By D. Surus. Valparaiso University.
It reduces the myocardial need for oxygen by reducing contractility of the myocardium and slowing the fre- quency of cardiac contractions discount 60caps ashwagandha with mastercard. It reduces tonicity of smooth musculature generic ashwagandha 60caps fast delivery, peripheral arteries, and overall periph- eral vascular resistance. Verapamil is used to prevent attacks of stenocardia, arterial hypertension, and to treat and prevent supraventricular arrhythmia. This undergoes a reaction with phosphorous oxychloride, forming 1-chloroph- thalazine (22. It has an effect on arterial vessels while having a minimal effect on venous ves- sels. As a result, resistance of peripheral vessels decreases, and blood pressure is reduced (diastolic more than systolic). It does not have a substantial effect on nonvascular smooth musculature or cardiac tissues. Homeostatic circulatory reflexes remain natural, and the resulting hypotension activates car- diovascular reflexes, which are expressed as an increase of heart work, power, and volume of cardiac output. The hypotensive effect is caused by peripheral vasodilation resulting from a direct effect on both arterial and venous vessels. Side effects also appear very quickly; however, they last for a very short time because of their extremely short half-life. Sodium nitroprusside is biotransformed to cyanide and thiocyanate, which upon overdose can result in thiocyanate and cyanide intoxication. The presence of drugs such as diazoxide and sodium nitroprusside has significantly decreased the possibility of a sharp drop in arterial blood pressure and urgent situations; which, how- ever, should be used under the constant care of medical personnel. Angiotensin I is a prohormone that is formed as a result of the action of renin on a pep- tide substrate produced by the liver. Renin, in turn, is a proteolytic enzyme that is produced by the kidneys, and it controls the physiological functions of other organs. The secretion of renin itself is controlled by the nervous system, and possibly by a recently discovered cardiac peptide hormone. As a result, peripheral resistance of vessels increases as heart rate increases, cardiac output increases, and water and sodium ion retention takes place. In turn, induced elevation of pressure by reverse binding causes a decrease in renin secretion. There is a hypothesis that irregularity of the rennin–angiotensin system lies at the base of etiology of all cases of essential hypertension. However, despite all of the apparent attractiveness of this theory, there is still not enough proof for it to be accepted as the sin- gle reason of elevated arterial blood pressure. Moreover, whether or not hypertension is caused by an elevated level of renin or other reasons, angiotensin-converting enzyme inhibitors lower both systolic and diastolic arte- rial pressure in hypertensive patients, and their effects are enhanced by diuretics. Angiotensin-converting drugs of this series (captopril, enalapril) are effective antihyper- tensive drugs used both independently and in combination with other drugs to treat all types of hypertension as well as to treat cardiac insufficiency. L-proline is acylated by phenylacetyl chloride, giving N-benzyloxycarbonyl L-proline (22. This is reduced using hydrogen and a palladium-on-carbon catalyst, which gives the L-proline tert-butyl ester 22. The ester part of the molecule is hydrolyzed using trifluoroacetic acid, giving 1-(3-acetylthio-2-methyl- propanoyl)-L-proline (22. Overall vascular peripheral tension is reduced, which results in the lowering of arterial pressure. Oxidation of this product with 3-chloroperbenzoic acid gives 2,4-diamino-6-(2,4- dichlorophenoxy)pyrimidine-3-oxide (22. Open calcium channels cause hyperpolarization of smooth muscle cells, which in turn, reduces the flow of calcium ions into the cell, which is necessary for sup- porting vascular tonicity. However, when taking minoxidil, tachycardia, elevated renin secretion, and water and sodium ion retention all appear simultaneously with hypotension. Because of potentially serious side effects, it is used only for severe hypertension that does not respond to treatment with other drugs, and absolutely in combination with two other antihypertensive drugs. In addition to hypotensive action, diazoxide causes a sharp increase in the level of glucose in the blood as a result of the inhibition of insulin release from adre- nal glands. Some of the undesirable effects are water and sodium ion retention in the body and increased concentrations of uric acid in the blood. It is used in urgent situations where blood pressure needs to be reduced in severe hypertension. Therapy of respiratory system ill- nesses generally consists of restoring appropriate physiological functions.
