, lipid solubility, exposure to enzymes in the digestive tract, and blood flow to the site of drug administration also affect absorption. Because drugs administered IV directly enter the bloodstream, absorption to the tissues after the infusion is very rapid. IM medications take longer to absorb. Drug distribution

Other factors that influence the absorption of medications include the following: Drug formulation and dose, Size of the drug molecule, Surface area of the absorptive site, Digestive motility or blood flow, Lipid solubility, Degree of ionization, Acidity or alkalinity (pH), Interactions with food and other medications. The degree of ionization of a drug also affects its absorption. A drug’s ability to become ionized depends on the surrounding pH. Aspirin provides an excellent example of the effects of ionization on absorption. In the acid environment of the stomach, aspirin is in its non-ionized form and thus readily absorbed and distributed by the bloodstream. As aspirin enters the alkaline environment of the small intestine, however, it becomes ionized. In its ionized form, aspirin is not as likely to be absorbed and distributed to target cells.

Unlike acidic drugs, medications that are weakly basic are in their nonionized form in an alkaline environment; therefore, basic drugs are absorbed and distributed better in alkaline environments such as in the small intestine. The pH of the local environment directly influences drug absorption through its ability to ionize the drug.

Drug–drug or food–drug interactions may influence absorption. Many examples of these interactions have been discovered. For example, administering tetracyclines with food or drugs containing calcium, iron, or magnesium can significantly delay absorption of the antibiotic.  High-fat meals can slow stomach motility significantly and delay the absorption of oral medications taken with the meal. Dietary supplements may also affect absorption.

RELATED;

1.  DRUG DISTRIBUTION  

2.  PHARMACOKINETICS

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

EDEMA

 

Objectives of the discussion:  By the end of this discussion, the learner/medical student will be able to;

1.  Explain the cause of the swelling of the different human body parts

2.  Describe the difference between systemic and localised edema

Introduction: Edema is an abnormal increase in the amount of tissue fluid, which may be localized or systemic. Sometimes edema is inapparent, and sometimes it is apparent as swelling. 

Localized edema follows injury and inflammation of a body part.  I have discussed a lot about inflammation and the drugs used to treat it.  You can read more about inflammation from the link in the related below.

Pathophysiology of edema: Spraining an ankle, for example, damages tissues that then release histamine. Histamine increases the permeability of capillaries, and more tissue fluid is formed. As tissue fluid accumulates, the ankle may become swollen.

Systemic edema:  Systemic edema is the result of an imbalance between the movement of water out of and into capillaries, that is, between filtration and osmosis. Excessive filtration will occur when capillary pressure rises. This may be caused by venous obstruction due to blood clots or by congestive heart failure.  Edema of this type is often apparent in the lower extremities. Systemic bacterial infections may increase capillary permeability, and loss of plasma to tissue spaces is one aspect of septicemia. In this situation, however, the edema is of secondary importance to the hypotension, which may be life-threatening. 

Insufficient osmosis, the return of tissue fluid into capillaries, is a consequence of a decrease in plasma proteins, especially albumin. This may occur in severe liver diseases such as cirrhosis, kidney disease involving loss of protein in urine, malnutrition, or severe burn injuries.  Because edema is a symptom rather than a disease, treatment is aimed at correcting the specific cause. If that is not possible, the volume of tissue fluid may be diminished by a low-salt diet and the use of diuretics

RELATED;

1. THE INFLAMMATORY PROCESS

2. BIOCHEMISTRY OF HISTAMINE

3. CONGESTIVE HEART FAILURE

4.  MEDICAL CONDITIONS

REFERENCES

GRAPE SEED EXTRACT FOR HYPERTENSION

 

Grapes and grape seeds have been to maintain and improve health used for thousands of years. Their primary use has been for cardiovascular conditions such as hypertension (HTN), high blood cholesterol, and atherosclerosis, and to generally improve circulation. Hypertension: Atherosclerosis

