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

PHARMACOKINETICS

 

INTRODUCTION: The term pharmacokinetics is derived from the root words pharmaco, which means “medicine,” and kinetics, which means “movement or motion.” Pharmacokinetics is thus the study of drug movement throughout the body. In practical terms, it describes how the body deals with medications. Pharmacokinetics is a core subject in pharmacology, and a firm grasp of this topic allows the medical professionals to better understand and predict the actions and side effects of medications in patients. Drugs face numerous obstacles in reaching their target cells.  When we are addressing pharmacokinetic aspects of a drug, we shall be looking at its absorption from the site of injection or administration, distribution in the body tissues, metabolism and then it excretion from the body.

ABSORPTION OF DRUGS:  For most medications, the greatest barrier is crossing the many membranes that separate the drug from its target cells. A drug taken by mouth, for example, must cross the plasma membranes of the mucosal cells of the gastrointestinal tract and the capillary endothelial cells to enter the bloodstream. The plasma membrane

To leave the bloodstream, the drug must again cross capillary cells, travel through the interstitial fluid, and depending on the mechanism of action, the drug may also need to enter target cells and cellular organelles such as the nucleus, which are surrounded by additional membranes.  These are examples of just some of the barriers that a drug must successfully penetrate before it can produce a response. 

METABOLISM OF DRUGS:  While moving toward target cells and passing through the various membranes, drugs are subjected to numerous physiological processes. For medications given by the enteral route, stomach acid and digestive enzymes often act to break down the drug molecules. Enzymes in the liver and other organs may chemically change the drug molecule to make it less active.  If the drug is seen as foreign by the body, phagocytes may attempt to remove it, or an immune response may be triggered. 

DRUG EXCRETION:  The kidneys, large intestine, and other organs attempt to excrete the medication from the body. These examples illustrate pharmacokinetic processes: how the body handles medications. The many processes of pharmacokinetics are grouped into four categories: absorption, distribution, metabolism, and excretion as we have briefly seen here, and we shall be seeing in our next discussions in details.

RELATED;

1.  ROUTES OF DRUG ADMINISTRATION  

2.  BIOAVAILABILITY

3.  DYNAMICS OF DRUGS AND THE HUMAN BODY

4.  DRUG METABOLISM

5.  THE PLASMA MEMBRANE

6.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

THE ORIGIN OF CANCER

 

INTRODUCTION: There are more than 200 different types of cancer, all of which are characterized by abnormal cellular functioning. Normally, our cells undergo mitosis only when necessary and stop when appropriate. A cut in the skin, for example, is repaired by mitosis, usually without formation of excess tissue. The new cells fill in the damaged area, and mitosis slows when the cells make contact with surrounding cells. This is called contact inhibition, which limits the new tissue to just what is needed. 

ABNORMAL CELLULAR DIVISION: Malignant (cancer) cells, however, are characterized by uncontrolled cell division. Our cells are genetically programmed to have particular life spans and to divide or die. One gene is known to act as a brake on cell division; another gene enables cells to live indefinitely, beyond their normal life span, and to keep dividing. Any imbalance in the activity of these genes may lead to abnormal cell division. Such cells are not inhibited by contact with other cells, keep dividing, and tend to spread.

MALIGNANCY: A malignant tumor begins in a primary site such as the colon, then may spread or metastasize. Often the malignant cells are carried by the lymph or blood to other organs such as the liver, where secondary tumors develop. Metastasis is characteristic only of malignant cells; benign tumors do not metastasize but remain localized in their primary site. A malignant cell is created by a mutation, a genetic change that brings about abnormal cell functions or responses and often leads to a series of mutations. 

CAUSES OF CANCER: Environmental substances that cause mutations are called carcinogens. One example is the tar found in cigarette smoke, which is definitely a cause of lung cancer. Ultraviolet light may also cause mutations, especially in skin that is overexposed to sunlight. For a few specific kinds of cancer, the trigger is believed to be infection with certain viruses that cause cellular mutations. Carriers of hepatitis B virus, for example, are more likely to develop primary liver cancer than are people who have never been exposed to this virus. Research has discovered two genes, one on chromosome 2 and the other on chromosome 3, that contribute to a certain form of colon cancer. Both of these genes are the codes for proteins that correct the “mistakes” that may occur when the new DNA is synthesized. When these repair proteins do not function properly, the mistakes (mutations) in the DNA lead to the synthesis of yet other faulty proteins that impair the functioning of the cell and predispose it to becoming malignant.