For the Child--Pugh classification discount ashwagandha 60 caps with mastercard, five clinical measures of liver disease are given scores of 1 buy ashwagandha 60 caps amex, 2 or 3 points in increasing severity as shown in Table A10. The scores for each parameter are added together and the degree of hepatic impairment is categorised as Child--Pugh class A to C as follows: * 5--6 points Class A * 7--9 points Class B * 10--15 points Class C Table A10. For the purposes of certain monographs this classification is all that may be needed. As a prog- nostic tool, however, the classification is used by clinicians to determine the survival chances of apatient. The risk scores are presented as a grid displaying pictorial icons for theindividual risk category and the score is the summation of these categories. The eight risk categories are: Therapeutic risk: where there is a significant risk of patient harm if the injectable medicine is not used as intended. Use of a concentrate: where further dilution after reconstitution is required before use, i. Complex calculation: any calculation with more than one step required for prep- aration and/or administration, e. Complex method: where more than five non-touch manipulations are involved, or other steps including syringe-to-syringe transfer, preparation of a burette, the use of a filter. Reconstitution of powder in a vial: where a dry powder has to be reconstituted with a liquid. Use of a part vial or ampoule, or use of more than one vial or ampoule is required: e. This risk is symbolised by showing more than one vial with the second vial only half used. Use of a pump or syringe driver: all pumps and syringe drivers require some element of calculation and therefore have potential for error; and the potential risk is considered less significant than the risks associated with not using a pump when indicated. Appendix 11 Risk ratings | 899 Use of non-standard giving set/device required: examples include light-pro- tected products, low adsorption, use of an in-line filter or air inlet. This risk is symbo- lised by a square peg in a round hole to indicate something of a non-standard nature. Itispossible thattheriskscoremayvarydependingonthemethodofadministration;for example, a direct intravenous injection may score lower than an infusion as there is no further dilution involved and therefore one less risk factor. In these scenarios the risk rating at the end of each monograph is always for the highest rated assessment unless otherwise stated. It is vital that a local risk assessment accounts for method of administration in any given clinical area, so the risk score may be moderated to reflect local practice. In all areas, appropriate competence is essential for healthcare professionals working with injectable medicines to give assurance of safety. Local policies and procedures must be adhered to but individuals should also include injectable therapy in their continuing professional development. Hodder Headline’s policy is to use papers that are natural, renewable and recyclable products and made from wood grown in sustainable forests. The logging and manufacturing processes are expected to conform to the environmental regulations of the country of origin. Whilst the advice and information in this book are believed to be true and accurate at the date of going to press, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular, (but without limiting the generality of the preceding disclaimer) every effort has been made to check drug dosages; however it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side-effects recognized. Yonkers and I dedicated Treatment of Psychiatric Disorders in Pregnancy to our spouses. Accordingly, Drugs and Pregnancy – A Handbook is dedicated to the future generation: Christian Carroll Ian Carroll Lauren DelHomme Leslie DelHomme Luke DelHomme Catherine DelHomme Madeline DelHomme Nicole Hery, Pharm. Raven Little White Savannah White This page intentionally left blank Contents Preface ix Acknowledgements xi 1 Introduction to drugs in pregnancy 1 2 Antimicrobials during pregnancy: bacterial, viral, fungal, and 22 parasitic indications 3 Cardiovascular drugs during pregnancy 51 4 Endocrine disorders, contraception, and hormone therapy during 75 pregnancy: embryotoxic versus fetal effects 5 Antiasthma agents during pregnancy 101 6 Anesthetic agents and surgery during pregnancy 114 7 Antineoplastic drugs during pregnancy 126 8 Analgesics during pregnancy 149 9 Anticonvulsant drugs during pregnancy 165 10 Psychotropic use during pregnancy 181 11 Antihistamines, decongestants, and expectorants during pregnancy 206 12 Nutritional and dietary supplementation during pregnancy 216 13 Use of dermatologics during pregnancy 240 14 Drug overdoses during pregnancy 254 15 Miscellaneous drugs during pregnancy: tocolytics and 279 immunosuppressants 16 Substance abuse during pregnancy 296 Appendix – Drug names 333 Index 352 This page intentionally left blank Preface The purpose of this volume was originally to condense and update Drugs and Pregnancy second edition. The total length of the original typescript was approximately three times the number of pages for which the publisher contracted. First strategy suggested was to eliminate the large number of references, but this was not acceptable. The final compro- mise developed was to post the full bibliography and supporting materials on a website for the book – http://www. It is intended for the content of this book to be updated and corrected – as necessary – approximately four times per year. These additions to the book will be posted to the website above, which will be maintained by the publisher.