Some claim that grape seed extract improves wound healing, prevents cancer, slows the progression of neurodegenerative diseases, and lowers the risk for the long-term consequences of diabetes. Woundhealing: Diabetes

The grape seeds, usually obtained from winemaking, are crushed and placed into tablet, capsule, or liquid forms. Typical doses are 50 to 300 mg/ day. Grape seed extract has antioxidant properties that have the potential to improve wound healing and repair cellular injury. Grape seed extract is well tolerated in most people, with the most common side effects being dry, itchy scalp; dizziness; headache; hives; indigestion; and nausea. It has few adverse effects but caution should be used if taking anticoagulant drugs because increased bleeding may result.

RELATED;

1.  ARTERIOSCLEROSIS  

2.  GARLIC  

3.  BLOOD PRESSURE CONTROL

4.  TRADITIONAL AND COMPLIMENTARY MEDICATIONS

REFERENCES

DEPRESSION

 

INTRODUCTION:  Depression is a disorder characterized by a sad or despondent mood. Many symptoms are associated with depression, including lack of energy, sleep disturbances, abnormal eating patterns, and feelings of despair, guilt, or hopelessness. Depression is the most common mental health disorder of elderly adults, encompassing a variety of physical, emotional, cognitive, and social considerations.

CRITERIA FOR DIAGNOSIS OF DEPRESSION:  The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), describes the following criteria for diagnosis of a major depressive disorder:

A depressed affect plus at least five of the following symptoms lasting for a minimum of 2 weeks: 

1)  Difficulty sleeping or sleeping too much.  

2)  Extremely tired; without energy.

3)  Abnormal eating patterns (eating too much or not enough).

4)  Vague physical symptoms (gastrointestinal [GI] pain, joint/muscle pain, or headaches).

5)  Inability to concentrate or make decisions.

6)  Feelings of despair, guilt, and misery; lack of self-worth.

7)  Obsessed with death (expressing a wish to die or to commit suicide).

8)  Avoiding psychosocial and interpersonal interactions.

9)  Lack of interest in personal appearance or sex.

10)  Delusions or hallucinations. 

AGGREVIATING FACTORS TO DEPRESSION:  The majority of depressed patients are not found in psychiatric hospitals but in mainstream society. For proper diagnosis and treatment to occur, recognition of depression is often a collaborative effort among health care providers.  For example, it might be the pharmacist who recognizes that a customer is depressed when the customer buys natural or over-the-counter (OTC) remedies to control anxiety symptoms or to induce sleep.

Situational depression occurs when the depression is the result of a circumstance in a person’s life, for example, loss of a job or unfavorable event at home such as death, children leaving home, or divorce.  Dysthymic disorder is characterized by less severe depressive symptoms that may prevent a person from feeling well or functioning normally. Because depressed patients may be found in multiple settings, health workers should be proficient in the assessment of patients afflicted with these conditions. Some women experience intense mood shifts associated with hormonal changes during the menstrual cycle, pregnancy, childbirth, and menopause. 

WOMEN AND DEVELOPMENT DEPRESSIVE DISORDER:  Up to 80% of women who give birth experience postpartum depression during the first several weeks after birth of their baby. About 10% of new mothers experience a major depressive episode within 6 months related to the dramatic hormonal shifts that occur during postdelivery. Along with the hormonal changes, additional situational stresses, such as responsibilities at home or work, single parenthood, and caring for children or for aging parents, may contribute to the onset of symptoms. If mood is severely depressed and persists long enough, many women will likely benefit from medical treatment, including women with premenstrual dysphoric disorder, depression during pregnancy, postpartum mood disorders, or menopausal distress. Because of the possible consequences of perinatal mood disorders, some state agencies mandate that all new  mothers receive information about mood shifts prior to their discharge after giving birth.  Health care providers in obstetrician’s offices, pediatric outpatient settings, and family medicine centers are encouraged to conduct routine screening for symptoms of perinatal mood disorders.

