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