PROGRESSION OF CANCER: Once cells have become malignant, their functioning cannot return to normal, and though the immune system will often destroy such cells, sometimes it does not, especially as we get older. Therefore, the treatments for cancer are directed at removing or destroying the abnormal cells. Surgery to remove tumors, radiation to destroy cells, and chemotherapy to stop cell division or interfere with other aspects of cell metabolism are all aspects of cancer treatment. New chemotherapy drugs are becoming more specific, with very precise targets. For example, the cells of several types of solid-tumor cancers have been found to have mutations in the gene for the cell membrane receptor for a natural growth factor (epidermal growth factor receptor, or EGFR). These altered receptors, when triggered by their usual growth factor, then cause the cell to divide uncontrollably, an abnormal response. Medications that target only these altered receptors have already been developed for some forms of lung cancer and breast cancer. Not only do they show promise in treating the cancer, they do not have the side effects of other forms of chemotherapy.

RELATED;

1.  APOPTOSIS

2.  BREAST CANCER

3.  CERVICAL CANCER

REFERENCES

CORTICOSTEROIDS (GLUCOCORTICOIDS)

 

OBJECTIVES OF THE DISCUSSION:  By the end of this discussion the learner/medical student will be able to;

1.  Describe the role of corticosteroids in management of pain

2.  Explain the effect of corticosteroids on the human body

3.  List the possible side and adverse effect encountered with use of corticosteroids

INTRODUCTION:  Corticosteroids have numerous therapeutic applications. One of their most useful properties is the ability to suppress severe inflammation. Because of potentially serious adverse effects, however, systemic corticosteroids are reserved for the short-term treatment of severe disease. Corticosteroids are often referred to as glucocorticoids.

TREATING ACUTE OR SEVERE INFLAMMATION WITH CORTICOSTEROIDS:  Corticosteroids are natural hormones released by the adrenal cortex that have powerful effects on nearly every cell in the body. When corticosteroids are used as drugs to treat inflammatory disorders, the doses are many times higher than the amount naturally present in the blood. The uses of corticosteroids include the treatment of neoplasia, asthma, arthritis, and corticosteroid deficiency.  Asthma 

PHARMACODYNAMICS:  Like the NSAIDs, corticosteroids inhibit the biosynthesis of prostaglandins. Corticosteroids, however, affect inflammation by multiple mechanisms. They have the ability to suppress histamine release and can inhibit certain functions of phagocytes and lymphocytes. These multiple actions markedly reduce inflammation, making corticosteroids the most effective medications available for the treatment of severe inflammatory disorders.  Inflammation 

ADVERSE EFFECTS:  When given by the oral or parenteral routes, corticosteroids have a number of serious adverse effects that limit their therapeutic utility. These include suppression of the normal functions of the adrenal gland a condition known as adrenal insufficiency, hyperglycemia, mood changes, cataracts, peptic ulcers, electrolyte imbalances, and osteoporosis.  Peptic ulcers

Because of their effectiveness at reducing the signs and symptoms of inflammation, corticosteroids can mask infections that may be present in a patient. This combination of masking signs of active infection and suppressing the immune response creates a potential for infections to grow rapidly and remain undetected. In that regard therefore, active infection is usually a contraindication for corticosteroids therapy. 

Because the appearance of these adverse effects is a function of the dose and duration of therapy, treatment is often limited to the short-term control of acute disease. When longer therapy is indicated, doses are kept as low as possible and alternate-day therapy is sometimes implemented; the medication is taken every other day to encourage the patient’s adrenal glands to function on the days when no drug is given.

RELATED;

1.  OPIOID ANALGESICS

2.  OPIOID ANALGESICS

3.  MORPHINE

4.  INFLAMMATORY CONDITIONS OF THE HUMAN BODY

REFERENCES

DYNAMICS OF INFECTIOUS DISEASES

INTRODUCTION: For an infectious disease to perpetuate there has to be a reservoir of microorganism from where the causative agent should be transmitted to a susceptible host either directly or through the agency of a vehicle or a vector.

SOURCE AND RESERVOIR: The source of infection is the person, animal, object or substance from which an infectious agent passes or disseminates to the host whereas a reservoir is defined as any person, animal, arthropod, plant, soil or substance (or combination of these) in which an infectious agent lives and multiplies. These can be of three types: 1) Humans 2) Animals 3) Non-living substances. Humans For infectious diseases of human beings, man is the most important reservoir. He may be a case or a carrier.

