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Clinical Safety
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Clinical Safety
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Basic
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Infection
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CNT Principles
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Acupuncture
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Precautions
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Risk Management
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Patients and Their Records
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Herbal Safety
Why clinic safety is important and what will be in it?
What is Patient Safety?
•Patient Safety aims to prevent and reduce risks, errors and harm that occur to patients during provision of health care.
•Patient safety is fundamental to delivering quality essential health services.
Acupuncture: basic safety principles
•Ensure that acupuncture is the most appropriate treatment for your patient
•Check for significant underlying diseases and ‘red flag’ symptoms and signs and inform the patient’s general practitioner or specialist immediately if signs or symptoms of a serious condition are evident.
•Minimize the risk of trauma or injury
•Pneumothorax is a serious adverse event. When needling over the thoracic region use superficial oblique insertion. The depth of needle insertion must be within safe limits for each patient and each location related to the underlying anatomy.
•Always note the number of needles retained during treatment and ensure that the same number are removed and disposed of safely.
•Reduce the risk of infection
•Wash your hands before patient contact, before inserting and removing needles and whenever there is a risk of cross infection from practitioner or patient to patient.
•Maintain a clean field for any equipment you use in your practice.
•Skin surface should be clean and free from emollients.
•Check your equipment.
•Needles must be sterile, disposable and single use only.
•Maintain your practice in line with current laws
•Dispose of sharps containers and clinical waste in line with current hazardous waste legislation.
•Practitioners must be legally registered or licensed with the local authority.
•Scope of practice
•Work only within your limits of competence and professional training, and within the scope of your professional practice.
•Joining an appropriate professional body that can keep you abreast of current best practice in acupuncture.
•Report serious adverse events or notifiable diseases immediately to:
•your professional body
•your professional insurers
•the Health and Safety Executive
•your local authority or local health protection team (in the case of notifiable diseases).
Infection Prevention and Control
•Infection prevention and control is an essential consideration for TCM practitioners when providing patients with safe health care services.
•Infections can occur with or without direct skin penetration.
•Sharps (e.g., acupuncture needles, dermal needles) are intended to penetrate the skin thereby becoming easily and regularly contaminated by blood or body fluids. The contaminated sharp can infect the practitioner through inadvertent penetration caused by unsafe disposal or handling of the sharps.
•Infections may be the result of the use of contaminated equipment or utensils coming in contact with open cuts or contaminated hands inadvertently touching mucous membranes at the eye, nose, or mouth.
Chain of Infection
Infectious Agent
•A pathogenic micro-organism causing the infection or disease.
•The four types of infectious agents that cause most infectious disease are viruses, bacteria, fungi and parasites.
Reservoir
•The reservoir is where the organism lives and grows between outbreaks. This can be food, water source, feces, in the environment, or in a living organism.
Portal of Exit
•Portal of exit identifies how the infectious agent is able to leave the reservoir (e.g., blood, mucus, secretions, and open wounds).
Transmission
•Transmission identifies how the agent is able to move from one host to another host (e.g., human-to-human through blood contact, respiratory droplets or other secretions, on the hands of a health care worker, through the air in an unfiltered ventilation system, attached to a living organism like a mosquito).
•Knowing how the infection is transmitted is essential for deciding the infection control measures that will be the most effective.
•In a TCM practice setting, the four main transmission routes that are important to understand are direct contact, indirect contact, droplet, and airborne.
Portal of Entry
•This describes how the agent enters the vulnerable host (e.g., insect bite, inhaling, break in the skin, mouth when eating).
•The portal of entry (nose, mouth, skin) informs the practitioner on the personal protective equipment that may be required.
Vulnerable Host
•The vulnerable host is the person infected by the agent. The most vulnerable are often the very young and the very old, or those who have their immune systems suppressed.
•Because of the occupational exposure of health care workers, TCM practitioners and staff have increased opportunities to be exposed to infectious diseases.
Contamination
•Contamination is the spread of infectious micro-organisms to an object (such as an acupuncture needle or herb storage container).
Sterilization & Disinfection
Infections
•Infectious micro-organisms in human blood (blood borne pathogens) can cause disease in humans.
•Use of sharps can expose TCM practitioners to blood borne pathogens. Sharps include objects such as needles, broken glass, and razor blades.
•the following diseases and conditions are highlighted for special attention for TCM practitioners.
•Hepatitis A – contact Food or drink
•Hepatitis B -- blood and other body fluids
•Hepatitis C -- contaminated blood
•Tuberculosis-- breathing in droplets
•AIDS-- blood and other body fluids
•Influenza-- breathing in droplets
•Skin Infections-- broken skin
Hepatitis
•Hepatitis A is common source of Hepatitis A virus (HAV).
•Hepatitis A is more frequently evidenced in locations with poor sanitation. Eating food and drinking water that is contaminated by fecal matter containing Hepatitis A is common source of Hepatitis A virus (HAV).
•Hepatitis A is less severe than Hepatitis B or C.
•Hepatitis A infected blood presents a smaller risk to practitioners.
• There is a vaccine that can be administered for Hepatitis A.
• An effective means of prevention against HAV infection is regular hand washing.
•Hepatitis B is an irritation and swelling of the liver caused by infection with the Hepatitis B virus (HBV).
•Hepatitis B can cause acute illness but can become chronic (lifelong).
•Vaccination is an effective means to prevent HBV infection.
•Health care workers who regularly come in contact with blood and other body fluids are particularly at risk and should be immunized against Hepatitis B.
•The use of the clean needle technique greatly reduces the risks of infection.
•Hepatitis C is caused by the Hepatitis C virus (HCV).
•HCv transmit by contaminated blood
•Hepatitis C has an acute and chronic form.
•There are some treatments, but there is no vaccine.
•The use of the clean needle technique greatly reduces the risks of infection.
Tuberculosis
•Tuberculosis is contagious bacterial infection that mainly involves the lungs.
•it can also spread to bone, skin, gastrointestinal tract.
•Tuberculosis can be transmitted by breathing in droplets from a cough or sneeze of an infected person.
Acquired Immune Deficiency Syndrome (AIDS).
•AIDS caused by infection with Human Immunodeficiency Virus (HIV)
•HIV is spread through direct blood-to-blood contact and through direct contact with certain body fluids, including blood.
HIV can lead to Acquired Immune Deficiency Syndrome (AIDS), which is a collection of diseases that a person can contract when their immune system is weakened.
HIV can be diagnosed with a blood test.
•Health care workers who regularly come in contact with blood and other body fluids should take appropriate precautions.
Influenza
•Influenza or the flu affects primarily the respiratory tract and is caused by the influenza virus.
•Influenza is spread through droplets when someone coughs or sneezes, through the air in enclosed spaces, through direct contact with contaminated hands, and indirect contact with contaminated objects (e.g., door knobs).
•Influenza often has seasonal strains. The elderly or weak are at greater risk of worsening complications.
Pneumonia
•Pneumonia is a respiratory condition caused by an infection of the lungs.
•Pneumonia may be caused by bacteria, viruses, or fungi.
•In adults, bacterial infection is the most common cause (e.g., bacteria from the sinuses or mouth may spread to the lungs). In infants and children, viruses can commonly cause pneumonia.
Skin Infections
• Skin infections can range in cause (bacterial, fungal), visibility (from small spot to covering large portions of the body) and in seriousness (from harmless to life threatening).
•The most common types of bacterial skin infections are caused by Staphylococcus and Streptococcus. Bacteria can invade through broken skin causing a range of discomfort and ulcerations. The nature of TCM practice requires practitioners to be vigilant of skin disorders on themselves and on their patients.
CNT Basic Principles
Clean Needle Technique (CNT) includes the following basic principles
•1. Always wash hands between patients, and before and after needling.
•2. Always establish a clean field before performing acupuncture.
•3. Always use sterile single-use needles and other instruments that may break the skin, such as seven-star hammers, press intradermal needles, and lancets.
•4. Always immediately isolate used needles and other sharps.
•5. Follow Standard Precautions.
1. Hand Hygiene
•Hand washing should be done:
· before and after patient contact or acupuncture treatment;
· when hands are contaminated during the treatment;
· immediately after inadvertent exposure to blood or body fluids;
· after contact with environmental surfaces or equipment;
· after removing gloves;•Remove any hand or wrist jewelers and avoid use of artificial nails. Follow these 6 steps when hand washing.
•1. Wet your hands in warm running water.
•2. Apply sufficient liquid soap to achieve lather.
•3. Wash all surfaces of your hands including backs of hands, fingertips, between fingers, wrists, base of thumbs, and around and under finger nails. Scrubbing should last approximately 15 seconds.
•4. Rinse well and leave water running.
•5. Dry thoroughly with a disposable paper towel or electric hand dryer.
•6. Turn off the water with the towel, and not with your bare hands.
2. Establish a Clean Field
•Use a metal tray or clean paper towel:
• Ensure area for supplies is clean, lay out the clean field without contaminating it.
• Place only clean supplies in field, set out needles, cotton balls. lay out an appropriate number of needles for the procedure without contaminating the site or the needles. Sterile needles must not be placed on a non-sterile environment (e.g., tray, cotton).
• Touch clean supplies only with clean hands
• The waste bag and sharps container must be established in an area away from the clean field.
3. use sterile single-use needles
•Prior to use, acupuncture practitioners need to inspect the packaging of any single-use sterile needles (and other sterile sharps) to ensure that the protective barrier has not been breached or damaged by exposure to water.
•The expiration date of all needles in a clinic should be checked regularly (i.e., monthly) and all expired needles be discarded.
•Discard any package of needles that has been punctured, torn or damaged, or past the expiration date of sterilization.
•When using acupuncture needles from packages that contain more than one needle, all needles left over at the end of a treatment must also be treated as non-sterile sharps and must therefore be discarded in an appropriate sharps container. Any unused but unsterile needles.
4. Safe Handling and Disposal of isolate used needles and other sharps.
•Sharp Container must be:
• Puncture resistant, • Leak proof
• Designed to allow sharps to be easily deposited, but difficult to remove
• Designed with a secure lid and handle for carrying
• Clearly marked “Biohazard” with easily identifiable symbol
• Large enough to hold all sizes of sharps
• Disposed of in a suitable manner when 3/4 full
5. Follow Standard Precautions
Skin Preparation
Acupuncture needles should be used only where the skin is clean and free of disease.
Acupuncture needles should never be inserted through inflamed, irritated, diseased, or broken skin. Otherwise, infections can be carried directly into the body past the broken skin barrier.
The areas to be needled should be clean prior to treatment. Alcohol swabbing is recommended but not essential before acupuncture needle insertion as long as an area is clean.
If swabbing an area, 70% alcohol is required.
Palpating the Point
It is acceptable clean technique to palpate the acupuncture point after cleaning the skin, as long as the hands are clean and have not been contaminated.
However, it is strongly recommended that before picking up the needle or palpating the point, the hands should be washed with soap and water or an alcohol-based hand sanitizer if they have been contaminated since the last handwashing by some activity such as arranging clothing or taking notes.
After this second cleaning of the hands, nothing should be touched but the needle handle, guide tube, and the skin over the point.
If anything else is touched, the fingers should be cleaned again as described above before proceeding.
Can I touch the needle during needle insertion?
If you need to support the shaft of the needle during needle insertion, either because you are using a thin needle (e.g., 0.15 mm width) or a long needle (e.g., more than 25 mm length) or both, you must use a sterile barrier between your fingers and the shaft of the needle.
While washing your hands removes most of the transient bacteria from the skin of the hands and fingers, it does not dislodge the resident bacteria. Some people carry resident bacteria on their skin that is pathogenic to other people.
Any object that pierces the skin must be sterile. To support the shaft of the needle, when necessary, use sterile gauze or sterile cotton between the fingers and the needle shaft.
Managing Used Needles
Used instruments that have penetrated the skin must be isolated immediately in an appropriate sharps container. Used needles, lancets and the head of a seven star/plum blossom should not be reused.
Used needles present risk for practitioners, staff, and children waiting for their parents.
When using needles from packages that contain more than one needle, all needles left over at the end of a treatment.
A sharps container for the used needles should be right beside the treatment table, on a flat, stable surface (not directly on the treatment table)
Sharps containers should be replaced regularly and not be filled over 75%.
Mycology
Basic Mycology
•There are two types of fungi: yeasts and molds.
• Yeasts grow as single cells that reproduce by asexual budding.
•Molds grow as long filaments (hyphae菌丝) and form a mat (mycelium菌丝体).
