By A. Faesul. Presbyterian College. 2018.

Other ophthalmic emulsions have been used to formulate prednisolone discount 75 mg elavil mastercard, piroxicam and amphotericin B emulsion buy cheap elavil 75mg. Although emulsions can produce sustained therapeutic effects and reduced irritancy of drug buy discount elavil 50mg on-line, their application in ophthalmology have been limited due to problems of stability. Soft contact lenses and ocular inserts The rationale for corneal contact devices has not been fully explored in therapy. In conventional dosing, there is a gradient across the eye caused by lacrimal flow, opposing drag of material above the equatorial axis by the upper lid as illustrated in Figure 12. Thus it is difficult to sustain high drug concentrations in the upper hemisphere unless the eye is bathed or the patient is supine. A corneal device such as a collagen shield or contact lens overcomes this problem by providing a slowly equilibrating reservoir. It is generally accepted that soft contact lenses can act as a reservoir for drugs, providing improved release of the therapeutic agent. The therapeutic value of contact lenses was first demonstrated in a study which showed a significant increase in aqueous humor levels produced by drug-soaked lenses when compared with the conventional eyedrop. The use of Bionite contact lenses for delivery of idoxuridine, polymyxin B and Pilocarpine also showed that instillation of a drug solution onto an unmedicated contact lens was significantly more effective than instillation of a more concentrated drug solution directly to the cornea. However, the soaking of lenses in ophthalmic formulations to incorporate the drug into the lens may cause toxicity to corneal epithelium because preservatives, such as benzalkonium chloride, have a great affinity for the hydrophilic contact lens material and are concentrated in the contact lens. Contact lens for sensitive wearers may also cause foreign-body sensation, blurring and decreased oxygen tension on the corneal surface resulting from occlusion by contact lens. An alternative system, manufactured as a wafer-like insoluble implant, has been developed (Ocusert). The system is preprogrammed to release pilocarpine at a constant rate of 20 or 40 μg/hr for a week to treat chronic glaucoma; however, release from inserts may be incomplete and approximately 20% of all patients treated with the Ocusert lose the device without being aware of the loss. The device also presents problems including foreign-body sensation, expulsion from the eye, and difficulty in handling and insertion. An alternative to the advanced non-erodible systems is an erodible insert for placement in the cul-de-sac. The bioavailability of pilocarpine was shown to be increased sixteen-fold using this system. The system showed considerable promise for prolonged drug delivery since vision is minimally affected by the presence of an insert positioned on the sclera. When the device is placed in the lower fornix, the contact area for the released drug is the sclera and little material is in contact with the cornea. Furthermore, topical application of drugs for the treatment of posterior segment disorders is severely limited by the highly efficient clearance mechanisms and attempts to improve precorneal residence time of the drugs by addition of viscosity enhancing agents, gelling agents, mucoadhesive polymers etc. Moreover, most diseases affecting the posterior segment are chronic in nature and require prolonged drug administration. An intravitreal injection provides therapeutic concentrations of the drug adjacent to the intended site of activity and a much smaller dose is required. Following injection, the drug diffuses through the vitreous gel with little restriction to diffusion. For most drugs the diffusion coefficient through the vitreous humor is close to that through water. Once distributed throughout the vitreous humor, rapid elimination of the drug is observed. Drug loss from the vitreous takes place via two routes: • anteriorly—by simple diffusion to the posterior chamber and followed by removal to the systemic circulation along with the aqueous humor drainage; • posteriorly—across the retina where it is removed by active secretion. Drugs lost primarily by anterior chamber diffusion have a long half-life in the vitreous, usually in the order of 20–30 hours. In contrast, drugs lost via the trans-retinal route, such as the penicillins, have typically 314 much shorter half-lives of 5–10 hours. Ocular inflammation results in the breakdown of blood retinal barrier and increases the elimination of non-transported drugs from the vitreous. In contrast to the elimination of non-transported drugs, drugs that are removed by the active transport systems reside longer in the vitreous following ocular inflammation due to the failure in the transport system. As the majority of the posterior segment disorders are chronic in nature, sustained delivery of medications is highly desirable. Liposomes and microparticulates are such systems designed to release the encapsulated drug gradually and over an extended period of time. For reviews on intra-ocular drug delivery systems see Gregoriadis and Florence (1993), Metrikin and Anand (1994), and Peyman and Ganiban (1995) detailed at the end of this chapter. For example, liposome-encapsulated amphotericin B produced less toxicity than the commercial amphotericin B solution when injected intravitreally. Liposomes have also been used to study the release and distribution of dyes, which in turn reflect the integrity of the retinal vascular constitution. Direct intravitreal injection of liposomal-encapsulated drugs has shown enhanced vitreal levels for extended periods of time in the vitreous of rabbit models. Biodistribution of dexamethasone sodium phosphate has been evaluated following intraocular delivery in rabbits.

