Drugs in Everyday Life GES 1510 John H.K. Yeung Department of Pharmacology C.U.H.K

Drugs in Everyday LifeGES 1510

Drugs in Everyday LifeGES 1510

John H.K. YeungJohn H.K. Yeung

Department of Pharmacology Department of Pharmacology C.U.H.K.C.U.H.K.

PHARMACOLOGYPHARMACOLOGY

Scientific study of the interactions Scientific study of the interactions between drugs and the body between drugs and the body

What are drugs?What are drugs?

Where do drugs come Where do drugs come from?from?

Origin of DrugsOrigin of Drugs

PlantPlant

AnimalAnimal

SyntheticSynthetic

The relationships between science and medicineThe relationships between science and medicine

Pharmaceutical(Medicinal)Chemistry

Pharmacology and

Toxicology

Therapeutics

Pharmacy

Patients

HO NHCOCH3

Chemical : N-acetyl-p-amino-phenol

.

Naming of a Drug

HO NHCOCH3

Chemical : N-acetyl-p-amino-phenol

Generic : Paracetamol (BP)Acetaminophen (USP)

.

Naming of a Drug

HO NHCOCH3

Chemical : N-acetyl-p-amino-phenol

Generic : Paracetamol (BP)Acetaminophen (USP)

Trade : Panadol (500)Tylenol (300)Calpol etc.

Naming of a Drug

Drugs = Medicines only?Drugs = Medicines only?

DRUG LivingTissue

DRUG LivingTissue

Effect

DRUG LivingTissue

Effect

MEDICINE

POISON

AIRPOLLUTANTS

INSECTICIDES

FOODADDITIVES

COSMETICS

HERBICIDES

Drugs in Everyday LifeDrugs in Everyday Life

Medical useMedical use Non-medical useNon-medical use

““Social Drugs”Social Drugs” Health and diet supplementsHealth and diet supplements Drugs of abuseDrugs of abuse

Pharmacological Effects of SmokingPharmacological Effects of Smoking

CNS effectsCNS effects inhibits spinal reflexes to produce skeletal inhibits spinal reflexes to produce skeletal

muscle relaxationmuscle relaxation produces sense of alertnessproduces sense of alertness

Pharmacological Effects of SmokingPharmacological Effects of Smoking

Peripheral effectsPeripheral effects increases cardiac outputincreases cardiac output increases blood pressureincreases blood pressure vasoconstrictionvasoconstriction sweatingsweating decreases gastrointestinal motilitydecreases gastrointestinal motility

Addictive ?Addictive ?

Withdrawal Syndrome to NicotineWithdrawal Syndrome to Nicotine

Increased irritabilityIncreased irritability

Impaired performance of psychomotor Impaired performance of psychomotor taskstasks

AggressivenessAggressiveness

Sleep disturbanceSleep disturbance

Harmful Effects of SmokingHarmful Effects of Smoking

CancerCancer mouth, throat, oesophagus and lungmouth, throat, oesophagus and lung

Coronary heart diseaseCoronary heart disease

Chronic bronchitisChronic bronchitis

Affects pregnancy Affects pregnancy decrease in birth weightdecrease in birth weight increase perinatal mortalityincrease perinatal mortality

Pharmacological Effects of AlcoholPharmacological Effects of Alcohol

Depressant effect on the Central Nervous Depressant effect on the Central Nervous SystemSystem

Impairs intellectual and motor performanceImpairs intellectual and motor performance

Produces cutaneous vasodilatation (central in Produces cutaneous vasodilatation (central in origin) which causes a warm feeling but origin) which causes a warm feeling but actually increase heat lossactually increase heat loss

Increases salivary and gastric secretionsIncreases salivary and gastric secretions

Diuretic effectDiuretic effect

Pharmacological Effects of AlcoholPharmacological Effects of Alcohol

Acute intoxicationAcute intoxication slurred speechslurred speech decrease in motor coordinationdecrease in motor coordination increased self-confidenceincreased self-confidence euphoriaeuphoria

Excessive consumption long-term causes liver Excessive consumption long-term causes liver damagedamage

Affects fetal developmentAffects fetal development

Withdrawal Symptoms of AlcoholWithdrawal Symptoms of Alcohol

Develops after about 8 hoursDevelops after about 8 hours severe tremor, sometimes hallucinations, severe tremor, sometimes hallucinations,

which lasts for about 24 hourswhich lasts for about 24 hours confused and agitated over the next few confused and agitated over the next few

daysdays aggressive behaviouraggressive behaviour nausea and vomiting, sweating and fevernausea and vomiting, sweating and fever

NITRITE

+

PROTEIN

CombustionNITROSAMINES

Good drugs vs. Bad drugs ?Good drugs vs. Bad drugs ?