RELATED;

1.  SEDATIVE-HYPNOTICS  

2.  ZOLPIDEM

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

DRUG METABOLISM

Introduction:  Metabolism, also called biotransformation, is the process of chemically converting a drug to a form that is usually more easily removed from the body. Metabolism involves complex biochemical pathways and reactions that alter drugs, nutrients, vitamins, and minerals. The liver is the primary site of drug metabolism, although the kidneys and cells of the intestinal tract also have high metabolic rates. Medications undergo many types of biochemical reactions as they pass through the liver, including hydrolysis, oxidation, and reduction.

Microsomal enzyme systems:  During metabolism, the addition of side chains, known as conjugates, makes drugs more water soluble and more easily excreted by the kidneys. Most metabolism in the liver is accomplished by the hepatic microsomal enzyme system. This enzyme complex is sometimes called the P-450 system, named after cytochrome P-450 (CYP-450), which is a key component of the system. The cytochrome P450 enzyme system

Enzyme induction and the role of prodrugs:  As they relate to pharmacotherapy, the primary actions of the hepatic microsomal enzymes are to inactivate drugs and accelerate their excretion. In some cases, however, metabolism can produce a chemical alteration that makes the resulting molecule more active than the original. For example, the narcotic analgesic codeine undergoes biotransformation to morphine, which has significantly greater ability to relieve pain. In fact, some agents, known as prodrugs, have no pharmacologic activity unless they are first metabolized to their active form by the body. Examples of prodrugs include benazepril and, proinsulin and losartan. Changes in the function of the hepatic microsomal enzymes can significantly affect drug metabolism. A few drugs have the ability to increase metabolic activity in the liver, a process called enzyme induction. For example, phenobarbital causes the liver to synthesize more microsomal enzymes. By doing so, phenobarbital increases the rate of its own metabolism as well as that of other drugs metabolized in the liver. In these patients, higher doses of medication may be required to achieve the optimum therapeutic effect. 

Considerations for liver functioning states:  Certain patients have decreased hepatic metabolic activity, which may alter drug action. Hepatic enzyme activity is generally reduced in infants and elderly patients; therefore, pediatric and geriatric patients are more sensitive to drug therapy than middle-age patients. Patients with severe liver damage, such as that caused by cirrhosis, will require reductions in drug dosage because of the decreased metabolic activity. Certain genetic disorders have been recognized in which patients lack specific metabolic enzymes; drug dosages in these patients must be adjusted accordingly. Metabolism has a number of additional therapeutic consequences.  

The roles of fast-pass effect:  For example, drugs absorbed after oral administration cross directly into the hepatic portal circulation, which carries blood to the liver before it is distributed to other body tissues. Thus, as blood passes through the liver circulation, some drugs can be completely metabolized to an inactive form before they ever reach the general circulation. This first-pass effect is an important mechanism, since a large number of oral drugs are rendered inactive by hepatic metabolic reactions. Alternative routes of delivery that bypass the first-pass effect (e.g., sublingual, rectal, or parenteral routes) may need consideration for these drugs. 

RELATED;

1.  ABSORPTION  

2.  PHARMACOKINETICS

REFERENCES

CERVICAL CANCER

INTRODUCTION: Cancer of the cervix is predominantly squamous cell cancer and also includes adenocarcinomas. It is less common than it once was because of early detection by the Pap test, but it remains the third most common reproductive cancer in women.

RISK FACTORS: Risk factors vary from multiple sex partners to smoking to chronic cervical infection all of which predispose one to exposure to human papillomavirus [HPV].

CLINICAL MANIFESTATIONS: Cervical cancer is most often asymptomatic. When discharge, irregular bleeding, or pain or bleeding after sexual intercourse occurs, the disease may be advanced. Vaginal discharge gradually increases in amount, becomes watery, and finally is dark and foul smelling because of necrosis and infection of the tumor. Bleeding occurs at irregular intervals between periods or after menopause, may be slight, and is usually noted after mild trauma. As disease continues, bleeding may persist and increase. Leg pain, dysuria, rectal bleeding, and edema of the extremities signal advanced disease.

