By F. Tukash. Bennett College.
Based on the manufacturing method for the nanopar- ticles levitra professional 20mg line, drug molecules can be either dissolved in a liquid core or dispersed within a dense polymeric matrix generic 20 mg levitra professional otc, resulting in nanocapsules or nanospheres trusted levitra professional 20 mg. Liposomes best levitra professional 20 mg, niosomes, and microemulsions are similar to polymeric nanoparticles with respect to their shape, size, and mode of administration, and thus serve as alternative modes of novel colloidal drug carrier systems. However, nanoparticles offer addi- tional advantages when compared with the other colloidal carriers, such as higher stability when in contact with biological ﬂuids, high drug-loading capacities, and protection by the solid matrix of the incorporated drug against degradation, thus leading to increased intracellular concentration of the drug (4). Also, because of 16 Polymeric Nanoparticles for Small-Molecule Drugs 17 their polymeric nature, controlled drug release can be obtained with nanopar- ticles. The surface of the polymeric nanoparticles can be covalently conjugated to folic acid, monoclonal antibodies, and aptamers to achieve targeted delivery and cell-speciﬁc uptake. While many reports have demonstrated the increase in solubility of poorly soluble small molecules by modifying the shape, size, and functional groups present on the molecule, as well as the increase in permeability by the incorporation of lipid components into the drug, the entrapment of drugs in nanoparticles offers opportunities for the modulation of both solubility and per- meability. They can be fabricated into various shapes and sizes, with tailored pore morphologies, mechanical properties, and degradation kinetics to suit a variety of applications. By selecting the appropri- ate polymer type, molecular weight, and copolymer blend ratio, the degradation/ erosion rate of the nanoparticles can be controlled to achieve the desired type and rate of release of the encapsulated drug. The common biodegradable poly- mers used in drug delivery include (i) polyesters, such as lactide and glycolide copolymers, polycaprolactones, poly( -hydroxybutyrates), (ii) polyamides, which includes natural polymers such as collagen, gelatin, and albumin, and semisyn- thetic pseudo-poly(amino acids) such as poly(N-palmitoyl hydroxyproline ester), 18 D’Mello et al. Owing to the presence of methyl groups in the lactide polymers, they are more hydropho- bic than the glycolide polymers. Also, the water uptake increases as the glycolide ratio in the copolymer increases (11). The transition glass tem- peratures of the copolymers range from 36◦C to about 67◦C. Furthermore, hydrolysis is enhanced by the accumu- lation of acidic products and the reduction of pH facilitated by the carboxylic acid end groups, which is an autocatalytic degradation process (13–15). The degrada- tion of these polymers differs in vivo and in vitro, mainly because, although in vivo there is no major inﬂuence of enzymes during the glassy state of the polymer, these enzymes can play a signiﬁcant role when the polymer becomes rubbery (15). Nor- mally, 50:50 lactide/glycolide copolymers have the fastest half-life of degradation, around 50 to 60 days, whereas 65:35, 75:25, and 85:15 lactide/glycolide copolymers have progressively longer degradation half-lives in vivo. The half-life of these linear polyesters can be increased by coblending with more hydrophobic comonomers such as polycaprolactone. Biocompatibility The evaluation of the biocompatibility of biodegradable polymers takes into con- sideration the incidence of the inﬂammatory and healing responses of the injected and implanted materials. The particles after an intramuscular or a subcutaneous injection usually have a high surface area/low volume ratio within a given tissue volume. Table 1 outlines the tissue responses to the polymer materials that are divided into three time phases (10). Nanoparticles, when given intravenously, can modulate the inﬂammatory and healing responses in their presence. These responses are usually lesser in mag- nitude because the particles are present as single, isolated particles and not in groups and also because the cellular injury at the site of the particle is minimal (21). By modifying the polymer type, the copolymer composition, the polymer molecular weight, and the porosity of the microspheres, their degradation rate can be varied from days to months. It undergoes bulk erosion by random hydrolytic chain cleavage in the ﬁrst phase, resulting in a decrease