In areas where there isrichadrenergic innervation order ashwagandha 60caps without prescription, beta blockers can have a pronounced effect buy ashwagandha 60caps low price. In areas where adrenergic innervationissparse, the electrophysiologic effect of beta blockers is relatively minimal. Beta block- ers have very little effectonconduction velocity or refractoriness in normal atrial or ventricular myocardium. Beta blockers can have a profound electrophysiologic effect, how- ever, in ischemic or damagedmyocardium. Fur- ther, beta blockers raise the threshold for ventricular ﬁbrillationinis- chemic myocardium and have been shown to reduce the risk of ven- tricular ﬁbrillationduring ischemia. There is also evidence that beta blockers can helpprevent the formation of reentrant arrhythmias in myocardium that has beendamaged by ischemia. In such damaged myocardium,amaldistribution of autonomic innervationcan arise and lead to regional differences in adrenergic stimulation. Regional differences can serve as substrate for reentranttachyarrhythmias by creating localizeddifferences in refractory periods. By “smoothing out” localizeddifferences in autonomic stimulation, beta blockers may help to prevent arrhythmias. In these cases, beta block- ers can have a directsuppressive effecton the pathways of reentry; thus, they can often terminate the arrhythmias and can helpprevent theirrecurrence. For arrhythmias arising within the atrial muscle (automatic or reentrant atrial tachycardias, atrial ﬁbrillation,and atrial ﬂutter), 82 Chapter 4 Table 4. In rare patients, beta blockers also help to prevent arrhythmias arising in the atria. In such instances, the atrial arrhythmias appear to be catechol dependentand patients often relate the onset of their arrhythmias to exercise. The effects of beta blockers on supraventricular arrhythmias are summarizedin Table 4. Ventricular arrhythmias Ingeneral, beta blockers are not particularly effective in suppressing ambientventricular ectopyorventricular tachycardias. In some cir- cumstances, however, generally when arrhythmias are dependent oncatecholamines or related to myocardial ischemia, beta blockers can be useful. Beta blockers are the drugsofchoice, for instance, for exercise-induced ventricular arrhythmias. Beta blockers have also been shown to reduce the number of episodes of ventricular ﬁbril- lationduring acute myocardial infarction,tosigniﬁcantly improve overall survival, and to reduce the risk of suddendeath and recurrent infarctioninsurvivors of myocardial infarction. Beta blockers, which along with left stellate sympathectomy have been effective in treating many patients with these disorders, can help to smooth out any resultantsympathetic imbalance, reduce nonuniform refractory periods, and make arrhythmias less likely. Clinical pharmacology of beta-blocking agents To a large extent, all the available beta blockers appear to be of comparable efﬁcacy in the treatment of arrhythmias and ischemia. Choosing among these agents for the purpose of treating arrhyth- mias is, then, mainly a matter of selecting a drug with an appropriate pharmacologic proﬁle for the patientbeing treated. Potency of a beta blocker is not a major consideration,but the recommendeddosages of various beta blockers differ markedly, and dosages must be adjusted accordingly for the drug being used. Receptor selectivity refers to β1-receptors (those in the heart) and β2-receptors (those in the peripheral vasculature and bronchi). Drugs with selectivity, suchasatenolol and metoprolol, produce minimal blockadeofβ2-receptors and thus are potentially safer to Table 4. Vasodilator activity is produced by some beta blockers either throughalpha-receptor blockade(carvedilol), or direct β2-receptor stimulation (dilevalol), or both (labetolol). Membrane-stabilizing activity refers to the factthatafew beta blockers exhibit Class I antiarrhythmic activity (slowing of the de- polarizationphase of the actionpotential) if serum levels are suf- ﬁciently high. However, the blood levels that must be achieved to demonstrate such Class I activity are greatly in excess of therapeutic levels. Thus, whether membrane-stabilizing activity is ever relevant with the use of beta blockers is very questionable. The lipid solubility of beta blockers partially determines how the agents are metabolized (lipid-soluble drugs are generally metabo- lizedinthe liver and water-soluble drugs are generally excreted by the kidneys) and whether they cross the blood–brain barrier (drugs that cross are more pronetocause central nervous system side ef- fects, suchasfatigue, depression, insomnia, or hallucinations). In summary, beta blockers as a class generally exhibitsimilar de- grees of effectiveness in the treatmentofcardiac arrhythmias. The major considerations in choosing among these drugs are the pre- dominantroute of elimination (to avoid accumulation of the drug in a patient with liver or kidney disease), side effects, and whether receptor selectivity or vasodilation are desired. Adverse effects and drug interactions The most common side effects of beta blockers are a direct con- sequenceofadrenergic blockade. These include bronchoconstric- tion, claudication, Raynaud’s phenomenon, intensiﬁcation of hypo- glycemic episodes, and fatigue.
Memory is assessed by the time taken for a food-deprived animal to reach the reward and the number of false arm entries buy ashwagandha 60caps low cost. This simple system can be made more complex by introducing many more arms and branches but the principle is the same buy ashwagandha 60 caps free shipping. In a radial maze a number of arms of equal length radiate from a central point, where the animal is placed. Initially food is placed at the end of each arm and the rat is expected to learn that fact by exploring and entering each arm. The test of memory is to see whether on re-exposure to the maze the rat remembers only to enter an arm not previously visited and so still containing food. A small platform, large enough to take the rat, is placed in the water with its top about 1. When placed in the water the rat finds and escapes to the platform, the position of which is apparently learnt by reference to peripheral visual markers. In this example rats were trained daily to find a platform just submerged below water in a circular (150 cm) glass tank painted black and the time taken to reach it recorded. Young (4-month) saline-treated rats (o) quickly learnt and from day 6 consistently swam to the platform in less than 10 s. By contrast, aged (22-month) rats (&) took significantly longer to acquire the task and by day 10 were still taking about 30 s. In experimental studies in both humans and animals they disrupt both the acquisition and the performance of learned behaviour. It is by no means certain, however, that the memory defects induced by antimuscarinics are identical to those seen in AzD. Any attempt to answer that question has to follow some consideration of how memory is thought to be processed. Many neuroscientists believe that memory is achieved by changes in the strength of synaptic connections (activation) between neurons and that increases in such synaptic activity somehow reinforce the pattern of neuronal activity during the memorising of an event so that it can be more easily restored later. This is not because it is a site of major degeneration in AzD, that finding can only be used to account for the memory loss if memory is known to be dependent on the hippocampus, but because lesions of that region are known to impair memory. Case reports in the medical literature are rightly mistrusted but few people have felt inclined to disregard the evidence presented by one 27-year-old male mechanic who underwent bilateral hippocampal removal for intractable epilepsy in Montreal in 1953. While that condition was improved the operation has not been repeated because memory loss was almost total, so while he appeared to behave reasonably normally (and still does), he cannot remember where he lives, what he has just eaten or the person he met a few minutes previously. Long-term potentiation can be defined as the increased effectiveness (potentiation) of synaptic transmission which may last for hours (possibly days) and is triggered experi- mentally by a brief burst of high-frequency stimulation of presynaptic inputs so that the response to any following input is much greater than normal. It was first demonstrated in vivo (Bliss and Loma 1973) but much studied in vitro. There is considerable debate as to whether the potentiation is of pre- or postsynaptic origin, or both, and while neurons can discharge spontaneously at an appropriate tetanic frequency (e. Removal of the posterior pituitary in rats shortens retention of a conditioned avoidance response, an effect which can be overcome by the administration of vasopressin. Variable but generally weak positive effects on cognition have been seen with this peptide in humans. Opioids tend to impair and their antagonists improve