Therapeutics July 4, 2014

Drug Therapy in the Young & in the Elderly

I. Drug therapy in the young: Not a miniature adult

Pharmaceutical factors: Injections

Oral

Fever and Vomiting

Liquid Preparations

Household Measure

Flavoring

Pharmacokinetic Factors

• Absorption

• Oral absorption • Infants & Children – Similar to adults

• Neonates – Low Gastric acid secretion

- Percutaneous Absorption Neonates, Infants & Children : Greater than Adults

- Burned or Excoriated Skin - Corticosteroid

- Ointments & Creams

- Boric Acid

- Aminoglycoside/Polymixin spray

Phramacodynamic Factor

• Knowledge – Sparse

• Digoxin

• Decreased GFR in neonates

• t ½ : 2-3 Times of adult value

• Rely on Long established

• Empirical dosage schedule

• Dosage calculation :

Dosage = Adult dose X Patient’s surface area (m2)

Adult body surface area (1.7 m2)

Metabolism • HEPATIC

• In New Born

• Oxidative metabolism • Glucoronide conjugation

• Diazepam • t ½

• Premature : 38 – 120 hours • Full term : 22 – 46 hours • One mo. Old : 10-12 hours • 1 – 15 years : 15 – 21 hours

• Adult : 24 – 48 hours

- Theophylline - t ½

- Premature : 14 – 58 hours - Adults : 3.4 – 8 hours

Distribution Plasma Protein Binding

Decreased in neonates

Reaches adult values at one year

Decreased plasma albumin

Decreased capacity of albumin to bind drugs

Phenytoin

Sulfonamides*

Aspirin*

* Kernicterus

Renal Excretion

• GFR & Tubular Function • Neonates – Immature : 6 months to reach

adult level

• 30% - 40% of adult

• Gentamycin & Penicillin • Adjust after 2-3 weeks

• TETRACYCLINE • Last Trimester

• Traverses placenta

• Deposits in fetal skeleton

• Retard skeletal growth in premature infants

• Localizes in epiphysis & deciduous teeth in children stained teeth enamel; enamel defect

•CHLORAPHENICOL • Aplastic anemia

• Agranulocytosis

• Dose related and duration of treatment

• Gray baby syndrome • Glucoronyl transferase deficiency

II. Drug Therapy in the Elderly 1. Developed Countries

Elderly – 12 % but consume 25 – 30% of health service expenditures on drugs

2. Adverse drug reaction 2 – 3 times or common

3. Polypharmacy

4. Error rate in taking drugs More than 3 drugs

ELDERLY

• Pharmacokinetics

• Renal function decreases 50% • Hepatic blood flow • Drug metabolizing enzymes – decreased • Cytochrome P450 = activity decreased • Elimination half life – increased

• Larger apparent volume of distribution • Reduction of renal or metabolic clearance

