Chapter 11 human variability

The Pharmacy The Pharmacy Technician 4ETechnician 4E

Chapter 11Chapter 11Factors Affecting Drug Factors Affecting Drug

ActivityActivity

Chapter OutlineChapter Outline

Human VariabilityHuman Variability Disease StatesDisease States Adverse Drug ReactionsAdverse Drug Reactions Drug-Drug InteractionsDrug-Drug Interactions Drug-Diet InteractionsDrug-Diet Interactions

Human Variability – AgeHuman Variability – Age

Overall, metabolism declines with age.Overall, metabolism declines with age. Neonates and infantsNeonates and infants

Drug distribution, metabolism, and excretion Drug distribution, metabolism, and excretion slower.slower. ChildrenChildren (age range from 1-12 yrs old.) (age range from 1-12 yrs old.)

Metabolize certain drugs Metabolize certain drugs more rapidlymore rapidly, e.g clindamycin, , e.g clindamycin, valproid acid, theophylline, ethosuximde and theophylline.valproid acid, theophylline, ethosuximde and theophylline.

The elderlyThe elderly Consume more drugs.Consume more drugs. Changes in gastric emptying, slow circulation, decline in liver Changes in gastric emptying, slow circulation, decline in liver

and kidney functions.and kidney functions.

Human VariabilityHuman Variability GenderGender

Women and men handle drugs differently.Women and men handle drugs differently. Pregnancy Pregnancy

Delayed gastric emptying.Delayed gastric emptying. Genetics Genetics

Determines type and amounts of proteins Determines type and amounts of proteins produced in the body.produced in the body.

Human VariabilityHuman Variability

Pharmacognetics Pharmacognetics Defines the hereditary basis of individual Defines the hereditary basis of individual

differences in the ADME process.differences in the ADME process. Body weight Body weight

Important in dosing medication to children.Important in dosing medication to children. Psychological factors Psychological factors

Influences patients responses to drugs, e.g. Influences patients responses to drugs, e.g. placebo effect.placebo effect.

Diseases that affect drug dispositionDiseases that affect drug disposition

The disposition and effect of some drugs can be influenced The disposition and effect of some drugs can be influenced by the presence of disease.by the presence of disease.

CirrhosisCirrhosis A chronic diseases that occurs with long term alcohol A chronic diseases that occurs with long term alcohol

abuse.abuse. Acute viral hepatitis Acute viral hepatitis

An inflammation condition of the liver caused by viruses.An inflammation condition of the liver caused by viruses. Obstructive jaundiceObstructive jaundice

Obstruction of the bile duct causing hepatic waste Obstruction of the bile duct causing hepatic waste products and bile to accumulate in the liver.products and bile to accumulate in the liver.

Renal DiseasesRenal Diseases

Reduced renal function can affect the elimination of Reduced renal function can affect the elimination of many drugs.many drugs.

Nephro (of kidney): Nephro (of kidney): As renal function decreases, the As renal function decreases, the dosage of a drug that is eliminated by the kidney dosage of a drug that is eliminated by the kidney should be reduced. should be reduced.

Decrease in renal function is measured by the amount Decrease in renal function is measured by the amount of creatinine in the blood.of creatinine in the blood.

Thyroid DiseaseThyroid Disease

Changes in thyroid function affects the disposition of Changes in thyroid function affects the disposition of many drugs.many drugs. E.g. hypothyroidism (under active thyroid) increases E.g. hypothyroidism (under active thyroid) increases

the bioavailability of digoxin, riboflavin.the bioavailability of digoxin, riboflavin. E.g. hyperthyroidism (overactive thyroid) causes E.g. hyperthyroidism (overactive thyroid) causes

increased metabolism of theophylline, propranolol, increased metabolism of theophylline, propranolol, propylthiouriacil, & methimazole.propylthiouriacil, & methimazole.

Adverse Drug ReactionsAdverse Drug Reactions

Drugs have a Drugs have a mixture of two effects .mixture of two effects . Therapeutic Therapeutic (desired) (desired) Adverse effects Adverse effects (undesired effects)(undesired effects)

Side effectsSide effects

Adverse Drug Event Adverse Drug Event

Harm caused by the drug.Harm caused by the drug.

Adverse Drug ReactionAdverse Drug Reaction

Harm directly caused by the drug at normal doses.Harm directly caused by the drug at normal doses.

Medication ErrorMedication Error

Inappropriate use of a drug.Inappropriate use of a drug.

