Loading

By A. Finley. Tuskegee University.

Hemodynamic effects Moricizine may have a mildnegative inotropic effect buy cialis super active on line, but in general best buy for cialis super active, exacerbation of congestive heart failure has been uncommonwith this drug purchase cialis super active from india. Therapeutic uses Moricizine is moderately effective in the treatment of both atrial and ventricular arrhythmias. It has beenused successfully in treat- ing bypass-tract-mediated tachyarrhythmias and may have some ef- ficacyagainst atrial fibrillation and atrial flutter. Cimetidine increases moricizine levels and moricizine decreases theophylline levels. Comparedwith other an- tiarrhythmic drugs, these agents are only mediocre at suppressing overt cardiac arrhythmias. Nonetheless, beta blockers exert a pow- erful protective effect in certain clinical conditions—they are among the fewdrugs that have been shown to significantly reduce the inci- denceofsuddendeath in anysubset of patients (an effect they most likely achieve by helping to prevent cardiac arrhythmias). Because of the success of the drugs in treating a myriad of medical problems, more than two dozen beta blockers have been synthesized and more than a dozen are available for clinical use in the United States. Electrophysiologic effects of beta blockers For practical purposes, the electrophysiologic effects of beta block- ers are manifested solely by theirblunting of the actionsofcat- echolamines. The effect of beta blockers on the cardiac electrical system, then, reflects the distribution of adrenergic innervation of the heart. In areas where there isrichadrenergic innervation, beta blockers can have a pronounced effect. 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. The suddenwithdrawal of beta blockers, especially the short- acting beta blockers like propranolol, can lead to unstable ischemic heart disease in patients with underlying coronary artery disease. The withdrawal syndrome issubstantially less likely with the longer- acting beta blockers. Other possible but much less common side effects of beta block- ers include rashes, fever, sexual dysfunction, mental depression, and gastrointestinal symptoms. Indiabetics, beta blockers canmask symptomsofhypoglycemiaand cancause hypoglycemiabyreducing gluconeogenesisorhyperglycemiabyreducing insulin levels. Some of the side effects related to beta blockade itself may be avoided by appropriate drug selection. Asnoted, drugs with β2- selectivity might helpinavoiding bronchospasm, worsening of hy- poglycemia, claudication,and Raynaud’s phenomenoninsome in- dividuals.