FUNGAL TOXINS & ALLERGIES
•In addition to mycotic霉菌性infections, there are two other kinds of fungal disease:
•(1) mycotoxicoses真菌[毒素]中毒症, caused by ingested toxins. The best-known mycotoxicosis occurs after eating Amanita mushrooms. These fungi produce five toxins.
•(2) allergies to fungal spores. Allergies to fungal spores are manifested primarily by an asthmatic reaction.
LABORATORY DIAGNOSIS
•There are four approaches to the laboratory diagnosis of fungal diseases:
•(1) direct microscopic examination
•(2) culture of the organism
•(3) DNA probe tests
•(4)serologic tests
ANTIFUNGAL THERAPY
•The drugs used to treat bacterial diseases have no effect on fungal diseases.
•The most effective antifungal drugs, amphotericin B两性霉素B and the various azoles氮唑类, exploit the presence of ergosterol in fungal cell membranes that is not found in bacterial or human cell membranes.
CANDIDA
•Diseases
•Candida albicans白念珠菌, the most important species of Candida, causes thrush鹅口疮, vaginitis阴道炎, esophagitis食管炎, diaper尿布rash, and chronic mucocutaneous candidiasis.
•Transmission
•As a member of the normal flora, C. albicans is already present on the skin and mucous membranes. The presence of C. albicans on the skin predisposes易于 to infections involving instruments that penetrate the skin, such as needles.
•Pathogenesis & Clinical Findings
•When local or systemic host defenses are impaired, disease may result. Overgrowth of C. albicans in the mouth produces white patches called thrush.
•Vaginitis with itching and discharge is favored by high pH, diabetes, or use of antibiotics. Antibiotics suppress the normal flora Lactobacillus乳酸杆菌, which keep the pH low. As a result, the pH rises, which favors the growth of Candida.
•Treatment & Prevention
•The drug of choice for oropharyngeal or esophageal thrush is fluconazole富康唑.
•Candida vaginitis is treated either with topical (intravaginal) azole 唑类 drugs, such as clotrimazole or miconazole, or with oral fluconazole. Mucocutaneous candidiasis can be controlled by ketoconazole酮康唑.
Dermatophytoses
•Dermatophytoses皮肤癣菌病are caused by fungi (dermatophytes) that infect only superficial keratinized角质细胞 structures (skin, hair, and nails), not deeper tissues.
•Dermatophytoses (tinea, ringworm) are chronic infections often located in the warm, humid areas of the body (e.g., athlete’s foot).
Typical ringworm lesions have an inflamed circular border containing papules and vesicles surrounding a clear area of relatively normal skin. The lesions are typically pruritic 痒的. Broken hairs and thickened broken nails are often seen. The disease is typically named for the affected body part (i.e., tinea capitis [head], tinea corporis [body], tinea cruris [groin], and tinea pedis [foot])
Cryptococcus neoformans
•Disease
•Cryptococcus neoformans新型隐球菌causes cryptococcosis 隐球菌病, especially cryptococcal meningitis.
•Cryptococcosis is the most common, life-threatening invasive fungal disease worldwide.
•It is especially important in AIDS patients.
•Properties
•C. neoformans is an oval, budding yeast surrounded by a wide polysaccharide capsule.
•Transmission
•C. neoformans occurs widely in nature and grows abundantly in soil containing bird (especially pigeon) droppings.
•The birds are not infected. Human infection results from inhalation吸入 of the organism.
•There is no human-to-human transmission.
•Pathogenesis & Clinical Findings
•Lung infection is often asymptomatic or may produce pneumonia. Disease caused by C. neoformans occurs mainly in patients with reduced cell-mediated immunity, especially AIDS patients, in whom the organism disseminates to the central nervous system (meningitis) and other organs.
•Subcutaneous nodules are often seen in disseminated disease. However, that roughly half the patients with cryptococcal meningitis fail to show evidence of immunosuppression.
•Laboratory Diagnosis
•In spinal fluid mixed with India ink, the yeast cell is seen microscopically surrounded by a wide, unstained capsule. Appearance of the organism in Gram stain is unreliable.
•Treatment
•Combined treatment with amphotericin B and flucytosine is used in meningitis and other disseminated disease.
HISTOPLASMA
•Disease
•Histoplasma 组织胞浆菌属 capsulatum荚膜 causes histoplasmosis组织胞浆菌病.
•Transmission & Epidemiology
•This fungus occurs in many parts of the world.
•It grows in soil, particularly if the soil is heavily contaminated with bird droppings, especially from starlings八哥.
•Although the birds are not infected, bats蝙蝠 can be infected and can excrete排泄 the organism in their guano粪便.
•Clinical Findings
•The organisms spread widely throughout the body, especially to the liver and spleen, but most infections remain asymptomatic. With intense exposure (e.g., in a chicken house or bat-infested cave), pneumonia and cavitary lung lesions may become clinically manifest.
•Severe disseminated histoplasmosis develops in a small minority of infected persons, especially infants and individuals with reduced cell-mediated immunity, such as patients with acquired immunodeficiency syndrome (AIDS). In AIDS patients, pancytopenia全血细胞减少 and ulcerated lesions on the tongue are typical of disseminated histoplasmosis.
•Treatment & Prevention
•No therapy is needed in asymptomatic or mild primary infections. With progressive lung lesions, oral itraconazole is effective.
•Oral itraconazole is used for chronic suppression in patients with AIDS. There are no means of prevention except avoiding exposure in areas of endemic infection.
•Disease
•Coccidioides immitis causes coccidioidomycosis球孢子菌病.
•Transmission & Epidemiology
•The fungus is endemic in arid regions of the southwestern United States and Latin America.
•In soil, it forms hyphae菌丝 with alternating arthrospores分节孢子 and empty cells. Arthrospores are very light and are carried by the wind.
•They can be inhaled and infect the lungs.
•Clinical Findings
•Infection of the lungs is often asymptomatic and is evident only by a positive skin test and the presence of antibodies.
•Some infected persons have an influenza like illness with fever and cough.
•About 50% have changes in the lungs
•Treatment & Prevention
•No treatment is needed in asymptomatic or mild primary infection.
•Amphotericin B (Fungizone) or itraconazole is used for persisting lung lesions or disseminated disease.
Parasitology
Classification of Parasites
•Parasites occur in two distinct forms:
•Single-celled protozoa原虫
•Multicellular metazoa多细胞后生动物called helminths寄生虫or worms 蠕虫.
Intestinal protozoa
•Entamoeba histolytica 阿米巴痢疾
Diseases
•Entamoeba. histolytica causes amebic dysentery and liver abscess.
•Entamoeba histolytica 阿米巴痢疾(溶组织阿米巴)
•The life cycle of E. histolytica has two stages: the motile ameba (trophozoite) and the nonmotile cyst. The trophozoite is found within the intestinal and extraintestinal lesions and in diarrheal stools. The cyst predominates in non-diarrheal stools. These cysts are not highly resistant and are readily killed by boiling but not by chlorination of water supplies. They are removed by filtration of water.
Clinical Findings
•Acute intestinal amebiasis presents as dysentery (i.e., bloody, mucus-containing diarrhea) accompanied by lower abdominal discomfort, flatulence, and tenesmus.
•Chronic amebiasis with low-grade symptoms such as occasional diarrhea, weight loss, and fatigue also occurs. Roughly 90% of those infected have asymptomatic infections, but they may be carriers, whose feces contain cysts包囊 that can be transmitted to others.
•In some patients, a lesion called an ameboma 阿米巴肿 may form in the colon.
•Amebic abscess of the liver is characterized by right-upper-quadrant pain, weight loss, fever, and a tender, enlarged liver. Right-lobe abscesses can penetrate the diaphragm and cause lung disease.
•Most cases of amebic liver abscess occur in patients who have not had overt intestinal amebiasis.
Laboratory Diagnosis
•Diagnosis of intestinal amebiasis rests on finding either ameba(trophozoites) in diarrheal stools or cysts in formed stools
Treatment
•The treatment of choice for symptomatic intestinal amebiasis or hepatic abscesses is metronidazole (Flagyl)甲硝唑or tinidazole替硝唑片.
Hepatic abscesses need not be drained.Prevention
•Prevention involves avoiding fecal contamination of food and water and observing good personal hygiene such as hand washing.
UROGENITAL泌尿生殖器的 PROTOZOA
•TRICHOMONAS VAGINALIS阴道毛滴虫
•Disease
•Trichomonas vaginalis 阴道毛滴虫 causes trichomoniasis 滴虫性阴道炎.
•Pathogenesis & Epidemiology
•The organism is transmitted by sexual contact. The primary locations of the organism are the vagina and the prostate. It is found only in humans; there is no animal reservoir.
•Trichomoniasis is one of the most common infections worldwide.
•The frequency of symptomatic disease is highest among sexually active women in their thirties and lowest in postmenopausal women. Asymptomatic infections are common in both men and women.
•Clinical Findings
•In women, a watery, foul-smelling, greenish vaginal discharge accompanied by itching and burning occurs. Infection in men is usually asymptomatic, but about 10% of infected men have urethritis.
•Laboratory Diagnosis
•In a wet mount of vaginal (or prostatic) secretions, the pear-shaped trophozoites have a typical jerky motion. Neutrophils are often seen in the fluid. There is no serologic test.
•Treatment & Prevention
•The drug of choice is metronidazole (Flagyl)甲硝唑 for both partners to prevent reinfection.
•Maintenance of the low pH of the vagina is helpful. Condoms limit transmission.
•No prophylactic drug or vaccine is available.
Blood & Tissue Protozoa 原虫
•PLASMODIUM 疟原虫
•Disease
•Malaria is caused by four plasmodia: Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium falciparum.
•P. vivax and P. falciparum are more common causes of malaria than are P. ovale and P. malariae. Worldwide, malaria is one of the most common infectious diseases and a leading cause of death.
•Pathogenesis
•Malaria is transmitted primarily by mosquito bites, but transmission across the placenta, in blood transfusions, and by intravenous drug use also occurs.
•Most of the pathologic findings of malaria result from the destruction of red blood cells. The enlarged spleen is characteristic of malaria.
•Epidemiology
•More than 200 million people worldwide have malaria, and more than 1 million die of it each year, making it the most common lethal infectious disease. It occurs primarily in tropical and subtropical areas, especially in Asia, Africa, and Central and South America.
•People who have lived or traveled in areas where malaria occurs should seek medical attention for febrile illnesses up to 3 years after leaving the malarious area.
•Clinical Findings
•Malaria presents with abrupt onset of fever and chills, accompanied by headache, myalgias肌痛, and arthralgias关节痛, about 2 weeks after the mosquito bite. Fever may be continuous early in the disease; the typical periodic cycle does not develop for several days after onset. The fever spike, which can reach 41°C, is frequently accompanied by shaking chills, nausea, vomiting, and abdominal pain. The fever is followed by sweats. Patients usually feel well between the febrile episodes. Splenomegaly 脾肿大is seen in most patients, and hepatomegaly 肝肿大occurs in roughly one-third. Anemia is prominent.
Laboratory Diagnosis
•Diagnosis tests on microscopic examination of blood.
Treatment
•The treatment of malaria is complicated. Chloroquine 氯喹is the drug of choice for treatment of uncomplicated malaria.
Prevention
•Chemoprophylaxis of malaria for travelers to areas. Other preventive measures include the use of mosquito netting, window screens, protective clothing, and insect repellents. The mosquitoes feed from dusk to dawn, so protection is particularly important during the night. Communal preventive measures are directed against reducing the mosquito population. There is no vaccine.
Nematodes 线虫类
•Taenia solium 猪肉绦虫
•Disease
•The adult form of T. solium causes taeniasis 绦虫病.
•T. solium larvae cause cysticercosis 猪囊虫病.
Taenia solium 猪肉绦虫
•Pathogenesis
•The adult tapeworm attached to the intestinal wall causes little damage.
•The cysticerci can become very large, especially in the brain, where they manifest as a space-occupying lesion.
•Living cysticerci幼虫do not cause inflammation, but when they die, they can release substances that provoke an inflammatory response. Eventually, the cysticerci calcify 钙化.
•Epidemiology
•The epidemiology of taeniasis and cysticercosis is related to the access of pigs to human feces and to consumption of raw or undercooked pork.
•The disease occurs worldwide but is endemic in areas of Asia, South America, and Eastern Europe. Most cases in the United States are imported.
•Clinical Findings
•Most patients with adult tapeworms are asymptomatic, but anorexia and diarrhea can occur. Some may notice proglottids节片 in the stools.
