PARASYMPATHOLYTICS

 

INTRODUCTION:  Drugs that block the action of Acetylcholine are known by a number of names, including anticholinergics, cholinergic blockers, muscarinic antagonists, and parasympatholytics.  Although the term anticholinergic is most commonly used, the most accurate term for this class of drugs is muscarinic antagonists, because at therapeutic doses, these drugs are selective for Ach muscarinic receptors and thus have little effect on Ach nicotinic receptors.

PHARMACODYNAMICS:  Anticholinergics act by competing with Ach for binding muscarinic receptors. When anticholinergics occupy these receptors, no response is generated at the neuroeffector organs. Suppressing the effects of Ach causes symptoms of sympathetic nervous system activation to predominate. Most therapeutic uses of the anticholinergics are predictable extensions of their parasympathetic-blocking actions: dilation of the pupils, increase in heart rate, drying of secretions, and relaxation of the bronchi.

THERAPEUTIC USES:  1. GI disorders:  These agents decrease the secretion of gastric acid in peptic ulcer disease. They also slow intestinal motility and may be useful for reducing the cramping and diarrhea associated with irritable bowel syndrome. 

2. Ophthalmic procedures:  Anticholinergics may be used to cause mydriasis or cycloplegia during eye procedures.

3. Cardiac rhythm abnormalities:  Anticholinergics can be used to accelerate the heart rate in patients experiencing bradycardia.

4. Preanesthesia:  Combined with other agents, anticholinergics can decrease excessive respiratory secretions and reverse the bradycardia caused by general anesthetics.

5. Asthma:  A few agents, such as ipratropium, are useful in treating asthma, because of their ability to dilate the bronchi.

6. Overactive bladder:  Anticholinergics treat urinary retention and incontinence.

7. Degenerative nervous system application:  Anticholinergics are used to treat patients who have Parkinson’s disease and whose main symptom is tremor. The prototype drug, atropine, is used for several additional medical conditions due to its effective muscarinic receptor blockade. These applications include reversal of adverse muscarinic effects and treatment of cholinergic agent poisoning, including that caused by overdose of bethanechol, cholinesterase inhibitors, or accidental ingestion of certain types of mushrooms or organophosphate pesticides.

 

RELATED;

1.  ACETYLCHOLINE

2.  CHOLINOMIMETICS

3.  GENERATION OF A NERVE IMPULSE

4.  DIVISIONS OF THE CENTRAL NERVOUS SYSTEM

5.  ATROPINE

REFERENCES

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

ARTEMISININ & ITS DERIVATIVES

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

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

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

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

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

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

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

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

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

RELATED;

1.  PENICILLINS  

2.  AZITHROMYCIN

3.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

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]

METFORMIN

 

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

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

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

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

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

RELATED;

1. DIABETES MELLITUS

2. INSULIN

3.  PATHOPHYSIOLOGY OF DIABETES

4.  PHARMACOLOGY AND THERAPEUTICS

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

OPIOID ANALGESICS

 

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

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

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

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

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

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

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

RELATED; 

1.  CORTICOSTEROIDS  

2.  CHRONIC INFLAMMATION

3.  MORPHINE

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

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