By D. Killian. Mansfield University. 2019.
Ascorbic acid thus plays a role in im- proving cell resistance due to a better use of lipids cheap vytorin 30 mg without a prescription cholesterol ratio score. Ascorbic acid is an anti-inﬂammatory agent that degrades and eliminates histamine buy discount vytorin 30 mg on-line cholesterol levels hereditary. Flavonoids cheap 20mg vytorin with mastercard cholesterol test how long for results, rich extracts from Gingko buy vytorin 20mg lowest price cholesterol score of 220, Fagopyrum (buckwheat), Eucalyp- tus sambucus (European elder), or Sophora japonica are used for their antioxidant and anti-free-radical properties (13). Rosmarinus (rosemary) extracts, rich in carnosic acid, are very potent anti- oxidants, used to protect food. They favor the exchanges between the inner and the outer compartment of the cells or between cells. Some of these have excep- tional healing properties that make them of particular value in sun or antiage products: camelia (tea), argania, medicago (alfalfa), spinacia (spinach), Butyro- spermomum (shea butter), Cucurbitaceae, Pongamia (hongay or pongamia oil). Phytosterols slow down the aging process by favoring fatty acid desatura- tion, which in turn maintains membrane ﬂuidity and catalytic activity. One can also ﬁnd plant waxes (sugar cane, Camauba, Ceroxylon, Jojoba, rose) which are used to protect lips, hands, or face from dehydration. Certain plants (yeast, wheat, apple, potatoes, rice bran, Agaricus, Morus alba, or white mulberry) are rich in ceramides and glycosylceramides. These may be used for their action on skin or hair to provide hydration or reconstitute epider- mal barrier function. Other plants are rich in oils containing very long-chain fatty acids (C22, 24, 26) like Pentaclethra or ewala oil used in Africa as a massage oil, or Lim- nanthes alba or shambrilla oil. Fat Storage and Slimming We are currently using botanical extracts with very speciﬁc actions that act at various levels of adipocyte metabolism. Phytosterols from plant oils are being investigated for their potential action Botanical Extracts 103 on fat storage or degradation, on adipocyte differentation or multiplica- tion. Antiage Ascorbic acid is a key element in collagen synthesis (also in ‘‘botanical colla- gen’’). They improve microcirculation leading to a better irrigation of the tissues and thus to nutrition, hydration, hormone transport, etc. Protection of elastic ﬁbers (collagens, elastin) is promoted by extracts hav- ing free-radical scavenging properties, activating the synthesis of these proteins or inhibiting the enzymes responsible for their degradation: streptomyces, black currant, Centella asiatica (rich in asiatic acid), Rudbeckia purpurea, Coleus, Areca,... Apigenin, extracted from Chamomile and its derivatives, and rutin from Fagopyrum have anti-inﬂammatory properties (by inhibiting histamine release), but they are also β-glucuronidase inhibitors. Other extracts rich in polyphenols—tanins—also have antihy- aluronidase activity (16–18). Recent studies show the importance of amino acids in protecting the skin barrier function. This hormone is very important to many biological processes and decreases rapidly with age. They con- tribute to the elimination of dead cells from the skin surface, hydration, as well as cell renewal. Selenium (Astrogalus) is said to play an important role in antiaging (immu- nity, inﬂammation, free radical scavenging), zinc (Taraxacum) in hair growth (action on testosterone) (24), and mother of pearl from shellﬁsh in wound healing or tissue repair. Saponins, a huge family of compounds, whether of a steroidal or triterpenic structure, are known for their detergent activity. Constant research shows that saponins, present in botanical extracts, have tremendous pharmacological and metabolic properties. Centella asiatica (asiaticosides)—stimulates synthesis of collagen and ﬁ- bronectin. Sterols from sabal, serenoa as well as ∆7 sterols are inhibitors of 5-α- reductase, an enzyme involved in androgenic alopecia, hyperseborrhea of the scalp or the skin, as well as acne. Glycyrrhizin from glycyrrhiza and harpagosides from harpagophytum are broadly used for their anti-inﬂammatory properties. Saponins have also been shown to increase stress resistance by increasing cortisol and prostaglandins, to protect membranes (Eleutherococcus), to increase metabolic efﬁcacy (Medicago), to stimulate cells (Ginseng, bupleurum). Extracts from ganodema are immunostimulating, immunoregulating, pro- long all life in culture, and act on endocrine functions. Extracts from arctophylos uva-ursi, coactis, and adenotricha rich in arbutin and methylarbutin are used for their depigmenting effect. The main difference between the two is really the intention of the manufacturer (i. Most cosmetic products today address both the rational and the emotional aspects that characterize their need in society, while they are often still considered as a ‘‘dream in a bottle’’ (Charles Revson). Botanicals are playing an increasingly important role in the activity and safety of cosmetics; they allow for a renewal of the source of active ingredients in drugs. Oriental herbs in cosmetics: Plant extracts are reviewed for their potential as cosmetic ingredients. The effect on rhino mouse skin of agents which inﬂu- ence keratinization and exfoliation. New raw materials and new technologies in cosmetics: Chouji and Gennoshouko extracts as a useful scavenger of reactive oxygen species for cosmetics. Prevention of second primary tumors by an acyclic retinoid, polypre- noic acid, in patients with hepatocellular carcinoma. Inhibitory effects of some natural products on the activation of hyaluronidase and their antiallergic actions. Arginine supple- mented diets inhibit endotoxin—induced bacterial translocation in mice Nutrition 1995; 11:371–374. Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females. Vitamin A generically encompasses retinol (vitamin A alcohol), retinal (vitamin A aldehyde), and retinoic acid (vitamin A acid) (Fig. In clinical use, retinoids have established their effectiveness in treating acneiform eruptions (e. Additional retinoids are currently being investigated, as are novel uses of retinoids already established in clinical practice. The main focus of retinoid usage in cosmeceuticals has been its role as the mythical ‘‘fountain of youth’’ (i. Retinoids, like all drugs, have adverse effects, the most infamous one being teratogenicity. Over 2000 derivatives have been developed in the hope of ﬁnding retinoids with increased therapeutic efﬁcacy coupled with diminished local and systemic toxicity. The recent focus of retinoids has been on topical delivery systems, as this route not only provides a safer adverse effect proﬁle, but also delivers a higher dose to a targeted area (i. Oral retinoids with no signiﬁcant cosmeceutical activity, such as acitretin, will not be covered. Note that the deﬁni- tion of drug versus cosmeceutical for this class is regulatory (man made) and not biological. However, it was not until the early twentieth century that deﬁnitive knowledge of this substance was discovered. In Table 2 The Roles of Naturally Existing Retinoids Retinoid Role Retinol Growth promotion Differentiation/maintenance of epithelia Reproduction Retinal Vision Retinoic acid Growth promotion Differentiation/maintenance of epithelia Topical Retinoids 109 Figure 1 Structure of retinoids. This substance, initially termed ‘‘fat-soluble A’’ (3) and later named ‘‘vitamin A’’ (4), was also found in butter fat and ﬁsh oils, demonstrating growth-promoting activity (5). Synthesis of vitamin A was achieved in the 1940s and from then on an upsurge of interest in the therapeutic uses of vitamin A became apparent. Topical tretinoin was ﬁrst used successfully by Stuttgen¨ to treat disorders of epidermal keratinization in the 1960s (6). However, the irritation produced by the concentrations and formulations used in these studies inhibited widespread acceptance. Subsequently, Kligman proved the therapeutic efﬁcacy of topical tret- inoin in acne vulgaris (7), and went on to pioneer and popularize the use of retinoids in cosmetic dermatology by demonstrating its effects on photoaged skin (8). At present, retinol is becoming an increasingly utilized ingredient in cosmetic preparations, such as moisturizers and hair products. It has also been demonstrated to be less irritating topically than retinoic acid (12), which makes retinol a more favorable cosmetic ingredient than retinoic acid. It is therefore necessary to review the scientiﬁc basis for use of retinoids and their purported efﬁcacy. Topical Retinoids 111 Vitamin A deﬁciency results in visual problems, such as xerophthalmia and nyc- talopia (night blindness), hyperkeratosis of the skin, epithelial metaplasia of the mucous membranes, and decreased resistance to infections. Retinol (vitamin A1) is present in esteri- ﬁed form in dairy products, meat, liver, kidney, and oily saltwater ﬁsh. For clinical purposes, vitamin A is available as retinol (vitamin A alcohol) or esters of retinol formed from edible fatty acids, primarily acetic and palmitica acid. This section presents evidence that the topical retinoids can be utilized effectively. An enzyme marker was utilized to demonstrate that penetration had occurred and to measure the potency of each retinoid. Therefore, this enzyme can qualitatively reﬂect penetration and potency in the epidermis. Utilizing microsomal preparations from human skin biopsies, a signiﬁcant induction in this enzyme was noted following topical application to human skin in vivo. The increase in enzyme induction was nonlinear, with the higher doses only causing a small increase in activity. Whether the induction of this or other enzyme markers in the skin reﬂects the ability of retinoids to produce a pharmacological effect is not clear. However, cosmetic-type preparations mandate sufﬁcient retinoid concentrations to allow adequate penetration for a pharmacological effect. As a threshold level could be identiﬁed for enzyme induction in the above study, there may also be a threshold for a pharmacological effect.