•Cysticercosis in the brain causes headache, vomiting, and seizures.
•Cysticercosis in the eyes can appear as retinitis, or the larvae can be visualized floating in the vitreous.
•Subcutaneous nodules containing cysticerci commonly occur.
•Cysts also are commonly found in skeletal muscle.
•Laboratory Diagnosis
•Identification of T. solium consists of finding gravid proglottids in the stools.
•Treatment
•The treatment of choice for the intestinal worms is praziquantel吡喹酮. The treatment for cysticercosis is either praziquantel or albendazole, but surgical excision切除 may be necessary.
•Prevention
•Prevention of taeniasis involves cooking pork adequately and disposing waste properly so that pigs cannot ingest human feces. Prevention of cysticercosis consists of treatment of patients to prevent autoinfection plus observation of proper hygiene, including handwashing, to prevent contamination of food with the eggs.
Disease
•Enterobius vermicularis 蛲虫 causes pinworm infection (enterobiasis).
Pathogenesis & Clinical Findings
•Perianal pruritus肛周瘙痒 is the most prominent symptom. Pruritus is thought to be an allergic reaction to the presence of either the adult female or the eggs. Scratching predisposes to secondary bacterial infection.
•Epidemiology
•Enterobius is found worldwide. Children younger than 12 years of age are the most commonly affected group.
•Laboratory Diagnosis
•The eggs are recovered from perianal skin by using the Scotch tape technique and can be observed microscopically.
•Unlike those of other intestinal nematodes, these eggs are not found in the stools. The small, whitish adult worms can be found in the stools or near the anus of diapered children. No serologic tests are available.
•Treatment
•Either mebendazole or pyrantel pamoate is effective. They kill the adult worms in the colon but not the eggs, so retreatment in 2 weeks is suggested. Reinfection is very common.
•Prevention
•Prevent reinfection.
Immunity
Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism and provide a defense against their harmful effect.
Immunity is classified in to two major groups
- Nonspecific immunity
- Specific immunity
Nonspecific (natural or innate) immunity
Non-specific immunity is the first line of defense against any infectious agent.
Non specific host responses provide an effective barrier that prevents the microorganisms from penetrating, inhibit or destroy the invader if it gains access to the tissues, and eliminate or neutralize any toxic substance elaborated by infectious agent.
The first line of defense against microorganisms is the intact skin, mucous membranes and phagocytic cells.
Physical or mechanical barrier
The unbroken skin and mucus membrane are effective mechanical barriers to infectious agents. The surface of the skin is also inhibitory to the growth of most microorganisms because of low moisture, low pH, and the presence of secreted inhibitory substance.
However, it is possible for some microorganisms to enter the skin through hair follicles, sebaceous glands or sweet glands.
Similarly, mucus membranes consist of an epithelial layer and an underlying connective tissue layer. They line the entire digestive, respiratory, urinary, and reproductive tracts.
Cellular mechanism
Neutrophils are the first phagocytes in the infected area that can non-specifically phagocytize some microbes.
Natural killer cells are large lymphocytes whose function is to kill undesirable cells such as tumor cells and virus infected cells.
Alveolar macrophages 肺泡巨噬细胞 like neutrophils and natural killers remove particles and organisms that enter the alveoli.
Specific (acquired or adaptive) immunity
The specific immune is a defense system that protects the body against pathogenic microorganisms and other type of disease such as cancer.
It allows the body to recognize, remember, and respond to a specific stimulus, an antigen.
Specific immunity can result in the elimination of microorganisms and in the recovery from disease, and it frequently leaves the host with specific immunologic memory.
This condition of memory or recall, acquired resistance, allows the host to respond more effectively if reinfection with the same microorganism occurs.
As a consequence of such acquired immunity, we usually suffer from many diseases only once, for example measles.
Specific immunity can be active or passive, and each of these types can in turn be naturally or artificially acquired.
Passive immunity
It is an immunity in which antibodies produced elsewhere are given to the individual. They are divided into two:
I. Naturally acquired passive immunity: refers to antibodies transferred from mother to fetus across the placenta and to the newborn in colostrums初乳and breast milk during the first few months of life.
II. Artificially acquired passive immunity: is introduction of antibodies that are formed by an animal or a human to an individual to prevent or treat infection.
Active immunity
It is a product of the individual’s own immune system in response to a foreign antigen.
I. Naturally acquired active immunity: It is immunity that comes from infections encountered in daily life.
II. Artificially acquired active immunity: It is stimulated by initial exposure to specific foreign macromolecules through the use of vaccines to artificially establish a state of immunity.
ANTIGENS and ANTIBODIES
Antigens are substances that are recognized by a particular immunoglobulin or T-cell receptor and they can serve as the target of an immune response.
Antibodies are glycoproteins糖蛋白, which are sensitized激活的, and secreted by plasma cells in response to specific antigenic stimulation and it forms about 20% of plasma protein.
Classes of Immunoglobulins
Five distinct classes of immunoglobulin molecules are recognized in most higher mammals哺乳动物:
IgG, IgM, IgA, IgD and IgE.
These immunoglobulin classes differ from each other in characteristics such as molecular weight, sedimentation coefficient沉降系数 between classes.
Complement System补体系统
The immune system is composed of a large and complex set of widely distributed elements.
The specific recognition system is ultimately composed of receptors on T and B lymphocytes the only specific components of the immune mechanism.
The immune system also has a nonspecific effecter mechanism that usually amplifies the specific functions.
The nonspecific features include the complement system. The complement system is a series of more than 18 plasma proteins. Normally, these proteins are in an inactive form, but specific signal can activate the first protein of the team.
The immune system
The immune system is a network of cells and organs that extend through out the body and function as a defense against infection.
The immune system has been recognized as a separate body system known as lymphoid system because its main cells are lymphocytes.
The Primary Lymphoid Organ
The thymus and bone marrow are referred to a primary lymphoid organ because they provide conducive microenvironments that are essential for initial production of lymphocytes from progenitor cells.
The thymus is a gland situated in front of the heart and behind the sternum. Progenitor cells that leave the bone marrow migrate to the thymus for proliferation增殖 and differentiation. This process is facilitated促进 by a hormone, thymosin胸腺肽.
The differentiated cell is known as thymus- derived T cell.
Involution of the thymus is the first age-related change occurring in the immune system of humans. The thymus gradually loses up to 95% of its mass during the first fifty years of life.
This will result in decreased synthesis of thymic hormone and loss of the ability to differentiate immature lymphocytes are reflected in an increased number of immature lymphocytes both with in the thymus and circulating peripheral blood T-cells.
Secondary Lymphoid Organ
The secondary lymphoid organs include lymph nodes, spleen, tonsils.
The function of the secondary lymphoid organs is to maximize encounters between lymphocytes and foreign substances, and it is from this site that most immune responses are launched.
The relative percentage of T and B cells are different in different locations.
Lymph nodes
Lymph nodes act like lymphoid filters in the lymphatic system.
It responds to antigens introduced distantly and routed to them by afferent lymphatic. Generalized lymph node reactivity can occur following systemic antigen challenge.
Spleen
The spleen act like a lymphatic filter within the blood vascular tree. It is an important site of antibody production in response to intravenous particulate antigen (e.g. bacterial). The spleen is also a major organ for the clearance of particles.
Tonsils
Tonsils are nodular aggregates of lymphoid tissues, their function is to detect and respond to pathogens in the respiratory secretion.
The lymphocytes
The lymphocytes are one of the classes of white blood cells, capable of responding to antigens in specific host defense mechanism.
The lymphocytes fall in to three large sets, the T, B. and natural killer (NK) cells.
T-lymphocytes
T- Cells
T-cell precursors differentiate into immunocompetent T cells within the thymus.
Prior to entering the thymus, stem cells lack antigen receptors and lack CD3, CD4, and CD8 proteins on their surface.
During passage through the thymus, they differentiate into T cells that can express both antigen receptors and the various CD proteins.
B-lymphocytes
B-cells represent less than 15% of the circulating lymphocytes and are derived from progenitor cells through an antigen independent maturation process occurring in the bone marrow.
These cells serve as the primary source for cells responsible for antibody response, which is a primary host defense against microorganisms.
Natural Killer Cells
Natural killer (NK) cells are large granular lymphocytes that do not pass through the thymus, do not have an antigen receptor, and do not bear CD4 or CD8 proteins. They recognize and kill target cells, such as virus-infected cells and tumor cells.
Macrophages
In contrast to T cells, B cells, and NK cells, which differentiate from lymphoid stem cells, macrophages arise from myeloid precursors骨髓前驱细胞. Macrophages have two important functions, namely, phagocytosis and antigen presentation.
They do not pass through the thymus and do not have an antigen receptor. On their surface, they display class II MHC proteins, which play an essential role in antigen presentation to helper T cells.
Macrophages also display class I MHC proteins, as do all nucleated cells. The cell surface proteins that play an important role in the immune response.
FUNCTION OF ANTIBODIES
The primary function of antibodies is to protect against infectious agents or their products. Antibodies provide protection because they can
(1) neutralize toxins and viruses
(2) opsonize 调理 microorganisms. Opsonization is the process by which antibodies make microorganisms more easily ingested by phagocytic cells. the other hand, inhibits organisms such as fungi, parasites, and certain intracellular bacteria such as Mycobacterium tuberculosis; it also kills virus-infected cells and tumor cells.
Antibodies are globulin球蛋白 proteins (immunoglobulins [Ig]) that react specifically with the antigen that stimulated their production.
They make up about 20% of the protein in blood plasma. Blood contains three types of globulins, alpha, beta, and gamma, based on their electrophoretic migration rate. Antibodies are gamma globulins.
There are five classes of antibodies: IgG, IgM, IgA, IgD, and IgE. Antibodies are subdivided into these five classes based on differences in their heavy chains.
THE PRIMARY RESPONSE
The primary response occurs the first time that antigen is encountered.
In the primary response, antibodies are detectable in the serum after a longer lag period than occurs in the secondary response.
This concept is medically important because the protection afforded by a vaccine the first time it is given is delayed, compared with the protection afforded by a booster shot后续疫苗注射in which a faster secondary response occurs.
The lag period of the primary response is typically 7 to 10 days but can be longer depending on the nature and dose of the antigen and the route of administration (e.g., parenteral or oral).
A small clone of B cells and plasma cells specific for the antigen is formed.
The serum antibody concentration continues to rise for several weeks, then declines and may drop to very low levels.
The first antibodies to appear in the primary response are IgM, followed by IgG or IgA.
IgM levels decline earlier than IgG levels.
THE SECONDARY RESPONSE
When there is a second encounter with the same antigen or a closely related (or cross-reacting) one, months or years after the primary response, there is a rapid antibody response (the lag period is typically only 3–5 days) to higher levels than the primary response.
This is attributed to the persistence of antigen-specific “memory cells” after the first contact.
These memory cells proliferate to form a large clone of specific B cells and plasma cells, which mediate the secondary antibody response.
Clinical Virology
Covid 19 (SARS- CoV-2)
covid-19 virus belongs to Coronavirus group,
it is a kind of zoonotic人畜共患的 single stranded RNA virus spreads between animals and humans.
It is the seven of coronaviruses could cause humans illness.The viruses were generally spherical, The diameter is between 60-140nm. Virus particles have obvious spinous processes, about 9-12nm, causing the virus to exhibit a coronal shape.
Transmission
COVID-19 is usually excreted through tiny particles formed by the patient's cough, sneeze, or breathing. The droplets usually fall to the ground or onto surfaces rather than travelling through air over long distances, Transmission may also occur through smaller droplets (called aerosol) that are able to stay suspended in the air for longer periods of time.
Aerosol transmission can happen during some medical procedures and potentially in crowded indoor spaces that are inadequately ventilated.
Less commonly, people may become infected by touching a contaminated surface and then touching their face.
Common symptoms
Fever
Cough
fatigue
shortness of breath,
loss of sense of smell.
Pneumonia
acute respiratory distress syndrome(ARDS).
Diagnosis
The standard test for current infection with SARS-CoV-2, uses RNA testing of respiratory secretions collected using a nasopharyngeal swab,
Chest X-ray examination
Since the disease manifests itself as pneumonia.
Chest computed tomography(CT)
Given the high sensitivity of the method, in particular
high-resolution CT (HRCT), is the method of choice in the study of COVID-19 pneumonia, even in the initial stages.
treatment
preventive measures
Primary treatment is symptomatic and supportive therapy.
hand washing,
wearing a face mask in public settings,
maintaining distance from other people,
covering one's mouth when coughing,
disinfecting surfaces,
increasing ventilation and air filtration indoors,
monitoring and self-isolation for people who suspect they are infected.