ELDERLY

• Pharmacodynamics

• CNS depressant – increased sensitivity

•Physiologic changes • Loss of homeostatic resilience

• Psychotropic medications • Hypotension

• Anticoagulants

• Hemorrhage

Factors Increased Dangers

• Frailty

• Degree of illness

• Inability to look after themselves

• Poor appetite & Nutrition

• Poor fluid intake

• Immobility

• Multiple illnesses

• Confusion & forgetfulness

• Lack of supervision

• Pharmaceutical Factors

Tablets

Capsules adhere to esophageal Mucosa

Elixirs

• Phamacokinetic Factors • Absorption – not well documented

• Decreased plasma protein binding

• Decreased plasma albumin

• *Diazepam - Increased

• Metabolism • Difficult

• Ecretion • Decreased GFR & tubular function

• Gentamicin

• Digoxin

• Procainamide

• Lithium

• Pharmacodynamic Factors • Drugs sesitivity altered

• Warfarin • Decreased dosage

• Increased sensitivity to anticoagulant effect

• Hypnotics • Sedatives • Tranquilizers • Antidepressants

AGE Decreased cardiac output

19 – 86 years

Decreased gastric emptying time

Decreased intestinal blood perfusion 40-50%

• Decreased albumin concentration Decreased elimination or unchanged

High protein bound

Fat

Decreased cytochrome P450 Dependent monooxygenases

• Decreased endogenous creatinine clearance • ½

DRUGS

• Antispasmodics

• Antacids

• H2 receptor antagonist

Abdominal Pain

• Site • Epigastric

• GIT

• CVS

• Periumbilical

• GIT

• Hypogastric • Urinary Tract

• Reproductive System

• Right Lower Quadrant • GIT

Elderly • Pharmacokinetics

• Renal function decreases – 50%

• Hepatic blood flow

• Drug metabolizing enzymes – decreased

• Cytochrome P450 – activity decreased

• Elimination half life – increased • Larger apparent volume of distribution

• Reduction of renal or metabolic clearance

• Pharmacodynamics • CNS depressants – increased activity

• Physiologic changes

• Loss of hemeostatic resilience

• Psychotropic medications • Hypotension

• Anticoagulants • Hemorrhage

Symptomatic Therapy

• Cough • Symptomatic Treatment

• Irritating Cough Suppressant

• Unproductive

• Irritating

• Productive sputum Expectorant

• Difficulty in expectoration

• Underlying Disease Not Treated

P O I S O N I N G

• 80 - 90% childhood poisoning 5 y/o

• 80% all poisoning victims - children

• 5M under 5 y/o - ingest toxic products

• 1% of all physicians - drug dependent

P O I S O N I N G

Accidental - elderly patients

Unintentional - children

Unknown - homicide

Overdose - intentional toxic exposure

BASIC PRINCIPLES IN THE MANAGEMENT OF POISONING CASES

• 1. EMERGENCY STABILIZATION

• 2. CLINICAL EVALUATION

• 3. ELIMINATION OF POISON

• 4. ANTIDOTE

• 5. ELIMINATION OF ABSORBED POISON

• 6. SUPPORTIVE THERAPY

• 7. OBSERVATION & DISPOSITION

1. EMERGENCY STABILIZATION

A

B

C

D

Naloxone HCl -IV 2 mg adult

0.1mg children

D50 - 1ml/kg adult

D10-20 children

Thiamine

2. CLINICAL EVALUATION

5 MAJOR MANIFESTATIONS

1. COMA

2. METABOLIC ACODOSIS

3. GIT DISTRUBANCES

4. ARRHYTHMIAS

5. SEIZURES

CAUSES OFA HIGH ANION GAP METABOLIC ACIDOSIS

Uremia Diabetic ketoacidosis

Lactic acidosis Salicylate toxicity

Methanol Ethylene glycol

Nondiabetic alcoholic Paraldehyde

ketoacidosis toxicity

COMMON AGENTS CAUSING SEIZURES

Camphor Organophosphate

Carbon monoxide Phencyclidine

Chlorinated Phenol

hydrocarbon Phenothiazines

Cocaine Propoxyphene HCl

Isoniazid Strychnine

Lithium TCA

CONTRAINDICATIONS TO EMESIS

1. Coma

2. Corrosives

3. <6 months old

4. Hydrocarbons

5. Pregnancy

6. Cardiac disease

7. Elderly/debilitated

COMMON TOXIC CAUSES OF CARDIAC ARRHYTHMIA

Amphetamine Phenol

Arsenic Phenothiazines

Carbon monoxide Physostigmine

Chloral hydrate Propranolol

Cocaine Quinine,Quinidine

Cyanide Succinylcholine

Digitalis Theophylline

Dinitrophenols TCA

3. ELIMINATION OF POISON

A. GIT

DILUENTS MILK EGG WHITE DEMULCENTS

SYRUP OF IPECAC

- 15 ml – CHILD

30 ml – ADULT

GASTRIC LAVAGE

- OROGASTRIC TUBE

3. ELIMINATION OF POISON

A. GIT

ACTIVATED CHARCOAL

- - 30 GMA +100 ML H2o

- - 50 GMS +150 ml

SLURRY

ANIMAL BONE

WOOD PULP

TEMPERATURE

PRESSURE

ADSORPTION

CATHARTICS

SORBITOL

SOIUM SULFATE

-ADULT - 15 gms +100 ml H2O

- CHILDREN – 250 mg/kg

NEUTRALIZERS

IRON – 5% Na HCO3

ODINE – 75 grams STARCH/L H2O

4. ANTIDOTE

ATROPINE – ORGANOPHOSPHATE

DEFEROXAMINE – IRON

INH – PYRIDOXINE

5. ELIMINATION OF ABSORBED SUBSTANCE

ACIDIFICATION – VIT. C

ALKALINIZATION – SODIUM BICARBONATE

FORCED DIURESIS

- FUROSEMIDE

- MANNITOL

DIALYSIS AND HEMOPERFUSION

- THEOPHYLLINE

- BARBITURATES

HYPERBARIC OXYGEN

- CARBON MONOXIDE

6. SUPPORTIVE THERAPY

VITAL SIGNS

IVF

INTENSIVE NURSING CARE

7. OBSERVATION AND DISPOSITION

- COMPLICATIONS

PERSONALITY DISORDER

EXAMPLES OF SYMPTOM COMPLEXES OR TOXIDROMES

CONCIOUSNESS RESPIRA- PUPILS OTHER POSSIBLE TOXIC AGENTS

TIONS

Coma Pinpoint Fasciculations Organophosphate insecticides

Coma Pinpoint Tracts Opiates

Coma Apneustic Pinpoint Decerebrate Pontine (brain stem) structural

lesion

Awake Torsion head/ Phenothiazines, haloperidol

neck

Coma Pinpoint Cardiac Phenothiazines

arrthythmia

Coma Dilated Cardiac Tricyclic

arrthythmia

Convulsions antidepressants

EXAMPLES OF SYMPTOM COMPLEXES OR TOXIDROMES

CONCIOUSNESS RESPIRA- PUPILS OTHER POSSIBLE TOXIC AGENTS

TIONS

Coma Uremic frost (Urimia)

