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Which agent listed below is an antipsychotic that can improve both positive and negative symptoms of schizophrenia Foods containing tyramine should be avoided when taken with which class of medications Acetylcholinesterase inhibitors acne inflammation buy cheap flexresan 10mg, also known as indirect-acting cholinergic agonists acne 4 week old baby flexresan 30mg low cost, increase the synaptic concentration of acetylcholine skin care advice order flexresan on line amex. This has utility in the treatment of the dementia of Alzheimer disease but does not have antidepressant activity acne causes order flexresan 5mg fast delivery. This elevates the levels of the amine neurotransmitter available for synaptic release. Answers A and C through E are agents that do not interfere with the catabolism of dietary amines. Answers B, 2adrenergic receptors (2-adrenoceptors), and C, muscarinic receptors, mediate some of the adverse effects of typical antipsychotic agents. There is no evidence for answer D, histamine receptors, in the clinical effects of typical antipsychotics, but they can be involved in sedative effects of the older, less-selective agents. Answer E, serotonin receptors, is correlated to the efficacy of the atypical agents and not the typical ones. The chapter closes with treatment consideration for various acute and chronic pain states. General characteristics of opioid analgesics are presented, followed by key features of specific agonists, 238 Pain is an unpleasant sensory and emotional experience that serves to alert an individual to actual or potential tissue damage. This damage can be caused by exposure to noxious chemical, mechanical, or thermal stimuli. Although pain serves a protective function by alerting a person to the presence of a health problem, its unbridled expression often leads to considerable morbidity and suffering. For this reason, analgesics or drugs that relieve pain are used for symptomatic treatment of pain from a wide variety of disease states, ranging from acute and chronic physical injuries to terminal cancer. Based on their mechanisms of action, analgesics can be classified as opioid analgesics or nonopioid analgesics. Opioid analgesics act primarily in the spinal cord and brain to inhibit the neurotransmission of pain. In contrast, nonopioid analgesics act primarily in peripheral tissues to inhibit the formation of algogenic or pain-producing substances such as prostaglandins. To facilitate the selection of an appropriate analgesic or anesthetic medication, patients are usually asked to describe their pain in terms of its intensity, duration, and location. These two types of pain are transmitted by different types of neurons and their primary afferent fibers (Box 23-1). Pain can be further distinguished on the basis of whether it is somatic, visceral, or neuropathic in origin. Somatic pain is often well localized to specific dermal, subcutaneous, or musculoskeletal tissue. Visceral pain originating in thoracic or abdominal structures is often poorly localized and may be referred to somatic structures. Neuropathic pain is usually caused by nerve damage, such as that resulting from nerve compression or inflammation, or from diabetes. Neuropathic pain is characteristic, for example, of trigeminal neuralgia (tic douloureux), postherpetic neuralgia, and fibromyalgia. Nonopioid analgesics reduce the activation of primaryafferentneuronsviainhibitionofprostaglandinsynthesis. According to this hypothesis, pain transmission by spinothalamic neurons can be modulated, or gated, by the inhibitory activity of other types of large fibers impinging on them. The activation of spinothalamic neurons is also inhibited by peripheral A sensory fibers that stimulate the release of met-enkephalin from spinal cord interneurons. These mechanisms explain the pain relief that may be produced by simply rubbing or massaging a mildly injured tissue. When these nerves release serotonin and norepinephrine in the spinal cord, they inhibit dorsal spinal neurons that transmit pain impulses to supraspinal sites. The enkephalins act presynaptically to decrease the release of pain transmitters from the central terminations of primary afferent neurons. They also act on postsynaptic receptors on spinothalamic tract neurons in the spinal cord to decrease the rostral transmission of the pain signal. Since ancient times, opium, the raw extract of the poppy plant Papaver somniferum, has been used for the treatment of pain and diarrhea. During the 19th century, morphine was isolated from opium, and its pharmacologic effects were characterized. The presence of stereoselective receptors for morphine in brain tissue indicated the likelihood of an endogenous ligand for these receptors, and this eventually led to the discovery of the three major families of endogenous opioid peptides: enkephalins, -endorphins, and dynorphins. The opioid peptides are derived from larger precursor proteins that are widely distributed in the brain. Endorphins and dynorphins are large peptides, whereas the two types of enkephalins are small pentapeptides containing Tyr-GlyGly-Phe-Met/Leu. Therefore the two types of enkephalins are called met-enkephalin and leu-enkephalin. Enkephalins activate opioid receptors in these areas and thereby block the transmission of pain impulses. The enkephalins appear to act as neuromodulators in that they exert a long-acting inhibitory effect on the release of excitatory neurotransmitters by several neurons. The physician asks him whether he had chickenpox as a child,towhichtheprofessorrepliesthathedid. Hisphysiciandiagnoseshimwithshinglesandtellshimtherashwill go away in about a week. Shinglesisthenamegivento a rash that develops from reactivation of chickenpox, the herpes varicella-zoster virus that lay dormant in the cell bodiesofthedorsalrootganglia.