memory in animals (see McGough, Introlni-Collison and Castellano 1993). Increased synthesis This requires the provision of the precursor choline which is often given as lecithin (phosphatidyl choline), a natural source of choline found in many foods such as eggs and fish. Brain penetration is modest but uptake into cholinergic nerve terminals is through a sodium-dependent high-affinity system that is normally adequately supplied and possibly saturated with choline. Whether choline could reverse the choline leakage and resulting autocannibalism (see above) of cholinergic neurons is not known. Blocking its activity with various anticholinesterases has been widely investigated and some improvement in memory noted. Such studies have invariably used reversible inhibition because of the toxicity associated with long-term irreversible inhibition of the enzyme. It is known to improve memory in animals and some small effects have been seen in humans (reduces number of mistakes in word-recall tests rather than number of words recalled), but it really needs to be given intravenously and has a very short half-life (30 min). The limited effectiveness of physostigmine did, however, encourage the development of longer-acting orally effective anticholinesterases such as tacrine (tetrahydroamino- acrydine), velnacrine and donepezil. Clinical evaluation ofanticholinesterases and other drugs in AzD The newer anticholinesterases have all been subject to large and often multicentred trials. These take various forms but generally include an initial assessment of disease severity over a few weeks while on placebo alone, then a drug-dose evaluation before the chosen drug dose(s) is compared directly with placebo for some weeks in two groups. Confirmation of any drug effect is usually obtained by finishing with all patients on placebo. Although performed double-blind generally, only patients that respond in the early evaluation period enter the final drug trial and those with severe AzD are excluded altogether. There is a need to record changes in both cognitive function and general performance. The former measures such things as memory, language, orientation, reason and praxis, on a 0±70 scale range. The higher the score, the more severe the condition, and as most patients normally decline at the acquisition rate of 5±10 extra points a year, any reduction of 4 or more points is considered a drug effect.
Various antibiotics (penicillin) and anticancer agents (taxol) are derived from natural product sources effective ashwagandha 60 caps. There is good reason to be optimistic about the potential future usefulness of such exogenous compounds as a continuing source of potential lead compounds cheap ashwagandha 60caps with mastercard. With many thousands of years of trial-and-error by evolution on her side, Mother Nature is a vastly superior experimentalist to any mere human organic chemist. Amphibian evolution has enabled the biosynthesis of antibacterial peptides on the skins of frogs so that they can avoid infections as they swim through stagnant swamp waters; peptides such as these could be a good starting point for the peptidomimetic design of novel antibacterial agents. Reptile evolution has culminated in the biosynthesis of neuroactive venoms for pur- poses of hunting and defense; these molecules have been fine-tuned by evolution as agents specific for neurotransmitter receptors. Plant evolution has culminated in a wide variety of biomolecules that affect any animal that may choose to eat them: it is bio- logically advantageous for some plants to be eaten so that their seeds can be dispersed in the stool of the animal that ate them; conversely, it is biologically advantageous for other plants to produce noxious chemicals to decrease the likelihood of their being eaten. Because of these diverse biological activities, any of these non-human biosyn- thetic molecules could, in principle, be a lead compound for human drug discovery. Another promising feature of animal- or plant-based natural products is that they are a superb source of molecular diversity. As a synthetic chemist, Nature is much more creative and is not constrained to the same finite number of synthetic reactions typically employed by human synthetic organic chemists. Furthermore, when developing compound libraries for high throughput screening (see section 3. Although ethnopharmacology, the scientific investigation of natural products, folk medicine, and traditional remedies, has led to some bona fide