PROCHLORPERAZINE

Therapeutic Class: Antiemetic

Pharmacologic Class: Phenothiazine antipsychotic

ACTIONS AND USES: Prochlorperazine is a phenothiazine, a class of drugs usually prescribed for psychoses. The phenothiazines are the largest group of drugs prescribed for severe nausea and vomiting, and prochlorperazine is the most frequently prescribed antiemetic in its class. Prochlorperazine acts by blocking dopamine receptors in the brain, which inhibits signals to the vomiting center in the medulla. Dopamine

As an antiemetic, it is frequently given by the rectal route, where absorption is rapid. It is also available in tablet, extended-release capsule, and IM formulations.

ADMINISTRATION ALERTS: Administer 2 hours before or after antacids and antidiarrheals. Pregnancy category C.

ADVERSE EFFECTS: Prochlorperazine produces dose-related anticholinergic side effects such as dry mouth, sedation, constipation, orthostatic hypotension, and tachycardia. When used for prolonged periods at higher doses, extrapyramidal symptoms resembling those of Parkinson's disease are a serious concern, especially in older patients.

Contraindications: This drug should not be used in patients with hypersensitivity to phenothiazines, in comatose patients, or in the presence of profound CNS depression. It is also contraindicated in children younger than age 2. Patients with narrow-angle glaucoma, bone marrow suppression, or severe hepatic or cardiac impairment should not take this drug.

INTERACTIONS: Drug-Drug: Prochlorperazine interacts with alcohol and other CNS depressants to cause additive sedation. Antacids and antidiarrheals inhibit the absorption of prochlorperazine. When taken with phenobarbital, metabolism of prochlorperazine is increased. Use with tricyclic antidepressants may produce increased anticholinergic and hypotensive effects.

RELATED;

1. NAUSEA AND VOMITING  

2. ENTERIC NERVOUS SYSTEM

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

ECHINACEA FOR BOOSTING THE IMMUNE SYSTEM

 

Echinacea purpurea, or purple coneflower, is a popular botanical native to the midwestern United States and central Canada. The flowers, leaves, and stems of this plant are harvested and dried. Preparations include dried powder, tincture, fluid extracts, and teas. No single ingredient seems to be responsible for the herb’s activity; a large number of potentially active chemicals have been identified from the extracts. Echinacea was used by Native Americans to treat various wounds and injuries. Wound healing

Echinacea is believed to boost the immune system by increasing phagocytosis and inhibiting the bacterial enzyme hyaluronidase. Some substances in echinacea appear to have antiviral activity; thus, the herb is sometimes taken to treat the common cold and influenza, an indication for which it has received official approval in Germany. Clinical evidence for the effects of echinacea on upper respiratory tract infections is mixed, with some studies showing no effect and others showing a beneficial effect. In general, echinacea is used as a supportive treatment for any disease involving inflammation and to enhance the immune system. Inflammation: Immunity

Side effects are rare; however, it may interfere with drugs that have immunosuppressant effects.

RELATED;

1.  PASSIVE IMMUNITY  

2.  ACTIVE IMMUNISATION  

3.  SEA VEGETABLES

REFERENCES

GARLIC FOR CARDIOVASCULAR HEALTH

 

INTRODUCTION: Garlic also scientifically known as Allium sativum, is one of the best-studied herbs. Several substances, known as alliaceous oils, have been isolated from garlic and shown to have pharmacologic activity.

Dosage forms include eating prepared garlic oil or the fresh bulbs from the plant. Modern claims for garlic uses have focused on the cardiovascular system: treatment of high blood lipid levels, atherosclerosis, and hypertension. Other modern claims are that garlic reduces blood glucose levels and has antibacterial and antiviral properties. Like many other supplements, garlic likely has some health benefits, but controlled, scientific studies are often lacking and the results are mixed. Garlic has been shown to decrease the aggregation or “stickiness” of platelets, thus producing an anticoagulant effect. There is some research to show that the herb has a small effect on lowering blood cholesterol. Evidence on the effects of the herb on blood pressure is mixed. An analysis of the research of the effect of garlic on the common cold concluded that there is insufficient clinical evidence to show any benefit. Garlic is safe for consumption in moderate amounts. Patients taking anticoagulant medications should limit their intake of garlic to avoid bleeding complications. Patients with diabetes should monitor their blood glucose levels closely if taking high doses of garlic.