in the molecular weight of the polymer. This is followed by the second phase, in which these low molecular weight fragments undergo phagocytosis or solubilization in the body ﬂuids. Their degradation rate can be enhanced by the addition of additives such as oleic acid and tertiary amines, which act as catalysts in the chain hydrolysis process. Also, copoly- merization with lactide and glycolide decreases crystallinity, and thus hastens the polymer degradation rate due to its higher water uptake (12,22,23). They could be considered safe because it was observed that (i) there were multinucleate, foreign-body giant cells, which are macrophagic cells present in normal processes of polymer degradation 20 D’Mello et al. Polyanhydrides Biodegradation These hydrophobic and crystalline materials have been shown to undergo erosion by surface hydrolysis, minimizing water diffusion into the bulk of the delivery device (25,26). The monomeric anhydride bonds have extreme reactivity toward water and undergo hydrolysis to generate the dicarboxylic acids (27). Although hydrolysis is catalyzed by both acid and base, an increase in pH enhances the rate of hydrolytic degradation. At low pH, oligomeric products formed at the surface of the matrix have poor solubility; this hinders the degradation of the core. The degradation rate of these polymers can be either accelerated by the incorporation of sebacic acid, a relatively more water-soluble aliphatic comonomer than carboxyphe- noxy propane, into the polymer or reduced by increasing the methylene groups or long-chain fatty acid terminal such as stearic acid into the polymer backbone, thereby increasing the monomeric chain length, its hydrophobicity, and the ero- sion rate (28,29). The branching of poly(sebacic acid) with either 1,3,5-tricarboxylic acid or low molecular weight poly(acrylic acid) results in an increased erosion rate (30). It is also known that aliphatic anhydrides and their copolymers undergo a ﬁrst-order, self-depolymerization reaction, under anhydrous conditions both in solid state and in solution (31). The rate of depolymerization is found to increase with temperature and the polarity of the solvent. Studies on copolymers of several polyanhydride families have shown that varying comonomer ratios produce ero- sion proﬁles ranging from days to years (32). Biocompatibility During biocompatibility testing of linear aliphatic polyanhydrides in rats, histopathological examination of tissue specimens that were in direct contact with the polymer device showed mild inﬂammation, but macroscopically, no swelling or pathological signs were observed (27). In another set of compatibility studies, these polyanhydrides were shown to be nontoxic, nonmutagenic, and nonteratogenic (36). A rabbit cornea bioassay indicated the absence of an inﬂammatory response with implanted polyanhydrides (37). In a rabbit animal model, blank polyanhy- dride particles did not elicit any inﬂammatory response; however, when a tumor angiogenic factor was incorporated within the polymer matrix, it resulted in a sig- niﬁcant vascularization response, further proving the innocence of the polymer by itself (38,39). When tested in rats, polyanhydrides based on ricinoleic acid did not show any signs of tissue necrosis 21 days postimplantation, while only minimal Polymeric Nanoparticles for Small-Molecule Drugs 21 subacute inﬂammation and mild ﬁbrosis were noted (40). Clinical trials in humans with a polyanhydride dosage form, Gliadel r , produced no systemic or central tox- icity, thus demonstrating its biocompatibility and acceptability for human use (41). Polyorthoesters Biodegradation Although polyorthoesters are hydrophobic in nature, their orthoester linkage is acid sensitive and highly unstable in the presence of water. The primary mechanism by which these polymers degrade is hydrolysis, and, depending on the reactants used during the polymer synthesis, the degradation products are a diol, a triol, or a mix- ture of diols and carboxylic acid. This in situ production of acid further catalyzes the breakdown of these orthoester linkages, thus resulting in the bulk erosion of the matrix. The rate of this acid-catalyzed hydrolysis of the pH-sensitive linkage can be controlled by incorporating either acidic or basic salts into the polymer matrix (42). This was demonstrated in experiments with 5-ﬂuorouracil-embedded poly- orthoester nanoparticles – when suberic acid was incorporated as an additive, the acidic excipient accelerated the rate of hydrolysis and caused signiﬁcantly faster release of the drug (43). Alternatively, when the interior