Drospirenone

By S. Jared. Lafayette College.

Syncope is unrelated to plasma concen- trations of quinidine or duration of therapy cheap drospirenone 3.03mg visa. Therapy for quinidine syncope requires immediate discontinuation of the drug and avoidance of other drugs that have similar pharmacological effects drospirenone 3.03 mg generic, such as disopyra- mide, since cross-sensitivity exists in some patients. Magnesium given intravenously (2 gm over 1–2 min, followed by an infusion of 3–20 mg/min) is probably the initial drug treatment of choice. Atrial or ventricular pacing can be used to suppress the ven- tricular tachyarrhythmia and may act by suppressing afterdepolarizations. Drugs that induce hepatic enzyme production, such as phenobarbital and pheny- toin, can shorten the duration of quinidine’s action by increasing its rate of elimination. Quinidine may elevate serum digoxin and digitoxin concentrations by decreasing total- body clearance of digitoxin and by decreasing the clearance, volume of distribution, and affinity of tissue receptors for digoxin. Fever and agranulocytosis may be due to hypersensitivity reactions, and white blood cell and differential blood counts should be performed at regular intervals. Toxic concentrations of procainamide can diminish myocardial performance and promote hypotension. In the absence of sinus node disease, procainamide does not adversely affect sinus node function. In patients with sinus dysfunction, procainamide tends to prolong corrected sinus node recovery time and can worsen symptoms in some patients who have the bradycardia-tachycardia syndrome. The syndrome can occur more frequently and earlier in patients who are “slow acety- lators” of procainamide and is influenced by genetic factors. Sixty to 70% of patients who receive procainamide on a chronic basis develop antinuclear anti- bodies, with clinical symptoms in 20–30%, but this is reversible when procainamide is stopped. The most common relates to the drug’s potent parasympatholytic properties and includes urinary hesitancy or retention, constipation, blurred vision, closed-angle glaucoma, and dry mouth. Some patients can have “cross- sensitivity” to both quinidine and disopyramide and develop torsades de pointes while receiving either drug. Finally, disopyramide can reduce contractility of the normal ventricle, but the depression of ventricular func- tion is much more pronounced in patients with preexisting ventricular failure. In patients with atrial tachyarrhythmias, ventricular rate acceleration has been noted. This phenomenon is unlikely to be clinically important, for the urine pH is normally acidic, and the amount of drug excreted in the urine unchanged is less than 10 and 30–50%, respectively. However, there remains the potential for patients with disorders of urinary acidification to accumulate either of these drugs to toxic levels. It does not appear that decreased renal function per se importantly influences the kinetics of either of these agents. Aggravation of existing ventricular arrhythmias or onset of new ventricular arrhythmias can occur in 5–30% of patients, the increased per- centage in patients with preexisting sustained ventricular tachycardia, cardiac decom- pensation, and higher doses of the drug. Failure of the flecainide-related arrhythmia to respond to therapy, including electrical cardioversiondefibrillation, may result in a mortality as high as 10% in patients who develop proarrhythmic events. Patients with sinus node dysfunction may experience sinus arrest, and those with pacemakers may develop an increase in pacing threshold. Mortality was highest in those with non-Q-wave infarction, frequent premature ventricular com- plexes, and faster heart rates, raising the possibility of drug interaction with ischemia and electrical instability. Exercise can amplify the conduction slowing in the ventricle produced by flecainide and in some cases can precipitate a proarrhythmic response. Proarrhythmic responses, more often in patients with a history of sustained ventricular tachycardia and decreased ejec- tion fractions, appear less commonly than with flecainide and may be in the range of 5%. Noncardiac adverse effects primarily involve the nervous system and include tremor, mood changes, headache, vertigo, nystagmus, and dizziness. Proarrhythmic effects have been reported in about 3–15% of patients and appear to be more common in patients with severe ven- tricular arrhythmias. Sudden withdrawal of propranolol in patients with angina pectoris can precipitate or worsen angina and cardiac arrhythmias and cause an acute myocardial infarction, possibly owing to heightened sensitivity to b-agonists caused by previous b-blockade (upregulation). Heightened sensitivity may begin several days after cessation of propranolol therapy and may last 5 or 6 d. Other adverse effects of propranolol include worsening of asthma or chronic obstructive pulmonary disease, inter- mittent claudication, Raynaud’s phenomenon, mental depression, increased risk of hypo- glycemia among insulin-dependent diabetic patients, easy fatigability, disturbingly vivid dreams or insomnia, and impaired sexual function. Most adverse effects are reversible with dose reduction or cessation of treatment. Of the noncardiac adverse reac- tions, pulmonary toxicity is the most serious; in one study it occurred between 6 d and 60 mo of treatment in 33 of 573 patients, with three deaths. The mechanism is unclear but may relate to a hypersensitivity reaction and/or widespread phospholipidosis. Dys- pnea, nonproductive cough, and fever are common symptoms, with rales, hypoxia, a positive gallium scan, reduced diffusion capacity, and radiographic evidence of pul- monary infiltrates noted.

