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By N. Iomar. Athena University.

Contraindicatons Hypersensitvity; prolactnoma purchase 40mg betapace visa, hepatc impairment; where increased gastro- intestnal motlity harmful; pregnancy; gastro intestnal haemorrhage; intestnal obstructon purchase betapace 40mg on-line. Precautons Children; renal impairment, interactons (Appendix 6c); history of breast cancer; allergies; pheochromocytoma; i. Adverse Efects Rarely, gastro-intestnal disturbances (including cramps) and hyperprolactnaemia; very rarely, extrapyramidal efects and rashes; headache; dizziness; dry mouth; nervousness; fushing. Dose Oral or intramuscular injecton or Slow intravenous injecton Adult- Nausea and vomitng, gastro- esophageal refux, gastroparesis: (over 1 to 2 min for slow intravenous injecton), 10 mg 3 tmes daily. Aid to gastrointestnal intubaton: 20 mg as a single dose 5 to 10 min before examinaton; Adolescent (15 to 19 years), 10 mg. Child- Up to 1 year (up to 10 kg) 1 mg twice daily; 1 to 3years (10 to 14 kg) 1 mg 2 to 3 tmes daily; 3 to 5 years (15 to 19 kg) 2 mg 2 to3 tmes daily; 5 to 9 years (20 to 29 kg) 2. Contraindicatons Gastrointestnal obstructon, haemorrhage or perforaton, 3-4 days afer gastrointestnal surgery; convulsive disorders; pheochromo- cytoma; hypersensitvity. Precautons Elderly, children and young adults; hepatc impairment (Appendix 7a); renal impairment (Appendix 7d); pregnancy (Appendix 7c); may mask underlying disorders such as cerebral irritaton; avoid for 3-4 days afer gastrointestnal surgery; lactaton (Appendix 7b); interactons (Appendix 6a); Parkinson’s disease; epilepsy; depression; porphyria; driving or operatng machines; hypertension; cirrhosis; congestve heart failure. Dose Oral Preventon of post-operatve nausea and vomitng: Adult 16 mg, 1 h before inducton of anaesthesia. Nausea and vomitng associated withcancer chemotherapy: Adult- 24 mg as a single dose taken 30 min before start of single day chemotherapy. Child (4-11 yrs)- 4 mg tablets 3 tmes a day; contnue for 1-2 days afer completon of chemotherapy. Adverse Efects Headache, constpaton or diarrhoea, dizziness; fushing, hypersensitvity reacton, anaphylaxis/anaphylactoid reactons, angioedema; bronchospasm, hypotension, laryngeal edema, urtcaria, hiccups, oculagyric crisis. Dose Oral and intravenous injecton Adult- Nausea, vomitng acute atack: initally 20 mg then 20 mg every 2 h. Adult- Labyrinthine disorder: 5 mg 3 tmes daily increased to 30 mg daily in divided doses that decrease afer meal to 5 to 10 mg daily. Most antpsychotcs are best avoided during pregnancy; hypersensitvity; prolactn dependant tumors. Cauton is also required in severe respiratory disease and in patents with a history of jaundice or who have blood dyscrasias (perform blood counts if unexplained infecton or fever develops). Cauton should be taken in elderly, who are partcularly susceptble to postural hypotension and to hyper- or hypothermia in very hot or cold weather. Serious consideraton should be given before prescribing these drugs for elderly patents. As photosensitsaton may occur with higher dosages, patents should avoid direct sunlight; extrapyramidal syndrome; pregnancy (Appendix 7c); interactons (Appendix 6a). Adverse Efects Less sedatng; extrapyramidal symptoms, partcularly dystonias, more frequent; respiratory depression may occur in suscep- tble patents; amenorrhoea; blurred vision; cholestatc jaundice; neuroleptc malignant syndrome; leucopenia; agranulocytosis. Moton sickness, preventon: 20 to 25 mg at bedtme on night before travel, repeated on day of travel if necessary. Child- Moton sickness, preventon; 2 to 5 years: 5 mg at night and on day of travel, if necessary. Precautons Prostatc hypertrophy; urinary retenton; glaucoma; hepatc disease (Appendix 7a); epilepsy; elderly and children (more susceptble to adverse efects); lactaton (Appendix 7b); pregnancy (Appendix 7c); interactons (Appendix 6a). May impair ability to perform skilled tasks, for example operatng machinery, driving. Adverse Efects Drowsiness, dizziness, sedaton (but para- doxical stmulaton may occur, especially with high doses or in children and eld- erly); headache, psychomotor impairment; urinary retenton, dry mouth, blurred vision, gastrointestnal disturbances; hypersensitv- ity reactons, rashes, photosensitvity reac- tons; jaundice; blood disorders; cardiovas- cular adverse efects-afer injecton; venous thrombosis at site of intravenous injecton; pain on intramuscular injecton; somnolence; tortcollis; tnnitus; leucopenia; thrombocy- topenia, agranulcytosis; apnoea; angioneu- rotc edema. It is transmited by the faeco-oral route and infecton is usually caused by ingeston of cysts from contaminated food and drink.

