By Q. Zapotek. University of the Sciences in Philadelphia.
Unwanted effects can include nausea cheap omeprazole 10 mg without a prescription, vomiting 10 mg omeprazole otc, perspiration, rapid pulse, breathing impairment, urinary difﬁculty, lowered body temper- ature and blood pressure, and dizziness. Compared to morphine, dextro- moramide is less likely to cause constipation or sleepiness. Persons taking dextromoramide are generally warned against driving cars or running other dangerous machinery. A case report mentions a drug abuser’s serious, but curable, heart damage caused by injecting crushed oral tablets of dextromoramide. Dextromoramide is chemically related to methadone, and some researchers believe that dextromoramide could be a useful supplemental drug for addicts being treated in methadone maintenance programs. Mor- phine and dextromoramide have enough cross-tolerance to prevent morphine withdrawal symptoms. Dextromoramide itself is addictive; around 1990 a sur- vey of 150 methadone patients in London found that 7 were being treated for Dextromoramide 115 dextromoramide addiction. At one time some medical observers doubted that dextromoramide is addictive, but negative results in their research were prob- ably due to the medical context in which the drug was being used. In rats the development of dextromoramide tolerance is so much slower than with mor- phine that one group of investigators doubted the phenomenon was really occurring. Researchers have disagreed about how fast tolerance appears in humans, but it does occur, as does dependence. Disagreement about how quickly tolerance emerges in humans may be related to which drug effects are being examined; tolerance does not necessarily develop to all of a drug’s ef- fects at the same rate. For example, tolerance to pain relief properties might emerge at a different point of treatment than tolerance to nausea or sleepiness caused by a drug. Taking this drug with antihistamines or depressants (such as alcohol) can be risky. Persons with breathing difﬁculty or poor thyroid activity should be careful about taking this drug. The drug produces massive birth defects in mice, but its ability to cause human malformations at normal medical dosage levels is unknown. Dextromoramide has been used to ease childbirth, but if pregnant women receive the drug shortly before giving birth, their infants may have trouble breathing. This substance is closely related to levorphanol and can produce a false positive for levorphanol in drug screen tests. The same trans- formation occurs in rats; when comparing results in males and females, researchers found that a given amount of dextrorphan lasts twice as long in female rats. Dextrorphan can ﬁght coughs and reduce epileptic seizures, although test results differ about how well it diminishes seizures. Mice research has found that the drug helps mice recover from strokes, and in humans the drug ap- pears useful for treating minor strokes. Some research indicates that the sub- stance has potential for treating various human neurological afﬂictions, but such potential has yet to be fulﬁlled. A rat experiment found dextrorphan ineffective in preventing brain damage caused by the chemical warfare agent soman. A rat study testing dextrorphan’s potential as an antidote for meth- cathinone poisoning had limited success. Unwanted side effects may include nausea, vomiting, sleepi- ness, high or low blood pressure, uncontrollable eye movement, and halluci- nations. When one group of researchers tested dextrorphan’s ability to pre- vent some types of brain damage, the scientists found instead that dextror- phan caused damage in rats. At one time dextrorphan was a Schedule I substance, but eventually it was removed from any schedule of controlled substances. Such a journey is most unusual; assorted drugs have been moved from one schedule to another over the years, but the direction is almost always to put the drugs under more controls rather than fewer. At sufﬁciently high levels, dextrorphan can make people feel as if they are intoxicated with alcohol. After male mice received dextrorphan in an experiment, they Dextrorphan 117 produced offspring having lower weight, delays in maturation, and abnormal swimming behavior. Whether the drug passes into a human fetus or the milk supply of a nursing mother is unknown. By the end of the twentieth century diazepam was one of the best- known antianxiety agents in America. Other medical uses of this fast-acting and long-lasting drug include treatment of insomnia, migraine, facial pain, muscle spasms, convulsions, vomiting, malaria, rattlesnake bite, alcohol and heroin withdrawal syndromes, cardiac difﬁculty created by cocaine, and mus- cle stiffness from tetanus and other causes. The body converts the drug into other chemicals, including temazepam and oxazepam. Unwanted actions of diazepam include weariness and weak- ness and occasionally headache, dizziness and vertigo, nausea, fuzzy or dou- ble vision, urinary control problems, and depressed mood. The