Metronidazole does concentrate in the breast milk and results in concentrations close to those found in maternal serum (Simms-Cendan generic 3.03mg drospirenone with amex, 1996) discount drospirenone 3.03 mg mastercard. Chloramphenicol Chloramphenicol interferes with protein synthesis and is bacteriostatic. It is rarely used today and generally is not recommended for use in pregnant women, although there is 32 Antimicrobials during pregnancy little or no scientific evidence to suggest that it is teratogenic. In a review from the Collaborative Perinatal Project of approximately 100 infants exposed to chlorampheni- col in the first trimester, there was no evidence of an increased frequency of congenital malformations (Heinonen et al. It has been associated with the ‘gray baby syn- drome’ (cyanosis, vascular collapse, and death) in the premature neonate given large doses of this drug. Although chloramphenicol does cross the placenta readily (Scott and Warner, 1950), transplacental passage of the drug rarely, if ever, causes gray baby syn- drome in the fetus or newborn (Landers et al. The most significant potential adverse maternal effect is aplastic anemia, which has been reported in approximately one of 100 000 cases. Sulfonamides The sulfonamides inhibit folate synthesis and are analogs of para-aminobenzoic acid, which is necessary for production of folic acid by bacteria (Landers et al. There are no scientific reports of an association between congenital malformations and the use of sulfonamides during pregnancy. Although the sulfonamides are not terato- genic, they do compete for bilirubin binding sites and, if used near delivery, may cause hyperbilirubinemia, especially in the premature infant (Landers et al. Maternal side effects include hypersensitivity, photosensitivity, blood dyscrasias, and gastrointesti- nal intolerance. Trimethoprim Although trimethoprim crosses the placenta, it has not been shown to cause adverse fetal effects. In one report of over 100 women treated with a combination of trimethoprim and sulfamethoxazole, there was no increase in the frequency of fetal anomalies (Williams et al. In another study of 186 pregnant women receiving either a placebo (66 patients) or trimethoprim plus sulfamethoxazole (120 patients), the inci- dence of fetal malformations was actually lower in the group receiving the antibiotics (3. Like sulfonamides, trimethoprim is associated with few adverse maternal effects (skin rash, gastrointestinal intolerance, and possible hematologic abnormalities). Nitrofurantoin Nitrofurantoin macrocrystals, commonly used for urinary tract infections during preg- nancy, have not been reported to be associated with adverse fetal effects. In a random- ized prospective study of 100 women treated with nitrofurantoin versus 100 controls, there were no significant differences in birth weight, head circumference, or body length of the offspring (Lenke et al. Nitrofurantoin has been reported to cause hemolytic anemia in women with glucose-6-phosphate dehydrogenase deficiency (Powell et al. However, in the authors’ experience of approximately 1000 pregnant women receiving this medication for urinary tract infections, hemolytic anemia has not occurred in either the mother or the fetus. Vancomycin Vancomycin is an antibiotic which does not belong to any other class of antimicrobial agents. It is both bactericidal and bacteriostatic, and is effective against a wide variety of Gram-positive organisms, including the Enterococci (Hermans and Wilhelm, 1987). It is the drug of choice for Clostridium-difficile-associated pseudomembranous colitis. It is also used in penicillin-allergic pregnant women for bacterial endocarditis prophylaxis. There is no available scientific information linking this agent with adverse pregnancy outcomes, including congenital malformations. However, vancomycin may be associ- ated with significant maternal side effects, such as nephrotoxicity and ototoxicity. Although there are no such reports, vancomycin could theoretically result in the same toxicity in the fetus, since this drug readily crosses the placenta. Aztreonam Aztreonam belongs to a relatively new class of antibiotics: the monobactams. It is effec- tive against most of the aerobic Gram-negative rods or Enterobacteriaceae, and is used as an alternative to the aminoglycosides. However, according to its manufacturer, aztreonam has not been shown to be teratogenic in several animal models given several times the human dose. Moreover, a particular advantage of this antibiotic over the aminoglycosides is that it is not associated with either nephrotoxicity or ototoxicity in either the mother or the fetus. It is presently combined with cilastatin, which inhibits the renal metabolism of imipenem. Imipenem is effective against a wide variety of 34 Antimicrobials during pregnancy Gram-positive and Gram-negative aerobic and anaerobic organisms. It has the potential to be very effective as single-agent therapy for polymicrobial pelvic infections in women.