drugs (e. However, natural products have always been and still are an inexhaustible source of drug leads as well as drugs. From each of these sources, extracts conducted with solvents with different polar- ities will yield different natural products. This complex extraction system ensures the identifica- tion of all possible candidate molecules from a plant source. Several research institutes and well-established groups (notably the Scripps Institute of Oceanography and the University of Hawaii) are producing some very promis- ing results in this field. The isolation of prostaglandins from a coral was one of the more startling recent discoveries in marine pharmacology. An extension of natural products chemistry is the biochemical information derived from the study of metabolic pathways, enzyme mechanisms, and cell physiological phenomena; this research has revealed exploitable differences between host and para- site (including malignant cells), and between normal and pathological function in terms of these parameters. The large and fertile area of antimetabolite (metabolic inhibitors) and parametabolite (metabolic substitutes) chemistry is based on such stratagems, and has found use in the field of enzyme inhibition and in conjunction with nucleic acid metabolism. The design of drugs based on biochemical leads remains a highly sophis- ticated endeavor, light-years removed from the random screening of sulfonamide dyes in which it has its origin. However, of the approximately 10200 “small” organic molecules that could theoretically exist in our world (1052 of which are drug- like molecules), many would be purely synthetic substances that do not occur naturally. The concept of rational drug design (in contrast to its logical counterpart, irrational drug design) implies that the disease under consideration is understood at some funda- mental molecular level and that this understanding can be exploited for purposes of drug design. Such an understanding would facilitate the design of purely synthetic mol- ecules as putative drugs. Although this ideal of rational drug design has been pursued for many years (see section 3. Recognizing its chemical similarity to iodine, French physicians immediately exploited it as an iodine alternative for the treat- ment of numerous conditions, including syphilis and thyroid goitre. Although no bene- ficial effects were reported for either bromine or its potassium salt, their widespread use persisted and eventually the depressant effect of potassium bromide on the nervous system, so-called ivresse bromurique, was recognized. However, it was a report in the German literature concerning bromide’s ability to induce impotence and hyposexuality, rather than ivresse bromurique, which lead to its discovery as an anticonvulsant. In 1857, Sir Charles Locock, the physician accoucheur to Queen Victoria, ascrib- ing to the then prevalent view that epilepsy arose from excessive sexuality, introduced bromide as an anaphrodisiac to suppress the supposed hypersexuality of epileptics. Although side effects had been considerable (and included psychoses and serious skin rashes), bromides were successful in 13 of the 14 patients treated. On 11 May 1857, at a meeting of the Royal Medical and Chirurgical Society, Locock proudly reported his success in treating “hypersexual” epilepsies with bromides. He argued that logical and rational drug development had finally been achieved for the time: epilepsy arises from excessive sexuality; potassium bromide suppresses sexual- ity; therefore, potassium bromide successfully treats epilepsy. In reality, it was little more than yet another serendipitous discovery, since hypersexuality has absolutely nothing to do with epilepsy. Regardless of the flawed reasoning, bromides were a major step forward in the treatment of epilepsy and their use persisted until the introduction of phenobarbital in 1912. Rational drug design is an iterative process, dependent upon feedback loops and new information. When the drug designer makes the first prototype molecule, this molecule becomes a probe with which to test the drug design hypotheses. The molecule can then be further designed and refined to better improve its ability to dock with the receptor site and elicit a biological response. This cycle of “design–test–redesign–retest” can go on for several iterations until the optimized molecule is achieved. The successful ratio- nal design of a drug is similar to solving a major puzzle using your wits and wisdom.