HERPES VIRUSES
HERPES VIRUSES ARE DNA ENVELOPED VIRUSES.
Three of the herpes viruses, HSV types 1 and 2 and varicella-zoster virus (VZV).
VARICELLA-ZOSTER VIRUS (VZV)
Disease
Varicella (chickenpox) is the primary disease;
Zoster (shingles) is the recurrent form.
Transmission & Epidemiology
The virus is transmitted by respiratory droplets and by direct contact with the lesions.
Varicella (chickenpox) is a highly contagious disease of childhood; Varicella occurs worldwide. use of the vaccine has significantly reduced the number of cases.
There is infectious VZV in zoster vesicles小囊泡. This virus can be transmitted, usually by direct contact, to children and can cause varicella.
Pathogenesis
VZV infects the mucosa of the upper respiratory tract, and then spreads via the blood to the skin, where the typical vesicular rash occurs. The virus infects sensory neurons and then flow into the cells of the dorsal root ganglia, where the virus becomes latent.
Later in life, frequently at times of reduced cell-mediated immunity or local trauma, the virus is activated and causes the vesicular skin lesions and nerve pain of zoster.
Clinical Findings
Varicella (chickenpox)
After an incubation period of 14 to 21 days, brief prodromal symptoms of fever and malaise 不适 occur. A papulovesicular丘疹性rash then appears in crops on the trunk and spreads to the head and extremities.
The rash evolves from papules to vesicles液胞, pustules, and, finally, crusts生痂. Itching (pruritus) is a prominent symptom, especially when vesicles are present.
Varicella is mild in children but more severe in adults.
Varicella pneumonia and encephalitis脑炎are the major rare complications, occurring more often in adults.
Immunity
Immunity following varicella is lifelong:
A person gets varicella only once, but zoster can occur despite this immunity to varicella.
Zoster usually occurs only once. The frequency of zoster increases with advancing age, perhaps as a consequence结果of waning immunity.
Prevention
There are two vaccines against VZV: one designed to prevent varicella, called Varivax, and the other designed to prevent zoster, called Zostavax.
Both contain live, attenuated减弱 VZV, but the zoster vaccine contains 14 times more virus than the varicella vaccine.
The zoster vaccine is effective in preventing the symptoms of zoster, but does not eradicate the latent state of VZV.
The varicella vaccine is recommended for children between the ages of 1 and 12 years, whereas the zoster vaccine is recommended for people older than 60 years and who have had varicella.
Because these vaccines contain live virus, they should not be given to immunocompromised people or pregnant women.
Hepatitis Viruses
Many viruses cause hepatitis. Of these, five medically important viruses are commonly described as “hepatitis viruses” because their main site of infection is the liver.
Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV)
Hepatitis E virus (HEV)
HEPATITIS A VIRUS (HAV)
Disease
HAV causes hepatitis A.
Transmission & Epidemiology
HAV is transmitted by the fecal–oral route.
Virus appears in the feces roughly 2 weeks before the appearance of symptoms.
Children are the most frequently infected group, and outbreaks occur in special living situations such as summer camps and boarding schools.
Common-source outbreaks arise from fecally contaminated water or food such as oysters grown in polluted water and eaten raw.
HAV is rarely transmitted via the blood, because the level of viremia 病毒血症 is low and chronic infection does not occur.
Clinical Findings
The clinical manifestations of hepatitis are virtually the same, regardless of which hepatitis virus is the cause
Fever, anorexia, nausea, vomiting, and jaundice are typical. Dark urine, pale feces, and elevated transaminase 转氨酶 levels are seen.
Most cases resolve spontaneously自然地in 2 to 4 weeks. Hepatitis A has a short incubation period (3–4 weeks).
No chronic hepatitis or chronic carrier state occurs, and there is no predisposition倾向 to hepatocellular carcinoma 肝细胞癌.
Laboratory Diagnosis
The detection of IgM antibody is the most important test.
Treatment & Prevention
No antiviral therapy is available.
Active immunization with a vaccine containing
inactivated HAV is available. The virus is grown in human cell culture and inactivated with formalin. Two doses, an initial dose followed by a booster 6 to 12 months later, should be given. No subsequent booster dose is recommended. The vaccine is recommended for travelers to developing countries, for children ages 2 to 18 years. If an unimmunized person must travel to an endemic area within 4 weeks, then passive immunization should be given to provide immediate protection and the vaccine given to provide long-term protection.
This is an example of passive–active immunization.
HEPATITIS B VIRUS (HBV)
Disease
HBV causes hepatitis B.
Transmission & Epidemiology
The three main modes of transmission are via blood, during sexual intercourse, and from mother to newborn.
The observation that needle-stick injuries can transmit the virus indicates that only very small amounts of blood are necessary.
Clinical Findings
Many HBV infections are asymptomatic and are detected only by the presence of antibody to HBsAg. The mean incubation period for hepatitis B is 10 to 12 weeks.
The clinical appearance of acute hepatitis B is similar to that of hepatitis A. However, with hepatitis B, symptoms tend to be more severe, and life-threatening hepatitis can occur. Most chronic carriers are asymptomatic, but some have chronic active hepatitis, which can lead to cirrhosis and death.
Laboratory Diagnosis
The two most important serologic tests for the diagnosis of early hepatitis B are the tests for HBsAg and for IgM antibody to the core antigen.
Treatment
No antiviral therapy is typically used in acute hepatitis B. For chronic hepatitis B, entecavir 抗病毒药 (Baraclude) or tenofovir抗病毒药(Viread) are the drugs of choice.
Prevention
Prevention involves the use of either the vaccine or hyperimmune globulin or both.
(1) The vaccine contains HBsAg produced. The vaccine is highly effective in preventing hepatitis B and has few side effects.
(2) Hepatitis B immune globulin (HBIG) contains a high titer of HBsAb. It is used to provide immediate, passive protection to individuals known to be exposed to HBsAg-positive blood (e.g., after an accidental needle-stick injury).
Arboviruses 虫媒病毒
Arbovirus is an acronym缩写 for arthropod-borne virus and highlights the fact that these viruses are transmitted by arthropods节肢动物, primarily mosquitoes and ticks 虱类.
It is a collective name for a large group of diverse viruses, more than 600 at last count.
In general, they are named either for the diseases they cause (e.g., yellow fever virus) or for the place where they were first isolated (e.g., St. Louis encephalitis virus圣路易斯脑炎病毒).
Transmission
For effective transmission to occur, the virus must be present in the bloodstream of the vertebrate host (viremia病毒血症) in sufficiently high titer to be taken up in the small volume of blood ingested during an insect bite.
After ingestion, the virus replicates in the gut 肠 of the arthropod and then spreads to other organs, including the salivary glands.
Only the female of the species serves as the vector 载体 of the virus, because only she requires a blood meal in order for progeny to be produced.
Arbovirus transmission cycle.
Arboviruses typically cycle between the vertebrate reservoir host, often a bird, and the vector, often a mosquito.
The infected vector can also bite other hosts, such as humans and horses, which are “dead-end” hosts because their viremia 病毒血症 is too low to provide the vector with an infectious dose.
Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS).
Both HIV-1 and HIV-2 cause AIDS, but HIV-1 is found worldwide, whereas HIV-2 is found primarily in West Africa.
Transmission & Epidemiology
Transmission of HIV occurs primarily by sexual contact and by transfer of infected blood.
Perinatal transmission from infected mother to neonate also occurs, either across the placenta, at birth, or via breast milk.
Clinical Findings
The clinical picture of HIV infection can be divided into three stages:
an early, acute stage;
a middle, latent stage;
and a late, immunodeficiency stage.
Clinical Findings
In the acute stage, which usually begins 2 to 4 weeks after infection, fever, lethargy, sore throat, and generalized lymphadenopathy 淋巴结病 occurs. Rash on the trunk, arms, and legs. Leukopenia白细胞减少症occurs.
In the middle stage of HIV infection, a long latent period, In untreated patients, the latent period typically lasts for 7 to 11 years.
The patient is asymptomatic during this period. Although the patient is asymptomatic and viremia 病毒血症 is low or absent, a large amount of HIV is being produced by lymph node cells but remains sequestered 使隔离 within the lymph nodes.
The late stage of HIV infection is AIDS, an increase in the frequency and severity of opportunistic infections.
The two most characteristic manifestations of AIDS are pneumonia and Kaposi’s sarcoma卡波济肉瘤.
Laboratory Diagnosis
The presumptive diagnosis of HIV infection is made by the detection of antibodies in the patient’s serum.
During the first month after infection, antibody tests may be negative. These false negative tests are due to insufficient antibody being made early in infection to be detected.
The average time for seroconversion血清转化is 10 to 14 days, and most of those infected, but not all, will have seroconverted by 4 weeks.
Treatment
The two specific goals of treatment are
(1) to restore immunologic function which reduces opportunistic infections and certain malignancies, and
(2) to reduce viral load, which reduces the chance of transmission to others.
Unfortunately, no drug regimen results in a “cure” (i.e., eradicates the virus from the body), but long-term suppression can be achieved获得. However, if drugs are stopped, the virus resumes active replication, and large amounts of infectious virus reappear.
Prevention
No vaccine is available. Prevention consists of taking measures to avoid exposure to the virus (e.g., using condoms, not sharing needles, and discarding donated blood that is contaminated with HIV).
Clinical Virology
Covid 19 (SARS- CoV-2)
covid-19 virus belongs to Coronavirus group,
it is a kind of zoonotic人畜共患的 single stranded RNA virus spreads between animals and humans.
It is the seven of coronaviruses could cause humans illness.The viruses were generally spherical, The diameter is between 60-140nm. Virus particles have obvious spinous processes, about 9-12nm, causing the virus to exhibit a coronal shape.
Transmission
COVID-19 is usually excreted through tiny particles formed by the patient's cough, sneeze, or breathing. The droplets usually fall to the ground or onto surfaces rather than travelling through air over long distances, Transmission may also occur through smaller droplets (called aerosol) that are able to stay suspended in the air for longer periods of time.
Aerosol transmission can happen during some medical procedures and potentially in crowded indoor spaces that are inadequately ventilated.
Less commonly, people may become infected by touching a contaminated surface and then touching their face.
Common symptoms
Fever
Cough
fatigue
shortness of breath,
loss of sense of smell.
Pneumonia
acute respiratory distress syndrome(ARDS).
Diagnosis
The standard test for current infection with SARS-CoV-2, uses RNA testing of respiratory secretions collected using a nasopharyngeal swab,
Chest X-ray examination
Since the disease manifests itself as pneumonia.
Chest computed tomography(CT)
Given the high sensitivity of the method, in particular
high-resolution CT (HRCT), is the method of choice in the study of COVID-19 pneumonia, even in the initial stages.
treatment
preventive measures
Primary treatment is symptomatic and supportive therapy.
hand washing,
wearing a face mask in public settings,
maintaining distance from other people,
covering one's mouth when coughing,
disinfecting surfaces,
increasing ventilation and air filtration indoors,
monitoring and self-isolation for people who suspect they are infected.
HERPES VIRUSES
HERPES VIRUSES ARE DNA ENVELOPED VIRUSES.
Three of the herpes viruses, HSV types 1 and 2 and varicella-zoster virus (VZV).
VARICELLA-ZOSTER VIRUS (VZV)
Disease
Varicella (chickenpox) is the primary disease;
Zoster (shingles) is the recurrent form.
Transmission & Epidemiology
The virus is transmitted by respiratory droplets and by direct contact with the lesions.
Varicella (chickenpox) is a highly contagious disease of childhood; Varicella occurs worldwide. use of the vaccine has significantly reduced the number of cases.
There is infectious VZV in zoster vesicles小囊泡. This virus can be transmitted, usually by direct contact, to children and can cause varicella.
Pathogenesis
VZV infects the mucosa of the upper respiratory tract, and then spreads via the blood to the skin, where the typical vesicular rash occurs. The virus infects sensory neurons and then flow into the cells of the dorsal root ganglia, where the virus becomes latent.
Later in life, frequently at times of reduced cell-mediated immunity or local trauma, the virus is activated and causes the vesicular skin lesions and nerve pain of zoster.
Clinical Findings
Varicella (chickenpox)
After an incubation period of 14 to 21 days, brief prodromal symptoms of fever and malaise 不适 occur. A papulovesicular丘疹性rash then appears in crops on the trunk and spreads to the head and extremities.