of the matrix is buffered with basic salts, the generated acid is neutralized and hydrolysis can be retarded. In this way, they stabilize the bulk of the matrix but allow the drug to escape from the surface region, thus converting the system into a surface-eroding polymer type. For example, the release of tetracycline from a polyorthoester matrix was found to be extremely rapid; however, the addition of 0. Certain poly- orthoesters containing glycolide sequences exist that undergo hydrolytic degrada- tion by autocatalysis without the use of any excipients (45). The control over the erosion rate can also be extended by altering the amount of catalyst, phthalic anhy- dride, present in the polymer (46). The var- ious parameters that can be externally controlled to yield nanoparticles of desired physicochemical characteristics, drug entrapment efﬁciency, and drug release rate properties include the nature and solubility of the drug to be encapsulated, polymer type and concentration, its molecular weight, composition of the copolymers, drug- loading concentrations, type and volume of the organic solvent, the water phase volume, pH, temperature, concentration, types of surfactants, and the mechanical speed of agitation. In vitro and in vivo responses from the nanoparticles are inﬂu- enced by their various properties, such as the particle size and size distribution, sur- face morphology, porosity, surface chemistry, surface adhesion, zeta-potential, drug 22 D’Mello et al. Conventionally, nanoparticles can be prepared either by dispersion of the preformed polymers or by the in situ polymerization of the monomers. Laboratory-Scale Production of Nanoparticles Phase Separation in Aqueous System The use of coacervation technique to develop polyester microspheres was ﬁrst reported by Fong in 1979 (48) and modiﬁcations of the same are used today for the production of nanoparticles. This technique depends on the precipitation of the drug-entrapping polymer either by the addition of a third compound to the poly- mer solution or by some other physical means. The point has to be reached where two liquid phases are formed, the polymer-rich coacervate and the supernatant liquid phase, which is depleted in the polymer. Brieﬂy, two steps are involved in the process: (i) the formation of liquid droplets of the polymer from the complete solution phase, which depends on the solubility parameters of the polymer, and (ii) subsequent hardening of the polymer droplets due to extraction or evaporation of the polymer solvent. A number of organic solvents, such as dichloromethane, isopropanol, and heptanes, have been used as solvent, coacervating agent, and hardening agent. If a drug is initially dispersed in the polymer solution, it can be coated by the coacervate.
Patents should be warned to report immediately any signs or symptoms of bone marrow suppression; for example unexplained bruising or bleeding; purpura; infecton; sore throat proven 20 mg levitra professional. Adverse Efects Hypersensitvity reactons requiring immediate and permanent withdrawal include malaise; dizziness; vomitng; diarrhoea; fever; rigors; myalgia; arthralgia; rash; hypotension and intersttal nephrits; dose-related bone marrow suppression; liver impairment; cholestatc jaundice; hair loss and increased suceptbility to infectons and colits in patents also receiving cortcosteroids; nausea; rarely generic 20 mg levitra professional with visa, pancreatts and pneumonits buy levitra professional 20mg with mastercard. Dose Oral Acute rheumatoid arthrits including juvenile idiopathic arthrits: 150 mg/day (max 20mg levitra professional otc. Lefunomide* Pregnancy Category-X Schedule H Indicatons Actve rheumatoid arthrits, psoriatc arthrits. Dose Oral Actve rheumatoid arthrits: Adults- 100 mg once daily as loading dose for 3 days. Precautons Liver disease, kidney disease, heart disease, women of child bearing age, monitor blood counts and blood pressure regularly. Adverse Efects Diarrhoea occurs in approximately 25% of patents, other adverse efect associated are mild alopecia, weight gain, increased blood pressure. Intramuscular, subcutaneous or intravenous route in severe atack under expert medical supervision at a dose of 7. Contraindicatons Lactaton (Appendix 7b); pregnancy (Appendix 7c); immunodefciency syndromes; signifcant pleural efusion or ascites. Patents should be warned to report immedi- ately any signs or symptoms of bone marrow suppression; for example unexplained bruising or bleeding; purpura; infecton; sore throat. Adverse Efects Blood disorders (bone marrow suppression); liver damage; pulmonary