RELATED;

1.  CARDIOVASCULAR CONDITIONS

REFERENCES

SEA VEGETABLES

Sea vegetables, or seaweeds, are a form of marine algae that grow in the upper levels of the ocean, where sunlight can penetrate. Examples of these edible seaweeds include spirulina, kelp, chlorella, arame, and nori, many of which are used in Asian cooking. Sea vegetables are found in coastal locations throughout the world. Kelp, or Laminaria, is found in the cold waters of the North Atlantic and Pacific Oceans. Sea vegetables contain a multitude of vitamins as well as protein. Their most notable nutritional aspect, however, is their mineral content. Plants from the sea contain more minerals than most other food sources, including calcium, magnesium, phosphorous, iron, potassium, and all essential trace elements. Because they are so rich in minerals, seaweeds act as alkalizers for the blood, helping to rid the body of acid conditions (acidosis). Spirulina, kelp, and chlorella are available in capsule or tablet form, or as part of a “greens” mix containing other nutritional ingredients.

RELATED;

1.  GINGER  

2.  GARLIC  

3.  FOOD-DRUG INTERACTIONS

4.  TRADITIONAL AND COMPLIMENTARY MEDICATIONS

REFERENCES

AZITHROMYCIN

 

Introduction: Azithromycin, a 15-atom lactone macrolide ring compound, is derived from erythromycin by addition of a methylated nitrogen into the lactone ring. Its spectrum of activity, mechanism of action, and clinical uses are similar to those of clarithromycin. Azithromycin is active against M. avium complex and T. gondii. Mycobacteria:  Azithromycin is slightly less active than erythromycin and clarithromycin against staphylococci and streptococci and slightly more active against H. influenzae. Azithromycin is highly active against Chlamydia sp. H.influenzae

Pharmacokinetic aspects of the drug: Azithromycin differs from erythromycin and clarithromycin mainly in pharmacokinetic properties. A 500-mg dose of azithromycin produces relatively low serum concentrations of approximately 0.4 mcg/mL. However, azithromycin penetrates into most tissues (except cerebrospinal fluid) and phagocytic cells extremely well, with tissue concentrations exceeding serum concentrations by 10- to 100-fold. The drug is slowly released from tissues (tissue half-life of 2–4 days) to produce an elimination half-life approaching 3 days. These unique properties permit once-daily dosing and shortening of the duration of treatment in many cases. For example, a single 1-g dose of azithromycin is as effective as a 7-day course of doxycycline for chlamydial cervicitis and urethritis.

Pharmacological Applications: Community-acquired pneumonia can be treated with azithromycin given as a 500-mg loading dose, followed by a 250-mg single daily dose for the next 4 days. A zithromycin is rapidly absorbed and well tolerated orally. It should be administered 1 hour before or 2 hours after meals. Aluminum and magnesium antacids do not alter bioavailability but delay absorption and reduce peak serum concentrations. Azithromycin does not inactivate cytochrome P450 enzymes and, therefore, is free of the drug interactions that occur with erythromycin and clarithromycin.  

RELATED;

1.  The cytochrome P450 enzyme system

2.  Pharmacology test questions

3.  Pharmacology and therapeutics

[REFERENCE]

DOPAMINE

 

Introduction: Dopamine plays several important roles in the brain and body. A member of the catecholamine and phenethylamine families, its name comes from the fact that it is an amine made by removing a carboxyl group from LDOPA. Dopamine is synthesized in the brain and kidneys. It is also made in plants, though its function in plants is not clear. Conversion of dopamine to norepinephrine requires vitamin C.  Dopamine is a neurotransmitter, being released by one nerve cell and then traveling across a synapse to signal an adjacent nerve cell. Generation of a nerve impulse  

Dopamine plays a major role in the brain’s reward-mediated behavior. Rewards, such as food or social interaction, increase dopamine levels in the brain, as do addictive drugs. Other brain dopamine pathways are involved in motor control and in managing the release of various hormones.

Chemical messenger: Outside the nervous system, dopamine is a local chemical messenger. In blood vessels, it inhibits norepinephrine release and causes vasodilation. In the kidneys, it increases sodium excretion and urine output. It reduces gastrointestinal motility and protects intestinal mucosa in the digestive system and in the immune system, it reduces lymphocyte activity. The effect dopamine has on the pancreas is to reduce insulin production. With the exception of the blood vessels, dopamine is synthesized locally and exerts its effects near the cells that release it.