HUMAN CASE: A case may be having a clinical disease or subclinical infection which remains unmanifested or abortive. In latter, the disease agent may multiply in the host but does not manifest itself by signs and symptoms.

HUMAN CARRIERS: Some microorganisms do not get completely eliminated from the host after natural cycle of disease or after treatment. Such persons become carriers of the agents. A carrier therefore is defined as an infected person or animal that harbours a specific infectious agent in the absence of overt clinical signs and serves as a potential source of infection for others.

Though carriers are less infectious than cases, they carry greater epidemiological importance because of the prolonged duration for which they can silently excrete organisms. The carriers can be: 1) incubatory 2) convalescent or 3) healthy. Depending upon the duration of excretion of microorganisms they can be designated as: 1) temporary (acute) or 2) chronic carriers.

The incubatory and convalescent carriers are usually temporary whereas chronic carriers are otherwise healthy individuals. Chronic carrier state occurs in various diseases notably typhoid fever and hepatitis B. Hepatitis B

ANIMALS: Animals and birds can also pass on microorganisms to man. These may also manifest as case or exist as carriers. The diseases which are naturally transmissible between man and animals are called as zoonoses. These diseases are of great importance in countries where a close contact between man and animals is inevitable such as occurs in rural areas of India and Sub-Saharan Africa. Some of the important zoonotic infections are rabies; plague, brucellosis, leptospirosis, hydatidosis. Brucellosis

NON-LIVING SUBSTANCES: Soil and inanimate objects can also occur as reservoir of some microorganisms such as causative agents of infectious tetanus, anthrax, hookworm disease and mycetoma.

MODES OF TRANSMISSION: The microorganisms can be transmitted to human beings directly or indirectly. Direct transmission occurs through: 1) Contact with man, animal or inanimate objects. 2) Droplet infection 3) Breach of skin or mucous membrane 4) Transplacental and congenital.

The indirect transmission is possible by any of the following mechanisms; 1) Vehicles (water, food etc.). 2) Vectors (mechanical or biological). 3) Air (droplet or dust). 4) Fomites. 5) Unclean hands and fingers.

MECHANISM OF INFECTION: To produce infection in man a microbe has to gain entry into the host. The most frequent portals of entry are the respiratory tract, the gastrointestinal tract and breaks in the superficial mucous membranes and skin. From the portal of entry the parasite may spread directly through the tissues or may proceed via lymphatic channels to the blood stream, which distributes it widely and permits it to reach tissues particularly suitable for its multiplication. Nevertheless, for the perpetuation of a parasitic species a satisfactory portal of exit of the parasite from the host and an effective mechanism for transmission to new hosts are also of paramount importance.

DEVELOPMENT OF DISEASE: Once the microorganism overcomes the defences of the host, development of infectious disease follows a sequence of events.

Period of Incubation: This is the time interval between the actual infection and the appearance of first clinical feature.

Prodromal Period: This relatively short period follows incubation period in some diseases. It is characterised by mild early symptoms such as general aches and malaise.

Period of Illness: This is the acute phase of illness characterised by typical clinical features of the infectious disease.

Period of Decline: During this period the signs and symptoms subside. The fever decreases and the feeling of malaise diminishes

Period of Convalescence: The person regains strength during this period and body returns to pre-diseased state.

LOCAL OR GENERALISED INFECTIONS: An infection may be restricted to the point of entry (local) or may spread throughout the body (generalized). 

Generalised Infections: Bacteraemia, septicaemia and pyaemia are some of the generalised infections which spread through blood:

Bacteraemia: Bacteraemia is defined as the circulation of bacteria in the blood. It may be transient or of long duration depending upon the duration for which bacteria are present in the blood. Transient bacteraemia is a frequent event which occurs even in healthy individuals while chewing, brushing of teeth and straining while passing stools. Bacteraemia of long duration occurs with pathogenic organisms such as Salmonella typhi and Brucella and is essential for the initiation of disease process.

Septicaemia: This is a condition in which bacteria circulate and multiply in the blood, form toxic products and cause high swinging type of fever. This can be due to both endotoxin as well as exotoxin producing organisms.

