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Some drugs or metabolites are excreted in bile reminyl 8 mg with visa, then eliminated in Serum Half-Life feces; others are excreted in bile purchase 8mg reminyl amex, reabsorbed from the small intestine discount 4mg reminyl overnight delivery, returned to the liver (called enterohepatic recircu- Serum half-life cheap reminyl 8 mg with visa, also called elimination half-life, is the time lation), metabolized, and eventually excreted in urine. Some required for the serum concentration of a drug to decrease by oral drugs are not absorbed and are excreted in the feces. Factors im- more frequent administration than one with a long half-life. Toxic concentration Steady-state serum drug level Regularly Waning scheduled doses serum Therapeutic Figure 2–5 Serum drug levels with single Drug action Last dose drug levels concentration and multiple oral drug doses. Drug action starts when enough drug is absorbed to starts reach the minimum effective concentration Minimum effective (MEC), continues as long as the serum level Duration of drug action concentration (MEC) is above the MEC, wanes as drug molecules Drug action are metabolized and excreted (if no more stops doses are given), and stops when the serum First dose of Time (days) Drug is eliminated level drops below the MEC. The goal of drug drug enters body from the body therapy is to maintain serum drug levels in the therapeutic range. Because maximal therapeutic effects do not occur until Receptor Theory of Drug Action equilibrium is established, some drugs are not fully effective for days or weeks. To maintain steady-state conditions, the amount Like the physiologic substances (eg, hormones and neuro- of drug given must equal the amount eliminated from the body. Receptors are mainly pro- continued, it is eliminated gradually over several half-lives. Specific receptors include enzymes involved in essen- tial metabolic or regulatory processes (eg, dihydrofolate re- PHARMACODYNAMICS ductase, acetylcholinesterase); proteins involved in transport (eg, sodium–potassium adenosine triphosphatase) or struc- Pharmacodynamics involves drug actions on target cells and tural processes (eg, tubulin); and nucleic acids (eg, DNA) in- the resulting alterations in cellular biochemical reactions and volved in cellular protein synthesis, reproduction, and other functions (ie, what the drug does to the body). When drug molecules bind with receptor molecules, the resulting drug–receptor complex initiates physiochemical re- actions that stimulate or inhibit normal cellular functions. Nursing Notes: Apply Your Knowledge One type of reaction involves activation, inactivation, or other alterations of intracellular enzymes. Because almost all cellular functions are catalyzed by enzymes, drug-induced A client has a drug level of 100 units/mL. For example, an epinephrine–receptor com- more drug is given, how long will it take for the blood level to plex increases the activity of the intracellular enzyme adenyl reach the nontoxic range? The receptor is often described as a lock into which the drug molecule fits as a key, and only those drugs Cytoplasm Da able to bond chemically to the receptors in a particular H body tissue can exert pharmacologic effects on that tis- Receptor site NT sue. Thus, all body cells do not respond to all drugs, even though virtually all cell receptors are exposed to any Db drug molecules circulating in the bloodstream. Nucleus NT The number of receptor sites available to interact with drug molecules also affects the extent of drug ac- H Da tion. Presumably, a minimal number of receptors must be occupied by drug molecules to produce pharmaco- NT Db logic effects. Thus, if many receptors are available but only a few are occupied by drug molecules, few drug ef- Receptor site H fects occur. In this instance, increasing the drug dosage increases the pharmacologic effects. Conversely, if only a few receptors are available for many drug molecules, Figure 2–6 Cell membrane contains receptors for physiologic sub- receptors may be saturated. In this instance, if most re- stances such as hormones (H) and neurotransmitters (NT). Drug molecules (Da and Db) ceptor sites are occupied, increasing the drug dosage also interact with receptors to stimulate or inhibit cellular function. Because all drugs are chemical substances, chemical character- monophosphate (cAMP). Minor changes in drug structure ability of cell membranes to one or more ions. In nerve cells, for example, sodium or calcium ion and client-related variables that affect drug actions are channels may open and allow movement of ions into the cell. At other times, potassium channels may open tors, the pharmacologic effects are those due to either and allow movement of potassium ions out of the cell. Agonists are drugs that produce action inhibits neuronal excitability and function. In muscle effects similar to those produced by naturally occurring cells, movement of the ions into the cells may alter intra- hormones, neurotransmitters, and other substances. Ag- cellular functions, such as the direct effect of calcium ions in onists may accelerate or slow normal cellular processes, stimulating muscle contraction. For ex- A third reaction may modify the synthesis, release, or ample, epinephrine-like drugs act on the heart to in- inactivation of the neurohormones (eg, acetylcholine, norepi- crease the heart rate, and acetylcholine-like drugs act nephrine, serotonin) that regulate many physiologic processes.