toxicity; gastrointestnal disturbances-if stomatts and diarrhoea occur; stop treatment; renal failure; skin reactons; alopecia; osteoporosis; arthralgia; myalgia; ocular irritaton; precipitaton of diabetes. Dose Oral Adult- Severe actve rheumatoid arthrits: initally 125 to 250 mg daily for one month, increased by increments of similar amount at intervals of not less than 4 weeks to usual maintenance dose of 500 to 750 mg daily in divided doses (max 1. If remission sustained for 6 months, reduce daily dose (125 to 150 mg every 12week may be atempted). Elderly- Severe actve rheumatoid arthrits: initally usual 125 mg daily for 1 month. Increase by increments of similar amount at intervals of not less than 4 weeks (max. Child- Severe actve rheumatoid arthrits: maintenance dose of 15 to 20 mg/kg daily, inital amount at intervals of 4 weeks over a period of 3 to 6 months. Precautons Monitor throughout treatment including blood counts and urine tests; renal impairment; avoid concurrent gold; chloroquine or immunosuppressive treatment; avoid oral iron within 2 h of a dose. Patents should be warned to report immediately any signs or symptoms of bone marrow suppression; for example unexplained bruising or bleeding; purpura; infecton; sore throat. Adverse Efects Initally nausea (less of a problem if taken before food or on retring; and if inital dose is only gradually increased); anorexia; fever; taste loss (mineral supplements not recommended); blood disorders including thrombocytopenia; neutropenia; agranulocytosis and aplastc anaemia; proteinuria; rarely, haematuria (withdraw immediately); haemolytc anaemia; nephrotc syndrome; lupus erythematosus- like syndrome; myasthenia-like syndrome; polymyosits (rarely, with cardiac involvement); dermatomyosits; mouth ulcers; stomatts; alopecia; bronchiolits and pneumonits; pemphigus; glomerulonephrits (Goodpasture syndrome) and erythema multforme (Stevens-Johnson syndrome); male and female breast enlargement; rash (early rash disappears on withdrawing treatment-reintroduce at lower dose and increase gradually; late rash is more resistant- either reduce dose or withdraw treatment). Dose Oral Acute rheumatoid arthrits: Adult- initally 500 mg daily increase by 500 mg at interval of one week (max. Contraindicatons Hypersensitvity to salicylates and sulfonamides; severe renal impairment; child under 2 years; porphyria. Patents should be warned to report immediately any signs or symptoms of bone marrow suppression; for example unexplained bruising or bleeding; purpura; infecton; sore throat. Adverse Efects Nausea; diarrhoea; headache; loss of appe- tte; fever; blood disorders (including Heinz body anaemia; megaloblastc anaemia; leu- kopenia; neutropenia; thrombocytopenia); hypersensitvity reactons (including rash; urt- caria; erythema multforme (Stevens-Johnson syndrome); exfoliatve dermatts; epidermal necrolysis; pruritus; photosensitzaton; ana- phylaxis; serum sickness; intersttal nephrits; lupus erythematosus-like syndrome); lung complicatons (including eosinophilia; fbros- ing alveolits); ocular complicatons (includ- ing periorbital oedema); stomatts; parotts; ataxia; aseptc meningits; vertgo; tnnitus; alopecia; peripheral neuropathy; insomnia; depression; hallucinatons; kidney reactons (including proteinuria; crystalluria; haematu- ria); oligospermia; rarely, acute pancreatts; hepatts; urine may be coloured orange. Salicylates, including acetylsalicylic acid are also not suitable because they may increase plasma-urate concentra- tons. It does not induce fuid retenton and can there- fore be given to patents with heart failure; it can also be given to patents receiving antcoagulants. Chronic Gout: For long-term control of gout in patents who have frequent atacks, the xanthine oxidase inhibitor allopurinol may be used to reduce producton of uric acid. It should not be used to treat an acute atack since it may prolong it indefnitely. Treatment for chronic gout should not be started untl afer an acute atack has completely subsided, usually 2-3 weeks. If an acute atack develops during treatment for chronic gout, then allopurinol should contnue at the same dosage and the acute atack should be treated in its own right. Treatment for chronic gout must be contnued indefnitely to prevent further atacks of gout. Dose Oral Adult- Initally 100 mg daily afer food, thereafer adjust according to uric acid concentraton. Contraindicatons Acute gout; if an acute atack occurs while receiving allopurinol; contnue prophylaxis and treat atack separately. Precautons Ensure adequate fuid intake of 2-3 litres daily; lactaton (Appendix 