RELATED;

1. SEPTIC SHOCK  

2. FEVERS  

3. BACTERIA TOXINS  

4. VIRULENCE OF MICROORGANISMS

5.  MEDICAL MICROBIOLOGY

REFERENCES

PROTON PUMP INHIBITORS

 

INTRODUCTION: Proton pump inhibitors act by blocking the enzyme responsible for secreting hydrochloric acid in the stomach. They are drugs of choice for the short-term therapy of PUD and GERD. Proton pump inhibitors (PPIs) reduce acid secretion in the stomach by binding irreversibly to K⁺/H⁺ATPase, the enzyme that acts as a pump to release acid (also called H⁺, or protons) onto the surface of the GI mucosa. The PPIs reduce acid secretion to a greater extent than the H2-receptor antagonists and have a longer duration of action.  PPIs heal more than 90% of duodenal ulcers within 4 weeks and about 90% of gastric ulcers in 6 to 8 weeks. Several days of PPI therapy may be needed before patients gain relief from ulcer pain. Beneficial effects continue for 3 to 5 days after the drugs have been stopped. These drugs are used only for the short-term control of peptic ulcers and GERD: Peptic ulcer disease

The typical length of therapy is 4 weeks. Omeprazole and lansoprazole are used concurrently with antibiotics to eradicate H. pylori. Esomeprazole and pantoprazole offer the convenience of once-a-day dosing.

OMEPRAZOLE

Therapeutic Class: Antiulcer drug

Pharmacologic Class: Proton pump inhibitor

ACTIONS AND USES: Omeprazole was the first PPI to be approved for PUD: Both prescription and OTC forms are available. Its pharmacodynamics is discussed in the introduction. Although this drug can take 2 hours to reach therapeutic levels, its effects last up to 72 hours. It is used for the short-term, 4- to 8-week therapy of active peptic ulcers and GERD. Most patients are symptom free after 2 weeks of therapy. It is used for longer periods in patients who have chronic hypersecretion of gastric acid, a condition known as Zollinger–Ellison syndrome.

It is the most effective drug for this syndrome. Omeprazole is available only in oral form.

ADMINISTRATION ALERTS: If possible, administer before breakfast on an empty stomach. It may be administered with antacids. Capsules and tablets should not be chewed, divided, or crushed.

Pregnancy category C. [read about drug use inrelation to pregnancy]

ADVERSE EFFECTS: Adverse effects are generally minor and include headache, nausea, diarrhea, rash, and abdominal pain. Although rare, blood disorders may occur, causing unusual fatigue and weakness. Therapy is generally limited to 2 months. Atrophic gastritis and hypomagnesemia have been reported rarely with prolonged treatment with PPIs.

CONTRAINDICATIONS: The only contraindication is hypersensitivity to the drug. OTC use is not approved for patients under 18 years of age.

INTERACTIONS:

Drug–Drug: Concurrent use with diazepam, phenytoin, and central nervous system (CNS) depressants may cause increased blood levels of these drugs. Concurrent use with warfarin may increase the likelihood of bleeding. Alcohol can aggravate the stomach mucosa and decrease the effectiveness of omeprazole.

Lab Tests: Omeprazole may increase values for ALT, AST, and serum alkaline phosphatase.

Herbal/Food: Ginkgo and St. John’s wort may decrease the plasma concentration of omeprazole.

RELATED;

1. PEPTIC ULCER DISEASE

2.  ANTIACIDS

REFERENCES

SALMONELLA (GASTROENTERITIS, TYPHOID FEVER, PARATYPHOID FEVER)

 

INTRODUCTION: All salmonellae are classified in the species Salmonella enterica with seven subspecies. Nearly all human pathogen salmonellae are grouped under S. enterica, subsp. enterica. Salmonellae are further subclassified in over 2000 serovars based on their O and H antigens, which used to be designated as species. Typhoid salmonelloses are caused by the serovars typhi and paratyphi A, B, and C.

MODES OF TRANSMISSION: The salmonellae are taken up orally and the invasion pathway is through the intestinal tract, from where they enter lymphatic tissue, first spreading lymphogenously, then hematogenously. A generalized septic clinical picture results. Human carriers are the only source of infection. Transmission is either direct by smear infection or indirect via food and drinking water.  Anti-infective agents are required for therapy including but not limited to; ampicillin, cotrimoxazole, 4-quinolones). An active vaccine is available to protect against typhoid fever. Enteric salmonelloses develop when pathogens are taken up with food. The primary infection source is usually livestock. These relatively frequent infections remain restricted to the gastrointestinal tract. Treatment with antiinfective agents is necessary in exceptional cases only.  It is not known why typhoid salmonellae only cause systemic disease in humans, whereas enteric salmonella infections occur in animals as well and are usually restricted to the intestinal tract.