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Radioactive for several days or weeks until the stored hormones have iodide is usually given to middle-aged and elderly people; it been used reminyl 8 mg. PTU is well absorbed with oral administration cheap reminyl 8mg amex, and peak Propranolol (Inderal) is an antiadrenergic discount reminyl 8mg on line, not an anti- plasma levels occur within 30 minutes cheap 4mg reminyl with amex. However, duration of action depends on the half-life cretion, or hormone metabolism. It is most often used to treat within the thyroid gland rather than plasma half-life. Because cardiovascular conditions, such as dysrhythmias, angina this time is relatively short, also, the drug must be given every pectoris, and hypertension. It is also well absorbed with oral thyroidism resulting from excessive stimulation of the sympa- administration and rapidly reaches peak plasma levels. During the course of treatment with thyroid weight gain, dry skin, and cold intolerance. In end of the continuum, signs and symptoms may be dra- addition, an increased intake of high-fiber foods is usually matic and obvious. As blood levels change toward normal needed to prevent constipation as a result of decreased as a result of treatment, signs and symptoms become less gastrointestinal secretion and motility. If presenting signs and symptoms are treated too appetite, hyperthyroid clients are often underweight be- aggressively, they may change toward the opposite end cause of rapid metabolism rates. They often need extra of the continuum and indicate adverse drug effects. These Thus, each client receiving a drug that alters thyroid func- can be provided by extra meals and snacks. The client tion must be assessed for indicators of hypothyroidism, may wish to avoid highly seasoned and high-fiber foods euthyroidism, and hyperthyroidism. An elevated serum TSH intake of low-calorie fluids to prevent constipation. With is the first indication of primary hypothyroidism and hyperthyroidism, clients need large amounts of fluids commonly occurs in middle-aged women, even in the (3000–4000 mL/day) unless contraindicated by cardiac absence of other signs and symptoms. The fluids are needed to eliminate heat used to monitor response to drugs that alter thyroid and waste products produced by the hypermetabolic state. With hypothyroidism, encourage activity to • Decreased Cardiac Output related to disease- or drug- maintain cardiovascular, respiratory, gastrointestinal, and induced thyroid disorders musculoskeletal function. With hyperthyroidism, encour- • Imbalanced Nutrition: Less Than Body Requirements with age rest and quiet, nonstrenuous activity. Because clients hyperthyroidism differ in what they find restful, this must be determined • Imbalanced Nutrition: More Than Body Requirements with each one. A quiet room, reading, and soft music may with hypothyroidism be helpful. The client is • Ineffective Thermoregulation related to changes in me- caught in the dilemma of needing rest because of the high tabolism rate and body heat production metabolic rate but being unable to rest because of ner- • Deficient Knowledge: Disease process and drug therapy vousness and excitement. Hypothyroid clients are likely to have edema Planning/Goals and dry skin. When edema is present, inspect pressure The client will: points, turn often, and avoid trauma when possible. Also, increased capillary fragility in- • Experience relief of symptoms of hypothyroidism or creases the likelihood of bruising from seemingly minor hyperthyroidism trauma. When skin is dry, use soap sparingly and lotions • Be assisted to cope with symptoms until therapy becomes and other lubricants freely. Hyperthyroid clients may have exophthal- • Avoid preventable adverse drug effects mos. For • Be monitored regularly for therapeutic and adverse effects example, dark glasses, local lubricants, and patching of of drug therapy the eyes at night may be needed. Diuretic drugs and el- evating the head of the bed may help reduce periorbital Interventions edema and eyeball protrusion.