Common Adverse Drug ReactionsCommon Adverse Drug Reactions

Central Nervous System EffectsCentral Nervous System Effects CNS stimulation: agitation, confusion, CNS stimulation: agitation, confusion,

disorientation.disorientation. CNS Depression: dizziness, drowsiness, sedation, CNS Depression: dizziness, drowsiness, sedation,

coma.coma. IdiosyncrasyIdiosyncrasy - -Unexpected reaction to a drug.Unexpected reaction to a drug. HepatotoxicityHepatotoxicity

Occurs with acetaminophen, isoniazide, Occurs with acetaminophen, isoniazide, nitrofurantoin.nitrofurantoin.

NephrotoxicityNephrotoxicity Occurs with aminoglycosides, nonsteroidal anti-Occurs with aminoglycosides, nonsteroidal anti-

inflammatory drugs.inflammatory drugs.

Hypersensitive or AllergyHypersensitive or Allergy

Any drug can produce an allergic reaction.Any drug can produce an allergic reaction. Involves Involves

Antibodies antigen reactionAntibodies antigen reaction Previous sensitization Previous sensitization with a drug or a similar drug with a drug or a similar drug

required.required. The reaction causes the release of The reaction causes the release of histaminehistamine that that

leads to rash, itching, and in severe cases difficulty of leads to rash, itching, and in severe cases difficulty of breathing and even death.breathing and even death.

Anaphylactic shock Anaphylactic shock - potentially fatal type of reaction - potentially fatal type of reaction and can and can occur within minutesoccur within minutes..

Common Adverse Drug ReactionsCommon Adverse Drug Reactions Gastrointestinal effectsGastrointestinal effects Occur with nonsteroidal Occur with nonsteroidal

anti-inflammatory drugs anti-inflammatory drugs (aspirin).(aspirin).

Drug dependenceDrug dependence Causes withdrawal effect Causes withdrawal effect

upon discontinuation. upon discontinuation. Results from chronic use Results from chronic use

of narcotic analgesics.of narcotic analgesics.

TeratogenicityTeratogenicity Substance causing Substance causing

abnormal fetal abnormal fetal development.development.

Hematological effectHematological effect Blood coagulation, Blood coagulation,

bleeding, and bone bleeding, and bone marrow disorder.marrow disorder.

CarcinogenicityCarcinogenicity Cancer causing drugs.Cancer causing drugs.

Drug-Drug InteractionsDrug-Drug Interactions

Definition - Definition - Administration ofAdministration of more than one drug at a time.more than one drug at a time.

Results in an Results in an increase or decrease increase or decrease of the therapeutic of the therapeutic effects.effects.

TimeTime of reaction varies.of reaction varies. EnzymesEnzymes involved in the metabolism of drugs involved in the metabolism of drugs

primarily occur in the liver.primarily occur in the liver.


Additive Effects Additive Effects Occurs when two drugs result in an effect equal to Occurs when two drugs result in an effect equal to

the sum of the individual effects.the sum of the individual effects. E.g.E.g. trimethoprim + sufamethoxazle trimethoprim + sufamethoxazle (Bactrim) for (Bactrim) for

antibiotic effect.antibiotic effect.

PotentiationPotentiation Occurs when one drug with no inherent activity of its Occurs when one drug with no inherent activity of its

own increases the activity of another drug that own increases the activity of another drug that produces an effect. produces an effect. E.g.E.g. carbidopa + dopa carbidopa + dopa = prolonged action and = prolonged action and

longer duration of action for Parkinson's disease.longer duration of action for Parkinson's disease.


SynergismSynergism Occurs when two drugs with similar pharmacological Occurs when two drugs with similar pharmacological

actions produce greater effects than the sum of actions produce greater effects than the sum of individual effects. individual effects. E.g. E.g. Acetaminophen + codeine Acetaminophen + codeine (Tylenol #3®) (Tylenol #3®)

caused increased analgesia.caused increased analgesia. E.g. E.g. penicillin + gentamicin penicillin + gentamicin = increased = increased

antibacterial effects.antibacterial effects.

Drug-Drug InteractionsDrug-Drug Interactions AntidoteAntidote

A particular drug given to block or reduce the toxic effect of A particular drug given to block or reduce the toxic effect of another drug.another drug.

E.g. E.g. Vitamin KVitamin K reverses the effect of reverses the effect of warfarinwarfarin (blood thinner (blood thinner medicine).medicine).

E.g. E.g. Naloxone + morphine Naloxone + morphine reverses the effect of morphine or reverses the effect of morphine or other narcotics.other narcotics.

