dr.srinivas ramaka. m.d.,dm. consultant cardiologist

DR.SRINIVAS RAMAKA. M.D.,DM. Consultant Cardiologist.

Individuals at extremes of the age - vulnerable to the toxic effects of drugs. The young - susceptible due to the incomplete development of certain organs eg.kidney or the lack of expression of certain drug metabolizing or transport proteins that play key pharmacokinetic roles. Elderlyincreased risk due to age-related changes in body composition,organ function,and drug metabolizng systemsdelay in drug clearance.

Identify a special population. Follow evidence-based guidelines in treatment. Pregnancy,lactation,old age and paediatrics. Identfiy factors affecting medication penetration in pregnancy and lactation. Identify FDA pregnancy categories. Identify common medications contraindicated during pregnancy and lactation.

Factors affecting the absorption, distribution, metabolism, and excretion of drugs in paediatric population. determine pediatric characteristics or challenges that increase the risk of medication errors. discuss common medication errors that occur in pediatric populations. recognize high alert medications in the pediatric population describe strategies to decrease the risk related to pediatric errors.

Identify the epidemiology of medication use in the elderly. Identify the role of the pharmacist & strategies to enhance safe medication use in the elderly.

Special Considerations in Geriatrics Pharmacotherapy : 1. Explain categories used to describe & assess an older adult 2. Describe age-related biologic changes & their clinical implications 3. Describe PD/PK changes in the elderly & their clinical implications 4. Evaluate pharmacotherapy based on PD/PK changes given a patient case

Special Considerations in Geriatrics Pharmacotherapy 1. Describe epidemiologic characteristics of the elderly as it relates to living & care environments, mortality causes, and functional limitations 2. Define polypharmacy, underuse, and inappropriate prescribing 3. Identify inappropriate medication use 4. Discuss the role of a pharmacist in geriatric assessment 5. Identify factors affecting medication non-adherence 6. Identify barriers to optimal pharmacotherapy based on a specific scenario 7. Evaluate a patient for risk of falls

Medications Safety in Geriatrics 1. Describe the epidemiology of medication use in the elderly 2. Identify types of and interventions for adverse drug reactions 3. Explain tools and guidelines used to assess medication appropriateness and safety 4. List medications or classes identified commonly to cause hospitalization or to be inappropriately omitted 5. Describe the role of the pharmacist & strategies to enhance safe medication use in the elderly

Diseases during pregnancy Heart failure, Hypertension, Arrhythmias, Valvular heart diseases. Cardiomyopathies.peripartum cardiomyopathy. Anticoagulation during pregnancy. Amiodaronedemonstrated fetal risk Only extreme maternal safety Issues justify use.

FDA Use-in-Pregnancy Ratings: Category A: no fetal risks documented. Category B: No evidence of risk in humans.,animal studies suggest risk..eg.methyldopa,thiazides and dipyridamole. Category C: animal studies demonstrated adverse fetal effects,but no controlled humn studies.risk cannot be ruled out. Adequate, well controlled human studies are lacking, and animal studies have shown a risk to fetus or are lacking as well. There is a chance of fetal harm if the drug is administered during pregnancy, but the potential benefits may outweigh the potential risk.eg.digoxin,hydrallazine,heparin,furosemide,quinidine,procainamide,verapamil. Category D: positive evidence of human risk. Studies in humans or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective..eg.phenytoin,captopril. Category X: Contraindicated in pregnancy. Documneted fetal abnormalities.eg.warfarin. Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive evidence of fetal abnormalities or risk that clearly outweighs any possible benefit to the patient.

General determinants of drug transfer across the placenta- Lipid solubility,extent of plasma binding and degree of ionization of weak acids and bases.

Statins and Pregnancy: The safety of statins during pregnancy has not been established. Women wishing to conceive should not take statins. During their childbearing years, women taking statins should use highly effective contraception. Nursing mothers also are advised to avoid taking statins

CARDIOVASCULAR DRUGS IN PREGNANCY Most cardiovascular drugs cross the placenta and are secreted in breast milk. Therefore, the risk to benefit ratio must be considered when administering any medication during pregnancy..

Pharmacologic management of congestive heart failure during pregnancy: The treatment of CHF is more difficult in pregnant women than in nonpregnant women owing to the hemodynamic changes associated with pregnancy and the limited number of safe treatment options available. Conservative measures such as salt restriction and limitation of activity are extremely important. Pharmacologic therapy may be required

Digoxin and diuretics: Digoxin can be safely administered during pregnancy and breast-feeding. Diuretics impair uterine blood flow and placental perfusion, but no teratogenic effects described. Cases of neonatal thrombocytopenia, jaundice, hyponatremia and bradycardia have been reported with thiazide diuretics and furosemide. Routine initiation of diuretic medications during pregnancy is not generally recommended. Maternal use of furosemide during pregnancy has not been associated with toxic or teratogenic effects, although metabolic complications have been observed.