RELATED;

1.  THE NEUROTRANSMITTER SYSTEMS

2.  THE NEUROMASCULAR JUNCTION IMPULSE TRANSMISSION

PHASES OF CLINICAL TRIALS

 

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

1.  List the intentions of phase 1 clinical trials

2.  Continue with the description of following clinical phases

PHASE 1: Safety and dosage: In some of my previous discussions I was talking about a drug being able to cure the intended disease but also have minimal side effects or in simple terms, safer for the patient.  Phase I trials are the first tests of a drug with a lesser number of healthy human volunteers. In most cases, 20 to 80 healthy volunteers with the disease or a condition participate in Phase 1. Patients are generally only used if the mechanism of action of a drug also known as pharmacodynamics, indicates that it will not be tolerated in healthy people. Pharmacodynamics

However, if a new drug is proposed for use in Parkinsonism patients lets say, researchers conduct Phase 1 trials in patients with that Parkinson’s disease. Phase 1 studies are closely monitored and collect information about Pharmacodynamics in the human body.

Researchers adjust dosage regimen based on animal study data to find out what dose of a drug can tolerate the body and what are its acute side effects. As a Phase 1 trial continues, researchers find out research mechanism of action, the side effects accompanying with increase in dosage, and information about effectiveness. This is imperative to the design of Phase 2 studies. Almost 70% of drugs travel to the next phase.

RELATED;

1.  CLINICAL TRIALS PHASE 2  

2.  CLINICAL TRIALS PHASE 3  

3.  CLINICAL TRIALS PHASE 4  

4.  EXPERIMENTAL STUDY DESIGNS

5.  EXPERIMENTAL STUDY DESIGNS

REFERENCES

BCG VACCINATION

 

Introduction: BCG vaccine consists of live bovine tubercle bacilli whose virulence has been attenuated by multiple passages through glycerinated potato. The bacilli of the vaccine are therefore alive, but have lost some of their virulence. BCG is the most widely used vaccine in the world.

EFFICACY OF THE VACCINE: The protection conferred by BCG when it is administered correctly at birth acts mainly on the severe extrapulmonary forms in children. It is currently estimated at between 60-90%.

INDICATIONS: In countries with a high prevalence of TB, BCG vaccination should be administered to infants as soon as possible after birth and in any case before the age of one year.

AVAILABILITY OF VACCINE: The vaccine is available in dry, lyophilised powder that is sensitive to heat, so the vaccine should be kept in a cold chain and away from light. To avoid exposure to light the vaccine is delivered in coloured vials. The vial is accompanied by another vial containing a solvent that must be used cold, by refrigerating it for at least 24 hours before use. After reconstitution the mixture must be kept in the refrigerator and used within 3-4 hours. 

DOSE: The dose of vaccine is 0.05 ml for newborns and children aged upto one year. It is 0.1 ml for children aged over one year. 

REQUIREMENTS: 1 ml syringe and intradermal needle.

SITE OF ADMINISTRATION: Usually same site is recommended for use in the whole of the country so that it is easy to detect the vaccination scar. Usually it is the front of the left upper arm.

ROUTE OF ADMINISTRATION: Vaccine is given intradermally. If by chance the needle goes beyond the dermis, the needle should be withdrawn and inserted at an adjacent spot. The injection should raise a wheal.

RELATED;  

1.  TECNIQUESAND ROUTES OF DRUG ADMINISTRATION  

2.  ACTIVE IMMUNISATION  

3.  ADAPTIVE IMMUNITY  

REFERENCES

ANTIMALARIAL ACTION AND RESISTANCE OF QUININE

 

INTRODUCTION: Quinine is a rapid-acting, highly effective blood schizonticide against the four species of human malaria parasites. The drug is gametocidal against P. vivax and P. ovale but not P falciparum. It is not active against liver stage parasites. The mechanism of action of quinine is unknown. Increasing in vitro resistance of parasites from a number of areas suggests that quinine resistance will be an increasing problem. Resistance to quinine is already common in some areas of Southeast Asia, especially border areas of Thailand, where the drug may fail if used alone to treat falciparum malaria. However, quinine still provides at least a partial therapeutic effect in most patients. Antimicrobial drug resistance

CLINICAL USES: Parenteral Treatment of Severe Falciparum Malaria. For many years, quinine dihydrochloride or quinidine gluconate have been the treatments of choice for severe falciparum malaria, although intravenous artesunate now provides an alternative for this indication. Quinine can be administered slowly intravenously or, in a dilute solution, intramuscularly. The drug can be administered in divided doses or by continuous intravenous infusion; treatment should begin with a loading dose to rapidly achieve effective plasma concentrations. Because of its cardiac toxicity and the relative unpredictability of its pharmacokinetics, intravenous quinidine should be administered slowly with cardiac monitoring. Therapy should be changed to an effective oral agent as soon as the patient has improved and can tolerate oral medications.