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These include the sensory systems responsible for vision acne vitamin deficiency buy flexresan toronto, hearing acne makeup flexresan 20 mg, olfaction skin carecom generic 30 mg flexresan otc, touch skin care obagi purchase flexresan with a visa, and pain. The spinothalamic tracts relay touch and pain sensations to the thalamus, which projects this information to the cortex. The brain stem region known as the reticular formation plays a significant role in filtering sensory information before it is relayed to the thalamus and hypothalamus and eventually to the cortex. The reticular formation includes the locus ceruleus and raphe nuclei, whose neurons release norepinephrine and serotonin, respectively, and play an important role in determining the level of consciousness, sleep, and wakefulness. The cortex of the parietal and occipital lobes and part of the temporal lobe is involved in the recognition and integration of sensory perceptions. Disorders in which sensory processing is defective include sleep disorders, chronic pain syndromes, and disorders of the special senses such as blindness, deafness, and taste and olfactory dysfunction. Among the drugs that affect sensory processing are antidepressants, hallucinogens, local and general anesthetics, opioid analgesics, and sedative-hypnotics. The structures involved in motor processing include the cerebellum, the motor strip of the frontal lobe cortex, the basal ganglia, and the suprasegmental nuclei that are found in the brain stem and are involved in the control of posture. Disturbances in motor processing occur in Parkinson disease, Huntington disease, and a variety of degenerative and demyelinating neuron disorders. Which of the following terms best describes a receptor located on a neuronal terminal that binds a neurotransmitter released from another neuron and decreases release of neurotransmitter from the neuronal terminal Neurotransmitters are made in neurons and released when vesicles fuse with the neuronal membrane. Which one of the following statements best describes the differences between classical neurotransmitters and neuropeptides A patient with metastatic lung cancer is treated for chronic pain with daily doses of a long-acting morphine formulation and oxycodone for breakthrough pain. Which one of the following mechanisms may explain the lack of effect of his medicines A heteroreceptor is a type of presynaptic receptor that is also located on the neuronal terminal but binds a different neurotransmitter than the one being released from the terminal. The signaling through this type of receptor usually causes decreased release of the neurotransmitter. Answer A, presynaptic receptor, is a general term for any type of receptor located on the neuronal terminal. Answer C, postsynaptic receptor, is incorrect because this receptor is located on the postsynaptic membrane. Answer D, autoreceptor, is a type of presynaptic receptor in which the binding of the same neurotransmitter released from the neuronal terminal decreases further release of that neurotransmitter. Answer E, ionotropic receptor, is the term for a receptor associated with an ion channel and could be located on either the presynaptic or postsynaptic membrane. Fusion of the neurotransmitter vesicle is triggered with an influx of Ca2+ into the presynaptic terminal. Answer B, phagocytosis, means the engulfing of cellular debris or bacteria by another cell, usually a macrophage. Answer C, endocytosis, is the process whereby receptors and other membrane proteins are recycled back into the neuron. Answer D, pinocytosis, refers to is a form of endocytosis in which small particles of liquids are brought into the cell within small vesicles formed from the membrane. Answer B, classical neurotransmitters have a longer duration of action, is not true in general, and many studies show that neuropeptides act more as neuromodulators with longer duration of action than classical neurotransmitters. Answer C, neuropeptides undergo rapid reuptake into the presynaptic terminal, is incorrect as there are no known transport proteins in presynaptic membranes to facilitate the reuptake of neuropeptides back into the terminal. Answer D, classical neurotransmitters are packaged into vesicles, is true but does not differentiate between the two types of substances because neuropeptides are also packaged into vesicles for release, albeit into different types called dense-core vesicles. Answer E, neuropeptides are degraded by acetylcholinesterase in the synapse, is incorrect because other enzymes called peptidases are responsible for the degradation of neuropeptides after release into the synapse. Chronic administration of an agonist, such as the opioid agonists morphine and oxycodone, will cause a decrease in the number of receptor proteins expressed by the neuron in an attempt to decrease