compound can make users tired and impair vigilance, judgment, re- action times, and movement. A person using diazepam should be cautious about operating dangerous machinery; simulated driving tests demonstrate reduced ability after a dose. A study of newborn rats receiving the drug found that it slowed learning, but their learning capacity was normal even though the rats needed more time to learn something. Diazepam can interfere with the ability to recognize an angry ex- pression on someone’s face—a disability with distinct potential for social con- sequences—and a laboratory experiment demonstrated the drug’s ability to make people more aggressive if they are provoked. Diazepam is given to treat epileptic seizures, but long-term use can increase Diazepam 119 epileptic seizures. Among epileptics the drug can also cause status epilepticus, a potentially fatal condition in which seizures occur back to back. This mishap has been known to occur even when medical professionals administer the drug, and most rec- reational users lack training in anatomy. Intravenous injection of diazepam can stop breathing and heart action; when administering the drug intravenously hospitals are prepared for such emergencies, but most street users are not. In a small percentage of human volunteers (5% or less), rectal administration has produced euphoria, breathing difﬁculty, skin rash, runny nose, or diarrhea.
The court held that the plaintiffs failed to controvert this testimony effective 40 mg omeprazole, that the defendant manufacturers were shielded from liability under the “learned intermediary doctrine omeprazole 40mg visa,” and that any failure to warn on the part of the defendants was therefore not the proximate cause of Mr. The plaintiffs had alleged that the defendant manufacturers had failed to label their products with adequate warnings of Dilantin’s propensity to interact with acetamin- ophen, placed defective and unreasonably dangerous products in the marketplace that caused Mr. Eck’s liver failure, and were negligent in the designing, testing, warning, and marketing of their products through their failure to provide adequate instructions or warnings, and by misrepresenting the safety of their products when used in conjunc- tion with one another. Applying Oklahoma law, the court reasoned that, in order to recover in a failure to warn case against a drug manufacturer, a plaintiff must establish both cause-in-fact (that the product in question caused the injury) and proximate cause (that the manufac- turer of the product breached a duty to warn of possible detrimental reactions, and this breach was a substantial contributing factor in causing the harm). Under Restatement (Second) Torts § 402A comment K, certain products, including prescription drugs, are “unavoidably unsafe products” that cannot be made completely safe, but serve a public benefit, so drug manufacturers cannot be held strictly liable merely because of the dan- gerous propensities of their products. Although the manufacturer has a duty to warn ultimate consumers of known dangers of prescription drugs and their interactions, there is an exception to this duty—the “learned intermediary doctrine”—under which the manufacturer is shielded from liability where the product is properly prepared and mar- keted and proper warning is given to prescribing physicians. The prescribing physician acts as a learned intermediary between the patient and the prescription drug manufac- turer by assessing the medical risks in light of the patient’s needs. No part of this book may be reproduced in any form, by photostat, microfilm, xerography or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc. Drugs for Inflammatory and Related Disorders Chapter 1: Histamine and Antihistamines 227 Chapter 2: Drugs Used in Gastrointestinal Dysfunction. Chapter 1: Anticancer Drugs 307 Chapter 2: Anticancer Drug Practice Questions 311 Sedion X: Immunopharmacology Chapter 1: Immunopharmacology 315 Chapter 2: Immunopharmacology Practice Questions. The Notes were designed to be accompanied by faculty lectures-live, on video, or on the web. To maximize the effectiveness of these Notes, annotate them as you listen to lectures. While these margins are occasionally punctuated by faculty high-yield "margin notes," they are, for the most part, left blank for your notations. Many students find that previewing the Notes prior to the lecture is a very effective way to prepare for class. It also affords you the opportunity to map out how the information is going to be presented and what sorts of study aids (charts, diagrams, etc. Pharmacokinetics Pharmacokinetic characteristics of drug molecules concern the processes of absorption, distri- bution, metabolism, and excretion. The biodisposition of a drug involves its permeation across cellular membrane barriers. Absorption into Plasma Drug"Excretion Drug Metabolism (Renal, Biliary, (Liver, Lung, Blood, etc. Ability to diffuse through lipid bilayers (lipid solubility) is important for most drugs; however, water solubility