Affects accuracy (bias) throughout range purchase 20mg vytorin free shipping cholesterol free eggs substitutes, seen as change in Y-Intercept 1000 Actual results 750 Line of identity Slope purchase online vytorin cholesterol level in boiled shrimp, m = 1 vytorin 30 mg without a prescription cholesterol levels diet nutrition. So order vytorin 20mg with visa cholesterol derivatives, variation from the line of identity due to proportional or constant error is assumed to be due to the new method Linear Regression • X Axis Old, Reference, “A” • Y Axis New, Comparative, “B” Old, Reference Linear Regression • Test Yields: Line equation Y = mX + b Correlation N, number of coefficient, r tested pairs Sy/x Linear Regression – 2 Tips • >50% points outside Reference Range • All points same weight Linear Regression – What You’ll See Y = mX + b Error Y = 1. Method Comparison – Bias Plot Method Comparison – Bias Plot Y - X X X axis the same; Y axis is the difference between Y and X Method Comparison – Bias Plot Fluke, or more points needed at this concentration? Original Regression, Revisited All points have the same weight – why was it reformulated? What may really happen Consider Constant and Proportional Errors Our Level 3 Linear Regression Tips • Conclusions: • Systems must be comparable • Look for exact new vs. Develop a range, example: Lab mean = 100 mg/dL; Decision Level = 10% Range = 90-110 mg/dL Medical Relevance – Sample Calculation • Example: Potassium • Set a Decision Limit, clinically: e. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Priority conditions are selected on the basis of current and estimated future public health relevance, and potential for safe and cost‐effective treatment. The complementary list presents essential medicines for priority diseases, for which specialized diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training are needed. In case of doubt medicines may also be listed as complementary on the basis of consistent higher costs or less attractive cost‐ effectiveness in a variety of settings. The square box symbol () is primarily intended to indicate similar clinical performance within a pharmacological class. The listed medicine should be the example of the class for which there is the best evidence for effectiveness and safety. In some cases, this may be the first medicine that is licensed for marketing; in other instances, subsequently licensed compounds may be safer or more effective. Where there is no difference in terms of efficacy and safety data, the listed medicine should be the one that is generally available at the lowest price, based on international drug price information sources. National lists should not use a similar symbol and should be specific in their final selection, which would depend on local availability and price. The a symbol indicates that there is an age or weight restriction on use of the medicine; details for each medicine can be found in Table 1. Where the [c] symbol is placed next to the complementary list it signifies that the medicine(s) require(s) specialist diagnostic or monitoring facilities, and/or specialist medical care, and/or specialist training for their use in children. Where the [c] symbol is placed next to an individual medicine or strength of medicine it signifies that there is a specific indication for restricting its use to children. The presence of an entry on the Essential Medicines List carries no assurance as to pharmaceutical quality. It is the responsibility of the relevant national or regional drug regulatory authority to ensure that each product is of appropriate pharmaceutical quality (including stability) and that when relevant, different products are interchangeable. Medicines and dosage forms are listed in alphabetical order within each section and there is no implication of preference for one form over another. Standard treatment guidelines should be consulted for information on appropriate dosage forms. The main terms used for dosage forms in the Essential Medicines List can be found in Annex 1. Definitions of many of these terms and pharmaceutical quality requirements applicable to the different categories are published in the current edition of The International Pharmacopoeia http://www. Injection for spinal anaesthesia: 5% (hydrochloride) in lidocaine 2‐ml ampoule to be mixed with 7. Tablet (slow release): 10 mg to 200 mg (morphine hydrochloride or morphine sulfate). Injection: 1 mg (as hydrochloride or hydrogen tartrate) in 1‐ml epinephrine (adrenaline) ampoule. Parenteral formulation: 2 mg/ml in 1‐ml ampoule; 4 mg/ml in lorazepam 1‐ml ampoule. Powder for reconstitution with water: 125 mg/5 ml; cefalexin [c] 250 mg/5 ml (anhydrous). Powder for injection: 250 mg (as monohydrate) + 250 mg (as sodium salt); 500 mg (as monohydrate) + 500 mg (as sodium salt) in vial. Meropenem is indicated for the treatment of meningitis and is licensed for use in children over the age of 3 months. Powder for oral liquid: 125 mg/5 ml (as stearate or estolate or erythromycin ethyl succinate). Scored tablets can be used in children and therefore can be considered for inclusion in the listing of tablets, provided adequate quality products are available. Capsule (unbuffered enteric‐coated): 125 mg; 200 mg; 250 