7b); renal and hepatc impairment (Appendices 7d and 7a); withdraw treatment if rash occurs; reintroduce if rash is mild but discontnue immediately if it recurs; interactons (Appendix 6c, 6d); pregnancy (Appendix 7c). Adverse Efects Rash (see precautons above); hypersensitvity reactons occur rarely, and include fever; lymphadenopathy; arthralgia; eosinophilia; erythema multforme (Stevens-Johnson syndrome) or toxic epidermal necrolysis; vasculits; hepatts; renal impairment. Colchicine* Pregnancy Category-C Schedule H Indicatons Acute gout; short-term prophylaxis during inital therapy with allopurinol. The drug must be stopped promptly at the frst sign of loose stools and symptomatc treatment must be given for diarrhoea. Precautons Elderly; gastrointestnal disease; cardiac impairment; hepatc impairment; renal impairment; lactaton (Appendix 7b). Adverse Efects Nausea; vomitng; abdominal pain; excessive doses may cause severe diarrhoea; gastrointestnal haemorrhage; rash; renal and hepatc damage; rarely, peripheral neurits; myopathy; alopecia; inhibiton of spermatogenesis with prolonged treatment; blood disorders. Diuretcs Diuretcs increase urinary excreton of water and electrolytes and are used to relieve oedema associated with heart failure, nephrotc syndrome or hepatc cirrhosis. Osmotc diuretcs are mainly used to treat cerebral oedema, and also to lower raised intraocular pressure. Most diuretcs increase urine volume by inhibitng the reab- sorpton of Sodium and chloride ions in the renal tubule; they also modify renal handling of potassium, calcium, magnesium and urate. Osmotc diuretcs act diferently; they cause an increase in urine volume by an osmotc efect. Although loop diuretcs are the most potent their duraton of acton is relatvely short, whilst thiazide diuretcs are moder- ately potent but produce diuresis for a longer period. Carbonic anhydrase inhibitors are weak diuretcs which are rarely, used for their diuretc efect and are principally used to lower intraocular pressure in glaucoma. Electrolyte Imbalance: The adverse efects of diuretc therapy are mainly due to the fuid and electrolyte imbalance induced by the drugs. The risk of hypoka- laemia, which may occur with both thiazide and loop diuretcs, depends more on the duraton of acton than on potency and is thus greater with thiazides than with loop diuretcs (when given in equipotent doses). Other electrolyte disturbances include hypercalcaemia (thiazides), hypocalcaemia (loop diuretcs) and hypomagnesaemia (thiazide and loop diuretcs). Symptoms of fuid and electrolyte imbalance include dry mouth, thirst, gastrointestnal disturbances (including nausea, vomitng), weakness, lethargy, drowsiness, restlessness, seizures, confusion, headache, muscle pains or cramps, hypo- tension (including postural hypotension), oliguria, arrhyth- mias. Elderly: The elderly are more susceptble to electrolyte imbalance than younger patents. Treatment should begin with a lower inital dose of the diuretc (commonly about 50% of the adult dose) and then adjusted carefully according to renal functon, plasma electrolytes and diuretc response. They produce diuresis within 1-2 h of oral administraton and most have a duraton of acton of 12-24 h. Thiazide diuretcs are used in the management of oedema associated with mild to moderate congestve heart failure, renal dysfuncton or hepatc disease; however, thiazides are not efectve in patents with poor renal functon (creatnine clear- ance of less than 30 ml per min). In hypertension, a thiazide diuretc is used at a low dose to lower blood pressure with very litle biochemical disturbance; the max. Higher doses should not be used because they do not neces- sarily increase the hypotensive response but may cause marked changes in plasma potassium, magnesium, uric acid, glucose and lipids. If a thiazide alone does not lower blood pressure adequately, it may be used in combinaton with another ant- hypertensive such as a beta-adrenoceptor antagonist. Urinary excreton of calcium is reduced by thiazide diuretcs and this property is occasionally utlized in the treatment of idiopathic hypercalciuria in patents with calcium-containing calculi. Paradoxically, thiazide diuretcs are used in the treat- ment of diabetes insipidus, since in this disease they reduce urine volume. Thiazide diuretcs, especially in high doses, produce a marked increase in potassium excreton which may cause hypoka- laemia; this is dangerous in patents with severe coronary artery disease and those being treated with cardiac glyco- sides. In hepatc failure hypokalaemia can precipitate enceph- alopathy, partcularly in alcoholic cirrhosis. Potassium-sparing diuretcs are used as a more efectve alternatve to potas- sium supplements for preventon of hypokalaemia induced by thiazide diuretcs; however supplementaton with potas- sium in any form is seldom necessary with the smaller doses of diuretcs used to treat hypertension. Loop Diuretcs: Loop diuretcs, or high-ceiling diuretcs, such as furosemide, are the most potent and rapidly produce an intense dose-de- pendent diuresis of relatvely short duraton.