Can influence permeation through aqueous phases. Diffusion down a concentration gradient--only free, unionized drug forms contribute to the concentration gradient. The larger the surface area and the greater the vascularity, In A Nutshell the better is the absorption of the drug. Clinical Correlate ~ • Only nonionized forms undergo active secretion and active or passive reabsorption. Renal Clearance of Drug Modes of Drug Transport Across a Membrane Bridge to Physiology Table 1-1-1. Mechanism Direction I mechanisms are discussed No No No I in greater detail in Section Passive diffusion Down gradient! Facilitated diffusion Down gradient No Yes Yes Active transport Against gradient Yes Yes Yes (concentration! For some drugs, their rapid hepatic metabolism decreases bioavailability-the "first- pass" effect. Effect of Rate of Absorption on Plasma Concentration Cmax and tmax are rate dependent. The faster the rate of absorption, the smaller the tmax and the larger the Cmax and vice versa. Drug + Protein ~ Drug-Protein Complex (Active, free) (Inactive, bound) - Competition between drugs for plasma protein-binding sites may increase the "free fraction," possibly enhancing the effects of the drug displaced. Example: levodopa versus dopamine Apparent Volume of Distribution 01d) A kinetic parameter of a drug that correlates dose with plasma level at zero time. This raises the possibility of displacement by other agents; examples: verapamil and quinidine can • blood volume (5 L) displace digoxin from tissue-binding sites. With a second dose, the blood/fat is less; therefore, the rate of redistribution is less and the second dose has a longer duration of action. A few compounds (prodrugs) have no activity until they undergo metabolic activation. Inactive metabolite(s) Active Metabolites Drug -----+ Active metabolite(s) Biotransformation of the Prodrug ---+~ Drug benzodiazepines diazepam results in formation of nordiazepam, a metabolite Figure 1-1-9. Biotransformation of Drugs with sedative-hypnotic activity and a long duration of action. Phase I • Definition: modification of the drug molecule via oxidation, reduction, or hydrolysis. Drugs with zero-order elimination include ethanol (except low blood levels), phenytoin (high therapeutic doses), and salicylates (toxic doses). Plots of Zero-Order Kinetics 12 ",~ical Pharmacokinetics First-Order Elimination Rate In A Nutshell • A constant fraction of the drug is eliminated per unit time (t1/2is a constant). Graphically, Elimination Kinetics first-order elimination follows an exponential decay versus time. Plasma Decay Curve-First-Order Elimination Figure 1-1-11 shows a plasma decay curve of-a drug with first-order elimination plotted on semilog graph paper. Plateau Principle The time to reach steady state is dependent only on the elimination half-life of a drug and is independent of dose size and frequency of administration. With such inter- " mittent dosing, plasma levels oscillate through peaks and troughs, with averages shown in the diagram by the dashed line. Regardless of the rate of infusion, it takes the same amount of time to reach steady state.
Serum potassium After 7 days * Heparininhibitsthe secretionofaldosterone and so may cause "K purchase omeprazole 10 mg otc. This assessment is based on the full range of preparation and administration options described in the monograph purchase omeprazole 10 mg fast delivery. Hyaluronidase 1500-unit dry powder ampoules * Hyaluronidase is an enzyme that makes body tissue more permeable to injected fluids. Pre-treatment checks * Do not use to reduce the swelling of bites or stings, or for anaesthetic procedures in unexplained premature labour. Extravasation: where dispersal rather than localisation is indicated, 1500 units infiltrated into affected area (as soon as possible after extravasation is noticed). With subcutaneous infusions Care should be taken to control the speed and total volume of fluid administered and to avoid over-hydration, especially in renal impairment. Alternatively, it may be injected into the tubing of the infusion set (about 2cm back from the needle) at the start of the infusion. Dissolve 1500 units directly in the solution to be injected (check compatibility). Technical information Incompatible with Benzodiazepines, furosemide, heparin sodium, phenytoin. Monitoring Measure Frequency Rationale Infusion site When the bag is changed or * The site should be moved if pain is more frequently for solutions experienced at the infusion site, if the other than NaCl 0. Additional information Common and serious Immediate: Anaphylaxis has been reported rarely. This assessment is based on the full range of preparation and administration options described in the monograph. The injection is used in management of hypertension with renal complications and hypertensive emergencies particularly those associated with pre-eclampsia and toxaemia of pregnancy. Pre-treatment checks * Avoid in patients with idiopathic systemic lupus erythematosus, severe "pulse, high output heart failure, myocardial insufficiency due to mechanical obstruction, cor pulmonale, dissecting aortic aneurysm; acute porphyria. The rate should be titrated to response and maintenance rate is usually within 50--150 micrograms/minute. Dose in renal impairment: if CrCl < 30mL/minute, the dose or dose interval should be adjusted according to clinical response. Hydralazine hydrochloride | 421 Dose in hepatic impairment: the dose or dose interval should be adjusted according to clinical response. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion (large-volume infusion) Preparation and administration 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion via a syringe pump Preparation and administration 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with Hydralazine is incompatible with glucose solutions. Additional information Common and serious Injection/infusion-related: Local: Pain. Pharmacokinetics Elimination half-life is 2--3 hours but is up to 16 hours in severe renal failure (CrCl <20mL/minute) and shortened to <1 hour in rapid acetylators. Antidote: No known antidote; stop administration and give supportive therapy as appropriate. This assessment is based on the full range of preparation and administration options described in the monograph. Hydrocortisone acetate 25mg/mL aqueous suspension in 1-mL ampoules * Hydrocortisone acetate is a corticosteroid formulated for local use only. Monitoring Measure Frequency Rationale Symptoms of septic Following * Marked "pain accompanied by local swelling, arthritis intra-articular further restriction of joint motion, fever, and injection malaise are suggestive of septic arthritis. Additional information Common and serious Injection-related: Intra-articular: Temporary local exacerbation with increased undesirable effects pain and swelling. Pharmacokinetics Absorption after local injection is very slow and is usually completed 24--48 hours after intra-articular injection. Significant A small number of local injections are unlikely to have any significant interactions interactions typical of corticosteroids. This assessment is based on the full range of preparation and administration options described in the monograph. Hydrocortisone sodium phosphate 100mg/mL solution in 1-mL and 5-mL ampoules * Hydrocortisone sodium phosphate is a corticosteroid with both glucocorticoid and, to a lesser extent, mineralocorticoid activity. Pre-treatment checks * Avoid where systemic infection is present (unless specific therapy is given). The dose may be repeated 3--4 times in 24 hours as determined by the patient’s response. Injection into soft tissues: 100--200mg daily; may be repeated on 2--3 occasions depending upon the patient’s response. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Hydrocortisone sodium phosphate | 427 Monitoring Measure Frequency Rationale Serum Na, K, Ca Throughout treatment * May cause fluid and electrolyte disturbances. Withdrawal During withdrawal and * During prolonged therapy with corticosteroids, symptoms and signs after stopping treatment adrenal atrophy develops and can persist for years after stopping. Signs of infection During treatment * Prolonged courses "susceptibility to infections and severity of infections. Signs of chickenpox * Unless they have had chickenpox, patients receiving corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox.
When designing drugs for the nervous system for example 20mg omeprazole mastercard, the rules for designing the drug to enter the brain will apply to all molecules being designed discount 20 mg omeprazole with mastercard. Nevertheless, this classification system is not ideal in connecting “disease to molecule. This system categorizes disease processes in terms of damage at the tissue and cellular level. Traumatic (pathology from injury) External source (destructive physical injury; e. Toxic (pathology from poisons) Biological toxins (snake venom) Chemical/physical toxins (toxic chemicals, radiation) 3. Hemodynamic/vascular (pathology from disorders of blood vessels) Ischemic (decreased blood supply to an organ or tissue; e. Hypoxic (pathology from inadequate supply or excessive demand for oxygen by a tissue) Generalized/organ specific (lung disease, anemia, decreased blood supply) Cellular hypoxia (cyanide poisoning of electron transport chain in mitochondria) 5. Inflammatory (pathology from abnormal inflammatory response in the body) Autoimmune and/or chronic diseases (systemic lupus erythmatosus, rheumatoid arthritis) Response to environmental triggers (asthma) 6. Infectious (pathology from microbes or infectious agents) Prions, viruses, bacteria, fungi, parasites (pneumonia, meningitis, gastroenteritis) 7. Neoplastic (pathology from tumors, cancer) Carcinoma (adenocarcinoma of the breast) Sarcoma (osteogenic sarcoma) 8. Nutritional (pathology from too much/too little food intake) Deficiency (vitamin deficiency secondary to reduced intake) Excess (obesity leading to diabetes) 9. Developmental (pathology in the chemistry of heredity) Inborn errors of metabolism (Fanconi’s syndrome, cystinuria) Genetic diseases (Huntington’s disease) 10. Degenerative (pathology from age-related tissue breakdown) Protein misfolding diseases (Alzheimer’s dementia, prion diseases) Apoptosis (pre-programmed cell death) Mechanical “wear-and-tear” (osteoarthritis [or, more correctly, osteoarthropathy]) This classification system is based on a traditional pathology approach to disease with emphasis on etiology (causative factors) and pathogenesis (mechanism of disease, particularly at a cellular level). For example, drug design that targets neoplasia may lead to drugs with many applications, including lung cancer, bowel cancer, or brain cancer. Likewise, drug design that targets inflammation could have applications to many dif- ferent diseases, affecting many organ systems. Nevertheless, this approach focuses more on cellular targets than on molecular targets. Neuropeptides and peptidergic receptors Opioid peptides Neurokinins Neuropeptide Y Galanin Cholecystokinin j. Steroid hormones and their receptors Estrogens Progestins Androgens Adrenal steroids b. Peptide hormones and their receptors Pituitary neurohormones Oxytocin and vasopressin Insulin and glucagon Renin–angiotensin hormones 3. Cytoplasmic organelle targets Mitochondrial targets Rough endoplasmic reticulum Smooth endoplasmic reticulum c. Proteins Enzyme proteins Hydrolases Amidases (proteases) Esterases (lipases) Ligases Carboxylases Synthetases Lyases Decarboxylases Dehydrases Oxidoreductases Oxidases Reductases Dehydrogenases Transferases Kinases Transaminases Enzyme cofactors Vitamins Non-enzyme proteins Abnormal folding proteins (amyloid) Growth factors (nerve growth factor) Endogenous proteins from other animals (snail conotoxins) b. Environmental toxins Biological Chemical Organic Inorganic Physical Within each of these categories there is a further refinement of targets. As discussed in chapter 9, for example, possible druggable targets for antifungal drug design may be subdivided as follows: 1. Fungal cell wall disruptors These subclassifications are given in detail in the corresponding chapters (4–9). Drug molecules were divided into acyclic and cyclic structures, which were then further subdivided. For example, the cyclic mol- ecules were categorized into steroids, heterocycles, and so on. These were then subcat- egorized; for instance, heterocycles had many subcategories including benzodiazepines, imidazolidinediones, dihydropyridines, etc. Regrettably, this classification system is too extensive and too cumbersome to be useful. It starts at the level of the biomolecule and works up to the pathological processes (traumatic, toxic, …), then to the physiological systems (cardiovascular, endocrine, …) and ultimately to the diseases affecting these systems. Because of its molecular-based approach, it offers def- inite advantages for drug design. The goal of medicinal chemistry is to design novel chemical compounds that will favorably influence ongoing biochemistry in the host organism in some beneficial manner. As discussed in chapters 4–6, one of the most obvious approaches is to either mimic or block endogenous messengers used by the organism itself to control or alter its own bio- chemistry. These endogenous messengers may be neurotransmitters (fast messengers), hormones (intermediate), or immunomodulators (slow), working at the electrical, mole- cular, or cellular levels, respectively. However, not all pathologies that afflict the human organism can be addressed by manipulation of these messengers. Accordingly, it becomes necessary to directly target other cellular components and/or endogenous macromolecules that are not normally directly controlled through binding to endogenous messengers. These endogenous macromolecules are the catalysts and molecular machinery that enable the cell to perform its normal metabolic functions; accordingly, they afford numerous druggable targets. Finally, if that approach is not sufficient, it would next be necessary to attack the agent causing the disease process, perhaps a bacterium or virus. Design the drug to manipulate endogenous messengers that would normally respond to the disease process. Design the drug to influence endogenous targets involved in the disease but not influenced by messenger systems. For example, when confronted with the task of designing drugs for systemic arterial hypertension and atherosclerosis, there are many targets. Following Step 1, drugs could be designed to interact with messenger neurotransmitter (adrenergic) receptors (e. Following Step 2, drugs could be designed to interact with non-messenger pro- tein targets such as enzymes involved in fluid homeostasis (e. Similarly, drugs used for the treatment of epilepsy may produce untoward events in individuals susceptible to heart arrhythmias because seizures and cardiac arrhythmias are both mediated by voltage-gated ion channels. It provides a structural and concep- tual framework that enables this knowledge and information to be stored and logically manipulated in a meaningful way for purposes of practical drug design. This page intentionally left blank 4 Messenger Targets for Drug Action I Neurotransmitters and their receptors 4. Since most of these messengers act on nerve cells (neurons), it is appropriate to review the anatomy and physiology of the nervous system and to discuss briefly the neuronal networks that can be manipulated therapeutically.