The rash evolves from papules to vesicles液胞, pustules, and, finally, crusts生痂. Itching (pruritus) is a prominent symptom, especially when vesicles are present.
Varicella is mild in children but more severe in adults.
Varicella pneumonia and encephalitis脑炎are the major rare complications, occurring more often in adults.
Immunity
Immunity following varicella is lifelong:
A person gets varicella only once, but zoster can occur despite this immunity to varicella.
Zoster usually occurs only once. The frequency of zoster increases with advancing age, perhaps as a consequence结果of waning immunity.
Prevention
There are two vaccines against VZV: one designed to prevent varicella, called Varivax, and the other designed to prevent zoster, called Zostavax.
Both contain live, attenuated减弱 VZV, but the zoster vaccine contains 14 times more virus than the varicella vaccine.
The zoster vaccine is effective in preventing the symptoms of zoster, but does not eradicate the latent state of VZV.
The varicella vaccine is recommended for children between the ages of 1 and 12 years, whereas the zoster vaccine is recommended for people older than 60 years and who have had varicella.
Because these vaccines contain live virus, they should not be given to immunocompromised people or pregnant women.
Hepatitis Viruses
Many viruses cause hepatitis. Of these, five medically important viruses are commonly described as “hepatitis viruses” because their main site of infection is the liver.
Hepatitis A virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Hepatitis D virus (HDV)
Hepatitis E virus (HEV)
HEPATITIS A VIRUS (HAV)
Disease
HAV causes hepatitis A.
Transmission & Epidemiology
HAV is transmitted by the fecal–oral route.
Virus appears in the feces roughly 2 weeks before the appearance of symptoms.
Children are the most frequently infected group, and outbreaks occur in special living situations such as summer camps and boarding schools.
Common-source outbreaks arise from fecally contaminated water or food such as oysters grown in polluted water and eaten raw.
HAV is rarely transmitted via the blood, because the level of viremia 病毒血症 is low and chronic infection does not occur.
Clinical Findings
The clinical manifestations of hepatitis are virtually the same, regardless of which hepatitis virus is the cause
Fever, anorexia, nausea, vomiting, and jaundice are typical. Dark urine, pale feces, and elevated transaminase 转氨酶 levels are seen.
Most cases resolve spontaneously自然地in 2 to 4 weeks. Hepatitis A has a short incubation period (3–4 weeks).
No chronic hepatitis or chronic carrier state occurs, and there is no predisposition倾向 to hepatocellular carcinoma 肝细胞癌.
Laboratory Diagnosis
The detection of IgM antibody is the most important test.
Treatment & Prevention
No antiviral therapy is available.
Active immunization with a vaccine containing
inactivated HAV is available. The virus is grown in human cell culture and inactivated with formalin. Two doses, an initial dose followed by a booster 6 to 12 months later, should be given. No subsequent booster dose is recommended. The vaccine is recommended for travelers to developing countries, for children ages 2 to 18 years. If an unimmunized person must travel to an endemic area within 4 weeks, then passive immunization should be given to provide immediate protection and the vaccine given to provide long-term protection.
This is an example of passive–active immunization.
HEPATITIS B VIRUS (HBV)
Disease
HBV causes hepatitis B.
Transmission & Epidemiology
The three main modes of transmission are via blood, during sexual intercourse, and from mother to newborn.
The observation that needle-stick injuries can transmit the virus indicates that only very small amounts of blood are necessary.
Clinical Findings
Many HBV infections are asymptomatic and are detected only by the presence of antibody to HBsAg. The mean incubation period for hepatitis B is 10 to 12 weeks.
The clinical appearance of acute hepatitis B is similar to that of hepatitis A. However, with hepatitis B, symptoms tend to be more severe, and life-threatening hepatitis can occur. Most chronic carriers are asymptomatic, but some have chronic active hepatitis, which can lead to cirrhosis and death.
Laboratory Diagnosis
The two most important serologic tests for the diagnosis of early hepatitis B are the tests for HBsAg and for IgM antibody to the core antigen.
Treatment
No antiviral therapy is typically used in acute hepatitis B. For chronic hepatitis B, entecavir 抗病毒药 (Baraclude) or tenofovir抗病毒药(Viread) are the drugs of choice.
Prevention
Prevention involves the use of either the vaccine or hyperimmune globulin or both.
(1) The vaccine contains HBsAg produced. The vaccine is highly effective in preventing hepatitis B and has few side effects.
(2) Hepatitis B immune globulin (HBIG) contains a high titer of HBsAb. It is used to provide immediate, passive protection to individuals known to be exposed to HBsAg-positive blood (e.g., after an accidental needle-stick injury).
Arboviruses 虫媒病毒
Arbovirus is an acronym缩写 for arthropod-borne virus and highlights the fact that these viruses are transmitted by arthropods节肢动物, primarily mosquitoes and ticks 虱类.
It is a collective name for a large group of diverse viruses, more than 600 at last count.
In general, they are named either for the diseases they cause (e.g., yellow fever virus) or for the place where they were first isolated (e.g., St. Louis encephalitis virus圣路易斯脑炎病毒).
Transmission
For effective transmission to occur, the virus must be present in the bloodstream of the vertebrate host (viremia病毒血症) in sufficiently high titer to be taken up in the small volume of blood ingested during an insect bite.
After ingestion, the virus replicates in the gut 肠 of the arthropod and then spreads to other organs, including the salivary glands.
Only the female of the species serves as the vector 载体 of the virus, because only she requires a blood meal in order for progeny to be produced.
Arbovirus transmission cycle.
Arboviruses typically cycle between the vertebrate reservoir host, often a bird, and the vector, often a mosquito.
The infected vector can also bite other hosts, such as humans and horses, which are “dead-end” hosts because their viremia 病毒血症 is too low to provide the vector with an infectious dose.
Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) is the cause of acquired immunodeficiency syndrome (AIDS).
Both HIV-1 and HIV-2 cause AIDS, but HIV-1 is found worldwide, whereas HIV-2 is found primarily in West Africa.
Transmission & Epidemiology
Transmission of HIV occurs primarily by sexual contact and by transfer of infected blood.
Perinatal transmission from infected mother to neonate also occurs, either across the placenta, at birth, or via breast milk.
Clinical Findings
The clinical picture of HIV infection can be divided into three stages:
an early, acute stage;
a middle, latent stage;
and a late, immunodeficiency stage.
Clinical Findings
In the acute stage, which usually begins 2 to 4 weeks after infection, fever, lethargy, sore throat, and generalized lymphadenopathy 淋巴结病 occurs. Rash on the trunk, arms, and legs. Leukopenia白细胞减少症occurs.
In the middle stage of HIV infection, a long latent period, In untreated patients, the latent period typically lasts for 7 to 11 years.
The patient is asymptomatic during this period. Although the patient is asymptomatic and viremia 病毒血症 is low or absent, a large amount of HIV is being produced by lymph node cells but remains sequestered 使隔离 within the lymph nodes.
The late stage of HIV infection is AIDS, an increase in the frequency and severity of opportunistic infections.
The two most characteristic manifestations of AIDS are pneumonia and Kaposi’s sarcoma卡波济肉瘤.
Laboratory Diagnosis
The presumptive diagnosis of HIV infection is made by the detection of antibodies in the patient’s serum.
During the first month after infection, antibody tests may be negative. These false negative tests are due to insufficient antibody being made early in infection to be detected.
The average time for seroconversion血清转化is 10 to 14 days, and most of those infected, but not all, will have seroconverted by 4 weeks.
Treatment
The two specific goals of treatment are
(1) to restore immunologic function which reduces opportunistic infections and certain malignancies, and
(2) to reduce viral load, which reduces the chance of transmission to others.
Unfortunately, no drug regimen results in a “cure” (i.e., eradicates the virus from the body), but long-term suppression can be achieved获得. However, if drugs are stopped, the virus resumes active replication, and large amounts of infectious virus reappear.
Prevention
No vaccine is available. Prevention consists of taking measures to avoid exposure to the virus (e.g., using condoms, not sharing needles, and discarding donated blood that is contaminated with HIV).
-
Moxibustion
-
Cupping
-
E-Stim
-
Bleeding
-
Gua Sha
-
Tui Na
Pharmacology is the study of interaction of drugs with living organisms.
Clinical Pharmacology: It evaluate the pharmacological action of drug preferred route of administration and safe dosage range in human by clinical trails.
Drugs are obtained from:
1. Minerals: magnesium sulfate
2. Animals: Insulin, thyroid extract
3. Plants: Morphine, atropine
4. Synthetic source: Aspirin, paracetamol
5. Micro organisms: Penicillin, streptomycin and many other antibiotics.
6. Genetic engineering遗传工程: Human insulin, human growth hormone
Out of all the above sources, majority of the drugs currently used in therapeutics are from synthetic source.
Pharmacokinetics （PK） 药物代谢动力学
A. Biotransport 生物转运 of drug (Liberation)
B. Drug absorption
C. Distribution of drugs
D. Metabolism of drugs
E. Excretion of drugs
A. Biotransport of drug
1. Structure of biological membrane
The outer surface of the cell covered by a very thin structure known as plasma membrane. It is composed of lipid and protein molecules.
The plasma membrane is a semipermeable membrane allowing certain chemical substances to pass freely e.g. it allows water, glucose, etc.
2. Passage of drug across membrane-a
(a) Passive transfer
i) Simple diffusion: Movement of a solute through a biological barrier from the phase of higher concentration to phase of lower concentration. No need of energy e.g. highly lipid soluble drugs.
ii) Filtration: Is the process by which water soluble drug of relatively low molecular weight crosses the plasma membrane through pores as a result of hydrodynamic pressure gradient across the membrane e.g. urea.
2. Passage of drug across membrane – b
(b) Specialized transport
i) Facilitated diffusion: It means the passage of drug across the biological membrane along the concentration gradient by the protein carrier mediated system.
ii) Active transport: The process by which drugs pass across the biological membrane most often against their concentration gradient with the help of carriers along with the expenditure of energy
¢iii) Endocytosis内噬作用: It is the process by which the large molecules are engulfed by the cell membrane and releases them intracellularly
B. Drug absorption
1. Routes of drug administration
2. Bioavailability生物利用度
1. Routes of drug administration
a) From the alimentary tract:
Advantages of oral route: This route is safe, convenient and economical.
Disadvantages of oral route: Onset of drug action is slow, irritant 有刺激性的drugs cannot be administered and it is not useful in vomiting and severe diarrhea, gastric acid and digestive enzymes may destroy some drugs, and water soluble drugs are absorbed poorly.
b) From the parenteral 注射用药物 route
(i) Intradermal: This is given into the layers of the skin e.g. B.C.G. vaccine
(ii) Subcutaneous: This is given into subcutaneous tissue e.g. insulin
(iii) Intramuscular:
(iv) Intravenous:
(v) Intrathecal膜内的: Injected into subarachnoid space of spinal cord. e.g. spinal anaesthetics.
(vi) Intraperitonial: Injections given into the abdominal cavity
(vii) Intra-articular: Injected directly into a joint e.g. hydrocortisone.
c) Transcutaneous经皮的route
i) Iontophoresis离子电渗疗法: Galvanic current电流 is used for bringing about the penetration of drugs into the deeper tissue.
ii) Inunctions涂擦剂: Absorbed when rubbed in to the skin.
d) Topical/ local route:The absorption through skin is a passive process. The absorption occurs more easily through the cell lining e.g. dusting powder, paste, lotion, drops, ointment, suppository for vagina and rectum.
e) Inhalation: Drugs may be administered as dry powders, and nebulized 使成雾状 particles when sprayed as fine droplets get deposited over the mucous membrane producing local effects and may be absorbed for systemic effects absorbed for systemic effects.
2. Bioavailability生物利用度
It is the rate and amount of drug that is absorbed from a given dosage form and reaches the systemic circulation. When the drug is given IV, the bioavailability is 100%. It is important to know the manner in which a drug is absorbed.
Drugs given by mouth may be inactive for the following reasons:
a) Enzymatic degradation of polypeptides多肽 within the lumen 腔of the gastrointestinal tract e.g. insulin, ACTH.
b) Poor absorption through gastrointestinal tract
c) Inactivation by liver e.g. testosterone睾丸素during first passage through the liver before it reaches systemic circulation.
C. Distribution of drugs
Penetration of a drug to the sites of action through the walls of blood vessels from the administered site after absorption is called drug distribution.