buy cialis super active with mastercard

Especially relevant from thirty-five onward as you march toward menopause discount cialis super active 20 mg, age is associated with fewer ripe eggs buy cheap cialis super active line, less ovulation generic cialis super active 20 mg with visa, and low progesterone. If your problem is unmanaged and chronic emotional stress, cortisol blocks your progesterone receptors, and your body will make cortisol at the expense of pregnenolone and progesterone, causing Pregnenolone Steal. Ovulation is key to the regular, monthly production of progesterone during your fertile years. If you don’t ovulate, either because you’ve run out of eggs or you have another hormonal problem such as excess testosterone, you will have progesterone deficiency. Thyroid hormone is essential to the smooth operation of the hormone pathways I’ve described. You need adequate thyroid hormone to make pregnenolone from cholesterol, and then to make progesterone. Additionally, there’s a vicious cycle that occurs: when you have low progesterone, it raises thyroid requirements. If your thyroid gland is already borderline, it will worsen your low progesterone. Some women make too much prolactin, a hormone in the pituitary of the brain that controls lactation in women. High blood prolactin interferes with the function of the ovaries in premenopausal and perimenopausal women, and as a result, secretion of ovarian hormones such as progesterone, and eventually estrogen, decreases. The Solution: The Gottfried Protocol for Low Progesterone Addressing progesterone deficiency is sometimes more complicated than simply adding more hormone to the equation. The problem of progesterone resistance means that some women don’t respond to the addition of progesterone cream or pills. You can increase your body’s progesterone level in several ways: vitamin C and chasteberry for women who are premenopausal, and over- the-counter progesterone cream or progesterone pills for women who’ve reached menopause. When you’re premenopausal, your ovaries still may be able to produce progesterone, but they need a nudge. Once you’ve had your final period and a year has passed (the official definition of menopause), topical or oral progesterone is the best choice. I suggest tweaking your protocol to adjust to the realities of your life stage, so use these steps as a starting point. Step 1: Targeted Lifestyle Changes and Nutraceuticals Vitamin C is the lone but mighty solution in this arena. It’s the only over-the-counter nutraceutical treatment for low progesterone proven to be effective. At doses of 750 mg/day, vitamin C has been shown to raise progesterone in women with both low progesterone and luteal phase defect. Within three menstrual cycles, the group receiving vitamin C saw progesterone levels increase on average from 8 to 13 ng/mL. Taking 750 mg/day is completely safe, even though the recommended daily allowance is an abysmally low 75 to 90 mg/day. Incidentally, a daily dose of 500 to 1,000 mg of vitamin C also helps prevent cancer and stroke, keeps your eyes working well, boosts immunity, and increases longevity. Progesterone is another stress-related hormone, and affiliation helps women to calm down. I’m guessing the answer is no, because many American physicians are addicted to caffeine themselves. Sorry to be the bearer of bad news, but one of the first steps I recommend in treating low progesterone is weaning yourself from caffeine. Caffeine boosts energy temporarily by raising cortisol, but as we’ve seen, high cortisol can block progesterone receptors: your daily jolt may be decreasing the ability of your progesterone to bind to its receptor and do its job. I have a systematic approach: switching from regular coffee to yerba mate or green tea, and from yerba mate or green tea to decaffeinated green tea, and then to flavorful herbal teas, such as rooibos and fruit teas. While you are abstaining from coffee and nonherbal tea, consider ditching other drinks that can adversely affect your hormonal balance. Alcohol intake is associated with premenstrual anxiety, mood problems, and headache. This sidetracks your fat-burning mechanism and may slow down your rate of fat burning by more than half. Step 2: Herbal Therapy There are several herbs worth mentioning, but chasteberry is the most effective and safe. Other botanical therapies that raise progesterone include bladderwrack and saffron. Also known by several other terms, including chaste tree, chaste tree berry, and vitex, this herb is available as capsules or liquid tincture, and the average dose is 500 to 1,000 mg/day. Chasteberry, used by the ancient Greeks more than two thousand years ago, restores normal progesterone levels in the body. Most researchers believe that chasteberry increases the release of luteinizing hormone from the pituitary, which raises progesterone and normalizes the second half of the menstrual cycle. The progesterone boost stimulated by chasteberry has been demonstrated in blood- hormone levels, in endometrial biopsies documenting progesterone effect on the uterine lining, and in analysis of vaginal secretions. After six months of treatment, 32 percent of the women taking chasteberry became pregnant, compared with 10 percent of the group taking a placebo. Among this small percentage, the most common complaints are malaise and gastrointestinal complaints, including nausea and diarrhea. Chasteberry has been proven to help low progesterone in more than sixty years of clinical research, including five randomized trials. When performed properly, they allow the least amount of bias and demonstrate causation—unlike lesser- quality study approaches, such as observational studies or case-control studies. As we try to find what truly, effectively helps women with hormone imbalances, any kind of bias is the enemy. The number of products out there can seem dizzying; it’s hard to know what to look for and where to find it. I’ve spent twenty years testing products, following the studies, and experimenting for the benefit of my patients. I recommend it even if you don’t have an issue with fertility but have symptoms of low progesterone. One nonrandomized but large study found that chasteberry increases fertility, which led to a well- designed randomized trial that documented increased fertility in women taking 31 chasteberry. A company in Cologne, Germany, makes this proprietary blend of chasteberry fruit tincture, which contains 9 grams of 1:5 tincture for each 100 grams of aqueous alcoholic solution. Most herbalists are able to create a tincture with this formula, or you can purchase the proprietary blend from Europe. Bladderwrack, an edible brown seaweed, has been used for thousands of years in Ayurveda, the traditional medicine of India. If your low progesterone symptom is a shortened menstrual cycle, consider bladderwrack, which has been shown in one study to raise progesterone levels and lengthen a shortened menstrual cycle. It peaks a few days before my period and I can go from zero to sixty in a nanosecond if, for instance, my fiancé picks a fight or does anything annoying.