ORAL TREATMENT OF FALCIPARUM MALARIA: Quinine sulfate is appropriate therapy for uncomplicated falciparum malaria except when the infection was transmitted in an area without documented chloroquine-resistant malaria. Quinine is commonly used with a second drug (most often doxycycline or, in children, clindamycin) to shorten quinine’s duration of use (usually to 3 days) and limit toxicity. Quinine is less effective than chloroquine against other human malarias and is more toxic. Therefore, it is not used to treat infections with these parasites.

MALARIAL CHEMOPROPHYLAXIS: Quinine is not generally used in chemoprophylaxis owing to its toxicity, although a daily dose of 325 mg is effective.

BABESIOSIS: Quinine is first-line therapy, in combination with clindamycin, in the treatment of infection with Babesia microti or other human babesial infections.

ADVERSE EFFECTS: Therapeutic dosages of quinine and quinidine commonly cause tinnitus (ringing in the ears), headache, nausea, dizziness, flushing, and visual disturbances, a constellation of symptoms termed cinchonism. Mild symptoms of cinchonism do not warrant the discontinuation of therapy. More severe findings, often after prolonged therapy, include more marked visual and auditory abnormalities, vomiting, diarrhea, and abdominal pain. Hypersensitivity reactions include skin rashes, urticaria, angioedema, and bronchospasm. Hematologic abnormalities include hemolysis (especially with G6PD deficiency), leukopenia, agranulocytosis, and thrombocytopenia. Therapeutic doses may cause hypoglycemia through stimulation of insulin release; this is a particular problem in severe infections and in pregnant patients, who have increased sensitivity to insulin. Quinine can stimulate uterine contractions, especially in the third trimester. However, this effect is mild, and quinine and quinidine remain drugs of choice for severe falciparum malaria even during pregnancy. Intravenous infusions of the drugs may cause thrombophlebitis. Severe hypotension can follow too-rapid intravenous infusions of quinine or quinidine. Electrocardiographic abnormalities (QT interval prolongation) are fairly common with intravenous quinidine, but dangerous arrhythmias are uncommon when the drug is administered appropriately in a monitored setting. Blackwater fever is a rare severe illness that includes marked hemolysis and hemoglobinuria in the setting of quinine therapy for malaria. It appears to be due to a hypersensitivity reaction to the drug, although its pathogenesis is uncertain.

CONTRAINDICATIONS & CAUTIONS: Quinine (or quinidine) should be discontinued if signs of severe cinchonism, hemolysis, or hypersensitivity occur. It should be avoided if possible in patients with underlying visual or auditory problems. It must be used with great caution in those with underlying cardiac abnormalities. Quinine should not be given concurrently with mefloquine and should be used with caution in a patient with malaria who has previously received mefloquine chemoprophylaxis. Absorption may be blocked by aluminum containing antacids. Quinine can raise plasma levels of warfarin and digoxin. Dosage must be reduced in renal insufficiency.

RELATED;

1.  ARTEMISININ COMBINATION THERAPIES

2.  PLASMODIUM

references

SILDENAFIL (VIAGRA)

Therapeutic Class: Drug for erectile dysfunction

Pharmacologic Class: Phosphodiesterase (PDE)-5 inhibitor

ACTIONS AND USES: Sildenafil acts by relaxing smooth muscles in the corpora cavernosa, thus allowing increased blood flow into the penis. The increased blood flow results in a firmer and longer lasting erection in about 70% of men taking the drug. The onset of action is relatively rapid, less than 1 hour, and its effects last up to 4 hours. Sildenafil blocks the enzyme phosphodiesterase-5. Sildenafil is also used for the treatment of pulmonary arterial hypertension. Blocking phosphodiesterase-5 in pulmonary vascular smooth muscle causes vasodilation and reduction in arterial hypertension. The drug improves exercise capacity in these patients. An off-label indication for sildenafil is the treatment of Raynaud’s phenomenon resistant to vasodilator therapy.

ADMINISTRATION ALERTS: Avoid administration of sildenafil with meals, especially high-fat meals, because absorption is decreased. Avoid grapefruit juice when administering sildenafil.

ADVERSE EFFECTS: Sildenafil is well tolerated and adverse effects are usually transient and mild. Common adverse effects include headache, dizziness, flushing, rash, and nasal

congestion. The most serious adverse effect, hypotension, occurs in patients concurrently taking organic nitrates for angina and can result in myocardial infarction (MI) and sudden cardiac death. Sildenafil can produce blurred vision, increased sensitivity to light, or changes in color perception. Priapism, a sustained erection lasting longer than 6 hours, has been reported with sildenafil use and this may lead to permanent damage to penile tissues. Contraindications: Sildenafil is contraindicated in patients taking nitrates and in those with hypersensitivity to the drug. These drugs are contraindicated in patients with severe cardiovascular disease, recent MI, stroke, heart failure, dysrhythmias, and in the presence of anatomic deformities of the penis.