the signaling through that pathway and establish homeostasis. Answer B, pain intensity has greatly increased, could also be true, but there is no information given in the question to assume that this might be the case. Answer C, the efficiency of G protein coupling is decreased, is a mechanism more noted for acute changes after agonist administration, whereas down-regulation is Chapter 18 y Introduction to Central Nervous System Pharmacology more likely with long-term or chronic administration of an agonist. Answer E, the patient is a "drug seeker" and addicted to opioid medications, is very unlikely because metastatic lung cancer can be a very painful condition and less than 4% of patients treated with opioid analgesics develop substance abuse disorders. Answer A, lithium, is incorrect as this agent to treat 185 bipolar disorder acts at the level of signal transduction. Answer B, morphine, is incorrect as this opioid agonist acts by receptor activation. Answer D, levodopa, is an antiparkinsonian agent that acts by a strategy known as precursor loading, which feeds the biosynthetic pathway for the synthesis of dopamine. Answer E, donepezil, is incorrect as this drug to treat Alzheimer disease acts by inhibiting the breakdown of acetylcholine, the neurotransmitter that is reduced in Alzheimer disease. Anxiety is characterized by changes in mood (apprehension and fear), sympathetic nervous system arousal, and hypervigilance. Moreover, chronic anxiety often leads to visceral organ dysfunction and unpleasant symptoms. For example, patients with chronic anxiety may develop gastrointestinal, cardiovascular, and neurologic problems, including diarrhea, tachycardia, sweating, tremors, and dizziness. Ultimately, anxiety can contribute to heart disease and other disorders, including self-medication, which may lead to substance abuse. The sedative part of their name refers to the ability of these agents to calm or reduce anxiety, known as an anxiolytic effect.

That is skin care during pregnancy purchase flexresan 40mg with mastercard, malignant transformation simply results in the overexpression or underexpression of the same gene products made by normal cells skin care 35 discount flexresan 10mg on-line. As a result acne help cheap flexresan 40mg fast delivery, cancercellsemploythesamemetabolicmachineryasnormalcells acne questionnaire purchase flexresan line,usethesame signaling pathways as normal cells, and express the same surface antigens as normal cells. Nonetheless, even though these changes in cellular function are only quantitative, they are still sufficient to allow unrestrained growth and avoidanceofcelldeath. Epidemiology the American Cancer Society estimated that 589,430 Americans died from cancer in the year 2015. Cancer is a leading cause of death among all age groups, including children aged 1 to 18 years, in whom it is the leading nonaccidental cause of death. Cancers with a high cure rate include Hodgkin disease, testicular cancer,andacutelymphocyticleukemia. Formanypatientswhosecancerisnot yet curable, chemotherapy can still be of value, offering realistic hopes of palliationandprolongedlife. However,althoughprogressinchemotherapyhas been encouraging, the ability to cure most cancers with drugs alone remains elusive. In contrast, drug therapy is the treatment of choice for disseminated cancers (leukemias, disseminated lymphomas, and metastases) along with several localized cancers. Drug therapy also plays an important role as an adjunct to surgery and irradiation: by suppressingorkillingmalignantcellsthatsurgeryandirradiationleavebehind, adjuvantdrugtherapycanreducerecurrenceandimprovesurvival. Youshouldnotethattheterm cancer chemotherapyapplies only to the cytotoxic drugs-it does not apply to theuseofhormones,biologicresponsemodifiers,ortargeteddrugs. IntroductiontotheCytotoxicAnticancerDrugs the cytotoxic agents constitute the largest class of anticancer drugs. The cytotoxicdrugscanbesubdividedintoeightmajorgroups:(1)alkylatingagents, (2) platinum compounds, (3) antimetabolites, (4) hypomethylating agents, (5) antitumorantibiotics,(6)mitoticinhibitors,(7)topoisomeraseinhibitors,and(8) miscellaneous cytotoxic drugs. As a result, these drugs are most toxic to tissues that haveahighgrowthfraction(i. About half of the cytotoxic anticancer drugs are phase specific, and the other half are phase nonspecific. TheCellCycle the cell cycle is the sequence of events that a cell goes through from one mitoticdivisiontothenext. Oncompletingmitosis,theresultingdaughtercellshavetwo options: they can enter G1 and repeat the cycle, or they can enter the phase known as G0. Cells that enter G0 become mitotically dormant; they do not replicateandarenotactiveparticipantsinthecycle. Atissuewithalargepercentageofproliferatingcellsandfewcellsin G0 has a high growth fraction. ImpactofTissueGrowthFractiononResponsivenessto Chemotherapy