Nerve involvement, producing excruciating pain in the back and legs, occurs as cancer advances and tissues outside the cervix are invaded, including the fundus and lymph glands anterior to the sacrum. Extreme emaciation and anemia, often with fever due to secondary infection and abscesses in the ulcerating mass, and fistula formation may occur in the final stage.

ASSESSMENT AND DIAGNOSTIC FINDINGS: Pap smear and biopsy results show severe dysplasia, highgrade epithelial lesion, or carcinoma in situ. Other tests may include x-rays, laboratory tests, special examinations (eg, punch biopsy and colposcopy), dilation and curettage (D & C), CT scan, MRI, IV urography, cystography, PET, and barium x-ray studies.

MEDICAL MANAGEMENT: Disease may be staged (usually TNM system) to estimate the extent of the disease so that treatment can be planned more specifically and prognosis. Conservative treatments include monitoring, cryotherapy (freezing with nitrous oxide), laser therapy, loop electrosurgical excision procedure (LEEP), or conization (removing a cone-shaped portion of cervix). Simple hysterectomy if preinvasive cervical cancer (carcinoma in situ) occurs when a woman has completed childbearing. Radical trachelectomy is an alternative to hysterectomy. For invasive cancer, surgery, radiation (external beam or brachytherapy), platinum-based agents, or a combination of these approaches may be used.

RELATED;

1.  THE ORIGIN OF CANCER

2.  PATHOPHYSIOLOGY OF CANCER

3.  PATHOLOGY

4.  BIOCHEMISTRY

REFERENCES

IMIPRAMINE

 

Therapeutic Class: Antidepressant; treatment of nocturnal enuresis in children

Pharmacologic Class: Tricyclic antidepressant

ACTIONS AND USES: Imipramine blocks the re-uptake of serotonin and norepinephrine into nerve terminals. It is used mainly for major depression, although it is occasionally used for the treatment of nocturnal enuresis (bed wetting) in children. It may also be prescribed for a number of unlabeled uses, including intractable pain, anxiety disorders, and withdrawal syndromes from alcohol and cocaine. Therapeutic effectiveness may not occur for 2 or more weeks.

ADMINISTRATION ALERTS: Paradoxical diaphoresis can be a side effect of TCAs; therefore, diaphoresis may not be a reliable indicator of other disease states such as hypoglycemia.

Imipramine causes anticholinergic effects and may potentiate effects of anticholinergic drugs administered during surgery. Do not discontinue abruptly because rebound dysphoria, irritability, or sleeplessness may occur. Pregnancy category C.

ADVERSE EFFECTS: Side effects include sedation, drowsiness, blurred vision, dry mouth, and cardiovascular symptoms such as dysrhythmias, heart block, and extreme hypertension. Agents that mimic the action of norepinephrine or serotonin should be avoided because imipramine inhibits their metabolism and may produce toxicity. Some patients may experience photosensitivity and hypersensitivity to tricyclic drugs.

Warning: Antidepressants increase the risk of suicidal thinking and behavior, especially in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. This drug is not approved for use in pediatric patients. 

Contraindications: This drug should not be used in cases of acute recovery after MI, defects in bundle-branch conduction, narrow-angle glaucoma, and severe renal or hepatic impairment. Patients should not use this drug within 14 days of discontinuing MAOIs. 

INTERACTIONS: Drug–Drug: Concurrent use of other CNS depressants, including alcohol, may cause sedation. Cimetidine may inhibit the metabolism of imipramine, leading to increased serum levels and possible toxicity. Imipramine may reverse the antihypertensive effects of clonidine and potentiate CNS depression. Use of oral contraceptives may increase or decrease imipramine levels. Disulfiram may lead to delirium and tachycardia. Antithyroid agents may produce agranulocytosis. Phenothiazines cause increased anticholinergic and sedative effects. Sympathomimetics may result in cardiac toxicity. Methylphenidate or cimetidine may increase the effects of imipramine and cause toxicity. Phenytoin is less effective when taken with imipramine. MAOIs may result in neuroleptic malignant syndrome.