DIAGNOSIS: The method of choice is detection of the pathogens in cultures. Selective indicator mediums are used to isolate salmonellae in stool. Identification is done using metabolic patterns. Serovar classification is determined with specific antisera in the slide agglutination test. Culturing requires at least two days. Typhoid salmonelloses can be diagnosed indirectly by measuring the titer of agglutinating antibodies to O and H antigens (according to Gruber-Widal). To provide conclusive proof the titer must rise by at least fourfold from blood sampled at disease onset to a sample taken at least one week later.

THERAPY: Typhoid salmonelloses must be treated with anti-infective agents, whereas symptomatic treatment will suffice for enteric infections. Symptomatic treatment encompasses slowing down intestinal activity (e.g., with loperamide) and replacing fluid and electrolyte losses orally as required. Eliminating the infection in chronic stool carriers of typhoid salmonellae, 2–5% of cases, presents a problem. Chronic carriers are defined as convalescents who are still eliminating pathogens three months after the end of the manifest illness. The organisms usually persist in the scarified wall of the gallbladder. Success is sometimes achieved with high-dose administration of anti-infective agents, e.g., 4-quinolones or aminopenicillins.

PREVENTION: The main method of effective prevention is to avoid exposure: this means clean drinking water, prevention of food contamination, avoidance of uncooked foods in countries where salmonellae occur frequently, disinfection of excreta containing salmonellae or from chronic carriers, etc. It is also important to report all cases to health authorities so that appropriate measures can be taken.

RELATED;

1.  BRUCELLA  

2.  GRAM NEGATIVE ENTERIC BACTERIA

3.  BACTERIOLOGY

4. MEDICAL MICROBIOLOGY

REFERENCES

METRONIDAZOLE (FLAGYL)

 

Introduction:  Metronidazole also sometimes referred to as fragyl, is one of the most commonly prescribed and used drugs because of availability, being cheap and broad spectrum of activity.  This drug can act against both bacteria, and protozoa.

Therapeutic Class: Anti-infective, antiprotozoan, and Antibacterial

Pharmacologic Class: Drug that disrupts nucleic acid synthesis and sometimes act as a proton sink, by depriving the microbe of oxidative potential.

Actions and uses: Metronidazole is the prototype drug for most forms of amebiasis, being effective against both the intestinal and hepatic stages of the disease. Resistant forms of E. histolytica have not yet emerged as a clinical problem with metronidazole therapy. Metronidazole is also a preferred drug for giardiasis and trichomoniasis. 

Metronidazole is unique among antiprotozoan drugs in that it also has antibiotic activity against anaerobic bacteria and thus is used to treat a number of respiratory, bone, skin, and CNS infections. 

Topical forms of metronidazole (MetroGel, MetroCream, MetroLotion) are used to treat rosacea, a disease characterized by skin reddening and hyperplasia of the sebaceous glands, particularly around the nose and face.

ADMINISTRATION ALERTS: The extended-release form must be swallowed whole and taken on an empty stomach. Metronidazole is contraindicated during the first trimester of pregnancy. Pregnancy category B

ADVERSE EFFECTS: Although adverse effects occur relatively frequently, most are not serious enough to cause discontinuation of therapy. The most common adverse effects of metronidazole are anorexia, nausea, diarrhea, dizziness, and headache. Dryness of the mouth and an unpleasant metallic taste may be experienced. Although rare, metronidazole can cause bone marrow suppression. 

Contraindications: Metronidazole is contraindicated in patients with trichomoniasis during the first trimester of pregnancy and those with hypersensitivity to the drug. Metronidazole can cause bone marrow suppression; thus, it is contraindicated for patients with blood dyscrasias.

INTERACTIONS: Drug–Drug: Metronidazole interacts with oral anticoagulants to potentiate hypoprothrombinemia. In combination with alcohol, or other medications that may contain alcohol, metronidazole may elicit a disulfiram reaction. In patients who are taking lithium, the drug may elevate lithium levels.

RELATED;

1.  FLOROQUINOLONES  

2.  PENICILLINS  

3.  CEPHALOSPORINS

4.  DRUG USE IN RELATION TO PREGNANCY

5.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES