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By W. Tufail. Concord College. 2018.

Approximately 5% of patients taking lithium (E) Serum prolactin level over the long term develop hypothyroidism 20mg levitra free shipping, and 4 10mg levitra fast delivery. Which of the following antidepressants requires thyroid status should be followed as routine care for therapeutic blood monitoring for safe use? Impairment in glucose metabolism, (B) Phenelzine (Nardil) hepatic function, red blood cell production, and (C) Nortriptyline (Pamelor) prolactin secretion are not typical complications of (D) Venlafaxine (Effexor) lithium therapy. Which of the following statements about antide- these drugs require at least one steady-state blood pressant medications is most appropriate? Nardil is a MAOI, which can be 396 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM lethal in overdose, but blood levels are not used to orders and pain. Selective serotonin in- bution of the newer antidepressants is in their im- hibitors in affective disorders: I. Case Study Treatment of Depression ary Smith is a 46-year-old secretary who com- history of major depression, successfully treated Mplains to her primary care physician mainly of with sertraline. Her ap- pression (depressed mood, loss of interest in pleas- petite has been low and she has lost 10 pounds over urable activities, decreased attention and concentra- this time. Her husband has noticed that she has lost tion, fatigue, sleep disturbance, low appetite, weight interest in her hobbies and has withdrawn from loss, ideas of death). She should be warned about nausea ate in conversation, but worried about why she has and possibly loose stools, anorgasmia, and insomnia become unable to execute her tasks at work and en- before she begins therapy. She becomes tearful plained that the medication will take at least 2 when describing this, feels guilty, and describes her weeks to begin working and that a complete trial of mood as down. She expresses concern that she may the medication to assess its efficacy will take 4 to 6 not get better and has had thoughts of death but no weeks. She has after her symptoms have remitted before consider- no active medical problems and takes no prescrip- ing discontinuation of drug therapy. Lasley DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Chlorpromazine 399 Pimozide 400 Clozapine 399 Risperidone 399 Dibenzodiazepine 400 Thioridazine 399 Haloperidol 399 Thiothixene 399 Olanzapine 400 The term psychosis refers to a variety of mental dis- ably to these drugs, but the latter term refers more ap- orders characterized by one or more of the following propriately to the older agents, whose extrapyramidal symptoms: diminished and distorted capacity to process side effects (parkinsonism, dyskinesias, akathisia) are information and draw logical conclusions, hallucina- more prominent. Antipsychotic drugs lessen these THE DISEASE OF SCHIZOPHRENIA symptoms regardless of the underlying cause or causes. These agents are prescribed for the treatment of mania, Schizophrenia is a group of heterogeneous, chronic psy- some movement disorders, and various types of non- chotic disorders. Key symptoms include hallucinations, specific agitated behaviors but are most frequently em- delusions, and abnormal experiences, such as the per- ployed in the therapy of schizophrenia. Patients lose empathy with others, impaired behavioral function, and disturbances of become withdrawn, and demonstrate inappropriate or thinking and affect. The disorder has a strong genetic compo- years, and the first agents introduced, such as chlorpro- nent, as demonstrated by a concordance of 40 to 50% mazine, revolutionized the practice of psychiatry. Many between monozygotic twins, but no objective physiolog- newer agents have since been developed, reflecting sig- ical or biochemical diagnostic tests exist. Positive symptoms are those that can chotics and neuroleptics have been applied interchange- be regarded as an abnormality or exaggeration of 397 398 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM normal function (e. The primary defect could emanate from antipsychotic drugs are generally more effective in con- nondopaminergic systems that exert a regulatory effect trolling these signs. Negative symptoms are those that on dopamine neurons, leading to disinhibition of some indicate a loss or decrease in function, such as poverty dopaminergic pathways. Negative signs are considered to be more chronic and persistent and less ANTIPSYCHOTIC MECHANISMS responsive to some antipsychotic agents. Although any OF ACTION of these symptoms may undergo partial remission, per- sistent dysfunction and exacerbations are typical. Several lines of evidence demonstrated long ago that Schizophrenic patients appear to have small brains antipsychotic drugs blocked the synaptic actions of with large ventricular volumes, indicating a relative dopamine and should be classified as dopaminergic an- deficit of neurons. Three dopaminergic pathways in the brain ing studies have strongly suggested that regions of the serve as primary substrates for the pharmacological ef- medial temporal lobe (e. The nigrostriatal system consists of ished numbers of neurons and also have demonstrated neurons with cell bodies in the substantia nigra that the inability of individuals with schizophrenia to acti- project to the caudate and putamen, and it is primarily vate the frontal cortex and successfully execute tasks involved in the coordination of posture and voluntary that require frontal cortical function. The mesolimbic–mesocortical system pro- lationship between behavioral signs, neuropathology, jects from cell bodies in the ventral mesencephalon to and a postulated functional excess of dopamine (dis- the limbic system and neocortex, pathways associated cussed later) is unknown, and no theory of causation is with higher mental and emotional functions. The antagonism of Schizophrenia of dopamine in the mesolimbic–mesocortical system is The dopamine hypothesis of schizophrenia is the most thought to be the basis of the therapeutic actions of the fully developed theory of causation for this disorder, antipsychotic drugs, while antagonism of the nigrostriatal and until recently, it has been the foundation for the ra- system is the major factor in the extrapyramidal side ef- tionale underlying drug therapy for this disease.

Ppostcap) purchase 10mg levitra visa, while the sharply generic 20mg levitra fast delivery, receptors in the alveoli emit local sig- area near the base of the lung (! A, zone 3) is con- nals that trigger constriction of the supplying tinuouslysuppliedwithblood(P. This throttles shunts in poorly Q per unit of lung volume therefore decreases from the apex of the lung to the base (! Life- decreases from the apex to the base of the lung threatening lung failure can quickly develop if (! The mean VA/Q for the entire fusion barrier, or surfactant disorder exists lung is 0. V /Q can A Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Regional blood flow in the lung (upright chest position) Alveolus Zone 1 PA> Pprecap> Ppostcap Pulmonary Pulmonary artery vein Zone 2 Pprecap> PA> Ppostcap Lung Zone 3 Pprecap> Ppostcap> PA Pprecap PA Ppostcap Perfusion Q · · B. Effect of ventilation-perfusion ratio (VA/Q) ventilation of lung on partial pressures in lung Pressures in kPa Ambient air: PO2= 20, PCO2= 0 VA/Q 0 3 Apex VA= 0 VA VA 2 VA Q PO2 = 5. Deoxygenated hemoglobin (Hb) can bycellsofthebodyundergoesphysicaldissolu- take up more H+ ions than oxygenated tion and diffuses into adjacent blood capillar- hemoglobin (Oxy-Hb) because Hb is a weaker ies. This promotes CO2 uptake in the dissolved,whiletherestischemicallyboundin peripheral circulation (Haldane effect) because form of HCO3– and carbamate residues of of the simultaneous liberation of O2 from ery- hemoglobin (! Since the PCO2 CO2 entering the pulmonary capillaries is re- in alveoli is lower than in venous blood, CO2 leased from the compounds (! HCO3– and Hb carbamate whereby H+ ions (re- The enzyme carbonic anhydrase (carbonate leased from Hb) are bound in both reactions dehydratase) catalyzes the reaction (! A7, A8), and the direction of HCO3–/Cl– ex- HCO3– + H+ CO2 + H O2 change reverses (! Because it acceler- toOxy-Hbinthelungpromotesthisprocessby ates the establishment of equilibrium, the increasing the supply of H+ ions (Haldane ef- short contact time (! CO2 distribution in blood (mmol/L blood, CO2 diffusing from the peripheral cells (! The HCO3– Mixed venous blood: concentration in erythrocytes therefore be- Plasma* 0. Percentage of total arteriovenous difference H+ ions are liberated when CO2 in red cells 9% 78% 13% 100% circulating in the periphery is converted to * Approx 0. Since the removal of H+ ions Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. CO2 transport in blood Expelled from lung 8 Oxy- Hb CO Hb 2 NH COO– NH2 CO2 Alveolus H+ O2 Hb Oxy- H Hb H In lung H O + 2 H 7 – 9 – CO HCO3 HCO3 2 Carbonic anhydrase Cl– Erythrocyte In plasma In periphery 5 Carbonic anhydrase HCO– HCO– CO2 3 3 Bicarbonate formation 2 – 4 Cl H2O H+ 6 Hb Hemoglobin Oxy- H as buffer Hb H O2 H+ Hemoglobin carbamate Oxy- Hb formation Hb 3 NH2 NH COO– Hemoglobin CO2 CO2 carbamate 1 Tissue 125 Metabolism Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. TheCO2dis- CO2 in Cerebrospinal Fluid sociation curve illustrates how the total CO2 concentration depends on PCO (! Unlike HCO3– and H, CO+ 2 can cross the blood- 2 TheconcentrationofdissolvedCO2,[CO2],in cerebrospinal fluid (CSF) barrier with relative plasma is directly proportional to the PCO2 in ease (! The PCO2 in CSF there- plasma and can be calculated as follows: fore adapts quickly to acute changes in the PCO2 [CO ] =2 αCO2! The dissociation curve for total CO2 is The concentration of non-bicarbonate calculated from the sum of dissolved and buffers in blood (hemoglobin, plasma pro- bound CO2 (! When the CO2 concentration in- CO2 binding with hemoglobin depends on creases, the liberated H+ ions are therefore ef- the degree of oxygen saturation (SO2) of fectively buffered in the blood. Blood completely saturated with HCO3– concentration in blood then rises rela- O2 is not able to bind as much CO2 as O -free2 tively slowly, to ultimately become higher blood at equal PCO levels (! B2), result- loaded with O,2 the buffer capacity of ing in a renewed increase in the pH of the hemoglobin and, consequently, the levels of CSF because the HCO3–/CO2 ratio increases chemical CO2 binding decrease due to the Hal- (! Venous blood is never respiratory activity (via central chemosen- completely void of O, but is always O -satu-2 2 sors), a process enhanced by renal compensa- rated to a certain degree, depending on the tion, i. The SO2 of mixed venous blood is ultimately adapts to chronic elevation in PCO2— about 0. The normal range of CO2 Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved.