Asarule,chemotherapeuticdrugsaremuchmoretoxictotissuesthathavea high growth fraction than to tissues that have a low growth fraction. Having established the relationship between growth fraction and drug sensitivity,wecanapplythisknowledgetopredicthowspecificcancerswill respondtochemotherapy. Incontrast,onlysomerarercancers -suchasacutelymphocyticleukemia,Hodgkindisease,andcertaintesticular cancers-have a high growth fraction, so they tend to respond well to cytotoxicdrugs. Vincristine,forexample,actsbycausing mitotic arrest and hence is effective only during M phase. Because of their phase specificity, these drugs are toxic only to cells that are active participants in the cell cycle; cells that are "resting" in G0 will not be harmed. Alternatively,theycanbegivenin multiple doses at short intervals over an extended time. Because the dosing schedule is so critical to therapeutic response, phase-specific drugs are also knownasschedule-dependentdrugs. Because phase-nonspecific drugs can injure cells throughout the cell cycle, whereas phase-specific drugs cannot, phasenonspecific drugs can increase cell kill when combined with phase-specific drugs. Although the phase-nonspecific drugs can cause biochemical lesions at any timeduringthecellcycle,asarulethesedrugsaremoretoxictoproliferating cellsthantocellsinG0. Thisismuchlikeinflictingaflattire on an automobile: the tire can be deflated at any time; however, loss of air is consequentialonlyifthecarismoving. That is, dosage cannot exceed an amountthatproducesthemaximallytoleratedinjurytonormalcells. That is, they cannot kill target cells without also killing other cells with which the target cells are in intimate contact. Asnotedthere,successfulantimicrobial therapy is possible because antimicrobial drugs are highly selective in their toxicity. Penicillin, for example, can readily kill invading bacteria while being virtually harmless to cells of the host. This high degree of selective toxicity stands in sharp contrast to the lack of selectivity displayed by cytotoxic anticancerdrugs. Because neoplastic cells and normal cells are very similar: differences betweenthemarequantitativeratherthanqualitative. Unfortunately, we have yet to identify unique biochemical features thatwouldrendercancercellsvulnerabletoselectiveattack. Nevertheless,there is reason for hope: our expanding knowledge of cancer biology is revealing potentialnewtargetsforanticancerdrugs.

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This is because hepatic drug elimination includes Drug Clearance Clearance (Cl) is the most fundamental expression of drug elimination skin care myths order flexresan overnight delivery. It is defined as the volume of body fluid (blood) from which a drug is removed per unit of time skin care anti aging buy flexresan 10 mg. Whereas the clearance of a particular drug is constant skin care yg bagus order 10mg flexresan with visa, it is important to Chapter2 y Pharmacokinetics 21 the biotransformation and biliary excretion of parent compounds skin care questions buy flexresan 20 mg online. For this reason, hepatic clearance is usually determined by multiplying hepatic blood flow by the arteriovenous drug concentration difference. First-order kinetics Plasma drug concentration (mg/L) 8 Plasma drug concentration (mg/L) Most drugs exhibit first-order kinetics, in which the rate of drug elimination (amount of drug eliminated per unit time) is proportional to the plasma drug concentration and follows an exponential decay function. Note that the rate of drug elimination is not the same as the elimination rate constant, ke (fraction of drug eliminated per unit time). For drugs that exhibit first-order kinetics, the plasma drug concentration can be determined from the dose of a drug and its clearance. It can be calculated from the elimination rate constant, but it is usually determined from the plasma drug concentration curve. The formula for relating half-life to clearance and volume of distribution is given in the legend of Figure 2-11. Disease, age, and other physiologic variables can alter drug clearance or volume of distribution and thereby change the elimination half-life (see Chapter 4). The following principles pertain to zero-order kinetics: the rate of drug elimination is constant. In many cases, the reason that the rate of drug elimination is constant is that the elimination process becomes saturated. In first-order kinetics (A), the rate of drug elimination is proportional to the plasma drug concentration. The kinetic order of a drug is derived from the exponent n in the following expression: [Drug]/t = -k e [Drug]n Zero-Order Kinetics where represents change, [Drug] represents the plasma drug concentration, and t is time. When the drug is first administered, the rate of administration is much greater than the rate of elimination, because the plasma concentration is so low. As the drug continues to be