Download - Cology of Pediatrics n Geriatrics
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OF PEDIATRICS &
GERIATRICS
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PHARMACOLOGY
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INTRODUCTION
Many drugs have not been adequately evaluated in infants in terms of their
pharmacokinetic & pharmacodynamic properties.
Pediatric drug data are not readily available
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DRUG THERAPHY IN INFANTS
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PHARMACOKINETICS
• Absorption and Bioavailability.
• Protein binding and Drug distribution.
• Metabolism and excretion.
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Absorption
• From the GI tract .
• Transdermal absorption .
• Transrectal drug therapy .
• Absorption of drugs from the lung .
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Absorption from the GI tract
It is affected by :
• Gastric acid secretion• Bile salt formation• Gastric emptying time• Intestinal motility• Bowel length and effective
absorptive surface• Microbial flora
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Reduced gastric acid secretion
Increases bioavailability of acid-labile drugs
eg, penicillin
decreases bioavailability of weakly acidic drugs
eg, phenobarbital
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Injected drugs are often erratically absorbed because of
• Variability in muscle mass among children
• Illness (eg, compromised circulatory status)
• Differences in absorption by site of injection
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• IM injections are generally avoided in children .
• Transdermal absorption may be enhanced in neonates and young infants because the stratum corneum is thin .
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Distribution
• The volume of distribution of drugs changes in children with aging.
• These age-related changes are due to changes in body composition and plasma protein binding.
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Changes in body proportions of body
composition with growth and aging.
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Metabolism and elimination
• Drug metabolism and elimination vary with age and depend on the substrate or drug .
• The cytochrome P-450 (CYP450) enzyme system in the small bowel and liver is the most important known system for drug metabolism.
• The neonatal liver has less capacity for oxidation and conjugation reactions.
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Pharmacodynamics
• It is assumed that the MOA is similar in infants and adults.
• But ,immaturity in receptor or neurotransmitter development may contribute to age-dependent differences in drug responses.
• Appropriate use of drugs have increased the survival of neonates with severe abnormalities who would otherwise die within days or weeks after birth.
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Adverse Effects
• Some Adverse effects are peculiar to neonates and infants due to immaturity
• Some of the documented toxicities are :
Ototoxicity with Aminoglycosides.
Tetracyclines : Tooth discolouration
Delayed bone growth
Hepatoxicity with asprin or paractamaol
Stunted growth with Corticosteroids
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Dosage Calculations
• Ideally the dosage for neonates and infants should be individualized, taking into consideration age, weight, body surface area and pharmacokinetic realities.
• Doses based on body surface area are possibly the best way to scale down adult doses for infants and young children.
• This method is not reliable for prematures.
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Paediatric doses can be calculated from one of the following methods:
• 1.Dosage based on weight (Clark’s rule )
Dose = Adult dose * Weight (kg)/60.
2.Dosage based on age (Young’s rule)
Dose = Adult dose * Age (yrs)/Age +12
3.Dose based on surface area.
Dose =Adult dose * Body surface area(m2) /Adult body surface area
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CONTRAINDICATED DRUGS
• Asprin.• Ampicillin.• Cephalexin.• Phenytoin.• Vitamin K or Novobiocin
Chloromphenical
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DRUG THERAPHY IN GERAITRICS
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Absorption
• The conditions which alter the rate of absorption at aging are:
1.Altered nutritional habits.
2.Greater consumption of non-prescription drugs
3.Changes in gastric emptying time
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Distribution
• Compared to young adults, the elderly have:
1.reduced lean body mass,
2.reduced total and percentage
body water,
3.increase in fat as a percentage of body mass
There is a decrease in serum albumin
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Metabolism
• The capacity of the liver to metabolize drugs does not appear to decline consistently with age for all drugs.
• The greatest changes are in phase I reactions
• These changes may be caused by decreased liver blood flow an important variable in the clearance of drugs.
• In addition, there is a decline of the liver's ability to recover from injury.
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Effects of Age on Hepatic Clearance of Some Drugs
• Age-Related Decrease in Hepatic Clearance Found
• Alprazolam• Barbiturates• Diazepam• Propranolol• Quinidine, quinine
• No Age-Related Difference Found
• Nitrazepam• Oxazepam• Prazosin• Salicylate• Ethanol
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Elimination
• Since kidney is the major organ for clearance of drugs from the body, there is a decline in the renal functional capacity.