ACE inhibitors and Angiotensin II receptor blockers : The use of ACE inhibitors and Angiotensin II receptor blockers is contraindicated during pregnancy. Fetal exposure to ACE inhibitors during the first trimester of pregnancy increased the risk of congenital cardiovascular and central nervous system malformations. Use of ACE inhibitors during the second trimester of pregnancy increases the risk of early delivery, low birth weight, oligohydramnios, or neonatal anuria and renal failure. Can be used safely during lactation.

Thromboembolic complications. Hypertensioncalcium channnel drugsnifedipine and alphamethydopa. PAHmaternal mortality3070%.and fetal loss is 40 %. Arrhyhmias-SVTadenosine.oral drugs-betablockers or verapamil.

Treatment of afteroad reduction as in HTN,AR or MR or LV dysfunction-hydrallazine and methyldopa. PAHSildenafil. ACEI AND ARBSCONTRANDICATED AS they cross the placenta.

Management of Arrhythmias during pregnancy Digoxin and Quinidine: Digoxin is thought to be safe for treating arrhythmias except for an increased risk of prematurity and intrauterine growth retardation. Adverse fetal effects have not been reported with qunidine given at a threapeutic dose, but toxic doses may induce premature labour. Limited information is available on the use of procanamide, disopyramide and propafenone during pregnancy, but no adverse fetal effects have been noted.

Amiodarone during pregnancy -may result in fetal hypothyroidism. Amiodarone use should be limited to patients with refractory life-threatening arrhythmias and serum amiodarone levels as to be kept as low as possible. Fetal electrocardiographic monitoring should be performed before, during and after birth and neonatal thyroid function should be monitored at birth and continued during the exposure to amiodarone. Amoidarone and its active metabolite have been found in human breast milk in significant concentrations; therefore, the use of amiodarone is not recommended in women who are breast feeding their infants.

Verapamil-used in pregnancy to manage supra-ventricular arrthythmias, No adverse effects reported. Recommended that verapamil therapy be discontinued at the onset of labour to prevent dysfunctional labour or postpartum hemorrhage.

Betablockers The use of -blockers during pregnancy has been reported to cause intrauterine growth retardation, apnea at birth, fetal bradycardia, hypoglycemia, hyperbilirubinemia. Relatively safe,cross the placenta nd are present in breast milk. WHO considrs Atenolol unsafe during breastfeeding as it causes hypoglycemia and bradycardia.Metoprolol is an alternative.

Adenosine has been used safely to treat acute supre- ventricular tachycardia in pregnancy. Beta-blockers and calcium channel blockers can be used for supre-ventricular tachycardia prophyaxis in pregnancy. But their use should be discontinued near the time of delivey. Atenolol should be avoided during pregnancy and lactation.

Management of CAD in pregnancy Heparin,low dose asprin,nitrates,betablockers safe in pregnancy. Safety of thrombolytics,GpIIb/IIIa inhibitors,clopidogrel not established.

Management of anticoagulation during pregnancy Hematologic changes during normal pregnancy Increase in clotting factor concentrations, Increase in platelet adhesiveness, and A decrease in fibrinolysis and protein S activity. These changes result in an overall increase in risk of thrombosis or embolism.

Anticoagulation recommendations for pregnant patients who have a mechanical heart valve Before pregnancy to week 6 of pregnancy Warfarin Weeks 6 to 12 of pregnancy UFH (IV or SC) or LMWH (SC) or warfarin (increased fetal risk) Week 37 of pregnancy to delivery Stop use of SC UFH, LMWH, or warfarin Stop continuous use of IV UFH Plan delivery After delivery Resume use of warfarin when bleeding is controlled Continue the use of IV UFH until the INR is therapeutic Anti-coagulation monitoring UFH - aPTT at least twice the control value LMWH anti-Xa 0.7 1.2 units/ml (4 hrs after LMWH dose) Warfarin INR 3 (range 2.5 3.5)

Warfarin has a low molecular weight, crosses the placenta and results in fetal anticoagulation.retroplacental heorrhage and fetal intraccranial hemorrhage are additional risks to the fetus.

Anticoagulants-Warfarin containdicated durig the first 3 months of pregnancy as it crosses the placenta and is associated with a 1%--25% incidence of malformations. Warfarin embryopathy syndrome---facial abnormalities,optic atrophy,digital abnormalities,epithelial changes and mental impairment. Risk of fetal and maternal bleeding. FDA class X drug in first trimester. Class b drug in remainder of pregnancy.

Heparin-does not cross the placentafetal risk minimal. Anticoagulation during pregnancy-UFH or LMWH during first trimester,switch to Warfarin in next 5 months and heaprin during labor and delivery. Aspirin-associated with increased incidence of abortion and fetal growth retardation.