Narcotics OriginNarcotics Origin

MorphineMorphine

EndorphinsEndorphins

MethadoneMethadone

PlantPlant

AnimalAnimal

SyntheticSynthetic

Narcotic PropertiesNarcotic Properties

AnalgesiaAnalgesia

EuphoriaEuphoria

ConstipationConstipation

Pupil constrictionPupil constriction

Respiratory Respiratory depressiondepression

Nausea vomitingNausea vomiting

HypotensionHypotension

AddictionAddiction

NSAID OriginNSAID Origin

SalicylatesSalicylates

----

AspirinAspirin

PlantPlant

AnimalAnimal

SyntheticSynthetic

NSAID = Non-Steroidal Anti-Inflammatory Drug

Properties of AspirinProperties of Aspirin

AnalgesiaAnalgesia

Anti-inflammatoryAnti-inflammatory

AntipyreticAntipyretic

Anti-platelet Anti-platelet aggregationaggregation

Gastric bleedingGastric bleeding

Acid-base Acid-base imbalanceimbalance

Reye’s syndromeReye’s syndrome

How do drugs work ?How do drugs work ?

HOW DRUGS WORK

Non-specific

Specific

Receptor Drug

More serious stuff More serious stuff starts here !!starts here !!

Basic Concepts in PharmacologyBasic Concepts in Pharmacology

PharmacodynamicsPharmacodynamics

PharmacokineticsPharmacokinetics

Routes of AdministrationRoutes of Administration

Dosage and dosing intervalsDosage and dosing intervals

Drug receptors and specificityDrug receptors and specificity

ToxicityToxicity

Pharmacodynamics and PharmacokineticsPharmacodynamics and Pharmacokinetics

PharmacodynamicsPharmacodynamics

DrugDrug BodyBody

PharmacokineticsPharmacokinetics

DRUGSITEOF

ACTION

EFFECTS

BLOOD

SYSTEMICCIRCULATION

PharmacokineticsPharmacokinetics

AAbsorptionbsorption

DDistributionistribution

MMetabolismetabolism

EExcretionxcretion

Disposition : Disposition : DD + + MM + + EE

Drug BodyDrug Body

Molecular sizeMolecular size

Lipid solubilityLipid solubility

IonizationIonization

AbsorptionAbsorption

DistributionDistribution

EliminationElimination

Routes of administrationRoutes of administration

Enteral administrationEnteral administrationSublingualSublingual

OralOral

RectalRectal

Routes of administrationRoutes of administration

Parenteral administrationParenteral administrationintravenousintravenous

intra-muscularintra-muscular

subcutaneoussubcutaneous

intrathecalintrathecal

intra-arterialintra-arterial

Routes of administrationRoutes of administration

OthersOtherstopicaltopical

inhalationinhalation

intra-vaginalintra-vaginal

How fast does the drug act ?How fast does the drug act ?

How long does the drug effect How long does the drug effect lasts ?lasts ?

0 2 4 6 8 10 12Time (hour)

Dru

g co

ncen

trat

ion

in b

lood

Onset and duration of drug action

0 2 4 6 8 10 12Time (hour)

Dru

g co

ncen

trat

ion

in b

lood

MEC

Onset and duration of drug action

0 2 4 6 8 10 12Time (hour)

Dru

g co

ncen

trat

ion

in b

lood MTC

MEC

Onset and duration of drug action

0 2 4 6 8 10 12Time (hour)

Dru

g co

ncen

trat

ion

in b

lood MTC

MEC

Onset and duration of drug action

How are new drugs discovered ?How are new drugs discovered ?

Drug DiscoveryDrug Discovery

Chemical modification of a known Chemical modification of a known moleculemolecule

Screening of natural products or Screening of natural products or previously discovered chemical entities previously discovered chemical entities for biological activityfor biological activity

Rational drug design based on an Rational drug design based on an understanding of biological mechanismsunderstanding of biological mechanisms

natural drug source

Possible Pathways in Drug Development

pharmacological profileof active principle

chemical synthesisprogramme

mechanism of action

potential clinical utility

animal models ofthe disease state

use in medicineclinical trials

metabolism

toxicology

formulation

Pharmacological Profile TestsPharmacological Profile Tests

Molecular levelsMolecular levels

Cellular levelsCellular levels

System / Disease ModelsSystem / Disease Models

Pharmacological Profile TestsPharmacological Profile Tests

Molecular levelsMolecular levelsReceptor bindingReceptor binding

affinity and specificityaffinity and specificity

Enzyme activityEnzyme activity inhibition and selectivityinhibition and selectivity

Cytochrome P450Cytochrome P450 effects on drug metabolismeffects on drug metabolism

Pharmacological Profile TestsPharmacological Profile Tests

Cellular levelsCellular levelsCell functionCell function

receptor activityreceptor activity

Isolated tissueIsolated tissue vascular activity vascular activity effects on other smooth muscleseffects on other smooth muscles

Pharmacological Profile TestsPharmacological Profile Tests

System / Disease ModelsSystem / Disease ModelsBlood pressureBlood pressure Central nervous systemCentral nervous systemCardiac effectsCardiac effects Gastrointestinal effectsGastrointestinal effectsRespiratory systemRespiratory system Diuretic activityDiuretic activityBlood coagulationBlood coagulationPeripheral autonomic nervous systemPeripheral autonomic nervous systemCirculating hormones, cholesterol and blood sugarCirculating hormones, cholesterol and blood sugar

