By B. Zapotek. Indiana University - Purdue University, Indianapolis.
The degree of ionization of a drug may be suppressed by the judicious use of buffering agents order 0.15mg levlen with visa. Drug solubility may be enhanced by the use of amorphous or anhydrous forms purchase 0.15mg levlen otc, or the use of the corresponding salt form of a lipophilic drug cheap levlen 0.15mg online. Low molecular weight analogues of an active moiety can be 69 developed order levlen 0.15mg line, to facilitate trans-membrane transport. Alternatively, derivatives may be prepared which are substrates of natural transport carriers. Considerable effort has been directed towards the stabilization of therapeutic peptides and proteins both in vitro and in vivo. Several methods of modifying peptide structure to improve metabolic stability have been investigated, as outlined in Section 1. Traditionally drug design has focused on optimizing the pharmacological properties of a drug with less concern for potential drug bioavailability, toxicity and metabolism, which all form part of the later pharmaceutical development process. However, with the increasing numbers of compounds entering pharmaceutical development there is a need to limit resource wastage in developing compounds with poor biopharmaceutical profiles. This has led to the development of more rationalized approaches to drug design in order to optimize the bioavailability of potential drug substances in the early stage of drug discovery process to ensure that new drugs can be effectively delivered to their site of action. The process of rational drug design and delivery is discussed in more detail in Chapter 16. Although the pharmaceutical industry strives to develop drugs with appropriate pharmacokinetic and pharmacodynamic properties to ensure effective drug delivery, it is often difficult to obtain effective potency, low toxicity and acceptable bioavailability. Methods to improve delivery by manipulating the dosage form are described below and in the relevant chapters. The mechanisms of absorption promotion proposed for the different compounds are numerous and it is likely that more than one mechanism is involved (see Section 8. The use of penetration enhancers to improve drug absorption by variety of delivery routes is presently under investigation; for example, various studies have recently been carried out to identify penetration enhancers to facilitate the absorption of peptides and proteins by various routes (Table 3. However, as mentioned previously, a serious drawback associated with the use of penetration enhancers is their potential deleterious effect to the epithelial tissue, either directly, by damaging vital cell structures 70 and/or functions, or indirectly, by increasing the permeability of the epithelium and thus paving the way for inward penetration of toxic agents and organisms. Some routes of drug delivery, such as the transdermal and buccal, allow the spatial containment of absorption enhancers within an adhesive patch, thereby limiting the adverse effects to a specific area. Mucoadhesives, which are generally hydrophilic polymers, may be included in a dosage form to increase drug bioavailability. These agents are believed to act by: • increasing the contact time of the drug at the absorbing surface; • increasing the local drug concentration at the site of adhesion/absorption; • protecting the drug from dilution and possible degradation. Several mechanisms by which mucoadhesives adhere to biological surface have been suggested, including the electronic, adsorption, wetting, diffusion, and fracture theories. It is likely that water movement from the mucosa to the polymer and physical entanglement of the adhesive polymer in the mucus glycoprotein chains are important in obtaining adherence. Work in this field has concentrated on the use of protease inhibitors to facilitate the absorption of therapeutic peptides and proteins. For example, because it does not have a dissolution step, the bioavailability from an aqueous solution will be greater than from a tablet, etc. Increasing the drug concentration increases the rate of drug absorption via passive diffusion mechanisms. Examples include the use of eutectic mixtures and supersaturated systems to enhance the transdermal penetration of drugs (see Chapter 8). Other formulation strategies include altering the formulation pH and tonicity to effect favorable absorption. Various further strategies are specific for the route in question, for example the use of iontophoresis to enhance the transdermal delivery of drugs. The following chapters provide a more in-depth discussion of each of the major routes of drug delivery and discuss both advantages and disadvantages of these routes. The existing technologies employed to maximize delivery using the various routes is discussed along with the perceived challenges and opportunities for the future. Explain the following terms: (a) sustained release, (b) zero-order release, (c) bio-responsive release, (d) rate-controlled release and (e) targeted drug delivery.