administered, the rate of drug elimination 22 SectionI y PrinciplesofPharmacology Ct Ct C0 ke e = = = = = C0. Because the time to reach the steady state is dependent on the time it takes for the rate of drug elimination to equal to the rate of drug administration, the time to reach the steady state is a function of the elimination half-life of the drug. Any first-order process requires about five half-lives to be completed; thus the time to reach the steady-state drug concentration is about five drug half-lives. If the half-life of a drug changes, then the time required to reach the steady state also changes. Note that the time required to reach the steady state is independent both of the drug dose and the rate or frequency of drug administration. Figure 2-13 illustrates typical plasma concentration curves after drugs are administered continuously or intermittently. Likewise, if the half-life is doubled, the steady-state concentration is doubled. A drug administered intermittently will accumulate to a steady state at the same rate as a drug given by continuous infusion, but the plasma drug concentration will fluctuate as each dose is absorbed and eliminated. The average steadystate plasma drug concentration with intermittent intravenous administration will be the same as if the equivalent dose were administered by continuous infusion. A comparison of the steady-state drug levels following continuous intravenous infusion, multiple oral doses, and a single oral dose is shown in Figure 2-13D. With intermittent oral administration, the bioavailability of the drug will also influence the steady-state plasma concentration. The elimination half-life (t1/2) is the time required to reduce the plasma drug concentration (C) by 50%. Loading Dose A loading dose, or priming dose, is given to rapidly establish a therapeutic plasma drug concentration. The loading dose can be calculated by multiplying the volume of distribution by the desired plasma drug concentration. The loading dose, which is larger than the maintenance dose, is generally administered as a single dose, but it can be divided into fractions that are given over several hours. A divided loading dose is sometimes used for drugs that are more toxic, for example, digitalis glycosides used to treat congestive heart failure. Maintenance Dose A maintenance dose is given to establish or maintain the desired steady-state plasma drug concentration. For drugs given intermittently, the maintenance dose is one of a series of doses administered at regular intervals. The amount of drug to be given is based on the principle that at the steady state the rate of drug administration equals the rate of drug elimination. The half-life is often determined from the plasma drug concentration curve shown here. The clearance (Cl) is the volume of fluid from which a drug is eliminated per unit of time. Eventually, as the plasma concentration rises sufficiently, the rate of drug elimination equals the rate of drug administration. The time required to reach the steady state depends on the half-life (t1/2); it does not depend on the dose or dosage interval. The maintenance dose is then calculated as the rate of drug elimination multiplied by the dosage intervals. If the drug is administered orally, its bioavailability must also be included in the equation. It is calculated by dividing the drug dose by the plasma drug concentration at time zero.

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The goal is to accelerate time to recovery of upper andlowerbowelfunction acne 10 gel generic 5mg flexresan with amex,whichcanbeimpairedbyopioidsusedforanalgesia duringandaftersurgery acne wiki buy flexresan 40 mg on-line. Caldolorissuppliedas a concentrated solution (100mg/mL) that must be diluted (to 4mg/mLor less) beforeuse acne 4 hour order 10mg flexresan overnight delivery. For patients with fever acne 70 off purchase flexresan 40 mg free shipping, treatment consists of an initial 400-mg dose, followed by either (1) 400mg every 4 to 6 hours or (2) 100 to 200mg every 4 hours as needed. Inallcases,thesmallerdosageoptionis employed for patients older than 65 years, patients with impaired kidney function,andpatientswhoweighlessthan50kg(110pounds). PepticUlcerDisease Antagonists Cimetidine Parenteral cimetidine (discussed in Chapter 62) is reserved for patients with hypersecretoryconditions. Thegoalsoftreatmentaretomaintainventilation,correcthypoglycemiaand precipitating factors, and terminate the seizure as quickly as possible. After 30 minutes, continued seizure activity can cause permanent neurologic injury (cognitive impairment, memory loss, worsening of the underlying seizure disorder)andevendeath. Clinical guidelines propose a stabilization phase followed by three therapy phases. All of these drugs can terminate seizures quickly: however, lorazepam is generally preferred for its longer duration of