INTERACTIONS: Drug–Drug: Cimetidine, erythromycin, and ketoconazole will increase serum levels of sildenafil and necessitate lower drug doses. Use with nitrates will result in hypotension. Protease inhibitors (ritonavir, amprenavir, others) will cause increased sildenafil levels, which may lead to toxicity. Rifampin may decrease sildenafil levels, leading to decreased effectiveness.

Herbal/Food: Administration of sildenafil with high-fat meals decreases the absorption of the drug. Grapefruit juice increases the plasma concentrations of sildenafil and may cause adverse effects. 

Treatment of Overdose: There is no specific treatment for overdose.

RELATED;

1.  BENIGN PROSTATIC HYPERPLASIA

REFERENCES

CAYENNE FOR MUSCULAR PAIN AND TENSION

INTRODUCTION: Cayenne (Capsicum annum), also known as chili pepper, paprika, or red pepper, has been used as a remedy for minor muscle pain or tension. Capsaicin, the active ingredient in cayenne, diminishes the chemical messengers that travel through the sensory nerves, thereby decreasing the sensation of pain. A review of the existing literature concluded that capsaicin is effective in reducing neuropathic pain when used topically as a repeated application at low doses (0.075%), or as a single application of a high dose. Capsaicin cream (0.025% to 0.075%) is available over the counter and may be applied directly to the affected area up to four times a day. The highest dose (8%) is available as a patch by prescription and its use must be carefully monitored by a health care provider. The topical creams are well tolerated, with reddening of the skin and local stinging being the most common side effects. It should be kept away from the eyes and mucous membranes to avoid burning, and the hands must be washed thoroughly after use.

RELATED;

1.  BACK PAIN  

2.  CARNITINE FOR HEART DISEASE

3.  TRADITIONAL AND COMPLIMENTARY MEDICATIONS

REFERENCES

FLOROQUINOLONES

INTRODUCTION: Although the first drug in this class, nalidixic acid, was approved by the FDA in 1962, it had a narrow spectrum of activity, and its use was restricted to UTIs. Nalidixic acid is still used for the pharmacotherapy of UTI, although it is not a preferred drug for this infection. Since then, four generations of fluoroquinolones have become available, differing in their antibacterial spectrums. All fluoroquinolones have activity against gram-negative pathogens; the newer ones are significantly more effective against gram-positive microbes, such as staphylococci, streptococci, and enterococci. Enterobacteriaceae

SPECTRUM OF ACTIVITY: The fluoroquinolones are bacteriocidal and affect DNA synthesis by inhibiting two bacterial enzymes: DNA gyrase and topoisomerase IV.

CLINICAL APPLICATIONS: Clinical applications of fluoroquinolones include infections of the respiratory, GI, and genitourinary tracts, and some skin and soft-tissue infections. Their effectiveness against gram-negative organisms makes them preferred drugs for the treatment of uncomplicated UTIs. A newer drug in this class, moxifloxacin (Avelox), is effective against anaerobes, a group of bacteria that are often difficult to treat. The most widely used fluoroquinolone, ciprofloxacin (Cipro), is a drug of choice for the postexposure prophylaxis of Bacillus anthracis, the organism responsible for causing anthrax. Bacillus spp

Ciprofloxacin is also indicated for postexposure prophylaxis to other potential biologic warfare pathogens such as Yersinia pestis (plague), Francisella tularensis (tularemia), and Brucella melitensis (brucellosis). Two drugs in this class, gatifloxacin and besifloxacin, are available only as drops to treat infections of the external eye.

PHARMACOKINETICS: A major advantage of the fluoroquinolones is that most are well absorbed orally and may be administered either once or twice a day. Although they may be taken with food, they should not be taken concurrently with multivitamins or mineral supplements because calcium, magnesium, iron, or zinc ions can reduce the absorption of some fluoroquinolones by as much as 90%. Fluoroquinolones are well tolerated by most patients, with nausea, vomiting, and diarrhea being the most common adverse effects. The most serious adverse effects are dysrhythmias (moxifloxacin) and potential hepatotoxicity.

CNS effects such as dizziness, headache, and sleep disturbances affect 1% to 8% of patients. Most recently, fluoroquinolones have been associated with cartilage toxicity with an increased risk of tendonitis and tendon rupture, particularly of the Achilles tendon. The risk of tendon rupture is increased in patients over age 60 and those receiving concurrent corticosteroids. Because animal studies have suggested that fluoroquinolones affect cartilage development, these drugs are not approved for children under age 18. Use in pregnancy or in lactating patients should be avoided.