mg; didanosine (ddI) 400 mg. Ritonavir is recommended for use in combination as a pharmacological booster, and not as an antiretroviral in its own right. Tablet: 200 mg + 300 mg (disoproxil fumarate equivalent to 245 mg tenofovir disoproxil). Tablet (dispersible): lamivudine + nevirapine + stavudine 30 mg + 50 mg + 6 mg [c]; 60 mg + 100 mg + 12 mg [c]. Tablet: 30 mg + 50 mg + 60 mg [c]; lamivudine + nevirapine + zidovudine 150 mg + 200 mg + 300 mg. Injection for intravenous administration: 800 mg and 1 g in 10‐ml phosphate buffer solution. Complementary List Vial or prefilled syringe: pegylated interferon alpha (2a or 180 micrograms (peginterferon alfa‐2a); 2b)* 80 micrograms; 100 micrograms (peginterferon alfa‐2b). Injection: ampoules, containing 60 mg anhydrous artesunic acid with a separate ampoule of 5% sodium bicarbonate solution. Rectal dosage form: 50 mg [c]; 200 mg capsules (for pre‐ artesunate* referral treatment of severe malaria only; patients should be taken to an appropriate health facility for follow‐up care) [c]. Injection: 80 mg + 16 mg/ml in 5‐ml ampoule; sulfamethoxazole + trimethoprim 80 mg + 16 mg/ml in 10‐ml ampoule. Medicines for the treatment of 2nd stage African trypanosomiasis Injection: 200 mg (hydrochloride)/ml in 100‐ml bottle. In view of this, no changes were made to this section during the 19th Expert Committee. Solid oral dosage form: 200 mg; 250 mg; 300 mg; 400 mg; 500 mg; hydroxycarbamide 1 g. Injection: 40 mg/ml (as sodium succinate) in 1‐ml single dose vial and methylprednisolone [c] 5‐ml multidose vials; 80 mg/ml (as sodium succinate) in 1‐ml single dose vial. Tablet equivalent to 60 mg iron + 400 micrograms folic acid ferrous salt + folic acid (nutritional supplement for use during pregnancy). Injection: 1 mg (as acetate, hydrochloride or as sulfate) in 1‐ml hydroxocobalamin ampoule. Injection: 100 micrograms/ml (as acid tartrate or epinephrine (adrenaline) hydrochloride) in 10‐ml ampoule. Its use in the treatment of essential hypertension is not recommended in view of the availability of more evidence of efficacy and safety of other medicines. Its use in the treatment of essential hypertension is not recommended in view of the availability of more evidence of efficacy and safety of other medicines. However, as the stability of this latter formulation is very poor under tropical conditions, it is only recommended when manufactured for immediate use. Complementary List [c] Lugolʹs solution Oral liquid: about 130 mg total iodine/ml. This site will be updated as new position papers are published and contains the most recent information and recommendations. Complementary List epinephrine (adrenaline) Solution (eye drops): 2% (as hydrochloride). Complementary List mifepristone* – misoprostol* Where permitted under national Tablet 200 mg – tablet 200 micrograms. Complementary List Concentrate for oral liquid: 5 mg/ml; 10 mg/ml (hydrochloride). Inhalation (aerosol): 100 micrograms per dose; budesonide [c] 200 micrograms per dose. Injection: 1 mg (as hydrochloride or hydrogen tartrate) in epinephrine (adrenaline) 1‐ml ampoule. It implies that there is no difference in clinical efficacy or safety between the available dosage forms, and countries should therefore choose the form(s) to be listed Solid oral dosage form depending on quality and availability. The term ʹsolid oral dosage formʹ is never intended to allow any type of modified‐release tablet. Refers to: uncoated or coated (film‐coated or sugar‐coated) tablets that are intended to be swallowed whole; unscored and scored ;* tablets that are intended to be chewed before being swallowed; Tablets tablets that are intended to be dispersed or dissolved in water or another suitable liquid before being swallowed; tablets that are intended to be crushed before being swallowed. The term ʹtabletʹ without qualification is never intended to allow any type of modified‐release tablet. Refers to a specific type of tablet: chewable ‐ tablets that are intended to be chewed before being swallowed; dispersible ‐ tablets that are intended to be dispersed in water or another suitable liquid before being swallowed; soluble ‐ tablets that are intended to be dissolved in water or another suitable liquid before being swallowed; crushable ‐ tablets that are intended to be crushed before being swallowed; scored ‐ tablets bearing a break mark or marks where sub‐division is Tablets (qualified) intended in order to provide doses of less than one tablet; sublingual ‐ tablets that are intended to be placed beneath the tongue. The term ʹtabletʹ is always qualified with an additional term (in parentheses) in entries where one of the following types of tablet is intended: gastro‐resistant (such tablets may sometimes be described as enteric‐coated or as delayed‐release), prolonged‐release or another modified‐release form. Capsules The term ʹcapsuleʹ without qualification is never intended to allow any type of modified‐release capsule. The term ʹcapsuleʹ with qualification refers to gastro‐resistant (such capsules may sometimes be described as enteric‐coated or as delayed‐ Capsules (qualified) release), prolonged‐release or another modified‐release form. Preparations that are issued to patient as granules to be swallowed without further preparation, to be chewed, or to be taken in or with water or another suitable liquid. Granules The term ʹgranulesʹ without further qualification is never intended to allow any type of modified‐release granules.