• Decreased renal functions include :
– decreased blood flow to the kidneys
– decreased glomerular filtration
– decreased tubular secretion
– decline in creatinine clearance
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• Dosing recommendations should be done for the elderly people.
• If dosage is not reduced in size or frequency there is a possibility of accumulation to toxic levels
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Pharmacodynamics
• Physiological changes in elderly patients affecting pharmcodynamics
Target organ physiological changes
• increased sensitivity to pharmacological agents
• decreased desirable effects of pharmacotherapy
• increased adverse effects
Homeostasis changes
• decreased capacity to respond to physiological challenges and the adverse side effects of drug therapy
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MAJOR DRUG GROUPS FOR GERIATRICS
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CENTRAL NERVOUS YSTEM
SEDATIVE-HYPNOTICS
• The half-lives of many benzodiazepines and barbiturates increase 50–150% between age 30 and age 70.
• For many of the benzodiazepines, both the parent molecule and its metabolites are pharmacologically active
• Since decline in renal function and liver disease, if present, both contribute to the reduction in elimination of these compounds.
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• Therefore due to toxicities of these drugs, ataxia and other aspects of motor impairment should be particularly watched for in order to avoid accidents
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ANALGESICS
The opioid analgesics show variable changes in pharmacokinetics with age.
• Therefore, this group of drugs should be used with caution until the sensitivity of the particular patient has been evaluated, and the patient should then be dosed appropriately for full effect
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ANTIPSYCHOTIC & ANTIDEPRESSANT
The antipsychotic agents have been very heavily used in the management of a variety of psychiatric diseases in the elderly people.
eg., phenothiazines and haloperidol
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CARDIOVASCULAR DRUGS
Antiarrhythmic Agents
• The treatment of arrhythmias in the elderly is particularly challenging because of the lack of good hemodynamic reserve.
• The clearances of quinidine and procainamide decrease and their half-lives increase with age.
• Disopyramide should probably be avoided due to major toxicities.
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Anti-Inflammatory Drugs
Osteoarthritis is a very common disease of the elderly.
• The nonsteroidal anti-inflammatory agents must be used with special care in the geriatric patient because they cause toxicities to which the elderly are very susceptible
• In the case of aspirin, the most important is gastrointestinal irritation and bleeding
• In the case of the newer NSAIDs, the most important is renal damage, which may be irreversible
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Adverse Drug Reactions
The elderly are 2-3 times more at risk for adverse drug reactions due to:
1. reduced stature.
2. reduced renal and hepatic functions.
3. cumulative insults to the body (eg., disease, diet, drug abuse)
4. multiple and potent medications.
5. altered pharmacokinetics.
6. noncompliance.
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ADR: Anticoagulants
• Elderly patients are more sensitive to the effects of anticoagulants
• Pharmacodynamic changes: vitamin K-dependent clotting factors deficiency
• Pharmacokinetic changes: anticoagulants such as
warfarin have a very narrow therapeutic value and are highly protein bound
• drug interactions (eg., phenytoin)
• adverse effect: excessive internal bleeding
• Frequent monitoring by primary care physician
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ADR: NSAIDs
• Non-Steroidal Anti-Inflammatory Drugs are frequently prescribed in the elderly patients
• Pronounced adverse gastrointestinal side effects
• Other adverse drug reactions in the kidney and CNS have also been associated with chronic NSAID therapy in the elderly
• Alternate therapies:
– acetaminophen (Tylenol) for analgesia
– new COX-2 inhibitors for anti-inflammatory actions
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ADR: Cardiovascular Agents• congestive heart failure is a common age-
related condition
• Digoxin used to be the drug of choice for congestive heart failure
– drug elimination is reduced in the elderly;– often worsens cardiac symptoms
• Replaced by newer therapeutic agents: betaaderenergic receptor blocker and angiotensinconverting enzyme inhibitors
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Commonly used medications best avoidedin the elderly
• Anticholinergic preparations
– diphenhydramine (Benadryl)– doxepin (Sinequan)– dicyclomine (Bentyl)
• Benzodiazepines with active metabolites
– diazepam (Valium)– flurazepam (Dalmane)
• Central acting CNS agents– alpha methyldopa (Aldomet)– clonidine (Catapres)
• Analgesics
– propoxyphene (Darvon)– indomethacin (Indocin)
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CONCLUSION
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References
• Pharmacology 2nd edition, Bhattacharya, pg no 501-514.
• Katzung : Clinical pharmacology.
• www.merk&co.in
• http://www.med.yale.edu/library/heartbk/23.pdf
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QUERIES?
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