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Cology of Pediatrics n Geriatrics

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Page 1: 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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THANK YOU


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