Myocardial remodeling consists of several molecular and cellular events that lead to changes in heart structure and function buy discount drospirenone 3.03 mg on line. These events include hypertrophy purchase 3.03mg drospirenone with amex, myocyte apoptosis, re- activation of fetal gene programs, and alterations in the quantity and composition of the extra-cellular matrix. Myocardial remodeling on the cellular and subcellular levels often leads to changes in left ventricle geometry and progressive deterioration of left ventricle contractile force. These changes in left ventricle geometry can lead to mitral valve regurgitation due to an increase in the size of the mitral annulus and altered physical relationships of the mitral valve structures. Release of norepinephrine from sympathetic nerve terminals innervating the heart leads to the cellular and sub-cellular effects described above. Release of epinephrine from the adrenal glands contributes to further vasoconstriction mediated by α1 adrenergic receptors. Substantial inter-individual variability in terms of disease progression and the response to therapeutic agents is observed. The Arg389 variant demonstrates a more robust therapeutic response to β adrenergic receptor blocking agents. Widespread use of genetic analysis and prognostication is still not available but promises to be an important clinical tool in the near future. Correction of the precipitating process, whenever possible, is the first step in effective therapy. Individuals with ischemic cardiac disease may benefit from angioplasty or coronary artery bypass surgery. Heart transplantation is an option that may be available when life expectancy is extremely limited and resource utilization is warranted. Diuretics – act directly on the kidney to inhibit sodium, potassium, and water re-absorption. However, the use of loop diuretics is supported by a long history of clinical success. Examples: hydrochlorothiazide (thiazide), furosemide (loop) Congestive Heart Failure – Andrew Patterson, M. Aldosterone promotes sodium retention, magnesium and potassium loss, sympathetic nervous system activation, parasympathetic nervous system inhibition, myocardial and vascular fibrosis, and baroreceptor dysfunction. This peripheral “pooling” of blood reduces the volume of blood in the ventricles and reduces cardiac filling pressures. A major limitation to the use of nitroglyerin is the rapid development of tolerance to the drug’s effect. Limitations of Dobutamine include enhanced atrioventricular node conduction that may lead to rapid ventricular response in patients with atrial fibrillation cardiac rhythm. In addition, Dobutamine increases myocardial oxygen demand and oxygen consumption. Digoxin – works by inhibiting myocyte sodium/potassium pumps, which leads to increased intracellular calcium levels and better inotropic performance of the heart. Digoxin also reduces conduction through the atrioventricular node and, therefore, is useful for treating heart failure patients in atrial fibrillation cardiac rhythm with rapid ventricular response. Digoxin should be avoided in patients with hypokalemia, bradycardia, and heart block. They are not useful in the setting of acute cardiac dysfunction because they impede the action of endogenous and exogenous inotropic agents. Examples: Metoprolol (1 blocker), Atenolol (1 blocker), Bisoprolol (1 blocker), Carvedilol (α, 1, 2 blocker), Esmolol (1 blocker), Propranolol (1 and 2 blocker) Congestive Heart Failure – Andrew Patterson, M. One hypothesis is that the adverse effects were caused by impairment of renal function. Amiodarone is the safest antiarrhythmic drug in heart failure and can help to maintain sinus rhythm. Mitral regurgitation may also occur, and atrioventricular coupling may be disturbed. Vasopressin is a hormone synthesized by the hypothalamus that controls free water clearance. It also acts on V1a receptors in vascular smooth muscle and the myocardium to cause peripheral and coronary vasoconstriction and myocyte hypertrophy. Three vasopressin antagonists are currently being studied, Conivaptan, Tolvaptan, and Lixivaptan. Long term results with regard to mortality and impact upon ventricular remodeling and renal function are pending. Istaroxime was found to lower pulmonary capillary wedge pressure, increase cardiac index, and decrease left ventricle end diastolic volume at the highest dose studied. It also increased systolic blood pressure, lowered heart rate, and induced a lusitropic effect. Istaroxime has not been studied over long time periods or in patients with hypotension associated with acute decompensated heart failure. The tip of the device is advanced into the descending aorta distal to the take-off of the left subclavian artery. During systole a balloon on the tip of the device deflates, facilitating blood flow through the aorta.