buy generic cialis super active on line

If the arrhythmiabeing exacerbatedisventricular tachycardia best cialis super active 20 mg, the clinical manifestation of proarrhythmia may be suddendeath buy online cialis super active. Treating any drug-related exacerbation of a reentrant arrhythmia requires the recognition that the “new” arrhythmia is caused by a Common adverse events with antiarrhythmic drugs 121 drug purchase cialis super active online. In general, one should be alert for anysign of proarrhythmia whenever treating a reentrant arrhythmia with antiarrhythmic drugs. If proar- rhythmia issuspected, the offending drugs should be immediately stopped and the patientsupported hemodynamically until the drug metabolizes (a particular problemwhenusing a drug withalong half-life). Proarrhythmic reentry, like spontaneous reentry, can of- ten be terminated by antitachycardia pacing techniques. If needed, atemporary pacemaker can be placed for antitachycardia pacing until the patient stabilizes. Adding additional antiarrhythmic drugs when thistypeofproarrhythmia is present often only makes things worse and should be avoidedif possible. As outlinedinChapter 1, these arrhythmias are thought to be caused by the development of afterdepolarizations, which, in turn, are a common result of using antiarrhythmic drugs. Proarrhythmia caused by this mechanism should be strongly suspectedwhenever a patientbeing treatedwith quinidine, pro- cainamide, disopyramide, sotalol, or dofetilide complainsofepisodes of light-headedness or syncope. Toxic levels of digoxin canproduce polymorphic ventricular tachycardiabycausing delayed afterdepolarizations (see Figure 1. A new onset of polymorphic ventricular tachycardia or the developmentofsyn- cope in patients treatedwith digoxin shouldprompt measurement of a digoxin level. Acute cardiac failure can leaddirectly to arrhythmias by causing abnor- mal automaticity (i. Hypotensioncancause arrhythmias by the same mechanism or by causing reflex sympathetic stimulation. Thus, antiarrhythmic drugs that decrease the inotropic state of the heart (beta blockers, calcium blockers, disopyramide, or flecainide) or drugs that cause vasodila- tion (calcium blockers, some beta blockers, and the intravenousad- ministration of quinidine, procainamide, bretylium,oramiodarone) can occasionally lead to cardiac arrhythmias. Proarrhythmia in perspective Although the potential for antiarrhythmic drugstoworsencardiac arrhythmias has been known for decades, the potential magnitude of the problem has been recognized for only a few years. The hypothesis of the study was that suppressing these patients’ ambient ectopy would improve their mortality. Instead, the results showed that patients treatedwith encainideorflecainidehad afourfoldin- crease in the risk of suddendeath (patients treatedwith moricizine showednobenefit fromdrug treatment) and had asignificant in- crease in overall mortality. The increase in risk for fatal arrhythmias was not limited to the first fewdays or weeks of drug therapybut persisted throughout the follow-up period. Other trials have suggested, for instance, that uses of both quinidine for atrial fibrillation and Class I drugs in survivors of myocardial infarction have produced significant increases in mortality. As a result, most electrophysiologists have become convinced that the proarrhythmic effects of Class I drugsoutweigh the antiarrhyth- mic effects, at least in patients with underlying heart disease. Using antiar- rhythmic drugsalways involves the risk of making heart rhythm worse instead of better. One shouldprescribe these drugsonly if it is necessary for prolongation of survival or for amelioration of significantsymptoms. Most impor- tantly, whenever one is compelled to prescribe antiarrhythmic drugs, one should feel obligated to do whatever possible to minimize the risk of symptomatic or life-threatening proarrhythmia. Since reentrantventricular tachycardia(and therefore drug- inducedworsening of reentry) generally is seen only in the presence of underlying cardiacdisease, one must be especially cautious about using antiarrhythmic drugs in patients with heart disease. When prescribing antiarrhythmic drugs in this setting, it is importantto assure that serum electrolytes (especially potassium) are kept well within the normal range. In addition, cardiac function should be optimized because hemodynamic compromise canworsen arrhyth- mias. Not only 124 Chapter 9 does ischemia itself precipitate arrhythmias, but ischemia also ren- ders drug-inducedproarrhythmia more likely. Torsades de pointes probably occurs in individuals who