Statins and Pregnancy: The safety of statins during pregnancy has not been established. Women wishing to conceive should not take statins. During their childbearing years, women taking statins should use highly effective contraception. Nursing mothers also are advised to avoid taking statins. Statins use in childern: Some statins have been approved for use in childern with heterozygous familial hypercholesterolemia. Atorvastatins, lovastatin and simvastatin are indicated for childern 11 years. Pravastatin is approved for childern 8 years. Salicylates and pregnancy: Infants born to women who ingest salicylates for long periods may have signifiacntly reduced birth weight. When administered during the third trimester, there also is an increase in perinatal mortality, anemia, antepartum and postpartum hemorrhage, prolonged gestation and complicated deliveries; thus, its use during this period should be avoided. Administration of NSAIDs during the third trimester of pregnancy also can cause premature closure of the ductus arteriosus. The use of aspirin has been advocated for the treatment of women at high risk of preeclampsia, but it is estimated that treatment of 90 women is required to prevent one case of preeclampsia. Proton pump inhibitors and pregnancy: Most of the drugs fall in FDA category B, with the exception of omeprazole (category C)

Warfarin: Warfarin has a low molecular weight, crosses the placenta and results in fetal anticoagulation. It increases the risk of spontaneous abortion, prematurity, fetal deformity and stillbirth. However, warfarin use throughout the pregnancy, until near term, provides the lowest risk of maternal thromboembolic events, complications and death. Warfarin embryopathy: Incidence of warfarin embryopathy is less than 10%. Warfarin embryopathy results in bone and cartilaginous abnormalities with chondrodysplasia, nasal hypoplasia, optic atropathy, microphthalmia, blindness, minor neurologic dysfunction, reduced intelligence quotient and seizures. Warfarin doesnot enter breast milk and thus can be administered safely to women who breast-feed the infants.

Warfarin embryopathy : Incidence of warfarin embryopathy is less than 10%. Warfarin embryopathy results in bone and cartilaginous abnormalities with chondrodysplasia, nasal hypoplasia, optic atropathy, microphthalmia, blindness, minor neurologic dysfunction, reduced intelligence quotient and seizures. Warfarin does not enter breast milk and thus can be administered safely to women who breast-feed the infants.

Biological and Pharmacological Considerations in the Elderly The elderly experience a shift of the hemostatic balance towards increased clotting and decreased fibrinolysis. Aging may also lead to changes intrinsic to the platelet that are associated with increased platelet reactivity. Increased platelet activity has been correlated with a higher content of platelet phospholipids, suggesting an age-related increase in platelet transmembrane signaling or second messenger accumulation. Although hemostatic factors vary significantly with age, additional factors such as blood stasis and vessel wall degeneration with endothelial dysfunction play a key role and contribute to increased platelet activation and arterial thrombosis in the elderly.

age-related changes in absorption, distribution, metabolism, and clearance of antithrombotic drugs (Figure 1). Since polypharmacy is common in elderly patients, this exposes them to a greater risk of adverse drugdrug interactions. In addition to pharmacokinetics, age-related changes in pharmacodynamics may also occur, leading to a reduction of homeostatic mechanisms (3,8). This implies138

Numerous factors challenge the identification of the optimal antithrombotic drug regimens in the elderly. These include factors that may affect therapeutic agents in general (e.g., renal function, hepatic metabolism, body mass distribution) as well as factors more specific to thrombosis and hemostasis (e.g., platelet dysfunction, coagulation disorders). The greater risk of adverse drugdrug interactions due to polypharmacy in the elderly further enhances these concerns

Heart disease in the elderly Cardiac drugs in renal failure.- Warfarinclose monitoring of INR. Clopidogrel and aspirin-in dialysis patient increases risk of bleeding. ACEI ans ARBSRisk of worsening of renal function when used with aggresive diuretic regimens.,risk of hyperkalemia when used with potassium sparing diuretics.

Aldosterone receptor antagonistsuse along with ACEI/ARBS and betablockers increase risk of hyperkalemia. Antiarrhythmicsneed dose adjsutments in CKD.

MCQS Which of the folowing is contraindicated in a pregnant patient with CHF- A.Digoxn. B.Diuretic. C.ACEI. D.Betablocker.

A 25 yrs. Married patient with RHD.Mitral Regurgitation on furosemide,Enalapril 2.5 mg. And inj. Benjathine penicillin plans to conceive.which of the above drugs will you ask her to stop Furosemide, Enalapril. Benjathine penicillin.

Which of the following is a safe antihypertensive in pregnancy- A.thiazide diuretic B.enalapril C.alphamethyldopa. D.losartan.

Which of the following is NOT safe from the fetal point of view- A.DIGOXIN. B.METOPROLOL. C.AMIODARONE. D.VERAPAMIL.

dr.srinivas ramaka. m.d.,dm. consultant cardiologist

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