Fluid accumulation distends the bowel and promotes peristalsis levitra professional 20mg lowest price, resulting in a bowel movement discount 20mg levitra professional visa. Adverse reactions to hyperosmolar laxatives Adverse reactions to most hyperosmolar laxatives involve fluid and electrolyte imbalances purchase 20mg levitra professional with amex. Glycerin • Hypovolemia • Hyperphosphatemia • Weakness • Increased blood glucose • Hypocalcemia • Fatigue level • Cardiac arrhythmias • Shock Lactulose Saline compounds • Abdominal distention and • Weakness Polyethylene glycol cramps order levitra professional 20 mg without a prescription, gas • Lethargy • Nausea • Nausea and vomiting • Dehydration • Explosive diarrhea • Diarrhea • Hypernatremia • Bloating • Hypokalemia • Hypermagnesemia Drug interactions A diet high in Hyperosmolar laxatives don’t interact significantly with other fiber is the best drugs. Bulking up Bulk-forming laxatives, which resemble dietary fiber, contain natural and semisynthetic polysaccharides and cellulose. These laxatives include: • methylcellulose • polycarbophil • psyllium hydrophilic mucilloid. Pharmacokinetics Dietary fiber and bulk-forming laxatives aren’t absorbed systemi- cally. The polysaccharides in these drugs are converted by intesti- nal bacterial flora into osmotically active metabolites that draw water into the intestine. Pharmacodynamics Dietary fiber and bulk-forming laxatives increase stool mass and water content, promoting peristalsis. Drug interactions Decreased absorption of digoxin, warfarin, and salicylates occurs Warning! This detergent action allows water and fats to stool that can’t be re- penetrate stool, making it softer and easier to eliminate. Pharmacokinetics Stimulant laxatives are minimally absorbed and are metabolized in the liver. Pharmacodynamics Stimulant laxatives promote peristalsis and produce a bowel movement by irritating the intestinal mucosa or stimulating nerve endings of the intestinal smooth muscle. Adverse They’re also used to treat constipation caused by prolonged reactions to bed rest, neurologic dysfunction of the colon, and constipating stimulant drugs such as opioids. However, because these laxatives produce increased intesti- clude: nal motility, they reduce the absorption of other oral drugs admin- • weakness istered at the same time, especially sustained-release forms. Pharmacokinetics In its nonemulsified form, mineral oil is minimally absorbed; the emulsified form is about half absorbed. Absorbed mineral oil is distributed to the mesenteric lymph nodes, intestinal mucosa, liv- er, and spleen. Metabolism and excretion Mineral oil is metabolized by the liver and excreted in stool. Pharmacodynamics Mineral oil lubricates stool and the intestinal mucosa and prevents water reabsorption from the bowel lumen. Adverse reactions to mineral oil Adverse reactions to mineral oil include: • nausea and vomiting • diarrhea • abdominal cramping. Mineral oil can impair the Impacting impaction absorption of some oral Administered orally or by enema, this lubricant laxative is also drugs. To minimize drug interactions, adminis- ter mineral oil at least 2 hours before these medications. Top of the charts Ondansetron is currently the antiemetic of choice in the United States. Pharmacodynamics Some antiemetics block the vomiting The action of antiemetics may vary. The mechanism of action that produces the antiemetic effect of antihistamines is unclear. Phenothiazines produce their antiemetic effect by blocking the dopaminergic receptors in the chemoreceptor trigger zone in the brain. Lend me your ear Antihistamines are specifically used for nausea and vomiting caused by inner ear stimulation. Scopolamine prevents motion sickness, but its use is limited because of its sedative and anti- Dronabinol cholinergic effects. It has also been used to motility disorders including gastroparesis in di- stimulate appetite in the patient with acquired abetic patients. However, its use is limit- tive when given before activities that produce motion sickness and are much less effective when nausea or vomiting has