Drugs distribute through various body fluid compartments.
D. Metabolism of drugs
Drugs are chemical substances, which interact with living organisms and produce some pharmacological effects and then, they should be eliminated from the body unchanged or by changing to some easily excretable molecules.
The process by which the body brings about changes in drug molecule is referred as drug metabolism or biotransformation.
E. Excretion of drugs
a) Renal excretion：A major part of excretion of chemicals is metabolically unchanged or changed.
b) Hepatobiliary excretion: the conjugated结合的drugs are excreted by hepatocytes in the bile. After excretion of drug through bile into intestine, certain amount of drug is reabsorbed into portal vein leading to an enterohepatic cycling肠肝循环 which can prolong the action of drug
c) Gastrointestinal excretion: When a drug is administered orally, a part of the drug is not absorbed and excreted in the faeces.
d) Pulmonary excretion:Drugs that are readily vaporized, such as many inhalation anaesthetics and alcohols are excreted through lungs. The rate of drug excretion through lung depends on the volume of air exchange, depth of respiration, rate of pulmonary blood flow and the drug concentration gradient.
e) Sweat: A number of drugs are excreted into the sweat either by simple diffusion or active secretion
f) Mammary excretion: Many drugs are accumulated into the milk. Therefore lactating mothers should be cautious about the intake of these drugs because they may enter into baby through breast milk and produce harmful effects in the baby
Half-life of the drugs 药物的半衰期
Half-life (t1/2) of a drug is the time taken for the concentration of drug in the blood or plasma to decline to half of original value or the amount of drug in the body to be reduced by 50%.
A half-life value can be readily determined for most drugs by administering a dose of the drug to a subject, taking blood samples at various time intervals and then assaying the samples.
For example if a blood level of drug A is 8.6 mg/ml at 10 minutes and 4.3 mg/ml at 60 minutes, so the half – life of that drug is 50 minutes.
Pharmacodynamics（PD）药效学
What is Pharmacodynamics 药效学?
It involves how the drugs act on target cells to alter cellular function.
A. Receptor and non-receptor mechanisms: Most of the drugs act by interacting with a cellular component called receptor. Some drugs act through simple physical or chemical reactions without interacting with any receptor.
B. Site of drug action: A drug may act:
(i) Extracellularly细胞外
(ii) On the cell surface
(iii) Inside the cell
C. Dose Response relationship: The relationship between the dose and the response depends on the biological object.
D. Structural activity relationship: The activity of a drug is intimately related to its chemical structure.
Drug safety and effectiveness
A. Factors modifying the dosage and action of drugs
1. Drug intolerance
2. Sex difference
a) Menstruation
b) Pregnancy
c) Breast feeding
3. Body Weight
4. Age
The adverse effects
1)Side effects
2)untoward effects
3)allergic reactions
4)idiosyncratic特殊的reactions
5)teratogenic 产生畸形 effects.
1) Side effects: Side effects are in fact pharmacological effects produced with therapeutic dose of the drug.
e.g: Dryness of mouth with atropine阿托品which is troublesome in peptic ulcer patients.
2) Untoward effects: Untoward effects develop with therapeutic dose of a drug. They are undesirable and if very severe, may necessitate the cessation of treatment.
e.g: Diarrhoea with ampicillin and potassium loss with diuretics.
3) Allergic reactions: Most of the drugs and sera血清 used in therapeutics are capable of causing allergic or hypersensitive reactions.
These reactions may be mild or very severe. When an individual has been sensitized to an antigen (allergen) further contact with that antigen can some times lead to tissue damaging reactions.
4) Idiosyncratic特殊的 reactions: The term idiosyncrasy means one’s peculiar response to drugs.
Many idiosyncratic reactions have been found to be genetically determined.
5) Teratogenic effect: Some drugs given in the first three months of pregnancy may cause congenital abnormalities and are said to be teratogenic.
The best known example is thalidomide反应停 which results in early easily recognizable abnormalities such as absent or grossly abnormal limbs.
Development and evaluation of new drugs
The ultimate aim of pharmacological studies in animals is to find out a therapeutic agent suitable for clinical evaluation in man.
Drug development comprises of two steps.
a) Preclinical development and
b) Clinical development
Drugs acting on autonomic nervous system
The nervous system controls all the major functions of the body.
It is divided into central and peripheral nervous systems.
The peripheral nervous system includes the somatic and autonomic nervous systems which control voluntary and involuntary functions respectively.
Autonomic Nervous Systems
The ANS controls the vegetative植物性的functions of the body.
These include functions like circulation, respiration, digestion and the maintenance of body temperature.
The ANS is subdivided into two major sub-divisions; the two subdivisions are sympathetic and parasympathetic.
Autonomic nerves are actually composed of two neuron systems, termed preganglionic and postganglionic, based on anatomical location relative to the ganglia.
A preganglionic neuron has its cell body in the spinal cord or brain.
Sympathetic & Parasympathetic
The sympathetic nervous system arises from the thoracic and lumbar areas of the spinal cord.
The parasympathetic nervous system arise from the cranial and sacral nerves.
The postganglionic neurons send their axons directly to the effector organs.
Neurotransmitters
There are two important neurotransmitters in the autonomic nervous system.
These are acetylcholine(Ach) and noradrenaline(NA) (norepinephrine)(NE)
Acetylcholine(Ach)
Ach is a neurotransmitter which is released after stimulation of the parasympathetic nervous system to act on effector organs (cells) to elicit their response, but it also acts as a neurotransmitter:
• At the ganglia of both sympathetic and parasympathetic nervous system
• At postganlionic sympathetic nerve endings to blood vessels of skeletal muscles and sweat glands
• At the neuromuscular junction of skeletal muscles (somatic motor fibers to skeletal muscle)
Noradrenaline(NA) /Norepinephrine(NE)
Noradrenaline is the neurotransmitter released by post ganglionic sympathetic nerves to elicit its effect on effectors cells.
Sympathetic nerve activity may be demonstrated by sympathetic nerve stimulation or by application of noradrenaline or adrenaline or other sympathomimetics, i.e. ‘adrenergic activity’, except in the case of sweat glands and blood vessels to skeletal muscles where acetylcholine is released as a neurotransmitter.
Receptors
Receptors that respond to adrenergic nerve transmitter are termed adrenergic receptors.
These receptors are subdivided into alpha and beta adrenoreceptor types on the basis of both agonist and antagonist selectivity.
The receptors have subclasses depending on drug selectivity.
These are alpha 1 and 2 and beta 1, 2 and 3.
AUTONOMIC DRUGS
There are several drugs affecting the autonomic nervous system which are classified into groups.
1. Drugs acting on the sympathetic nervous system
a) Sympathomimetics or adrenergic drugs: are drugs that mimic模仿the effects of sympathetic nerve stimulation.
b) Sympatholytics: are drugs that inhibit the activity of sympathetic nerve.
2. Drugs acting on the parasympathetic nervous system
a) Parasympathomimetics or cholinergic 拟胆碱药 drugs: are drugs which mimic acetylcholine or the effects of parasympathetic nerve stimulation.
b) Parasympatholytics: are drugs that inhibit parasympathetic nervous system activity or cholinergic drugs.
ADRENALINE
This is the prototype原形 of adrenergic drugs and is produced in the body by the cells of the Adrenal medulla and by chromaffin嗜铬的tissues.
Pharmacokinetics 药物动力学
Adrenaline is rapidly destroyed in the gastrointestinal tract, and oxidized in the liver.
It is therefore ineffective when given orally and should be given intramuscularly or subcutaneous. Intravenous injection is highly dangerous and is likely to precipitate促成 ventricular fibrillation心室颤动.
The drug may be given by nebulizer 喷雾器 for inhalation when its relaxing effect on the bronchi is desired or it may be applied topically to mucus membranes to produce vasoconstriction血管收缩.
Extensive metabolism of the drug in liver, little is excreted unchanged in the urine.
Pharmacodynamics 药效学
Adrenaline directly stimulates all the adrenergic receptors both and brings about effects of sympathetic nerve stimulation.
Its action may be divided in to two, depending on the type of receptor stimulated.
The α effects consist of vasoconstriction in skin and viscera内脏, mydriasis瞳孔散大, platelet aggregation and some increase in blood glucose.
The ß effects consists of increased contractility and rate of heart with a decreased refractory period不应期(ß1), vasodilatation in muscles and coronary vessels (ß2), bronchial relaxation (ß2) uterine relaxation (ß2), hyperglycemia高血糖症, and increased circulating free fatty acids.
Indications
1. Acute bronchial asthma
2. Anaphylaxis过敏反应
3. Local haemostatic to stop bleeding in epistaxis鼻衄
4. With local anesthesia to prolong the action
5. Cardiac arrest
Adverse reactions
1. Anxiety, restlessness, headache tremor
2. Anginal心绞痛pain
3. Cardiac arrhythmias and palpitations
4. Sharp rise in blood pressure
5. Sever vasoconstriction resulting in gangrene坏疽of extremities
6. Tearing, conjunctival hyperemia充血
Contra indications
1. Coronary diseases
2. Hyperthyroidism 甲亢
3. Hypertension
4. Digitalis毛地黄therapy
5. Injection around end arteries
NOR ADRENALINE (NA)
Nor adrenaline is the neurochemical mediator released by nerve impulses and various drugs from the postganglionic adrenergic nerves.
It also constitutes 20% of the adrenal medulla out put.
Pharmacokinetics
Like adrenaline, noradrenaline is ineffective orally so it has to be given intravenously with caution. It is not given subcutaneous or intramuscularly because of its strong vasoconstrictor血管收缩的 effect producing necrosis.
The metabolism is similar to adrenaline; only a little is excreted unchanged in urine.
Indication
Nor adrenalines is used as hypertensive agent in hypotensive states E.g. During spinal anesthesia or after sympathectomy交感神经炎.
Adverse effects include:
- Anxiety, headache, bradycardia心动过缓 are common side effects
- Severe Hypertension in sensitive individuals
- Extravasation溢出of the drug causes necrosis.
EPHEDRINE 麻黄素
Pharmacokinetics
Ephedrine in absorbed from the gastrointestinal tract and from all parenteral肠胃外的sites.}It has a good distribution through out the body and is resistant to hydrolysis水解by the liver enzymes.
Major proportion of the drug is excreted unchanged in the urine. Because of its stability to metabolism it has long duration.
Pharmacodynamics
Ephedrine stimulates both α and β receptors.
This effect is partly by a direct action on the receptors and partly indirectly by releasing noradrenaline from its tissue stores the effect of the drug to various organs and systems is similar to that of adrenaline.
It is also a mild CNS stimulant.
Indications
1. Bronchial asthma: - usually as a prophylactic for prevention of attacks
2. Nasal decongestion
3. Mydriasis (pupil dilated)
4. Heart block
5. Nocturnal enuresis遗尿症
Side effects
The side effects are similar to those of adrenaline; but in addition it may produce insomnia and retention of urine.
Contraindications
They are the same as Adrenaline.
Based on their selectivity to specific receptors the rest of the catecholamines, are classified but it is very difficult to exhaust all the drugs.
More over their effect and pharmacology is discussed where they are clinically indicated.
ADRENERGIC BLOCKERS
Adrenergic receptor blockers may be considered in two groups:
1. Drugs blocking the ą adrenergic receptor
2. Drugs blocking the β Adrenergic receptor
These drugs prevent the response of effectors organs to adrenaline, noradrenaline and other sympathomimetic amines胺whether released in the body or injected.
α- Adrenergic blockers
Pharmacologic Effects:
Alpha receptor antagonist drugs lower peripheral vascular resistance and blood pressure.
Hence, postural hypotension体位性低血压 and reflex tachycardia反射性心动过速are common during the use of these drugs.
Other minor effects include miosis瞳孔缩小, nasal stuffiness, etc.
Prazosin 哌唑嗪
This is an effective drug for the management of hypertension. It has high affinity 亲和性 for alpha1 receptor and relatively low affinity for the alpha2 receptor.
Prazosin leads to relaxation of both arterial and venous smooth muscles due to the blockage of alpha1 receptors. Thus, it lowers blood pressure, reduces venous return and cardiac output.
It also reduces the tone of internal sphincter of urinary bladder.
Indications:
- Essential hypertension
- Raynaud’s syndrome
β - ADRENERGIC BLOCKING DRUGS
The β - adrenergic receptor blocking drugs in use may be classified by their selectivity for receptors in different tissues.