RELATED;

1.  DEPRESSION

2.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

INFECTIVE ENDOCARDITIS

 

INTRODUCTION: Infective endocarditis is a microbial infection of the endothelial surface of the heart. A deformity or injury of the endocardium leads to accumulation on the endocardium of fibrin and platelets involving clot formation. Infectious organisms, usually staphylococci, streptococci, enterococci, pneumococci, or chlamydia invade the clot and endocardial lesion. Other causative microorganisms include fungi such as, Candida, Aspergillus and rickettsiae

RISK FACTORS: Prosthetic heart valves or structural cardiac defects such as, valve disorders, hypertrophic cardiomyopathy

Age: More common in older people, who are more likely to have degenerative or calcific valve lesions, reduced immunologic response to infection, and the metabolic alterations associated with aging.

Intravenous (IV) drug use: There is a high incidence of staphylococcal endocarditis among IV drug users.

Hospitalization: Hospital-acquired endocarditis occurs most often in patients with debilitating disease or indwelling catheters and in those receiving hemodialysis or prolonged IV fluid or antibiotic therapy.

Immunosuppression: Patients taking immunosuppressive medications or corticosteroids are more susceptible to fungal endocarditis.

CLINICAL MANIFESTATIONS: Primary presenting symptoms are fever and a heart murmur: Fever may be intermittent or absent, especially in elderly patients, patients receiving antibiotics or corticosteroids, or those who have heart failure or renal failure. Vague complaints of malaise, anorexia, weight loss, cough, and back and joint pain.

A heart murmur may be absent initially but develops in almost all patients. Small, painful nodules (Osler nodes) may be present in the pads of fingers or toes. Irregular, red or purple, painless, flat macules may be present on the palms, fingers, hands, soles, and toes. Hemorrhages with pale centers (Roth spots) caused by emboli may be observed in the fundi of the eyes. Splinter hemorrhages (ie, reddish brown lines and streaks) may be seen under the fingernails and toenails. Petechiae may appear in the conjunctiva and mucous membranes. Cardiomegaly, heart failure, tachycardia, or splenomegaly may occur.

ASSESSMENT AND DIAGNOSTIC METHODS: A diagnosis of acute infective endocarditis is made when the onset of infection and resulting valvular destruction are rapid, occurring within days to weeks. Blood cultures Doppler or transesophageal echocardiography.

COMPLICATIONS: Complications include heart failure, cerebral vascular complications, valve stenosis or regurgitation, myocardial damage, and mycotic aneurysms.

MEDICAL MANAGEMENT: Objectives of treatment are to eradicate the invading organism through adequate doses of an appropriate antimicrobial agent (continuous IV infusion for 2 to 6 weeks at home). Treatment measures include the following:

1) Isolating causative organism through serial blood cultures. Blood cultures are taken to monitor the course of therapy.

2) Monitoring patient’s temperature for effectiveness of the treatment. After recovery from the infectious process, seriously damaged valves may require debridement or replacement. For example, surgical valve replacement is required if heart failure develops, if patient has more than one serious systemic embolic episode, if infection cannot be controlled or is recurrent, or if infection is caused by a fungus.

REFERENCES;

1. HEART MURMURS

2. HEART FAILURE

3.  ANGINA PECTORIS

REFERENCES

LIDOCAINE

 

ACTIONS AND USES:  Lidocaine, the most frequently used injectable local anesthetic, acts by blocking neuronal pain impulses. It may be injected as a nerve block for spinal and epidural anesthesia. It acts by blocking sodium channels located within the membranes of neurons. Sodium channels

ROUTES OF ADMINISTRATION:  Lidocaine may be given IV, IM, or subcutaneously to treat dysrhythmias.  A topical form is also available.

