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.
Slide 3
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.
Slide 4
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.
Slide 5
Identify the epidemiology of medication use in the elderly.
Identify the role of the pharmacist & strategies to enhance
safe medication use in the elderly.
Slide 6
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
Slide 7
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
Slide 8
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
Slide 9
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.
Slide 10
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.
Slide 11
General determinants of drug transfer across the placenta-
Lipid solubility,extent of plasma binding and degree of ionization
of weak acids and bases.
Slide 12
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
Slide 13
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..
Slide 14
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
Slide 15
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.
Slide 16
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.
Slide 17
Thromboembolic complications. Hypertensioncalcium channnel
drugsnifedipine and alphamethydopa. PAHmaternal mortality3070%.and
fetal loss is 40 %. Arrhyhmias-SVTadenosine.oral drugs-betablockers
or verapamil.
Slide 18
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.
Slide 19
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.
Slide 20
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.
Slide 21
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.
Slide 22
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.
Slide 23
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.
Slide 24
Management of CAD in pregnancy Heparin,low dose
asprin,nitrates,betablockers safe in pregnancy. Safety of
thrombolytics,GpIIb/IIIa inhibitors,clopidogrel not
established.
Slide 25
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.
Slide 26
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)
Slide 27
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.
Slide 28
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.
Slide 29
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.
Slide 30
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)
Slide 31
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.
Slide 32
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.
Slide 33
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.
Slide 34
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
Slide 35
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
Slide 36
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.
Slide 37
Aldosterone receptor antagonistsuse along with ACEI/ARBS and
betablockers increase risk of hyperkalemia. Antiarrhythmicsneed
dose adjsutments in CKD.
Slide 38
MCQS Which of the folowing is contraindicated in a pregnant
patient with CHF- A.Digoxn. B.Diuretic. C.ACEI. D.Betablocker.
Slide 39
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.
Slide 40
Which of the following is a safe antihypertensive in pregnancy-
A.thiazide diuretic B.enalapril C.alphamethyldopa. D.losartan.
Slide 41
Which of the following is NOT safe from the fetal point of
view- A.DIGOXIN. B.METOPROLOL. C.AMIODARONE. D.VERAPAMIL.