Tremors discount 30 mg vytorin with visa cholesterol lowering foods and recipes, uneasiness purchase vytorin 30 mg with mastercard cholesterol stones, dif- ﬁculty with sleep buy vytorin 30 mg with mastercard cholesterol test ranges, visual and auditory hallucinations buy vytorin 30mg low cost gluten free cholesterol lowering foods, high blood pressure, faster heartbeat, sweating, nausea, and vomiting can be part of the withdrawal syndrome. Dosage affects severity of with- drawal, with heavy users having the most trouble. The drug has a high sodium content, which might be a problem for persons needing to limit their intake of sodium. It passes into the fetus if a pregnant woman takes a dose and can reduce fetal respiration. Additional scientiﬁc information may be found in: “Adverse Events Associated with Ingestion of Gamma-butyrolactone—Minnesota, New Mexico, and Texas, 1998–1999. With codeine: Doors & 4s, Dors & 4s, 4 Doors, G & C, Hits, Loads, Packets, Pancakes & Syrup, Sets, Setups, 3s & 8s Type: Depressant. It has also been used to help prevent jaundice in newborns and to reduce muscle tremors in adults. Glutethimide can have a rebound effect, meaning that if a per- son is taking the drug to combat anxiety or insomnia and stops taking it, those conditions can temporarily become worse than before. One study found that after several months the drug’s ability to induce sleep deteriorates so badly that users have more trouble falling asleep than insomniacs who don’t use any sleep-inducing drug. A test of the drug’s inﬂuence on mental ability found little effect, but to- bacco smokers seemed to be affected more than nonsmokers. A test of skills related to automobile driving found little inﬂuence from glutethimide. The drug produced inconsistent results in another experiment measuring alertness, reaction time, and decision making. Generally people are advised to be- come aware of how the drug affects them before attempting to run dangerous machinery. Long-term heavy abuse can reduce mental skills in ways that re- semble organic brain damage. Animal experiments suggest that the substance may worsen porphyria, a body chemistry disorder that can make a person violent. The drug can aggravate urinary tract blockage and should be used cautiously by persons with enlarged prostate. Glutethimide 187 A severe overdose can produce what looks like skin burns, and muscle spasms or even convulsions may occur. Case reports note that long-term use of glutethimide can decrease a person’s calcium levels; one report tells of bones softening in a person who took the drug routinely for 10 years, and another report notes seizures occurring due to low calcium. After a dozen years of daily glutethimide ingestion, one person had lost so much muscle control that speech was difﬁ- cult, unassisted walking was impossible, and control of urination and bowel movements was no longer possible. Others, how- ever, mention persons who took the drug for years without noticeable ill ef- fect. Users of the combination report increased sociability and feelings of intellectual in- sight in discussions that were actually about nothing. Some of these deaths involve dosages of each drug that were theoretically safe, outcomes implying that glutethimide and codeine may boost each other’s actions. Users of the com- bination have experienced typical unwanted actions of both drugs in addition to headaches, grouchiness, tremors, cramps, and trouble sleeping. Among persons taking medical doses of glutethimide for months, a withdrawal syndrome can include hallucinations, fever, delirium, and con- vulsions. For addiction treatment, phenobarbital can be substituted for glutethimide, and a person can then be gradually weaned off the phenobarbital. The drug reduces effectiveness of warfarin, a medicine that ﬁghts heart attack and stroke by reducing blood clotting. Glutethimide is also supposed to be avoided if someone is taking the anti-blood-clotting sub- stance coumarin. Army aerospace test found that using alcohol with glutethimide did not harm breathing. That ﬁnding has rather narrow signiﬁ- cance for most persons, but a more generally relevant ﬁnding came from an experiment showing that glutethimide raised blood alcohol levels of persons who had been drinking. Glutethimide is related to thalidomide, perhaps the most noto- rious pharmaceutical cause of human birth defects. In experimentation with rats and rabbits glutethimide did not produce physically apparent birth de- fects. The death rate among rabbit offspring was 6%, however, compared to a 2% rate among offspring with no fetal drug exposure—a rate three times higher for the glutethimide group than for the nondrug group. One experi- ment found the death rate of rats with prenatal glutethimide exposure to be three times that of rats with no