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Experimentally cheap 8 mg reminyl visa, it has been shown that phosphenes could be elicited in patients with advanced outer retinal degeneration via electrical stimulation (Potts and Inoue 4 mg reminyl, 1970; Weiland et al buy discount reminyl 4mg. These electrically elicited responses require and indicate the presence of functioning retinal cells cheap reminyl 4mg. As the human RGC axons exit the eye, they become myelinated and form the optic nerve. The cell bodies (somas) of these ganglion cells are mapped over the surface of the retina in a manner that approximates the projection of the visual world onto the surface of the retina. However, at any particular location on the sur- face of the retina, axons from distant sites overlay the individual ganglion cell bodies. If these superficial passing axons were preferentially stimulated, groups of ganglion cells from large areas of the retina would be excited. One might expect the visual perception of such a stimulus to appear as a wedge. On the other hand, if the gan- glion cell bodies or deeper retinal cells were stimulated, one would expect the visual perceptions to be focal spots. RP patients that were stimulated with 50–200-mm- diameter platinum disk electrodes reported seeing spots, not wedges, of light (Humayun et al. To explore the possibilities of retinal electrical stimulation, a computational model of extracellular field stimulation of the RGC has been constructed (Greenberg et al. The model predicted that the stimulation threshold of the RGC soma is 58– 73% lower than a passing axon, even though the axon was closer to the electrode. Nevertheless, a factor of less than 2 does not explain the source of visual perceptions observed during previous experiments with intraocular patients. Postmortem morphometric analysis of the retina of RP patients revealed that many more inner nuclear layer cells retain functionality (e. Early electrophysiological experiments showed that cathodic stimulation on the vitreous side of the retina depolarizes presynaptic end terminals of the photoreceptors (Knighton, 1975a,b) and bipolar cells (Toyoda and Fujimoto, 1984). Recently, latency experiments in frog retinas showed that higher currents stimulate the RGC directly, while lower currents activate other cells (photoreceptors, bipolar cells) (Greenberg, 1998). Another finding in those experiments was that shorter stimulating pulses (<0. There are well- defined relationships between the threshold current and the duration of the stimulus pulse required for neuronal activation (West and Wolstencroft, 1983). As the dura- tion of the stimulus pulse decreases, the threshold increases exponentially. Also, as the pulse duration increases, the threshold current approaches a minimum value, called the rheobase. A chronaxie is the pulse width for which the threshold current is twice the rheobase current. Greenberg (1998) showed that deeper retinal cells have unusually long chronaxies compared with RGCs. It can be specu- lated from these results that there is a preferential stimulation of RGC cells or axons for short pulses and deeper cellular elements for long pulses. Interfacing IRP Electrodes to Retinal Tissue A number of basic physiological questions and concerns arise when interfacing an electronic device to neural tissue. In 1939, Cole and Curtis found that during propagation of the action potential in the axon of the giant squid, the conductance of the membrane to ions increases dramatically (Cole and Curtis, 1939). The amount of current that must be generated by the voltage clamp to keep the membrane potential from changing provides a direct measure of the current flowing across the membrane. Hodgkin and Huxley (1952a,b) used the voltage clamp technique and the squid axon to give the first complete description of the ionic mechanisms underlying the action potential. According to the Hodgkin- Huxley model, an action potential involves the following sequence of events. A depo- larization of the membrane causes Naþ channels to open rapidly, resulting in an inward Naþ current (because of a higher resting concentration of this ion outside the cell membrane). This current causes further depolarization, thereby opening more Naþ channels, and results in increased inward current; the regenerative process causes the action potential.