Aggressive intravenous resuscitation generic levlen 0.15mg with mastercard, antibiotics buy cheap levlen 0.15 mg, and surgery are required for patients who present in this fashion buy levlen 0.15mg fast delivery. They are explored urgently cheap levlen 0.15mg otc, and a resection with descending colostomy and oversewing of the rectal stump is performed in all but the sickest patients. Fistulas develop in only 2% of patients with diverticulitis, but fistula is the indication for surgery in 20% of those undergoing surgery for diverticulitis and its associated complications (Fig. The bladder is affected most commonly, with nearly two thirds of all patients in one series having colovesical fistulas. Such patients may present with pneu- maturia, fecaluria, abdominal pain, urinary symptoms (frequency, urgency, dysuria), hematuria, and fever and chills. Colovaginal fistu- las, the next most common diverticular fistula, present with vaginal discharge, air, or stool per vagina. The indications for surgery for diverticulitis are recurrent attacks, a severe attack, age less than 50 years, immunocompromised pa- tients, or a severe complication of perforation such as significant 25. Note the air col- lection outside the colon that can be traced down to the bladder on serial images. Air in the bladder without a history of recent catheterization is diag- nostic of a communication with the gastrointestinal tract. The goals of sur- gical therapy are to minimize morbidity and mortality, remove the septic focus and diseased colon, avoid or at least minimize the risks of a second operation, and convert an emergent situation to an urgent or elective operation. Infectious Colitides Infections of the large bowel usually cause diarrhea and can produce fever or abdominal pain. It is critical to elicit a complete history from the patient, including recent travel, unusual ingestions suspect for food poisoning, similar illnesses among family members, recent hospitalizations, treatment with antibiotics, sexual history, immuno- suppression, and evidence of systemic disease. Diarrhea that develops during antibiotic administration may be related to a change in the bacterial flora of the colon. However, a minority of patients on antibiotics have a proliferation of the toxin-producing strains of Clostridium difficile, a gram-positive, anaerobic organism. Symp- toms can occur both during antibiotic administration and weeks to months after cessation of treatment. The diagnosis is made by rapid immunoassays that test for antigens or toxins in the stool. On endo- scopic exam, the mucosa can look inflamed or develop plaque-like membranes, which is why it has been called “pseudomembranous” colitis. Volvulus Intestinal volvulus is a closed-loop obstruction of the bowel resulting from an axial twist of the intestine upon its mesentery of at least 180 degrees; this results in luminal obstruction and progressive strangula- tion of the blood supply. The early diagnosis and treatment of volvu- lus are important in avoiding intestinal ischemia or gangrene that can lead to a high morbidity and mortality. The more common sigmoid volvulus usually presents with the triad of abdominal pain, distention, and obstipation. On exam, the abdomen is dis- tended dramatically, with high-pitched bowel sounds and tympany to percussion. When patients do not show signs of intestinal strangulation, the initial treatment of choice is endoscopic decompression; this allows the volvulus to reduce so that surgical treatment can be performed elec- tively, after a full mechanical bowel preparation, with lower morbidity and mortality. Rigid sigmoidoscopy can reduce and decompress the bowel, evaluate the rectal and colonic mucosa, and allow for the passage of a rectal tube to keep the bowel decompressed. The goals of treatment are to untwist and decompress the bowel before strangulation and to prevent recurrences. Those patients admitted with signs of sepsis indicative of gangrenous bowel must be resuscitated aggressively and taken emergently to the operating room. Cecal volvulus is the second most common type of volvulus, although it is the cause of only 1% of all intestinal obstructions. Most patients present with symptoms of a small-bowel obstruction: nausea, vomiting, cramping, abdominal pain, and distention. Two types of volvulus can occur: an ileocolic twisting, generally in a clockwise direc- tion; or a cecal bascule, which is an anterior and superior folding of the cecum over the ascending colon.