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As the concentration of drug in the poorly perfused tissues increases discount betapace 40mg with amex, there is a corresponding decrease in the concentration in the plasma and well-perfused tissues buy betapace 40 mg otc. Many drugs show an affinity for specific binding sites on plasma proteins such as albumin and α1-acid glycoprotein, which results in a reversible association, with some important consequences in therapeutics: • Drug binding lowers the concentration of free drug in solution, and thus the concentration of drug available to act at the receptor. This can result in the need to use high doses to compensate for drug wasteage, which is expensive. Unwanted deposition may also result in toxicity problems, arising from drug action at non-target sites. Classic examples of toxic side-effects resulting from unwanted drug distribution are found in cancer chemotherapy. The chemotherapeutic agent, a cytotoxic poison, lacks specificity and has the potential to kill all cells, both normal and malignant. The drug exploits the difference in the turnover of cancer cells, which is very much greater than normal cells. However, rapidly dividing normal cells, for example the hair follicles, and the cells of the gastrointestinal tract, are also susceptible to attack. This gives rise to typical side-effects associated with cancer chemotherapy such as hair loss and acute gastrointestinal disturbances. In the early 1900s Paul Ehrlich (who has been described as the father of drug delivery and therapeutics) pioneered the idea of the “magic bullet” approach, whereby therapy “could learn to aim”. The inherent premise of this concept is to try to improve therapy by targeting the drug to the site of action, thereby removing unwanted toxic sideeffects and minimizing drug wastage. It generally involves the transformation of a lipid-soluble drug (which can cross membranes and thus reach its site of action) into a more polar, water-soluble compound which can be rapidly eliminated in the urine. Metabolic processes have considerable implications for successful drug delivery: • Metabolic activity may result in premature degradation of the active moiety, prior to its arrival at the active site. Metabolic activity may also constitute a considerable biochemical barrier to drug absorption. As described above, extensive enzymatic degradation of labile drugs in the gastrointestinal tract can severely limit their oral bioavailability. Specific tubular uptake processes exist for carbohydrates, amino acids, vitamins etc. Drugs may pass from the tubule into the plasma if they are substrates for the uptake processes, or if they are lipid soluble (this process is highly dependent on the prevailing pH, see Section 1. Depending on the drug and the disease state, the timing of therapy may be optimal as either zero-order controlled release, or variable release. Considerable advances in controlling drug release from delivery systems have been made; such systems are described in detail in Chapters 3, 4 and 16. By effective management of the dose size and the dose frequency, it is possible to achieve therapeutic steady-state levels of a drug by giving repeated doses. An example of the type of plasma profile obtained after repeated oral dosing of a drug is shown in Figure 1. However, multiple oral dosing is associated with disadvantages: • The drug concentration does not actually remain constant in the plasma, but fluctuates between maximum (peak) and minimum (trough) values (Figure 1. These fluctuations in plasma concentration may mean that drug levels may swing too high, leading to toxic side-effects; alternatively drug levels may fall too low, leading to a lack of efficacy. An alternative approach to overcome these limitations is to use a delivery system which provides zero-order controlled release of the drug (Figure 1. Zero-order controlled release offers the advantage of improved control over drug plasma levels: the peaks and troughs of conventional therapy are avoided and constant plasma levels are attained. The risk of side- effects is minimized since possible toxic peak drug plasma levels are never obtained and the total amount of drug administered is lower than with frequent repeated dosing. There is also a reduction in symptom breakthrough which can occur if plasma concentrations drop too low.

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