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It is often characterized by increased ulcers are usually caused by the herpesvirus order 8mg reminyl. Di- attributed to frequent use of ophthalmic antibiotics and agnostic tests for glaucoma include ophthalmoscopic exami- corticosteroids purchase 8 mg reminyl fast delivery. CHAPTER 65 DRUGS USED IN OPHTHALMIC CONDITIONS 937 TYPES OF OPHTHALMIC DRUGS aqueous humor buy 8mg reminyl amex. When sent numerous therapeutic classifications purchase 4 mg reminyl free shipping, most of which are compared with twice-daily ophthalmic timolol, the drugs discussed in other chapters. The drugs may mology include the following: be used in conjunction with other antiglaucoma medica- • Antihistamines (H1 receptor antagonists) and mast cell tions (eg, a beta blocker or carbonic anhydrase inhibitor) stabilizers are used to decrease redness and itching as- if multiple drugs are required. In clinical trials, the incidence of systemic adverse • Antimicrobials are used to treat bacterial, viral, and effects was about the same as with placebo. Bacterial common adverse effects were ocular burning, stinging, infections include conjunctivitis, keratitis, blepharitis, and itching. The drugs are usually applied topi- darkening of eye color, especially in light-colored eyes, cally but may be given orally or intravenously. Some are used dling prostaglandin analogs because they may be ab- to dilate the pupil before ophthalmologic examinations sorbed through the skin. If accidental contact occurs, the or surgical procedures; some are used to decrease intra- exposed area should be washed immediately with soap ocular pressure in glaucoma. CAIs lower IOP by vasoconstricting drugs are commonly used to decrease decreasing production of aqueous humor. Ophthalmic beta blockers usually have the same contraindications and precautions as oral Drug therapy of ophthalmic conditions is unique because of or injected drugs (eg, bradycardia, heart block, bron- the location, structure, and function of the eye. In inflammatory conditions of the eye, thereby reducing general, penetration is greater if the drug achieves a high con- scarring and preventing loss of vision. Corticosteroids are centration in the blood, is fat soluble, and is poorly bound to generally more effective in acute than chronic inflamma- serum proteins, and if inflammation is present. Because these drugs are potentially toxic, Because of the difficulties associated with systemic ther- they should not be used to treat minor disorders or dis- apy, various methods of administering drugs locally have orders that can be effectively treated with safer drugs. The most common and preferred method is When used, corticosteroids should be administered in the topical application of ophthalmic solutions (eye drops) to lowest effective dose and for the shortest effective time. Drugs are distributed through the tear film Long-term use should be avoided when possible, be- covering the eye and may be used for superficial disorders cause it may result in glaucoma, increased IOP, optic (eg, conjunctivitis) or for relatively deep ocular disorders nerve damage, defects in visual acuity and fields of (eg, glaucoma). Topical ophthalmic ointments may also be vision, cataract, or secondary ocular infections. In addition, ophthalmologists may inject medications Ophthalmologic corticosteroids may be administered (eg, antibiotics, corticosteroids, local anesthetics) into or topically, systemically, or both. Drugs at a Glance: Ophthalmic Antimicrobial Agents, and • Prostaglandin analogs are newer antiglaucoma drugs Drugs at a Glance: Topical Ophthalmic Antiallergic and that apparently reduce IOP by increasing the outflow of Anti-Inflammatory Agents. This is especially im- Nursing Process portant among middle-aged and older adults, who are more likely to have several ocular disorders. Some nurses do vision test- • Promote handwashing and keeping hands away from ing and ophthalmoscopic examinations. These include • Cleanse contact lenses or assist clients in lens care, when trauma, allergies, infection in one eye (a risk factor for in- needed. Do not wait for transport to • Pain is usually associated with corneal abrasions or in- a first aid station, hospital, or other health care facility. Sudden, severe pain may indicate acute Damage continues as long as the chemical is in contact glaucoma, which requires immediate treatment to lower with the eye. Foreign bodies embedded in ocular ness) are especially evident with infection or inflam- structures must be removed by a physician. Topical application is the most common route of ad- and disease ministration for ophthalmic drugs, and correct admin- • Experience improvement in signs and symptoms (eg, de- istration is essential for optimal therapeutic effects.

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