In the next chapter buy discount omeprazole 10 mg line, you’ll learn more about those displayed on the videos and in the photographs— trigger points cheap omeprazole 10mg overnight delivery, how they develop and cause pain, and most making it easy to isolate what’s causing your back pain. In this chapter, I’ll discuss trigger-point therapy as the most effective treatment approach for most cases of knotted- muscle pain. Keep in mind that if you suffer from both nerve- and tissue-based back pain, trigger-point therapy will solve only part of your problem. In addition, while trigger-point therapy is great at getting rid of the knots that cause back pain, it doesn’t prevent those knots from forming in the first place. In severe cases of tissue-based pain, you’ll also want to prevent the creation of knots—or more typically, prevent preexisting trigger-point areas from flaring up. To do this, you’ll need to focus on changes in lifestyle, particularly dealing with problems in the mind (e. Imagine a muscle as a handful of spaghetti, with each straight, hanging noodle representing a muscle fiber. In a healthy muscle, all the fibers are long and even, like spaghetti, or like the hairs on the bow of a violin. A trigger point causes an unhealthy contraction, so that some of those fibers twist, or seize up, into a knot. First, the muscle loses access to the nutrients in the blood, and second, without healthy circulation passing through, toxins tend to build up in the contracted area. The muscle typically shortens as well, just like a strand of rope shortens when you tie a few knots in the middle of it. If you massage another person, when your fingers run over hard knots under the skin, they are usually trigger points. If you find one near the right shoulder blade, for instance, check near the left shoulder blade. If you find a similar hard spot, it’s probably a bone, but if you don’t, that first one was probably a trigger point. So if you press on it and the person yelps, you can bet you’ve hit a trigger point. Trigger points also can cause general pain, tightness or restriction of movement, false heart pain, headaches, neck and jaw pain, tennis elbow, joint pain, restless legs, and numbness in the hands and feet. You can find several videos about trigger points and trigger-point therapy on my website at: A trigger point is essentially a small, painful, hard knot within a muscle. In a healthy muscle, all the fibers are long and even, like Trigger Points Can Cause Many Other Problems spaghetti, or like the hairs on the bow of a violin. A trigger point causes an unhealthy contraction, so that some of those Once you have a trigger point, or several of them, you will fibers twist, or seize up, into a knot. Unfortunately, all this makes the problem The muscle typically shortens as well, just like a strand of worse, as then your body begins to adopt crooked postures rope shortens when you tie a few knots in the middle of it. If you massage another pain caused by muscle imbalances and tissue-based back pain person, when your fingers run over hard knots under the skin, caused by a knot or trigger point within a single muscle. Such postures then put pressure on joints and ligaments, To be certain, check for the same hard point on the further restricting your activities. If you find one near the right full circle, creating more trigger points and starting the shoulder blade, for instance, check near the left shoulder process all over again. If you find a similar hard spot, it’s probably a bone, but You can see how this quickly leads to lower-back pain if if you don’t, that first one was probably a trigger point. So if They also can cause upper-back pain, typically between the you press on it and the person yelps, you can bet you’ve hit a shoulder blades or at the base of the neck, as these muscles trigger point. To live a pain-free life, it’s critical to treat and relieve trigger points as quickly and thoroughly as possible. While there are many factors that contribute to the development of trigger points, one of the most common is blood circulation that’s too slow or restricted. When you’re experiencing too much stress, you tend to tense your muscles (reducing blood circulation in those muscles), drink too little water (reducing the blood volume available to clear out toxins in the muscles), eat too much unhealthy food (causing inflammation that makes trigger points swell), and forget to move around and stretch (reducing blood circulation in your muscles). These behaviors lead to shallow breathing, which delivers too little oxygen to your muscles. Your tenseness and anxiety lead to decreased blood flow—that