1. Drugs blocking all the β receptor effects of adrenaline (non-selective beta blockers) e.g. propanalol心得安, pinadolol 吡那多醇, timolol噻吗洛尔 etc
2. Drugs blocking mainly the β1 effects (those on the heart) with less effect on the bronchi and blood vessels (beta1-selective blockers), e.g. atenolol阿替洛尔 etc.
PROPRANOLOL 心得安
Propranolol is a non- selective β adrenergic blocker; it has also other actions like membrane stabilization.
Pharmacokinetics
Propranolol is almost completely absorbed following oral administration. How ever, the liver, leaving only 1/3 rd of the dose to reach the systemic circulations, metabolizes most of the administered dose. It is bound to plasma to the extent of 90-95%. It is excreted in the urine.
Pharmacodynamics
The drug has the following main actions.
1. Cardiovascular system
• Reduces heart rate
• Reduces force of contraction
• Reduces blood pressure
2. Respiratory system-Bronchoconstriction 支气管缩小
3. Metabolic system- Hypoglycemia 降低血糖
4. Central nervous system - Anti-anxiety action
5. Eye: Decrease the rate of Aqueous humor房水production
6. Kidneys- Decrease renin secretion
Indications
• Cardiac arrhythmias
• Hypertension
• Prophylaxis预防against angina
• Myocardial infarction梗塞形成
• Thyrotoxicosis 甲状腺危象
• Anxiety states
• Prophylaxis against migraine attacks
• Glaucoma青光眼
Adverse reactions
• GI disturbances like nausea, vomiting
• Heart failure
• Heart block
• Hypotension and severe bradycardia心动过缓
• Bronchospasm
• Allergic reaction
• Vivid dreams night mare and hallucinations幻觉
• Cold hands
• Withdrawal symptoms in case of abrupt discontinuation
• Masking掩盖of hypoglycemia血糖过低 in diabetic patients
Contraindications and Precautions
• Bronchial asthma
• Diabetes
• Heart failure
• Peripheral vascular disease
Cardiovascular drugs
The most commonly encountered cardiovascular disorders include hypertension, congestive heart failure, angina pectoris and cardiac arrhythmias.
Most drugs available currently are able to reduce the morbidity发病率and mortality due to these disorders, this chapter discusses the pharmacology of these drugs.
I. Antihypertensive drugs
Hypertension is defined as an elevation of arterial blood pressure above an arbitrarily defined normal value.
The American Heart Association defines hypertension as arterial blood pressure higher than 140/90mmHg -- systolic /diastolic (based on three measurements at different times).
Hypertension may be classified in to three categories, according to the level of diastolic blood pressure:
• Mild hypertension with a diastolic blood pressure between 95-105 mmHg
• Moderate hypertension with a diastolic blood pressure between 105 – 115mmHg
• Severe hypertension with a diastolic blood pressure above 115mmHg.
1. Non pharmacological therapy of hypertension
Several non-pharmacological approaches to therapy of hypertension are available.
These include:
• Low sodium chloride diet
• Weight reduction
• Exercise
• Cessation of smoking
• Decrease in excessive consumption of alcohol
• Psychological methods (relaxation, meditation …etc)
• Dietary decrease in saturated fats.
2. Pharmacological therapy of hypertension.
Most patients with hypertension require drug treatment to achieve sustained reduction of blood pressure.
Currently available drugs lower blood pressure by decreasing either cardiac output (CO) or total peripheral vascular resistance (PVR) or both although changes in one can indirectly affect the other.
Anti - hypertensive drugs are classified according to the principal regulatory site or mechanism on which they act. They include:
A) Diuretics, which lower blood pressure by depleting the body sodium and reducing blood volume. Diuretics are effective in lowering blood pressure by 10 – 15 mmHg in most patients.
B) Sympathoplegic agents (Depressants of sympathetic activity).
C) Direct vasodilators
D) Angiotensin 血管紧张素 converting enzyme inhibitors.
II. Drug used in heart failure
Congestive heart failure occurs when there is an inability of the heart to maintain a cardiac out put sufficient to meet the requirements of the metabolising tissues.
¢Heart failure is usually caused by one of the following:
• Ischaemic heart disease,
• Hypertension,
• Heart muscle disorders,
• Valvular瓣膜heart disease.
Drugs used to treat heart failure can be broadly divided into:
A. Drugs with positive inotropic 心肌收缩力 effect.
B. Drugs without positive inotropic effect.
A. Drugs with positive inotropic effect
Drugs with positive inotropic effect increase the force of contraction of the heart muscle. These include:
• Cardiac glycosides强心苷类
• Bipyridine 联吡啶 derivatives
• Sympathomimetics 拟交感神经药
• Methylxanthines 甲基黄嘌呤
B. Drugs without positive inotropic effect. These include:
• Diuretics
• Vasodilators
• Angiotensin 血管紧张素 converting enzyme inhibitors
III. Pharmacotherapy of Angina pectoris
Angina pectoris develops as a result of an imbalance between the oxygen supply and the oxygen demand of the myocardium.
It is a symptom of myocardial ischemia. When the increase in coronary blood flow is unable to match the increased oxygen demand, angina develops.
It has become apparent that spasm of the coronary arteries is important in the production of angina.
The action of nitrates begins after 2-3 minutes when chewed or held under tongue and actionlasts for 2 hours.
Beta adrenergic blocking agents e.g. propranolol心得安, atenolol 阿替洛尔, etc.
Organic nitrates 硝酸酯类 e.g. nitro-glycerine, isosorbide dinitrate. The effects of nitrates are mediated through the direct relaxant action on smooth muscles of coronary arteries.
Exercise and emotional excitement induce angina in susceptible subject by the increase in heart rate, blood pressure and myocardial contractility through increased sympathetic activity.
Beta receptor blocking agents prevent angina by blocking all these effects.
Calcium channel blocking agents e.g. verapamil, nifedipine, etc. calcium is necessary for the excitation contraction coupling in both the cardiac and smooth muscles. Calcium channel blockers appear to involve their interference with the calcium entry into the myocardial and vascular smooth muscle, thus decreasing the availability of the intracellular calcium
Miscellaneous drugs e.g. aspirin, heparin 肝素, dipyridamole潘生丁.
Acetylsalicylic acid (aspirin) at low doses given intermittently decreases the synthesis of thromboxne 血栓.
IV. Anti - arrhythmics
Electrophysiology电生理of cardiac muscle:
the pathophysiological mechanisms responsible for the genesis of cardiac arrhythmias are not clearly understood.
However, it is generally accepted that cardiac arrhythmias arise as the result of either of
a) Disorders of impulse formation and/ or
b) Disorders of impulse conduction.
Drugs used in the treatment of cardiac arrhythmias are traditionally classified into:
Class (I): Sodium channel blockers e.g.quinidine 奎尼丁. It blocks sodium channel so that there is an increase in threshold 阈值 for excitability.
Class (II): Beta adrenergic blockers. E.g. propranolol心得安, Myocardiac sympathetic beta receptor stimulation increases automaticity, enhances A.V. conduction velocity and shortens the refractory period. Propranolol can reverse these effects. Beta blockers may potentiate the negative inotropic action of other antiarrhythmics.
Class (III): Potassium channel blockers e.g. amiodarone胺碘达隆. This drug is used in the treatment of refractory 难治性supraventriculat tachyarrhythmias心动过速and ventricular tachyarrhythmias. It depresses S.A and A.V nodal function.
Class (IV): Calcium channel blockers e.g. verapamil异搏定. this drug acts by blocking the movement of calcium ions through the channels.
Class (V): Digitalis e.g.digoxin. Digoxin causes shortening of the atrial refractory period不应期 with small doses (vagal 迷走神经 action) and a prolongation with the larger doses (direct action). It prolongs the effective refractory period of A.V node directly and through the vagus.
V. Drugs used in hypotensive states and shock
Antihypotensive drugs or agents are used to elevate a low blood pressure and may be classified as follows:
I.Agents intended to increase the volume of blood in active circulation.
These include intravenous fluids such as whole blood, plasma, plasma components, plasma substitutes and solution of crystalloids
II. Vasoconstrictor drugs these include:
• Peripherally acting vasoconstrictors which are further divided into sympathomimetic drugs and direct vasoconstrictors.
Sympathomimetics used to elevate the blood pressure include adrenaline, noradrenaline, methoxamine拟肾上腺素药, phenylephrine, mephentermine and ephedrine.
Direct vasoconstrictors include vasopressin(Antidiuretic hormone-ADH) 抗利尿激素and angiotensin血管紧缩素.
Treatment of shock
Shock is a clinical syndrome characterized by decreased blood supply to tissues.
Common signs and symptoms include oliguria少尿, heart failure, mental confusion, seizures, cold extremities, and comma.
Most, but not all people in shock are hypotensive. The treatment varies with type of shock.
The choice of drug depends primarily on the patho-physiology involved.
Drugs used to treat the diseases of blood, Anti-inflammation and gout
用于治疗血液病、消炎和痛风的药物
INTRODUCTION
Hematopoiesis 造血作用, the production of circulating erythrocytes(RBC), platelets and leukocytes(WBC) from undifferentiated stem cells, is a remarkable process that produces over 200 billion new cells per day in the normal person and even greater number of blood cells in people with conditions that causes loss or destruction of blood cells.
The hemopoietic machinery resides primarily in the bone marrow in adults, and requires constant supply of three essential nutrients – iron, vitamin B12 and folic acid
ANEMIA
ANEMIA – a deficiency in oxygen carrying erythrocytes and very common in developing countries.
In this section anemia due to deficiency of iron, Vit B12 or a folic acid will be dealt with.
AGENTS USED IN ANEMIAS -- IRON
Iron forms the nucleus of the iron porphyrin卟啉 heme 血红素 ring, which together with globin 球蛋白 chains forms hemoglobin that reversibly binds oxygen and provides the critical mechanism for oxygen delivery from lungs to other tissues.
In the absence of adequate iron, small erythrocytes with insufficient hemoglobin are formed resulting in microcytic hypochromic小细胞低色素性anemia.
Causes of Iron Deficiency Anemia
1. Nutritional deficiency Low intake of iron containing foods, reduced absorption as a result of mucosal damage, coadministration同时服用of drugs.
2. Chronic blood loss
Chronic nose bleeding, Menorrhagia月经过多, Occult隐藏的GI bleeding, Worm infestation and Ulcers.
Pharmacokinetics of Iron
Daily requirement of Iron - Male 10mg, - Female 15 mg, Increases in growing children, pregnant and lactating women
Sources
- Dietary - mostly in the organic form from meat, cereals 谷类植物, etc.
Body composition of Iron
Total content of Iron in the body is about 4000mg in an adult male, of which about 2/3 – 2500 mg is present in circulating red blood cells.
Absorption
Iron is absorbed in duodenum and proximal jejunum. A normal individual without iron deficiency absorbs 5-10 % of daily intakes.
Absorption is increased in states with increased requirements or deficiencies (low iron stores, pregnancy, menstruation, growing children, and blood loss)
Storage: Iron is stored primarily as ferritin in intestinal mucosal cells and in macrophages in the liver, spleen and bone.
Elimination:
Very small amount are execrated in stool and trace amounts are execrated in bile, urine and sweat with total daily excretion not more than 1mg/day.
TREATMENT OF IRON DEFICIENCY ANEMIA
The cause should always be identified and treated whenever possible.
1. Oral Iron Therapy:
Only ferrous salts 亚铁盐 should be used because of most efficient absorption. Ferrous sulfate硫酸亚铁, ferrous gluconate葡萄糖酸亚铁, ferrous fumarate延胡索酸亚铁 are the most commonly used oral iron preparations.
About 25% of oral iron given as ferrous salt can be absorbed; therefore 200-400mg elemental irons should be given daily to correct iron deficiency most rapidly. Treatment should be continued for 3-6 months to replenish iron stores.
Side effects: Oral iron therapy can cause nausea, vomiting, epigastric discomfort, abdominal cramps, constipation and diarrhea.
2. Parenteral iron therapy:
Should be reserved for patient unable to tolerate or absorb oral iron. Patients with extensive chronic blood loss who can not be maintained with oral iron alone including patients with various post gastrectomy胃切除术conditions, previous small bowel resection, inflammatory bowel disease involving proximal small bowel and malabsorption syndromes need parenteral iron therapy.
Drugs for parenteral administration include:
- Iron dextran右旋糖酐铁, - Iron sorbitol山梨醇铁
They may be given by deep IM or occasionally IV. IV may result in very severe allergic reactions and should be avoided if possible.