drug exposure. Surviving rats with fetal ex- 188 Glutethimide posure to glutethimide exhibit abnormal behavior, but their own offspring behave normally. Pregnant women have routinely received glutethimide for insomnia, nausea, and vomiting. Nursing moth- ers who take the drug may have enough glutethimide in their milk to make their infants sleepy. Because the drug promotes drowsiness, it is sometimes prescribed to be taken at bedtime, aiding both sleep and calmness. One experiment found the compound to be more effective than clorazepate dipotassium in helping anxiety. Another study found that halazepam can diminish anxiety signiﬁcantly on the very ﬁrst day of administration. Halazepam is also used to treat symptoms of alcohol with- drawal and has had some experimental success in alleviating schizophrenic psychoses. Physicians have observed that halazepam can reduce stress and depression and can improve epilepsy. An experiment found that halazepam did not increase belligerence, unlike some benzodiazepine class drugs. Canine studies show that in the body the drug converts into nordiazepam and oxa- zepam, which are also metabolites of diazepam. With stronger dosages elderly persons sometimes experience difﬁculty in manual dexterity and other muscle control; during an experiment several elderly individuals fell. In an experiment some alcoholics had difﬁculty distinguish- ing halazepam from placebo, an outcome suggesting that the drug has low potential for abuse (as abusers of alcohol and other drugs should be particu- larly susceptible). Nonetheless, a person’s body can develop physical depen- dence with halazepam, which is a traditional sign of addictive potential. One group of researchers found withdrawal symptoms to be so mild, however, that a placebo could control them. The heartburn medicine cimetidine is suspected of inter- fering with halazepam’s effects. No cancer developed in rats and mice at daily dosage levels 5 to 50 times the maximum human dose. Experiments with rats and rabbits have produced no evidence that the drug causes birth defects. For most of the twentieth century drug addiction and heroin were synonymous in the United States; all substance abuse was assumed to lead to heroin. Only in the 1980s did heroin become displaced as the devil drug, supplanted in public fear and disapproval by cocaine. Being a Schedule I substance, heroin has no ofﬁcially approved medical use in the United States. Heroin is produced from morphine, and body chemistry converts a heroin dose back into morphine. One study of pain relief found heroin comparable to hydromorphone, a standard med- ication administered to ﬁght severe pain. Physicians have judged heroin to be a safe anesthetic for use during childbirth, with no apparent ill effect on mother or child. The drug is also used to treat porphyria, a body chemistry disorder making people sensitive to light and occasionally making them vio- lent. Heroin users of both genders have reported increased sexual activity upon starting the compound, with decline in that activity as usage continues. That sequence would be consistent with the drug at ﬁrst reducing psycholog- ical anxiety, an effect gradually evolving into indifference about the world. Extrapolating from severity of withdrawal symptoms, any particular size heroin dose taken by intravenous injection is ﬁve times stronger than one taken by inhaling heated vapor (“chasing the dragon”). Other measurements show a dose to be four times more potent when taken intravenously instead of by inhaling powder. Sometimes intravenous injection of heroin produces a rush of feeling lik- ened to a total body sexual orgasm. Heroin may allow some nonmedical users to experience euphoria, but more typically an intoxicating dose increases psy- Heroin 193 chic distance between the user and the world, making reality seem unimpor- tant. People using lesser doses of heroin in that way may function more productively, or they may experience trouble because they feel conﬁdent enough to get into situations they would otherwise avoid. Researchers ﬁnd, however, that injectors of a heroin variety called “black tar” have an increased risk for botulism infection at the injection site, no matter how hygienic their equipment and technique. Injectors of any type heroin are more prone to all sorts of infections, and some researchers suspect that heroin impairs the immune system. Inhaling heated heroin vapor can rapidly pro- duce enough brain damage to cripple a person, although case reports indicate that partial recovery is possible. Inhaling either the vapor or powder can also cause breathing trouble, and injection can cause swift ﬂuid buildup in the lungs. A study found reduced bone density in chronic male heroin users, making broken bones more likely, and researchers suspected the problem re- sulted from lower testosterone levels caused by heroin (a heroin action that is also known to reduce male sex drive). Apparently the bone density and testosterone problems can correct themselves if heroin use stops. Although stroke is an uncommonly reported outcome of heroin use, autopsy examina- tions of 100 heroin addict brains indicate that 5% to 10% of injectors suffer small strokes that may not cause the person to seek medical treatment but that may thereafter affect the person’s behavior. One experiment with heroin addicts found still another unwanted effect: Most of them see colors somewhat differently than nonusers do.