are genet- ically pronetodevelop afterdepolarizations whenever their cardiac actionpotentials become prolonged. Patients started on therapy with such drugs should be placed on a cardiacmonitor for several days, be- cause torsades de pointes is most often first seenduring the initial 3 or 4days of therapy (although it can occuranytime). Serum potassium levels should also be watched carefully;infact, one shoulduse torsades de pointes producing agents with trepidationinpatients requiring potassium-wasting diuretics. Drug–drug interactions Antiarrhythmic drugs seem to produce more than their share of interactions with other drugs. Interactions generally are related to competitionwith other drugs for serum proteinsonwhichtobind or to drug-inducedchanges in hepatic metabolism. The major in- teractions between antiarrhythmic drugsand other agents (see the discussionsoftheindividual antiarrhythmic drugs) are summarized in Table 9. It is relatively rare for antiarrhythmic drugstosignif- icantly interfere with pacemakers. Two major problems caused by antiarrhythmic drugs are that they canchange the en- ergy required for successful defibrillation and they canchange the characteristics of the arrhythmiabeing treated. The effects of various drugsondefibrillation energy requirements are summarized in Table 9. In thisfinal sec- tion, that informationisapplied to the use of antiarrhythmic drugs in the treatmentofspecificcardiac arrhythmias. Chapter 10 reviews some basic principles that should be kept in mind whenusing an- tiarrhythmic drugs. On the basisofthegenerally limited efficacyofantiarrhythmic drugsaswell as their inherent propensity to cause serious problems, the first principle should be completely self-evident;namely, one should avoid using antiarrhythmic drugs whenever possible. Thus, when one has decided to prescribe an antiarrhythmic drug, the final step before actually writing the order should be to ask, “Does this patient really need this drug? Before prescribing an antiarrhythmic drug, the physician should be certain that the arrhythmia meets one of these two conditions. The second basic principle istokeep the goal of treatment clearly in mind and to tailor the aggressiveness of one’s therapyaccordingly. If one is treating an arrhythmiatoprevent death or permanent in- jury, for instance, a relatively aggressive approach may be appropri- ate and necessary. In theory, if the object istospare life and limb, one should err on the side of efficacy, perhaps willingly accepting the risk of certain drug toxicities. Inpractice, however, as we will see in Chapters 11 and 12, there are relatively fewinstances today where oneought to rely primarily on antiarrhythmic drugs to treat arrhythmias that threaten life and limb. In these cases, one generally shoulduse a stepwise strategy, beginning with milder, less risky forms of treatment, and carefully reassessing the risk-to-benefit ratio before each potential escalation of therapy. All too oftenphysicians pursue the treatment of relatively insignificant arrhythmias with Ninja-like intensity, an error that can result in unnecessary injury or death. The final basic principle of using antiarrhythmic drugs is that, if one feels compelled to expose a patient to the risk of the drugs, one should also feel compelled to take every reasonable precaution to reduce the risks. For instance, given the almost universal risk of proarrhythmia, one should oftenconsider placing patients on a cardiacmonitor while antiarrhythmic drugs are being initiated be- cause, although proarrhythmia can occuranytime during the course of treatment, a significant proportion of these events occur during the first 3 or 4days of drug usage. The accompanying tables summarize the factors that should be consideredinchoosing antiarrhythmic drugs for patients with and withoutsignificant underlying cardiacdisease. Pro- cainamide, for instance, shouldnot be usedinpatients with systemic lupus erythematosus; quinidine shouldnot be usedinpatients with chronic colitis;patients with severe lung disease (in whommild drug-inducedpulmonary toxicity goes a long way) ideally shouldnot receive amiodarone;patients with a history of heart failure should not receive drugs with negative inotropic effects. Beyond these obvious individual considerations, the presenceor absenceofunderlying heart disease is the most important variable in choosing an antiarrhythmic drug,because heart disease predisposes patients to reentrant circuits and, therefore, to proarrhythmia.

buy line cialis super active

Leave a comment

Your email address will not be published. Required fields are marked *