One of the normal functions of the spleen is to clear abnormal and aged cellular elements from the blood cheap 0.15 mg levlen overnight delivery. If an increased number of abnormal cells are presented to the spleen with increased destruction cheap levlen 0.15 mg with visa, the patient has primary hyper- splenism discount levlen 0.15mg online. Alternatively generic levlen 0.15 mg, a patient may develop splenic enlargement due to intrinsic splenic disease that leads to secondary hyper- splenism (Table 22. In the case presented, the patient’s spleen is inherently normal, but it has enlarged as a consequence of increased clearance of abnormal platelets. A variety of bacterial, parasitic, and viral infections can lead to increased proliferation of immune system cells (e. Malaria Granulomatous disease Rheumatoid disease Hematologic disorders Cirrhosis Lymphoma Splenic abscess Storage disease Leukemia Splenic cysts Viral infection 420 T. Kearney Metabolic abnormalities, such as Gaucher’s disease, can lead to accu- mulation of unmetabolized products in the spleen. In primary hypersplenism, the spleen inherently is normal, but it enlarges in size and increases function in response to an increased work load. Disor- ders such as cirrhosis, portal vein obstruction, and congestive heart failure can lead to splenomegaly due to restricted venous outflow. In chronic myelogenous leukemia, massive spleno- megaly can develop and lead to difficult problems with anemia. All of these situations reflect secondary hypersplenism: increased function resulting from abnormally increased size. Splenectomy The most common reason for splenectomy in the United States today is splenic trauma. The diagnosis is made based on the mechanism of injury and left upper quadrant pain and tenderness. The degree of splenic injury and the presence of associated injuries guide the surgeon to either removal or repair. The presence of splenomegaly is not an indication for elective splenectomy by itself. Surgical staging of Hodgkin’s disease was per- formed in the past to help decide on treatment modalities. This tech- nique is used less today due to the increasing use of systemic chemotherapy even in early-stage patients. In the past, open splenec- tomy was performed through a left upper quadrant incision. During laparoscopic splenectomy, the spleen is morcellated into fragments and removed. The size of the spleen is the primary deter- minant of the decision to use laparoscopic or open techniques. Whether performed electively or emergently, there are some com- plications common to all splenectomies. Injury to the greater curvature of the stomach during ligation of the short gastric vessels can lead to perforation. Accessory splenic tissue is present in over 10% of patients and can cause relapse in some of the hematologic conditions. Patients without spleens are particularly susceptible to infection with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningi- tidis. He under- went exploratory laparotomy with en bloc resection of the mass includ- ing the left colon, the left kidney, and the adrenal gland. It is common to have microscopi- cally involved margins, even with en bloc resection of retroperitoneal sarcoma. Eventually, many of these low- grade sarcomas become high-grade with an increased chance of sys- temic (usually pulmonary) metastases.
Atropine – used to overcome spasm of involuntary muscles discount levlen 0.15 mg, to help decrease secretions order 0.15 mg levlen, also used to dilate pupils before testing eyes for glasses to relieve muscle spasm cheap levlen 0.15 mg, and to increase heart rate Atypical – deviating from the normal Auditory - pertaining to the sense of hearing Aura – the preepileptic phenomenon where one is aware of a seizure that will be occurring shortly Auscultation – listening for sounds within the body purchase 0.15mg levlen free shipping, especially, from the chest, neck, or abdomen. A stethoscope is used, applied to the patient’s skin surface gently but firmly, to eliminate any environmental noises that may be present. They contribute to some of the subconscious aspects of voluntary movement such as accessory movements and inhibiting tremor. They do not initiate movement but rather provide coordination of complex motor circuits. May produce inflammatory lesions of the skin (cutaneous form) or lungs or a generalized invasion of the skin, lungs, bones, central nervous system, kidneys, liver, and spleen Blepharoptosis – drooping of the upper eyelid Blepharospasm – a twitching or spasmodic contraction of the orbicularis oculi muscle due to tics, eyestrain, or nervous irritability Bone marrow – the soft tissue in the marrow cavities of the long bones (yellow marrow) and in the spaces between trabeculae (a cord of tissue) of spongy bone in the sternum and other flat and irregular bones (red marrow). Red marrow produces all the types of blood cells Bowel – the intestine, colon Bradycardia – a normal heart rhythm with a rate of 60 or below in an adult or 70 in a child Bradykinesia – extreme slowness of movement Brain stem – part of the brain at the base of the neck which includes center for regulating and coordinating body activities, perception, the seat of consciousness, thought, memory, reason, judgment and emotion, through reflex centers automatic 397 control of body activities are maintained most important being cardiac, vasomotor, and respiratory centers which regulate circulation and respiration Brompton’s Cocktail – a mixture