Researchers call this phenomenon a blunted response: you can’t deal appropriately with stress anymore because your feel- good neurotransmitters order 20mg vytorin overnight delivery cholesterol ranges for male, such as serotonin generic 20 mg vytorin otc cholesterol lowering foods in kerala, norepinephrine trusted vytorin 30mg cholesterol ratio values, and dopamine order discount vytorin line cholesterol in whole eggs, are depleted. Many of us are so accustomed to unremitting stress—whether from long work hours, or a difficult marriage, or demanding children—that we’ve actually rewired our brains to perceive danger when it’s no longer a threat, or when it’s relatively minor. There’s a significant cost to unskillfully managing stress, which is a problem for at least 75 percent of the adults in the United States. You can see how this could lead to exhaustion, a greater susceptibility to contagious illness, decreased sex drive, low blood pressure, and orthostatic hypotension (you can’t keep your blood pressure normal when you stand up, and feel like lying down again, literally and figuratively). Cortisol and Aging Women in their twenties are the hormonal gold standard, and under normal conditions, produce a tidy 15 to 25 mg of cortisol per day. In a survey of more than 300,000 Americans, those with the worst mental health scores were between ages thirty-five and fifty. High cortisol generates the long list of maladies associated with too much of this hormone. When we age, however, we don’t absorb cortisol into the cells the way we used to in our twenties and thirties (not to mention that high cortisol itself accelerates aging). These two imbalances—in the blood and in the cells— means that we feel tired (low cortisol) and wired (high cortisol). How High Cortisol Accelerates Aging Recall that cortisol’s main job is to normalize your blood- sugar levels. This may lead to prediabetes (as measured by a fasting glucose level between 100 and 125 mg/dL) or diabetes (fasting glucose > 125). The marathon runner has far higher cortisol levels from running, gets more injuries, and ages faster. Not only that, prolonged elevation of cortisol causes a domino effect: when your adrenals are monomaniacally producing cortisol, the rest of the hormone cascade falls into neglect. Here’s what concerns me most: extensive research demonstrates that prolonged exposure to high cortisol constricts blood flow to the brain. That adversely affects brain function, decreases your emotional intelligence, and accelerates age-related cognitive function. Yes, Alzheimer’s disease becomes established more than thirty years prior to symptoms. Ideally we make a lot in the morning, less during the day, very little at bedtime, and a minimal amount while we sleep. Referred to as diurnal variation —diurnal simply means a recognizable daily cycle, similar to how a flower opens and closes during a twenty- four-hour cycle—the process can be documented in a “diurnal cortisol” measurement at four points between about six a. It also sets up one of your most important circadian rhythms, another crucial aspect of hormonal control. Operating on a twenty- four-hour cycle, circadian rhythms establish your biochemical and physiological peaks and valleys, almost like a tide within the body. When the cortisol tide is out, around midnight, and your cortisol is at its lowest, your cells perform their greatest repair and healing. If your cortisol is still high at night, your body can’t do the repair work it needs. That’s no good: when you are most in need of rest, the high cortisol makes you feel you don’t need it—which only depletes your adrenals further, because your adrenals heal at night. Furthermore, depleting your adrenals will cause you to start running low on important feel-good neurotransmitters, including serotonin, dopamine, norepinephrine, and epinephrine. In addition, nighttime is when your hormones get a chance to harmonize and resync with one another. Melatonin and growth hormone, for instance, which help you fall asleep and stay asleep, are mainly secreted at night. If you are low in one or both, your cortisol may become inappropriately high at night; over time, the lack of sleep may make it harder to sleep because of higher cortisol. In older, traditional cultures, you’d start to unwind with the loss of light as the sun went down. Artificial light allows us to catch up on e-mail, finally listen to that webinar, sign our kid’s field-trip permission slip, and order a birthday gift, all while getting dinner together. With high evening cortisol, it’s no wonder you have trouble falling asleep, staying asleep, or sleeping deeply. I’ve had hundreds of women tell me they simply can’t understand why they feel tired in the morning after they’ve slept eight hours. More times than not, they’re checking e-mail, reviewing