already begun. They’re used when vomiting becomes severe and potentially haz- ardous, such as postsurgical or viral nausea and vomiting. Both types of drugs are also prescribed to control the nausea and vom- iting resulting from chemotherapy and radiotherapy. Adverse reactions to antiemetics Use of these antiemetic drugs may lead to ad- • The anticholinergic effect of antiemetics may verse reactions: cause constipation, dry mouth and throat, • Antihistamine and phenothiazine antiemetics painful or difficult urination, urine retention, im- produce drowsiness and sometimes paradoxi- potence, and visual and auditory disturbances. Ipecac syrup is used to induce vomiting in early management of oral poinsoning or drug overdose. The use of ipecac syrup has become controversial, however, be- cause it delays the use of activated charcoal. The American Academy of Pediatrics no longer recommends the routine use of ipecac syrup. The first action parents or caregivers should take if a child has ingested a poisonous substance is to call the poison control center and emergency medical services. Pharmacokinetics Little information exists concerning the absorption, distribution, and excretion of ipecac syrup. Adverse Pharmacodynamics reactions to Ipecac syrup induces vomiting by stimulating the vomiting center located in the brain’s medulla. It shouldn’t be used after ingestion of petroleum prod- ever, prolonged vomiting ucts, volatile oils, or caustic substances, such as lye, because of (for more than 1 hour) or the risk of additional esophageal injury or aspiration. If poisoning results from ingestion of a phe- Some people are very nothiazine, the phenothiazine’s antiemetic effect may decrease the sensitive to ipecac emetic effect of ipecac syrup. The antiemetic drug that would probably be best for a patient who experiences motion sickness on an airplane is: A. An antihistamine, such as dimenhydrinate, is the most effective antiemetic for a patient who experiences motion sickness during air travel. To prevent a postsurgical patient from straining during a bowel movement, the practitioner is most likely to prescribe: A. Docusate is commonly prescribed to prevent strain- ing during a bowel movement after surgery. Multitalented The kidneys perform several vital tasks, including: • disposing of wastes and excess ions in the form of urine • filtering blood, which regulates its volume and chemical make- up • helping to maintain fluid, electrolyte, and acid-base balances • producing several hormones and enzymes • converting vitamin D to a more active form • helping to regulate blood pressure and volume by secreting renin. Thiazide and thiazide-like diuretics Derived from sulfonamides, thiazide and thiazide-like diuretics are used to treat edema and to prevent the development and recur- rence of renal calculi. They’re also used for such cardiovascular diseases as hypertension and heart failure. Thiazide diuretics include: • bendroflumethiazide • chlorothiazide • hydrochlorothiazide • hydroflumethiazide • methyclothiazide • polythiazide. These drugs differ in how well they’re me- tabolized, but all are excreted primarily in urine. Chlor- thalidone is 90% bound to erythrocytes; little is known about its metabolism. Pharmacodynamics (how drugs act) Thiazide and thiazide-like diuretics promote the excretion of wa- ter by preventing the reabsorption of sodium in the kidneys. These drugs also increase the excretion of chloride, potas- sium, and bicarbonate, which can result in electrolyte imbalances. With long-term use, thiazide diuretics also lower blood pressure by causing arteriolar vasodilation. However, if therapy is maintained, car- diac output stabilizes but plasma fluid volume decreases. Adverse Pharmacotherapeutics (how drugs are used) reactions to Thiazides are used for the long-term treatment of hypertension; thiazide and they’re also used to treat edema caused by kidney or liver disease, thiazide-like mild or moderate heart failure, and corticosteroid and estrogen diuretics therapy. Because these drugs decrease the level of calcium in urine, they may be used alone or with other drugs to prevent the The most common ad- development and recurrence of renal calculi. Drug interactions Drug interactions related to thiazide and thiazide-like diuretics re- sult in altered fluid volume, blood pressure, and serum electrolyte Administering levels: thiazide diuretics • These drugs may decrease excretion of lithium, causing lithium along with toxicity. They under- go partial or complete metabolism in the liver, except for furo- semide, which is excreted primarily unchanged.