Side effect: include local pain, tissue staining, headache, light headedness, fever, arthralgia, nausea, vomiting, urticaria风疹, bronchospasm, and rarely anaphylaxis过敏反应 and death.
AGENTS USED IN ANEMIAS--VITAMIN B12
Vitamin B12 is made up of a porphyrin 卟啉-like ring with a central cobalt(Co)钴 atom attached to a nucleotide核苷酸.
Daily vitamin B12 requirement is 2-5 mg. It is mainly obtained from animal products and serves as a Co factor for essential biochemical reaction in humans.
Ultimate source of vit B12 is from microbial synthesis 微生物合成.
Pharmacokinetics
Absorbed in distal ileum once absorbed vit B 12 is transported to various cells of the body
Excess vitamin B12 is transported to the liver for storage and excreted in the urine.
Physiologic function
- Acts as a coenzyme in the synthesis of DNA and is also essential for various metabolisms in the body.
Clinical uses
- Vit B12 is used to treat or prevent deficiency of vit B 12
Deficiency of Vit B 12 results in: - Megaloblastic巨红血anemia
Causes:
Almost all cases of vit B12 deficiencies are caused by malabsorption. partial or total gastrectomy胃切除术, diseases that affect distal ileum, malabsoption syndrome e.g inflammatory bowel disease, small bowel resection.
Treatment
Vit B12 IM. patients with pernicious恶性的anemia will need life-long therapy.
AGENTS USED IN ANEMIAS--FOLIC ACID
Folic acids are required for essential biochemical reactions that provide precursors前驱 for the synthesis of amino acids, purines嘌呤 and DNA.
Daily requirement is 50 -100μg. Folic acid deficiency is not uncommon.
Sources include yeast, liver, kidney and green vegetables.
Phamacokinetics
folic acid is readily and completely absorbed in the proximal jejunum. 5 -20 mg of folates are stored in the liver and other tissues. Body stores of folates are relatively low and daily requirement is high and hence folic acid deficiency and magaloblasitc anemia can develop within 1 -6 months after the in take of folic acid stops.
Folates are excreted in the urine and stool.
Deficiency:
Common among elderly patients, poor patients, pregnant ladies. It results in megaloblasiic 巨成红细胞anemia. Congenital malformation in newborn are also consequences of folate deficiency during pregnancy.
Causes
Dietary deficiency, alcoholics with liver disease, hemolytic溶血性anemia, malabsorption syndrome, patients with cancer, leukemia, myeloprolferative disorders, chronic skin diseases, patients on renal dialysis and patients on drugs that impair absorption or metabolism e.g. phenrytoin, oral contraceptive, isoniazid, methotrexate etc.
Treatment
Folic acid 1mg orally per day.
Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk individuals including pregnant women, alcoholics and patients with hemolytic anemia, liver disease, certain skin disease, and patients on renal dialysis透析.
Drugs used in Disorder of coagulation凝血
Introduction
Hemostasis is spontaneous arrest of bleeding from a damaged blood vessel.
Steps:
Vascular injury
vasospasm
platelate adhesion
platelate aggregation
Coagulation
fibrin formationAspirin
Aspirin and other nonsteroidal anti-inflammatory drugs are weak organic acids. Aspirin is the drug of choice for treating the majority of articular and musculoskeletal disorders. It is also the standard against which all anti-inflammatory agents are compared.
Pharmacokinetics:
The salicylates水杨酸盐are rapidly absorbed from the stomach and upper small intestine. However, the drug may damage the mucosal barrier.
Aspirin may be excreted unchanged, but most is converted to water-soluble conjugates that are rapidly cleared by the kidney.
Anti-inflammatory Effects: Aspirin inhibits granulocyte 粒细胞adherence to damaged vasculature, and inhibits the migration of polymorphonuclear leukocytes and macrophages into the site of inflammation.
Analgesic Effects: Aspirin is most effective in reducing pain of mild to moderate intensity. Muscular, vascular, and dental origin, arthritis, and bursitis are alleviated by aspirin.
Antipyretic Effects: Aspirin reduces elevated temperature. The fall in temperature is related to increased dissipation of heat caused by vasodilation of superficial blood vessels. The antipyresis may be accompanied by profuse sweating.
Platelet Effects: Aspirin inhibits platelet aggregation. Because its action is irreversible, it inhibits platelet aggregation for up to 8 days.
Clinical Uses
Analgesic, antipyretics, and anti-inflammatory effects: Aspirin is one of the most frequently employed drugs for relieving mild to moderate pain of varied origin.
Aspirin is not effective in the treatment of severe visceral pain (acute abdomen, renal colic, pericarditis, or myocardial infarction). Used in the treatment of rheumatoid arthritis, rheumatic fever, and other inflammatory joint conditions.
Inhibition of platelet aggregation: Aspirin has been shown to decrease the incidence of transient ischemic attacks and unstable angina. It reduces the incidence of thrombosis in coronary artery.
It may also reduce the incidence of myocardial infarction.
DRUGS USED IN GOUT
Gout is a familial metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate 尿酸单钠 in joints and cartilage.
Formation of uric acid calculi in the kidneys may also occur. Gout is usually associated with high serum levels of uric acid, a poorly soluble substance that is the major end product of purine嘌呤 metabolism.
The treatment of gout is aimed at relieving the acute gouty attack and preventing recurrent gouty episodes and urate lithiasis 结石病.
Colchicine秋水仙碱
Colchicine is absorbed readily after oral administration. Metabolites of the drug are excreted in the intestinal tract and urine.
Colchicine dramatically relieves the pain and inflammation of gouty arthritis without altering the metabolism or excretion of urates非晶形尿酸盐 and without other analgesic effects.
Indications: Colchicine is used for alleviating the inflammation of acute gouty arthritis.
Adverse Effects: Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Colchicine may rarely cause hair loss and bone marrow depression.
NSAIDS in Gout
Indomethacin消炎痛 and other NSAIDs(Nonsteroidal Anti-inflammatory Drugs) 类固醇类 inhibit urate crystal phagocytosis吞噬作用.
Indomethacin may be used as initial treatment of gout or as an alternative drug when colchicine is unsuccessful or causes too much discomfort.
Indomethacin is the agent most often used today to treat acute gout. All other NSAIDs except aspirin can be used to treat acute gouty episodes.
DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM
The main CNS neurotransmitters
Noradrenaline.
Dopamine多巴胺.
5-HT. 5-羟色胺
Acetylcholine(Ach).
Noradrenaline. Noradrenergic transmission is important in control of mood (functional deficiency resulting depression) controlling wakefulness, and alertness.
Dopamine多巴胺. Dopamine is important in motor control (Parkinsonism is due to dopamine deficiency), has behavioural effects (excessive dopamine activity is implicated in schizophrenia精神分裂症), important in hormone release (prolactin催乳素, GH) and dopamine in chemoreceptor trigor zone causes nausea and vomiting.
5-HT. Feeding behaviour, behavioural response (hallucinatory幻觉的behaviour), control of mood and emotion, control of body temperature and vomiting.
Acetylcholine(Ach). Ach has effects on arousal觉醒, on learning, and on short-term memory. Dementia痴呆and parkinsonism are associated with abnormalities in cholinergic类胆碱pathways.
GENERAL ANESTHETICS 麻醉剂
General anesthesia involves the physiological changes:
Reversible loss of response to painful stimuli, loss of consciousness and loss of motor and autonomic reflexes.
General anesthetics are administered by inhalation or by intravenous静脉注射 routes.
They are classified into two on the basis of their route of administration as inhalation and intravenous anesthetics.
Inhalation anesthetics
The main agents are: Halothane, nitrous oxide, enflurane and ether.
1. Halothane三氟乙烷: Is the most widely used agent, highly lipid soluble, potent. It causes arrhythmia, and the risk of liver damage is high if used repeatedly.
2. Nitrous oxide: Oderless and colourless gas. It is rapid in action and also an effective analgesic agent. Its potency 效能is low, hence must be combined with other agents. It is a relatively free of serious unwanted effects.
3. Enflurane氟醚麻醉剂: Poorly metabolized in the liver, thus less toxic than halothane. It is faster in its action, less liable to accumulate in the body fat compared to halothane.
4. Ether醚: Has analgesic and muscle relaxant properties. It is highly explosive, causes respiratory tract irritation, postoperative nausea and vomiting. It is not widely used currently.
INTRAVENOUS ANESTHETICS
Intravenous anesthetics act much more rapidly, producing unconsciousness in about 20 seconds, as soon as the drug reaches the brain from the site of its injection.
These agents used for induction of anaesthesia followed by inhalation agent.
The main induction agent in current use is: thiopentone, etomidate, propofol, ketamine and short acting benzodiazepine (midazolam).
SEDATIVE AND HYPNOTIC催眠DRUGS
1. Benzodiazepines苯二氮. Benzodiazepines are the most important group, used as sedative and hypnotic agents.
2. Barbiturates巴比妥(phenobarbitone). They are nowadays less commonly used as sedative and hypnotics.
3. β -adrenoceptor antagonists (e.g. propranolol心得安). They are used to treat some forms of anxiety, where physical symptoms (sweating, tremor, and tachycardia心动过速), are troublesome. They are not used as hypnotics.
Clinical Uses
• Treatment insomnia
• Anxiety
• Preoperative术前 mediations
• Acute alcohol withdrawal
• As anticonvulsants
• Chronic muscle spasm and spasticity痉挛
Unwanted effects
• Toxic effects due to acute over dosage causes prolonged sleep.
• Unwanted effects occurring during normal therapeutic use includes: drowsiness, confusion, amnesia遗忘, and impaired motor coordination.
• Tolerance and dependance: Pharmacokinetic and tissue tolerance and also cause physical dependance. i.e. stopping treatment after weeks or months causes an increase in symptoms of anxiety.
MANAGEMENT OF PARKINSONISM
Parkinsonism: Parkinsonism is characterized by a combination of rigidity僵硬, bradykinesia运动迟缓, tremor, and postural instability. It is due to the imbalance between the cholinergic胆碱能的 and dopaminergic多巴胺能的 influences on the basal ganglia 基底核.
Thus, the aim of the treatment is either to increase dopaminergic activity (by dopamine agonist兴奋剂) or to decrease cholinegic (antimuscarinic drugs) influence on the basal ganglia.
ANTIPSYCHOTIC AGENTS
Psychotic精神病 illness is characterized by delusion 幻想, hallucinations幻觉, thought disorder, social withdrawal and flattering of emotional response.
Antipsychotics are a group of drugs used mainly for treating schizophrenia 精神分裂症.
Antipsychotic agents are classified into typical neuroleptics神经松弛剂(chlorpromazine氯丙嗪, thioridazine安定, haloperidol氟哌啶, flupenthixol三氟噻醇) and atypical neurolopitics 非典型的神经药(clozapine氯氮平, sulpiride止呕灵).
Most antipsychotic drugs are readily but incompletely absorbed.
Many of these drugs undergo significant first-pass metabolism. Very little of any of these drugs is excreted unchanged.
Clinical uses
• Schizophrenia精神分裂症
• Mania躁狂
Adverse Reactions
• Extrapyramidal reactions as PARKINSONISM
• Seizures
• Autonomic nervous system effects (antimuscarinic 抗胆碱effects(increase heart rate, muscle relax), orthostatic hypotension直立性低血压)
• Metabolic and Endocrine Effects (weight gain, infertility, loss of libido and impotence)
ANTIDEPRESSANT AGENTS:
Depression is one of the most common psychic disorders. Antidepressants are the drugs which are mainly used in the management of depression.
Types of antidepressant drugs
1. Tricyclic三环类 antidepressants (TCAs)
2. Monoamine oxidase inhibitors单胺氧化酶抑制剂(MAOI)
3. 5-HT uptake摄入 inhibitors
4. Atypical非典型的 antidepressants
Pharmacokinetics
Most tricyclics are incompletely absorbed and undergo significant first-pass metabolism.
Clinical Indications:
TCAs are endogenous depression, panic attacks, Phobic恐惧 and bed-wetting in children.
MAOIs are used in severe depression refractory难治性 to other treatment and phobias恐惧.
Adverse Effects:
Postural hypotension, dry mouth, blurred vision, constipation, urine retention, sedation, are the most important side effects of TCAs.
MAOI cause postural hypotension, weight gain, and CNS stimulation causing restlessness, tremor, and insomnia.
Drug dependence and drug abuse
There are many drugs that human beings consume because they choose to, and not because they are advised to by physicians.