Because of their ability to reduce blood pressure generic 75mg elavil amex, beta-adren- ergic blockers are also first-line therapy for treating hypertension order elavil 10mg on-line. Adverse reactions to beta- adrenergic blockers Beta-adrenergic blockers may • nausea and vomiting cause: • diarrhea • bradycardia • significant constriction of the • angina bronchioles buy generic elavil 25mg. As mentioned earlier, several of the calcium channel blockers are also used as antiarrhythmics and to treat hypertension. Calcium channel blockers used to treat angina include: • amlodipine • diltiazem • nicardipine • nifedipine • verapamil. How calcium channel blockers work Calcium channel blockers in- crease the myocardial oxygen Calcium ion supply and slow the heart rate. Apparently, the drugs produce these effects by blocking the slow calcium Some calcium channel. This action inhibits channel blockers Calcium channel the influx of extracellular cal- blocker slow the heart rate but don’t cium ions across both myo- change the level cardial and vascular smooth of calcium in the muscle cell membranes. Cell membrane Cell membrane No calcium = dilation This calcium blockade causes the coronary arteries (and, to a lesser extent, the peripheral arteries and arterioles) to di- late, decreasing afterload and Slow calcium increasing myocardial oxygen channel supply. Pharmacokinetics When administered orally, calcium channel blockers are absorbed quickly and almost completely. Because of the first-pass effect, however, the bioavailability of these drugs is much lower. Gone without a trace All calcium channel blockers are metabolized rapidly and almost completely in the liver. This causes dilation of the coronary and peripheral arteries, which decreases the force of the heart’s contractions and reduces Warning! The relaxation response Adverse Also, by preventing arterioles from constricting, calcium channel blockers reduce afterload. Decreasing afterload further decreases reactions to the oxygen demands of the heart. A slower heart rate reduces the heart’s need for additional lar reactions are the oxygen. Calcium channel thostatic hypotension (a blockers are particularly effective for preventing Prinzmetal’s drop in blood pressure angina. Diltiazem Drug interactions and verapamil can • Calcium salts and vitamin D reduce the effectiveness of calcium cause such arrhythmias channel blockers. Know the program Treatment for hypertension typically begins with a thiazide diuret- ic or a calcium channel blocker. Sympatholytic drugs Sympatholytic drugs include several different types of drugs, but all reduce blood pressure by inhibiting or blocking the sympathet- ic nervous system. They’re classified by their site or mechanism of action and include: • central-acting sympathetic nervous system inhibitors (clonidine and methyldopa) • alpha-adrenergic blockers (doxazosin, phentolamine, prazosin, and terazosin) • mixed alpha- and beta-adrenergic blockers (carvedilol and la- betalol) • norepinephrine depletors (guanadrel, guanethidine, and reser- pine—these are rarely used). Pharmacodynamics All sympatholytic drugs inhibit stimulation of the sympathetic ner- vous system, causing dilation of the peripheral blood vessels or decreased cardiac output, thereby reducing blood pressure. Pharmacotherapeutics If blood pressure fails to come under control with beta-adrenergic blockers and diuretics, an alpha-adrenergic blocker, such as pra- zosin, or a mixed alpha- and beta-adrenergic blocker, such as la- betalol, may be used. If the patient fails to achieve the desired blood pressure, the physician may add a drug from a different class, substitute a drug in the same class, or increase the drug dosage. Adverse reactions to sympatholytics Alpha-adrenergic blockers Guanadrel Reserpine • Hypotension • Difficulty breathing • Abdominal cramps, diarrhea • Excessive urination • Angina Central-acting drugs • Fainting • Blurred vision • Depression • Orthostatic hypotension • Bradycardia • Drowsiness • Bronchoconstriction • Edema Guanethidine • Decreased libido • Liver dysfunction • Decreased heart contrac- • Depression • Numbness, tingling tility • Drowsiness • Vertigo • Diarrhea • Weight gain • Fluid retention • Fatigue • Orthostatic hypotension • Hypotension Drug interactions Sympatholytic drugs can create these drug interactions: • Carvedilol taken with antidiabetics may result in increased hy- poglycemic effect. As blood pres- sure falls, the sympa- Pharmacokinetics thetic nervous system is Most of these drugs are absorbed rapidly and well-distributed. Other reactions to The direct vasodilators relax peripheral vascular smooth muscle, sympathetic stimulation causing the blood vessels to dilate. The increased diameter of the blood vessels reduces total peripheral resistance, which lowers include: blood pressure. Drug interactions • The antihypertensive effects of hydralazine and minoxidil are increased when they’re given with other antihypertensive drugs, such as methyldopa or reserpine. Normally, the kidneys maintain And that’s the way, blood pressure by releasing the hormone renin. Renin acts on the uh-huh, uh-huh plasma protein angiotensinogen to form angiotensin I. Aldosterone, in turn, pro- motes the retention of sodium and water, increasing the volume of blood the heart needs to pump. Captopril is also indicated for the long-term treatment of diabetic • transient elevations of neuropathy. They can also increase serum lithium protein in the urine, re- levels, possibly resulting in lithium toxicity. Also, antacids may impair the absorption of fos- inopril, and quinapril may reduce the absorption of tetracycline.