RELATED;

1.  DRUG USE AND PREGNANCY  

2.  SALFONAMIDES

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

STREPTOMYCIN

 

INTRODUCTION:  Streptomycin was isolated from a strain of Streptomyces griseus. The antimicrobial activity of streptomycin is typical of that of other aminoglycosides, as are the mechanisms of resistance.  Resistance has emerged in most species, severely limiting the current usefulness of streptomycin. Ribosomal resistance to streptomycin develops readily, limiting its role as a single agent.

CLINICAL USES:  

A. Mycobacterial Infections; Streptomycin is mainly used as a second-line agent for treatment of tuberculosis. The dosage is 0.5–1 g/d (7.5–15 mg/kg/d for children), which is given intramuscularly or intravenously. It should be used only in combination with other agents to prevent emergence of resistance.

B. Non-tuberculous Infections:  In plague, tularemia, and sometimes brucellosis, streptomycin, 1 g/d (15 mg/kg/d for children), is given intramuscularly in combination with an oral tetracycline. Penicillin plus streptomycin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis. Gentamicin has largely replaced streptomycin for these indications.  Streptomycin remains a useful agent for treating enterococcal infections, however, because approximately 15% of enterococcal isolates that are resistant to gentamicin (and therefore resistant to netilmicin, tobramycin, and amikacin) will be susceptible to streptomycin.

ADVERSE REACTIONS:  Fever, skin rashes, and other allergic manifestations may result from hypersensitivity to streptomycin. This occurs most frequently with prolonged contact with the drug either in patients who receive a prolonged course of treatment (eg, for tuberculosis) or in medical personnel who handle the drug. Desensitization is occasionally successful. Pain at the injection site is common but usually not severe. The most serious toxic effect with streptomycin is disturbance of vestibular function; vertigo and loss of balance. The frequency and severity of this disturbance are in proportion to the age of the patient, the blood levels of the drug, and the duration of administration. Streptomycin given during pregnancy can cause deafness in the newborn and, therefore, is relatively contraindicated.

 

RELATED;

1.  TUBERCULOSIS

2. ANTITUBERCULAR DRUGS

3. BRUCELLOSIS

4. GENTAMYCIN

5. DRUG USE IN RELATION TO PREGNANCY

6. ANTIMICROBIAL DRUG RESISTANCE

REFERENCES

BLACK COHOSH FOR MENOPAUSE

INTRODUCTION: Black cohosh (Actaea racemosa) is a perennial that grows in the eastern United States and parts of Canada. Use of the herb has been recorded by Native Americans for more than 100 years. Historically, black cohosh has been used in the management of menopausal hot flashes, vaginal dryness, and night sweats and to induce labor. 

DOSING: Doses of black cohosh are sometimes standardized by the amount of the chemical 27- deoxyactein, which is an active ingredient. A typical dose of black cohosh ranges from 40 to 80 mg of dried herb per day. (Approximately 1 mg of 27-deoxyactein is present in each 20-mg tablet or in 20 drops of the liquid formulation).

ADVERSE EFFECTS: Adverse effects include hypotension, uterine stimulation, and gastrointestinal (GI) complaints such as nausea. Black cohosh can increase the action of antihypertensives, so concurrent use should be avoided. Women with liver disorders should consult their health care provider before taking this herb.

RELATED;

1.  GINGER  

2.  VITAMINS

3.  GINSENG

REFERENCES

MILK THISTLE FOR ALCOHOL LIVER DAMAGE

Milk thistle is a plant found growing in North America that has been used as an herbal medicine for centuries. The active ingredient in the milk thistle plant (Silybum marianum), silymarin, has been confirmed to exhibit hepatoprotective qualities by different research studies. Studies have shown that silymarin is able to neutralize the effects of alcohol and actually stimulate liver regeneration. It acts as an antioxidant and free-radical scavenger. It is typically taken for liver cirrhosis, chronic hepatitis, and gallbladder disorders. The herb has few side effects, other than mild diarrhea, bloating, and upset stomach.

RELATED;

1.  HEPATITIS  

2.  VITAMIN A  

3.  GINGER

REFERENCES

FISH OILS FOR INFLAMMATION

Fish oils, also known as marine oils, are lipids found primarily in coldwater fish. These oils are rich sources of long-chain polyunsaturated fatty acids of the omega-3 type. The two most studied fatty acids found in fish oils are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are known for their triglyceride-lowering activity. Several mechanisms are believed to account for the anti-inflammatory activity of EPA and DHA. The two competitively inhibit the conversion of arachidonic acid to the proinflammatory prostaglandins, thus reducing their synthesis.