action. Thepatientmaypresentwitheithersymptomsofanginaatrest,new- onset exertional angina, or intensification of existing angina. The risk for dying is greatest initially and then declines to baselineinabout2months. TheHealthProductsandFoodBranch withinHealthCanadaisresponsibleforensuringthathealthproductsandfoods approved for sale to Canadians are safe and of high quality. TheBiologics&GeneticTherapiesDirectorateregulatesbiologicdrugs (drugs derived from living sources) and radiopharmaceuticals. Examples of biologic products are insulin analogues, blood products, and vaccines. The Natural and Non-prescription Health Products Directorate is the regulating authorityfornaturalhealthproductsforsaleinCanada. The Food and Drug Act (1927), accompanied by the Food and Drug Regulations(1953,1954,1979),reviewsthesafetyandefficacyofdrugsbefore they are marketed, and the legislation determines whether the medicine is classified as prescription or nonprescription status. The Act controls the requirements for good manufacturing practices, labeling, distribution, and sale, including advertising of the drug. They also prescribe the standards of composition,strength,potency,purity,andqualityofdrugsinCanada. PrescriptionDrugs(ScheduleF) All drugs that require a prescription, except for narcotics and controlled substances, are listed in Schedule F of the Food and Drug Regulations. Prescriptions for Schedule F medications may be written, including facsimiles andelectronicprescriptions(dependingontheprovince),ortransmittedverbally. The Controlled Drugs and Substances Act lists eight schedules of controlledsubstances. Assignmenttoascheduleisbasedonpotentialforabuse and the ease with which illicit substances can be manufactured in illegal laboratories. Thedegreeofcontrol,theconditionsofrecordkeeping,andother regulations depend on the specific schedule. For example, Schedule I, which includes the narcotic agents, requires written orders only, and no repeat prescriptions are allowed. The symbol must appearonthelabelsofcontrolledproducts,whiletheletterNisprintedonthe label of all the narcotic agents. Thecontentmustnotexceedtheequivalent of8mgcodeinephosphatepersoliddosageunitor20mg/30mLofaliquid,and the preparation must also contain two additional non-narcotic medicinal ingredients (usually acetylsalicylic acid or acetaminophen and caffeine). These preparations may not be advertised or displayed and may be sold only by pharmacists. NonprescriptionMedications-NationalDrug Schedules As previously mentioned, individual provinces have enacted their own legislationcontrollingthesaleofbothprescriptionandnonprescriptionproducts. Narcotics, controlled substances, and prescription medications are listed in Schedule I, while nonprescription medications are assignedtooneofthethreecategoriesdescribedbelow. Thereisgeneralsupport among the provincial regulatory bodies for the National Drug Schedules, althoughtherearesomedifferencesfromprovincetoprovinceoftheactuallist ofdrugsineachschedule. New-DrugDevelopmentinCanada TheprocessforapprovinganewdruginCanadaisverysimilar,ifnotidentical, to the process in the United States. TheprincipaldifferencebetweenCanadaandtheUnited States is one of nomenclature: Once preclinical testing is completed, the manufacturerinCanadaappliesforaPreclinicalNewDrugSubmission,versus anInvestigationalNewDrugintheUnitedStates. For these reasons, post-market surveillance plays a major role in monitoring new drugs. Post-market surveillance enables Health Canadatomonitorthesafetyprofileofhealthproductsoncetheyaremarketed to ensure that the benefits of the products continue to outweigh the risks. The Canada Vigilance Program also collects information for non-prescription drugs,naturalhealthproducts,biologics,radiopharmaceuticals,anddisinfectants andsanitizerswithdisinfectantclaims. Thisnew provision allowed generic drug companies to manufacture and distribute patented drugs in Canada, provided that a minimal 4% royalty fee was paid to the patent holder. Unfortunately, the system caused a decline in revenue to "innovative" pharmaceutical companies, with a resultant decline in research on new drug development. After much debate, and retroactive to June 1987, the Patent Act was amended to give patent holders market exclusivity either (1) for 7 to 10 years or (2) until the 17-year patent (from date of filing) expires, whichever comes first. This bill (1) eliminated compulsory licensing and (2) extended patent protection on brand-name drugs to 20 years, thereby making Canadian patent laws similar to those of the United States and other industrializednations. In order to respond to concerns arising from changes in the Patent Act, a PatentedMedicinePricesReviewBoardwascreated. Itsmandateisto(1)ensure thatpricesofpatentedmedicinesarenotexcessiveand(2)reportontheratiosof researchanddevelopmentexpendituresrelativetosalesforindividualpatentees and for the pharmaceutical industry as a whole.