the next day’s to-do list, or catching up on a crime show. It doesn’t take a Harvard-educated gynecologist to understand why these women can’t get some decent shut-eye. Most folks with symptoms of overwhelming stress have low cortisol in the morning and high cortisol at night—the opposite of what it’s supposed to be. What you want is that diurnal variation: a steep, downward slope to your cortisol levels. Find Out If You Have High Cortisol In mainstream medicine, you don’t often find a doctor who is interested in checking your cortisol levels unless you’re a textbook case of Cushing’s syndrome, a rare cause of excess cortisol found in just one out of 500,000 people. People with Cushing’s have a long list of symptoms, some of which overlap with those in my questionnaire, but most of which are more extreme. Most doctors will screen for this with a urine cortisol test, but even the best screening test for Cushing’s is subject to debate. Another reason to test your cortisol is a relatively new hormonal condition that is garnering more attention among conventional doctors: subclinical hypercortisolism, which lacks clear diagnostic criteria. The rate of hypertension, or high blood pressure, is 48 to 92 percent—a consequence of excess cortisol. But there’s no clear diagnostic criteria for how high is too high when it comes to cortisol, which makes distinguishing between stress- related excess cortisol and Cushing’s syndrome difficult. If you find you have five or more of the problems in the questionnaires of Part A and/or Part B of chapter 1, I recommend starting The Gottfried Protocol with the lifestyle adjustments, but test before going further and trying the botanical or bioidentical therapies. You can easily and inexpensively measure your cortisol level using the labs listed in Appendix E. I check cortisol in the blood, saliva, or urine; you can even check it in your hair. If you are still menstruating, there is one important variable, and that’s where you are in your menstrual cycle. I don’t know if men are less vigilant but my husband doesn’t wake up in the middle of the night. Vigilance and fear are mediated by the amygdala, which in turn is regulated by the prefrontal cortex, the area of the brain that controls temperament, flexibility, and joy. For women, vigilance seems to relax only in one particular circumstance: 17 orgasm. We know that female climax and release of oxytocin reduce activity in the parts of the brain responsible for anxiety and fear. As a result of decreased activity, specifically in the vigilance centers, the brain looks dark (that is, brain activity shuts down) during orgasm, and women enter a trancelike state. The brains of men at orgasm also indicate a decline in vigilance, but most of the female brain goes dark— significantly darker than the male brain— at orgasm. I think of fear and orgasm as a toggle switch; for women, the two sides can’t be on at the same time. Without telomeres, the chromosome would get shorter each time a cell divides; instead, the telomeres become shorter when cells divide. Excessive shortening of telomeres is associated with developing cancer and experiencing a higher risk of death, as well as with aging. Indeed, telomeres are considered the best marker of biological, as opposed to chronological, aging. You want long telomeres; shortened telomeres indicate premature or accelerated aging. Blackburn and her colleagues first got my attention when they found that women with children in intensive care had shorter telomeres than the 18 control groups. Since then, researchers have documented several connections between short telomeres and stress, attitude, sleep, and mood issues. A case of shrinking telomeres is not irreversible, however, at least not until closer to the end of your life. Fortunately, you don’t have to exercise excessively: one study found optimal telomere length in moderate exercisers. Meditation has been shown to contribute to a more positive cognitive-stress cycle, meaning that you feel you have more control, appraise challenges more realistically, and feel 19 more balanced. When she came to see me, she described her mood as optimistic and upbeat; her main symptoms were mild fatigue, intermittent insomnia, and occasional brain fog. Charlotte exercises regularly, mostly walking briskly with her husband in the Elmwood district of Berkeley. While she no longer has the grueling deadlines of her journalism days, she loves to work as an editor and tends to drive herself hard. When I looked at her diurnal cortisol, measured in saliva four times throughout the day, I found her cortisol was too high in the morning. Treatment protocol: We started a program of tyrosine, an amino acid that has been shown in a randomized trial to reduce the response to stress (although it may cause 20 anxiety in some people). I prescribed a nightly supplement that contained vitamins B6 and B12 plus taurine. In addition, Charlotte took on her insomnia like a breaking story and became a scholar of Dr. Even though it may seem counterintuitive, reducing your time in bed can work wonders in triggering your body to consolidate sleep.