RELATED;

1.  VITAMIN A  2.  GARLIC  3.  INFLAMMATION

REFERENCES

ACYCLOVIR

INTRODUCTION: Acyclovir is an acyclic guanosine derivative with clinical activity against HSV-1, HSV-2, and VZV, but it is approximately 10 times more potent against HSV-1 and HSV-2 than against VZV. In vitro activity against Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) is present but weaker.

PHARMACOKINETICS: Acyclovir requires three phosphorylation steps for activation. It is converted first to the monophosphate derivative by the virus pecified thymidine kinase and then to the di- and triphosphate compounds by host cell enzymes. Enzymes

Because it requires the viral kinase for initial phosphorylation, acyclovir is selectively activated and the active metabolite accumulates only in infected cells. Acyclovir triphosphate inhibits viral DNA synthesis by two mechanisms: competition with deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA template as an irreversible complex; and chain termination following incorporation into the viral DNA. DNA the genetic material

The bioavailability of oral acyclovir is low (15–20%) and is unaffected by food. An intravenous formulation is available. Topical formulations produce high concentrations in herpetic lesions, but systemic concentrations are undetectable by this route. Acyclovir is cleared primarily by glomerular filtration and tubular secretion. The half-life is 2.5–3 hours in patients with normal renal function and 20 hours in patients with anuria.

RELATED;

1.  NEVIRAPINE  2.  ZIDOVUDINE

REFERENCES

BETA-LACTAMASE INHIBITORS (CLAVULANIC ACID, SULBACTAM, & TAZOBACTAM)

Introduction: These substances resemble β-lactam molecules, but they have very weak antibacterial action and therefore we are not classifying them as antibiotics in nature. They are potent inhibitors of many but not all bacterial β-lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes. Beta-lactamase inhibitors are most active against Ambler class A β-lactamases (plasmid-encoded transposable element [TEM] β-lactamases in particular), such as those produced by staphylococci, H. influenzae, N. gonorrhoeae, salmonella, shigella, E. coli , and K. pneumoniae.

Spectrum of activity: They are not good inhibitors of class C β-lactamases, which typically are chromosomally encoded and inducible, produced by Enterobacter sp, Citrobacter sp, S. marcescens , and P. aeruginosa , but they do inhibit chromosomal β-lactamases of B. fragilis and M. catarrhalis . The three inhibitors differ slightly with respect to pharmacology, stability, potency, and activity, but these differences usually are of little therapeutic significance.

Formulations: Beta-lactamase inhibitors are available only in fixed combinations with specific penicillins. The antibacterial spectrum of the combination is determined by the companion penicillin, not the β-lactamase inhibitor. An inhibitor extends the spectrum of a penicillin provided that the inactivity of the penicillin is due to destruction by β-lactamase and that the inhibitor is active against the β-lactamase that is produced. Thus, ampicillin-sulbactam is active against β-lactamase-producing S. aureus and H. influenzae but not against serratia, which produces a β lactamase that is not inhibited by sulbactam.

Similarly, if a strain of P. aeruginosa is resistant to piperacillin, it is also resistant to piperacillin-tazobactam because tazobactam does not inhibit the chromosomal β-lactamase produced by P. aeruginosa. The indications for penicillin-β-lactamase inhibitor combinations are empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised and immunocompetent patients and treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections.

RELATED;

1.  PENICILLINS

2.  CEPHALOSPORINS

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

FIBRINOLYTIC DRUGS

INTRODUCTION: Fibrinolytic drugs rapidly lyse thrombi by catalyzing the formation of the serine protease plasmin from its precursor zymogen, plasminogen. These drugs create a generalized lytic state when administered intravenously. Thus, both protective hemostatic thrombi and target thromboemboli are broken down. Myocardial Infarction describes the use of these drugs in one major application.

PHARMACOLOGY: Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. Streptococci

This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin.

Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within.

Anistreplase (anisoylated plasminogen streptokinase activator complex; APSAC) consists of a complex of purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme’s active site. When administered, the acyl group spontaneously hydrolyzes, freeing the activated streptokinase-proactivator complex. This product allows for rapid intravenous injection, greater clot selectivity (ie, more activity on plasminogen associated with clots than on free plasminogen in the blood), and more thrombolytic activity. Plasminogen can also be activated endogenously by tissue plasminogen activators (t-PAs). These activators preferentially activate plasminogen that is bound to fibrin, which confines fibrinolysis to the formed thrombus and avoids systemic activation. Human t-PA is manufactured as alteplase by means of recombinant DNA technology.