ADMINISTRATION ALERTS: 1)  Solutions of lidocaine containing preservatives or epinephrine are intended for local anesthesia only and must never be given parenterally for dysrhythmias.  

2)  Do not apply topical lidocaine to large skin areas or to broken or abraded areas, because significant absorption may occur.

3) Do not allow it to come into contact with the eyes.

4) For spinal or epidural block, use only preparations specifically labeled for IV use.

ADVERSE EFFECTS:  When lidocaine is used for anesthesia, side effects are uncommon. An early symptom of toxicity is CNS excitement, leading to irritability and confusion. Serious adverse effects include convulsions, respiratory depression, and cardiac arrest. Until the effect of the anesthetic diminishes, patients may injure themselves by biting or chewing areas of the mouth that have no sensation following a dental procedure.

CONTRAINDICATIONS:  Lidocaine should be avoided in cases of sensitivity to amide-type local anesthetics. Application or injection of lidocaine anesthetic is also contraindicated in the presence of severe trauma or sepsis, blood dyscrasias, dysrhythmias, sinus bradycardia, and severe degrees of heart block.

INTERACTIONS:  Drug–Drug: Barbiturates may decrease the activity of lidocaine. Increased effects of lidocaine occur if taken concurrently with cimetidine, quinidine, and beta blockers. If lidocaine is used on a regular basis, its effectiveness may diminish when used with other medications.

RELATED;

1.  OPIOID ANALGESICS

2.  BARBITURATES

3.  BENZODIAZEPINES

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

KAPOSI'S SARCOMA

INTRODUCTION:  Kaposi’s sarcoma (KS) is the most common HIV-related malignancy and involves the endothelial layer of blood and lymphatic vessels. In people with AIDS, epidemic KS is most often seen among male homosexuals and bisexuals. AIDS related KS exhibits a variable and aggressive course, ranging from localized cutaneous lesions to disseminated disease involving multiple organ systems. 

CLINICAL MANIFESTATIONS:  Cutaneous lesions can occur anywhere on the body and are usually brownish pink to deep purple. They characteristically present as lower-extremity skin lesions.  Lesions may be flat or raised and surrounded by ecchymosis and edema; they develop rapidly and cause extensive disfigurement.  The location and size of the lesions can lead to venous stasis, lymphedema, and pain. 

COMMON SITES INVOLVED:  Common sites of visceral involvement include the lymph nodes, gastrointestinal tract, and lungs. Involvement of internal organs may eventually lead to organ failure, hemorrhage, infection, and death. 

ASSESSMENT AND DIAGNOSIS: Diagnosis is confirmed by biopsy of suspected lesions. Prognosis depends on extent of tumor, presence of other symptoms of HIV infection, and the CD4 count.  Pathologic findings indicate that death occurs from tumor progression, but more often from other complications of HIV infection. 

MEDICAL MANAGEMENT: Treatment goals are to reduce symptoms by decreasing the size of the skin lesions, to reduce discomfort associated with edema and ulcerations, and to control symptoms associated with  mucosal or visceral involvement. No one treatment has been shown to improve survival rates. Radiation therapy is effective as a palliative measure to relieve localized pain due to tumor mass (especially in the legs) and for KS lesions that are in sites such as the oral mucosa, conjunctiva, face, and soles of the feet. 

PHARMACOLOGICAL THERAPY:  Patients with cutaneous KS treated with alpha-interferon have experienced tumor regression and improved immune system function. Alpha-interferon is administered by the intravenous (IV), intramuscular, or subcutaneous route. Patients may self-administer interferon at home or receive interferon in an outpatient setting.  Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used as well. 

RELATED;

1.  INVASION OF HUMAN CD4 CELL BY HIV 

2.  HIV/AIDS  

3.  ANTIRETROVIRAL DRUGS (ARVs)

4.  MEDICAL CONDITIONS

REFERENCES