ChelatingChelating Drug binds with another drug forming a complex which Drug binds with another drug forming a complex which

reduces absorptionreduces absorption E.g. Aluminum or magnesium hydroxide (antacid) + E.g. Aluminum or magnesium hydroxide (antacid) +

tetracycline tetracycline inhibits the antibiotic effect of TTC.inhibits the antibiotic effect of TTC. E.g. Cholestyramine + thyroxineE.g. Cholestyramine + thyroxine binding of thyroxin reducing binding of thyroxin reducing

its absorption.its absorption.


DisplacementDisplacement One drug from a protein binding site is replaced by One drug from a protein binding site is replaced by

another drug.another drug. E.g. aspirin + warfarin = increased effect of E.g. aspirin + warfarin = increased effect of

warfarin.warfarin. InhibitionInhibition

One drug inhibits the breakdown of another agentOne drug inhibits the breakdown of another agent E.g. E.g. Cimetidine Cimetidine inhibit the breakdown of digoxin inhibit the breakdown of digoxin

causing digoxin toxicity.causing digoxin toxicity. InductionInduction

One drug increases an enzyme.One drug increases an enzyme. Pharmacogenetics Pharmacogenetics

ffect of a gene on drug disposition.ffect of a gene on drug disposition.

Drug-Drug InteractionDrug-Drug Interaction

InductionInduction:: One drug increases the metabolizing enzyme One drug increases the metabolizing enzyme that breaks down another drug.that breaks down another drug. E.g. Phenytoin + oral contraceptives = decreased E.g. Phenytoin + oral contraceptives = decreased

contraception effect.contraception effect. Urinary excretionUrinary excretion:: Drugs altering the urinary pH that Drugs altering the urinary pH that

cause a decrease in renal reabsorption.cause a decrease in renal reabsorption. E.g. E.g. Sodium bicarbonate + Phenobarbital Sodium bicarbonate + Phenobarbital = =

increased excretion of Phenobarbital.increased excretion of Phenobarbital. E.g. E.g. Quinidine + digoxin Quinidine + digoxin = digoxin excretion is = digoxin excretion is

reduced by 30-50%.reduced by 30-50%.

Drug-Diet InteractionDrug-Diet Interaction

When elements of ingested nutrients interact with a drug When elements of ingested nutrients interact with a drug affecting the disposition of the drug.affecting the disposition of the drug.

AbsorptionAbsorption TTC + Iron TTC + Iron = decreases TTC absorption.= decreases TTC absorption. Phenytoin + food Phenytoin + food = increased absorption.= increased absorption. Interactions that alter absorption with food or nutrient can be Interactions that alter absorption with food or nutrient can be

avoided by separating the administration of drugs and food avoided by separating the administration of drugs and food intake by about 2 hours.intake by about 2 hours.

Specific foodSpecific food E.g.E.g. Cruciferous vegetables Cruciferous vegetables like cabbage and brussels sprouts like cabbage and brussels sprouts

may stimulate the metabolism of some drugs. may stimulate the metabolism of some drugs. E.g. E.g. Spinach and other green vegetables Spinach and other green vegetables contain contain vitamin K vitamin K

and inhibit the action of warfarin.and inhibit the action of warfarin. E.gE.g. Tyramine containing food . Tyramine containing food + monoamine oxidase + monoamine oxidase (MAO) (MAO)

inhibitorsinhibitors = severe hypertension or intracranial hemorrhage. = severe hypertension or intracranial hemorrhage.

Terms to RememberTerms to Remember

1. Acute viral hepatitis1. Acute viral hepatitis2. Additive effects2. Additive effects3. Adverse drug reaction3. Adverse drug reaction4. Anaphylactic shock4. Anaphylactic shock5. Antidote5. Antidote6. Carcinogenicity6. Carcinogenicity7. Cirrhosis7. Cirrhosis8. Complexation8. Complexation9. Displacement9. Displacement10. Drug–diet interactions10. Drug–diet interactions

11. Enzyme induction11. Enzyme induction12. Enzyme inhibition12. Enzyme inhibition13. Hypersensitivity13. Hypersensitivity14. Hyperthyroidism14. Hyperthyroidism15. Hypothyroidism15. Hypothyroidism16. Idiosyncrasy16. Idiosyncrasy17. Obstructive jaundice17. Obstructive jaundice18. Pharmacogenetics18. Pharmacogenetics19. Potentiation19. Potentiation20. Synergism20. Synergism

Chapter 11 human variability

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