Coma Dilated Hypothermia Sedatives, barbiturates

Semicoma Diaphoresis Salicylates

Tinnitus

Fever

Agitated,

Hallucinating Dilated Fever Anticholinergics

Flushing

Dry skin and mucous

membranes

HOSPITAL MANAGEMENT 259

Table 14-5 DIAGNOSTIC ODORS

ODOR POSSIBLE SUBSTANCE

Acectone (sweet, like russet apples) Lacquer, alcohol, isoprophyl alcohol, chloroform, ketoacidosis

Acrid (pearlike) Paraldehyde, chloral hydrate

Alcohol (fruitlike) Alcohol, isophrophyl alcohol

Ammoniac Urea

Bitter almonds Cyanide (in choke cherry, apricot pits)

Carrots Cicutoxin

Coal gas (stove gas) Carbon monoxide (odorless but associated with coal gas)

Disinfectants Hydrogen sulfide, mercaptans, Antabuse

Eggs (rotten) Hepatic failure, zinc phosphide

Fish or raw liver (musty) Amyl nitrite, alcohol, isoprophyl alcohol

Fruitlike Phosphorus, tellurium, arsenic (breath and perspiration),

parathion, malathion, selenium, dimethyl sulfoxide

(DMSO), thallium

From Goldfrank LR: Toxicologic Emergencies. 2nd ed. Appleton-Century-Crofts, New York, 1982, p 253. Used with permission.

HOSPITAL MANAGEMENT 259

Table 14-5 DIAGNOSTIC ODORS

ODOR POSSIBLE SUBSTANCE

Halitosis Acute illness, poor oral hygiene

Mothballs Camphor-containing products

Peanuts RH-787 (Vacor)

Pungent, aromatic Ethchlorvynol (Placidyl)

Shoe polish Nitrobenzene

Tobacco (stale) Nicotine

Violets Urinary turpentine

Wintergreen Methyl salicylate

_____________________________________________________________________________________________________

From Goldfrank LR: Toxicologic Emergencies. 2nd ed. Appleton-Century-Crofts, New York, 1982, p 253. Used with permission.

Dose Basis for Approximately Toxicity Ratings and Factors Tending to Raise or Lower Rating

PROBABLE LETHAL DOSE

TOXICITY RATING PER KG, VOL. IN 2 YEARS OLD

========================================================================

Extreme 5 mg. A Swallow* or less

High 50-500 mg. 2-3 swallow*

Medium 0.5-5 gm. ½-6 oz.

Nil or Low 5 gm. More than 6 oz.

Raise Lower

Liquid Solid or semisolid

Pellets Powdered (unless caustic)

Flavorful Distasteful

Large volume Small Volume

Low viscosity hydrocarbon Viscous

Method of dispensing or packaging.

____________________________________________________________________________

*Modified from Gosselin13, and Gleason, Gosselin, and Hodge, 12

*Based upon average swallow volume of 4 to 5 ml. In a 2 years old child.15

TOXICITY RATING CHART

TOXICITY RATING

Description

Probable Oral lethal Dose for a 70 kg Human

6

Supertoxic

< 5 mg/kg

A taste (<7 drops)

5

Extremely toxic

5-’50 mg/kg

Between 7 drops and 1 tsp.

4

Very toxic

50-500 mg/kg

Between 1 tsp. and 1 oz.

3

Moderately toxic

0.5-5 gm/kg

Between 1 oz. and 1 pint

2

Slightly toxic

5-15 gm/kg

Between 1 pint and 1 qt.

1

Practically non-toxic

> 15 gm/kg

>1 quart

From Gosselin, R.E.,et al., Clinical Toxicology of Commercial Products, 4th ed. The Williams & Wilkins Co., Baltimore, 1976.

FERTILIZER and PESTICIDE AUTHORITY PESTICIDE TOXICITY

and HAZARD CLASSIFICATION

Category Signal Words Color band Toxicity

1 DANGER POISON RED EXTREMLY TOXIC

2 WARNING HARMFUL YELLOW HIGHLY TOXIC

3 CAUTION BLUE MODERATELY

4 ---- GREEN LEAST TOXIC