Phenytoin is one of very few drugs that displays Carbamazepine zero-order (or saturation) kinetics in its metabolism purchase levitra 10mg fast delivery. However purchase levitra 20mg online, at the higher blood levels usually erated by most patients, and exhibits fewer long-term required to control seizures, the maximum capacity of side effects than other drugs. Its half-life is reported to vary from 12 to of phenytoin may lead to a disproportionate increase in 60 hours in humans. Since the plasma levels says has markedly improved the success of therapy with continue to increase in such a situation, steady-state lev- this drug, since serum concentration is only partially els are not attained, and toxicity may ensue. Carbamazepine is metabolized in the liver, of half-life (t1/2) values for phenytoin often is meaning- and there is evidence that its continued administration less, since the apparent half-life varies with the drug leads to hepatic enzyme induction. They are gener- Carbamazepine is an effective agent for the treat- ally characterized by nystagmus, ataxia, vertigo, and ment of partial seizures and generalized tonic–clonic diplopia (cerebellovestibular dysfunction). Skin rashes, usually Like most of the agents that block sodium channels, morbilliform in character, are most common. Drowsiness is the most common side effect, followed by Other rashes occasionally have been reported, as have a nausea, headache, dizziness, incoordination, vertigo, and variety of blood dyscrasias and hepatic necrosis. These effects occur particularly when the drug The most common side effect in children receiving is first taken, but tolerance often develops over a few long-term therapy is gingival hyperplasia, or over- weeks. There appears to be little risk of cognitive im- growth of the gums (occurs in up to 50% of patients). Although the condition is not serious, it is a cosmetic Carbamazepine causes a variety of rashes and other problem and can be very embarrassing to the patient. Systemic lupus erythe- neous tissue, coarsening of facial features, and enlarge- matosus can occur, but discontinuation of the drug ment of lips and nose (hydantoin facies) are often seen leads to eventual disappearance of the symptoms. Idiosyncratic hematological reactions to carbamazepine 32 Antiepileptic Drugs 379 may occur, but serious blood dyscrasias are rare. The cipitate seizures in some patients, particularly those ex- plasma half-life after a single dose is about 24 hours. Unlike most drugs, lamotrigine is metabolized primarily While the number of side effects may be fairly large, by glucuronidation. Severe ad- lamotrigine will not induce or inhibit cytochrome P450 verse reactions occur less commonly than with pheny- isozymes, in contrast to most AEDs. The overall incidence of toxicity Severe skin rashes appear to be the major concern seems to be fairly low at usual therapeutic doses. The incidence of rash is greater in Most of the drug interactions with carbamazepine children than in adults. Other adverse effects are similar are related to its effects on microsomal drug metabo- to those of drugs with the same mechanism of action, lism. Carbamazepine can induce its own metabolism such as cerebellovestibular changes leading to dizziness, (autoinduction) after prolonged administration, de- diplopia, ataxia, and blurred vision. Disseminated in- creasing its clearance rate, half-life, and serum concen- travascular coagulation has been reported. Topiramate is most useful in patients with generalized Carbamazepine also can induce the enzymes that tonic–clonic seizures and those with partial complex metabolize other anticonvulsant drugs, including seizures. Topiramate causes a higher incidence of CNS- phenytoin, primidone, phenobarbital, valproic acid, related side effects (primarily cognitive slowing and clonazepam, and ethosuximide, and metabolism of confusion) than other AEDs. Similarly, other cause a significant incidence of rashes or other hyper- drugs may induce metabolism of carbamazepine; the sensitivity reactions; however, a significantly higher in- end result is the same as for autoinduction, and the dose cidence of kidney stones has been observed in persons of carbamazepine must be readjusted. A common receiving topiramate than in a similar untreated popu- drug–drug interaction is between carbamazepine and lation. After a few days of antibiotic therapy, symp- Zonisamide toms of carbamazepine toxicity develop; this is readily Zonisamide has only recently been approved for use in reversible if either the antibiotic or carbamazepine is the United States, although it has been available in discontinued. It is effective in partial complex Cimetidine, propoxyphene, and isoniazid also have and generalized tonic–clonic seizures and also appears been reported to inhibit metabolism of carbamazepine. It has a It is essential to monitor blood levels and adjust the long half-life (about 60 hours) and requires about 2 dose if necessary whenever additional drugs are given weeks to achieve steady-state levels. In addi- Oxcarbazepine tion, it appears to cause an increased incidence of kid- Oxcarbazepine is chemically and pharmacologically ney stones. This Valproic Acid (Sodium Valproate) property decreases the problems associated with drug Although it is marketed as both valproic acid interactions when oxcarbazepine is used in combination (Depakene) and as sodium valproate (Depakote), it is with other drugs. The clinical uses and adverse effect the valproate ion that is absorbed from the gastroin- profile of oxcarbazepine appear to be similar to those of testinal tract and is the active form.