Indeed generic ashwagandha 60 caps, for many years excessive drunkenness was considered a moral failing rather than a disease generic ashwagandha 60 caps visa, and not until the 1950s was alcoholism ofﬁcially recognized as an afﬂiction appropriate for medical treatment. Temperance societies, organizations whose members pledged to avoid beverage alcohol and to discourage consumption by other persons, became politically powerful. Before the Civil War such groups had been able to get laws passed outlawing the sale of beverage alcohol in various communities and sometimes throughout entire states. Shortly after World War I this agi- tation culminated in the Eighteenth Amendment to the Constitution of the United States, giving the federal government power to ban manufacture and sale of beverage alcohol. Although purchase and consumption remained legal, the majority of Americans became so displeased with Prohibition that the Twenty-ﬁrst Amendment to the Constitution was passed in the 1930s repeal- ing the earlier one. This calming and sleep-inducing substance is probably the most fre- quently prescribed drug in the benzodiazepine class. Alprazolam is used mainly to help persons suffering from panic attacks and other anxiety disor- ders, but it is not recommended for posttraumatic stress disorder. Theoretical reasons and results from a rat experiment suggest that alprazolam may help maintain bone mass. That action may be especially important to athletes and elderly women, who commonly suffer loss of bone mass—an afﬂiction making breakage easier. The drug has been tested as an asthma treatment with encouraging results, though reasons for success are unclear. In an experiment measuring alprazolam’s pain-relieving properties, the drug re- duced the severity but not the frequency of chronic tension headaches. The compound has antidepressant and anticonvulsant properties, has been used to treat ringing in the ears and to alleviate tremors and catatonia, and has been found useful in easing alcohol withdrawal symptoms in alcoholics. A rat study suggests that alprazolam may also have a place in treating cocaine addiction. Measurements ﬁnd the drug worsens snoring but improves quality of sleep (at least for the snorers). Experiments show that the drug reduces startle response in hu- mans, which may mean drivers are less alert or respond less vigorously to situations. Case reports tell of alprazolam (alone and in combination with other medicine) causing the skin to become extra sensitive to sunlight. Alprazolam 43 Although the drug normally encourages eating, about 20% of persons in one study experienced weight loss, along with unwanted effects such as dif- ﬁculty in controlling muscles (including urinary incontinence), peevishness, bellicosity, and lowering of inhibitions. Researchers generally believe the drug interferes with sexual function in men and women. A case report tells of the drug causing mania with euphoria, high self-conﬁdence, increased energy, and trouble with getting proper sleep—all rather untypical effects. Despite such possibilities, one team reviewing scientiﬁc literature found reports of unwanted actions to be uncommon for alprazolam, and another team con- cluded that alprazolam generally has fewer such reports than other benzodi- azepine class drugs. Analysts who examined medical records of 10,895 alprazolam patients found little mention of unwanted effects. In evaluating the infrequent accounts of mania, aggression, hallucinations, or other unex- pected psychological reactions to alprazolam, we should remember that many such cases involve persons already exhibiting psychiatric disturbances for which they are receiving the drug. An experiment showed no tendency for abuse of alprazolam among users even though it is a controlled substance. A 1993 review of human and animal studies of the drug concluded that scientiﬁc experimental evidence failed to support a popular belief that abuse of alprazolam was more likely than abuse of other benzodiazepine class drugs. Another 1993 report dis- agreed but described alprazolam abuse as minuscule and limited to persons already misusing other drugs, particularly opiates and alcohol. Brainwave and other measurements imply that alprazolam has more appeal to alcoholic men than it does to nonalcoholics. Experiments show that persons with a family history of alcoholism tend to experience more pleasure (even euphoria) when taking alprazolam than do persons lacking such a history. Tests ﬁnd the drug to have stronger effects (positive and negative) on women whose fathers were alcoholics, compared to women whose immediate family background does not include alcoholism. When experiments gave drug abusers a choice between diazepam or alprazolam, the abusers tried both but found alprazolam more pleasant. Craving and tolerance do not seem to develop, but alprazolam can produce bodily dependence, which is a traditional sign of addictive potential. Sudden stoppage can cause seizures or delirium, so practitioners customarily wean their patients with tapering dosages. Withdrawal symptoms may include per- spiration, tremors, cramps, vomiting, diarrhea, cloudy eyesight, prickling sen- sations on the skin, and general befuddlement. Kava is an intoxicating drink prepared from the kava plant, suspected of interacting so seriously with alprazolam that a coma may result. Persons taking antifungus drugs such as itraconazole or ketoconazole are supposed to avoid alprazolam, as those two drugs increase the power and prolong the effect of an alprazolam dose. In contrast, alprazolam’s effects are reduced by the epilepsy drugs phe- nytoin and carbamazepine, by the tuberculosis medicine rifampin, and by the asthma medication theophylline. A case of glaucoma resulting in blindness is attributed to a multidrug regimen of antidepressants and antianxiety medi- cines including alprazolam. Taking alprazolam with diazepam can cause persons to forget what happened while they were under the drugs’ inﬂuence.