of cocaine, morphine and antiemetics formerly used to alleviate pain and induce euphoria, especially in patients with cancer Bronchial – a primary division of the trachea, which extends into each lung Bronchitis – inflammation of the bronchial mucous membrane, which a bronchus splits off of the trachea and goes into each lung Bronchodilator – a drug that expand the bronchi by relaxing bronchial muscle. There are three classes of bronchodilators: B2adrenergic-receptor agonists, Methylxanthines and Anticholinergic agents; the B2 adrenergic receptor agonists produce the greatest bronchodilitation in patients with bronchial asthma. The beta2, adrenergic receptor agonists are the best drugs for patients with mild, intermittent asthma and for acute attacks of reactive airway disease Bronchopneumonia – a type of pneumonia marked by scattered consolidation (areas filled with inflammatory exudates) in one or more lobes of the lung. It occurs primarily in infants and in elderly persons, both of whom have decreased resistance to bacterial and viral infections. It is often a complication of bronchitis Broncho-spasm – spasm of the bronchus, which the trachea divides into 2 bronchi, which ends, one in each lung Bruxism – the grinding of the teeth in children especially during sleep. It is a constituent of some kidney stones Calculi – any abnormal concretion, commonly called a stone, within the animal body. A calculus is usually composed of mineral salts, and can be found in the gallbladder, kidneys, ureter, bladder, or urethra Candidiasis – infection of the skin or mucous membrane with any species of Candida. Candida grows in warm moist areas, causing superficial infections of the mouth, vagina, nails, and skin folds of healthy individuals. Sometimes very difficult to get rid of Cardiac arrest – heart stops due to many reasons with the main one being heart attacks Cardiomegaly – enlargement of the heart Cardiomyopathy – any disease that affects the heart muscle, diminishing heart performance Cardiovascular – pertaining to the heart and blood vessels Cardioversion – the restoration of normal sinus rhythm by chemical or electrical means. When preformed mechanically, the procedure relies on or the oral or intravenous administration of antiarrhythmic drugs. Electrical cardioversion relies instead on the delivery of synchronized shock of direct electrical current across the chest wall. It is used to terminate arrhythmias such as atrial fibrillation, atrial flutter, supraventricular tachycardia, and well tolerated ventricular tachycardia. Unlike defibrillation, which is an unsynchronized shock, applied during a dire emergency, electrical cardioversion is timed to avoid the T wave of cardiac repolarization to avoid triggering malignant arrhythmias. A patient will almost always require sedation and analgesia before the procedure Carnitine – a chemical important in metabolizing palmitic and stearic acids. It has been used therapeutically in treating myopathy due to carnitine deficiency. In children that are on Depakote, you need to have their Carnitine levels checked periodically due to the fact that Depakote pulls Carnitine from the body system Carpal tunnel – pain or numbness that affects some part of the median nerve distribution of the hand (the palmer side of the thumb, the index finger, the radial half of the ring finger, and the radial half of the palm) and may radiate to the arms. Patients may have a history of cumulative trauma to the wrist in carpenters, rowers, typists, computer users, or those who regularly use vibrating tools or machinery Cascara – It is the main ingredient in a laxative which is supposed to be fairly good 399 Cataplexy – a sudden brief loss of muscle control brought on by strong emotion or emotional response, such as a hearty laugh, excitement, surprise, or anger. Cataracts – opacity or cloudy looking of the lens of the eye or its capsule or both Catatonic – a phase of schizophrenia in which the patient is unresponsive, the tendency is to remain and assume in a fixed position, refusal to move or talk are characteristics Catecholamines – one of many biologically active amines, including Metanephrines, Dopamines, Epinephrine and Norepinephrine, derived from Amino and Tyrosine. It is composed primarily of secretions of the choroids plexi in the lateral ventricles and in the third and fourth ventricles in the brain. Openings in the roof of the fourth ventricle allow the fluid to flow into the subarachnoid spaces around the brain and the spinal cord. The flow of fluid is from the blood in the choroids plexi, through the ventricles, the central canal, the subarachnoid spaces, and back into the blood. Samples of the fluid may be removed by lumbar puncture Cerebrovascular – pertaining to the blood vessels of the brain especially to pathological changes Ceroids – morbid condition of membranes resembling wax-like scales 400 Cervical erosion – a wearing away of the cervix in the uterus of females Chemoreceptor trigger zone – a sense organ or sensory nerve ending that is stimulated by and reacts to certain chemical stimuli and that is located outside the central nervous system. The excess pigmentation often occurs in pregnant women, in women using oral contraceptives, or in patients with underlying liver disease. Sun exposure tends to worsen the condition Cholelithiasis - formation or presence of stones in the bladder or kidneys or bile- stones in the gallbladder or common duct Cholestatic – arrest of the flow of bile.