stagnation or “too slow” we mentioned in earlier chapters. Without adequate blood flow, the muscle cells in the trigger-point areas of your body are unable to activate the relaxation response that makes the trigger point disappear or at least go dormant. The mechanism that allows muscle cells to “let go” requires the oxygen and energy provided by good blood circulation. Trigger points also can occur as a result of muscle trauma (from car accidents, falls, sports- and work-related injuries, etc. Unfortunately, once you have a trigger point, it tends to undergo a self-reinforcing cycle—which means it sticks around for a while. Active and Inactive Trigger Points Most of us are walking around with trigger points. Whether or not they cause us pain hinges on whether or not they are “active” at any particular time. While there are many factors that contribute to the Active trigger points are the ones that feel painful. Inactive development of trigger points, one of the most common is ones don’t radiate pain but may still exist as knots and feel blood circulation that’s too slow or restricted. When you’re experiencing too After a trigger point has healed, that area of the muscle much stress, you tend to tense your muscles (reducing blood tends to have a good memory. The trigger point has circulation in those muscles), drink too little water (reducing “branded” it, so to speak, so the next time you experience the blood volume available to clear out toxins in the muscles), stress, overwork certain muscles, or fail to drink enough eat too much unhealthy food (causing inflammation that water, that muscle can contract again in the same place, makes trigger points swell), and forget to move around and activating the same trigger point as before. Let’s say that one day you These behaviors lead to shallow breathing, which delivers accidentally drop it and break the handle. But that handle lead to decreased blood flow—that stagnation or “too slow” now has an old old injury. Without adequate blood flow, the muscle cells in the Trigger points act the same way, particularly if they aren’t trigger-point areas of your body are unable to activate the healed completely. They tend to return again and again, relaxation response that makes the trigger point disappear or whenever the body is under stress. The mechanism that allows muscle cells adopt healing solutions and lifestyle habits that keep trigger to “let go” requires the oxygen and energy provided by good points relaxed and dormant—and keep new ones from blood circulation. Trigger points also can occur as a result of muscle trauma (from car accidents, falls, sports- and work-related injuries, Trigger Points and “Referred” Pain etc. Unfortunately, once you beyond the pain you’re experiencing so you can address the have a trigger point, it tends to undergo a self-reinforcing cause of that pain.
A review from five separate reports of pregnant women with Hodgkin’s disease gave details of 13 normal infants following maternal vinblastine ther- apy purchase 20mg omeprazole otc. Eleven of these infants had first-trimester exposure and two had second-trimester exposure purchase 10mg omeprazole free shipping. Among the offspring of five pregnant women who used vinblastine during the first trimester, congenital anomalies were observed in two infants, there was one spon- taneous abortion and two normal neonates (Metz et al. No anomalies were reported in 27 infants, 17 of whom were exposed during the first trimester (Aviles and Neri, 2001; Wiebe and Sipila, 1994). One normal infant was reported who was exposed following maternal vinblastine, bleomycin, and cisplatin therapy for a malignant ter- atoma during the second trimester (Christman et al. It should be noted that there is considerable overlap in the published reports included in the different reviews. Vinblastine was associated with an increased frequency of congenital anomalies in rats, mice, hamsters, and rabbits exposed during embryogenesis. It is also used to treat Miscellaneous agents 139 melanoma, trophoblastic tumors, and some carcinomas (breast, cervical, ovarian, and lung). The cytotoxic nature of vincristine suggests high potential to cause birth defects in exposed embryos, although no published studies document this. Among 35 infants born to women who received vincristine as part of polydrug antineoplastic regimens at various stages of gestation, there were two spontaneous and three therapeutic abortions, two intrauterine deaths (without anomalies), and 29 live-born infants with no gross anomalies (Caliguri and Mayer, 1989). It is important to note that only 11 of 29 infants were exposed to vincristine in the first trimester, and none were malformed. However, all vincristine- polytherapy-exposed newborns had significant transient pancytopenia, and one infant had polydactyly (most probably not drug-related). Among 31 infants exposed to antineoplas- tic agents during gestation in another review, two major birth defects occurred among those exposed to vincristine polytherapy regimens (Wiebe and Sipila, 1994). Of five infants born to women who sustained exposure to the drug during the first trimester, one had a major congenital anomaly (Metz et al. Vincristine and vinblastine were associated with an increased frequency of congenital anomalies in nonhuman primates and in rat studies (Courtney and Valenio, 1968; Demeyer, 1964, 1965). Acute leukemia, lymphomas, gestational trophoblastic tumors, and a variety of carcinomas are also treated with etoposide. No anomalies were reported in one infant exposed whose mother was treated with an etoposide-containing polytherapy during pregnancy (Rodriguez and Haggag, 1995). One infant was born with cerebral atrophy following first trimester expo- sure to etoposide (Elit et al. According to the manufacturer of the drug, this agent was teratogenic in animals, but these studies have not been subjected to peer review. No studies have been published regarding use of this drug dur- ing the first trimester of pregnancy. Treatment during the second and third trimesters was associated with pancytopenia. In a review of seven infants whose mothers were given L-asparaginase as part of polydrug therapy for leukemia, all were live-born and none had congenital anomalies (Caliguri and Mayer, 1989). Importantly, only one of these infants was exposed to the drug during the first trimester. Asparaginase was associated with an increased frequency of congenital anomalies in the offspring of pregnant rats, rabbits, and mice (Adamson and Fabro, 1970; Lorke and Tettenborn, 1970; Ohguro et al. Cisplatin is also used to treat a number of carcino- mas: adrenal, head and neck, lung, neuroblastoma, osteosarcoma, prostate, stomach, cervical, endometrial, and breast. A review of case reports suggested that cisplatin has been administered in the second and third trimesters without untoward fetal effects (Christman et al. Caution is recommended for its use in the first trimester because platinol interferes with neurolation (complete development of the neural tube) in experimental animals. This corresponds to the 3rd to 4th weeks postcon- ception in humans (Wiebe and Sipila, 1994). In animal teratology studies, investigators found growth retardation but no malformations following exposure during embryoge- nesis to cisplatin in mice, rats, and rabbits (Anabuki et al. It is also used to treat other types of cancer: bladder, brain, breast, endometrium, head and neck, lung, neuroblastoma, testis, and Wilms’ tumor. One case report of carboplatin treatment during the second trimester stated that subsequent fetal and neonatal development was normal (Henderson et al. Manufacturer package inserts report that carboplatin is embryotoxic and teratogenic in rats. In one study, in offspring of rats exposed to carboplatin during embryogenesis, fetal weight was reduced, but there were no congenital anomalies (Kai et al. Miscellaneous agents 141 Procarbazine is also used to treat lymphomas, lung and brain carcinoma, and melanoma. No studies have been published of infants born to women who were exposed to this drug during embryogenesis. A clinical series of six pregnancies were published follow- ing exposure to procarbazine in the first trimester (four in combination with other agents). Among these infants two were normal, one infant had hemangiomas on its extremities, one elective abortion occurred, and two miscarriages were reported. Of the miscarriages, one had malpositioned, hypoplastic kidneys and the other had four toes on each foot, with bilateral webbing (Gililland and Weinstein, 1983). In a review of col- lected cases, the authors summarized their findings, stating that procarbazine use ‘in early pregnancy, particularly during the period of fetal neurolization and morphogene- sis (3rd to 12th weeks menstrual in humans) does appear to be associated with the risk of teratologic effects’ (Wiebe and Sipila, 1994) (emphasis added). Congenital anomalies were increased in frequency among rats whose mothers were treated with procarbazine during embryogenesis (Chaube and Murphy, 1968; Tuchmann-Duplessis and Mercier- Parot, 1967). No studies have been published on the use of hydroxyurea during pregnancy in humans. A case report of two infants exposed to hydroxyurea during the second and third trimesters as part of polydrug therapy had no congenital anomalies in the fetus (therapeutic abortion) or the live born infant (Caliguri and Mayer, 1989). Three subsequent case reports of fetuses exposed in the first and second trimesters revealed no anomalies (Fitzgerald and McCann, 1993; Jackson et al. Among seven women treated from conception to delivery, one stillborn premature infant and one fetal death occurred (Koh et al. Five apparently normal infants were born after exposure to hydroxyurea throughout gestation. No studies of congenital anomalies in infants whose moth- ers used this agent during pregnancy have been published. Offspring of rats and rabbits exposed to hexamethylmelamine during embryogenesis had an increased frequency of congenital anomalies (Thompson et al.