Reteplase is another recombinant human t-PA from which several amino acid sequences have been deleted. Reteplase is less expensive to produce than t-PA. Because it lacks the major fibrin-binding domain, reteplase is less fibrinspecific than t-PA.

Tenecteplase is a mutant form of t-PA that has a longer half-life, and it can be given as an intravenous bolus. Tenecteplase is slightly more fibrin-specific than t-PA.

INDICATIONS & DOSAGE: Administration of fibrinolytic drugs by the intravenous route is indicated in cases of pulmonary embolism with hemodynamic instability, severe deep venous thrombosis such as the superior vena caval syndrome, and ascending thrombophlebitis of the iliofemoral vein with severe lower extremity edema. Thromboticdisorders

These drugs are also given intra-arterially, especially for peripheral vascular disease. Thrombolytic therapy in the management of acute myocardial infarction requires careful patient selection, the use of a specific thrombolytic agent, and the benefit of adjuvant therapy. Streptokinase is administered by intravenous infusion of a loading dose of 250,000 units, followed by 100,000 units/h for 24–72 hours. Patients with antistreptococcal antibodies can develop fever, allergic reactions, and therapeutic resistance. Drug resistance

Urokinase requires a loading dose of 300,000 units given over 10 minutes and a maintenance dose of 300,000 units/h for 12 hours. Alteplase (t-PA) is given by intravenous infusion of 60 mg over the first hour and then 40 mg at a rate of 20 mg/h. Reteplase is given as two intravenous bolus injections of 10 units each, separated by 30 minutes. Tenecteplase is given as a single intravenous bolus of 0.5 mg/kg. Anistreplase (where available) is given as a single intravenous injection of 30 units over 3–5 minutes. Recombinant t-PA has also been approved for use in acute ischemic stroke within 3 hours of symptom onset. In patients without hemorrhagic infarct or other contraindications, this therapy has been demonstrated to provide better outcomes in several randomized clinical trials. Clinicaltrials

The recommended dose is 0.9 mg/kg, not to exceed 90 mg, with 10% given as a bolus and the remainder during a 1 hour infusion. Streptokinase has been associated with increased bleeding risk in acute ischemic stroke when given at a dose of 1.5 million units, and its use is not recommended in this setting.

RELATED;

1.  VEIN DISORDERS  

2.  NOSE BLEEDING

3.  BLOOD CLOTTING AND IT'S PREVENTION

REFERENCES

TREATMENT OF ANXIETY AND INSOMNIA

Introduction:  Antidepressants are frequently used to treat symptoms of anxiety. These drugs have an ability to reduce anxiety symptoms by altering levels of two important neurotransmitters in the brain, norepinephrine and serotonin. Restoration of normal neurotransmitter balance helps to reduce symptoms associated with depression, panic, obsessive–compulsive behavior, and phobia.  Typical antidepressants include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs). Atypical antidepressants are more diverse. 

CNS depressants used for anxiety and sleep disorders are categorized into two major classes, the benzodiazepines and barbiturates. Benzodiazepines:  Barbiturates

A third class consists of miscellaneous drugs that are chemically unrelated to the benzodiazepines or barbiturates but have similar therapeutic uses. Other CNS depressants that have a calming effect in the body include the opioids and ethyl alcohol.  Opioid analgesics

CNS depression should be viewed as a continuum ranging from relaxation, to sedation, to the induction of sleep and anesthesia. Coma and death are the end stages of CNS depression. Some drug classes are capable of producing the full range of CNS depression from calming to anesthesia, whereas others are less efficacious. Medications that depress the CNS are sometimes called sedatives because of their ability to sedate or relax a patient. At higher doses, some of these drugs are called hypnotics because of their ability to induce sleep. Thus, the term sedative–hypnotic is often used to describe a drug with the ability to produce a calming effect at lower doses and the ability to induce sleep at higher doses. Sedative-hypnotics

Tranquilizer is an older term that is sometimes used to describe a drug that produces a calm or tranquil feeling. Many CNS depressants can cause physical and psychological dependence. The withdrawal syndrome for some CNS depressants can cause life-threatening neurologic reactions, including fever, psychosis, and seizures. Other withdrawal symptoms include increased heart rate and lowered blood pressure; loss of appetite; muscle cramps; impairment of memory, concentration, and orientation; abnormal sounds in the ears and blurred vision; and insomnia, agitation, anxiety, and panic. Obvious withdrawal symptoms typically last from 2 to 4 weeks. Subtle ones can last months.

RELATED;

1.  Sedative-hypnotics  

2.  Zolpidem

3.  Depression

REFERENCES