Pre-clinical Safety and ToxicityPre-clinical Safety and ToxicityAcute toxicityAcute toxicity

LDLD5050, maximum tolerated dose, use 2 species, 2 , maximum tolerated dose, use 2 species, 2 routes, single doseroutes, single dose

Sub-acute toxicitySub-acute toxicityUse 2 species and 3 doses to study up to 6 Use 2 species and 3 doses to study up to 6 monthsmonths

Chronic toxicityChronic toxicity1-2 years; for drugs intended for prolonged use,1-2 years; for drugs intended for prolonged use,usually runs concurrently with clinical trialusually runs concurrently with clinical trial

Pre-clinical Safety and ToxicityPre-clinical Safety and ToxicityEffect on reproductionEffect on reproduction

Animal mating behaviour, reproduction, Animal mating behaviour, reproduction, parturition, progeny, birth defectsparturition, progeny, birth defects

Carcinogenic potentialCarcinogenic potentialUse 2 species for 2 years, for drugs intended Use 2 species for 2 years, for drugs intended for prolonged usefor prolonged use

Mutagenic potentialMutagenic potentialEffects on genetic stability of bacterial and Effects on genetic stability of bacterial and mammalian cells in culturemammalian cells in culture

Clinical TestingClinical Testing

Volunteer studies (25-50)Volunteer studies (25-50)

Phase I clinical studies (25-50)Phase I clinical studies (25-50)

Phase II clinical studies (50-200)Phase II clinical studies (50-200)

Phase III clinical studies (250-1000)Phase III clinical studies (250-1000)

Clinical TestingClinical Testing

Volunteer studies (25-50)Volunteer studies (25-50) human pharmacologyhuman pharmacology adverse effectsadverse effects pharmacokinetics after single or multiple pharmacokinetics after single or multiple

dosedose

Clinical TestingClinical Testing

Phase I clinical studies (25-50)Phase I clinical studies (25-50) clinical pharmacology of the drugclinical pharmacology of the drug short term safety, efficacyshort term safety, efficacy pharmacological and pharmacokinetic pharmacological and pharmacokinetic

effects in diseaseeffects in disease

Clinical TestingClinical Testing

Phase II clinical studies (50-200)Phase II clinical studies (50-200) further evidence of efficacy and safety in further evidence of efficacy and safety in

larger number of patientslarger number of patients

Phase III clinical studies (250-1000)Phase III clinical studies (250-1000) full scale clinical trialfull scale clinical trial

PLACEBOPLACEBO

Drugs in Everyday LifeDrugs in Everyday Life

Commonly used drugsCommonly used drugs analgesicsanalgesics anti-inflammatory drugsanti-inflammatory drugs antibioticsantibiotics drugs for gastrointestinal tract drugs for gastrointestinal tract

disordersdisorders

AnalgesicsAnalgesics

Morphine-like drugsMorphine-like drugs opioidsopioids

Non-steroidal anti-inflammatory drugsNon-steroidal anti-inflammatory drugs aspirin and related substancesaspirin and related substances

Local anaestheticsLocal anaesthetics

Other drugs used for specific conditionsOther drugs used for specific conditions e.g. migraine, labore.g. migraine, labor

AntibioticsAntibiotics

Substances produced by some micro-Substances produced by some micro-organisms which kill or inhibit the organisms which kill or inhibit the growth of other micro-organismsgrowth of other micro-organisms antibacterial drugsantibacterial drugs antiviral drugsantiviral drugs antifungal drugsantifungal drugs

Basic concepts of antibioticsBasic concepts of antibiotics

Static and cidal effectsStatic and cidal effectsResistance to antibioticsResistance to antibioticsAdverse effectsAdverse effectsHost factorsHost factors

severity of infection, host defense severity of infection, host defense mechanisms, pharmacokinetic factorsmechanisms, pharmacokinetic factors

Drug combinationsDrug combinationsPatient compliancePatient compliance

Drugs for G.I. DisordersDrugs for G.I. Disorders

Ulcer healing drugsUlcer healing drugs

AntacidsAntacids

LaxativesLaxatives

Anti-diarrhoea drugsAnti-diarrhoea drugs

Drugs for G.I. DisordersDrugs for G.I. Disorders

Ulcer-healing drugsUlcer-healing drugsAcid secretion reducersAcid secretion reducers

cimetidine, ranitidine, omeprazole, cimetidine, ranitidine, omeprazole, pirenzipinepirenzipine

Mucosal strengthenersMucosal strengtheners sucralfate, bismuth subcitrate, sucralfate, bismuth subcitrate,

carbenoxolonecarbenoxoloneAntibioticsAntibiotics

metronidazole, tetracycline or amoxycillinmetronidazole, tetracycline or amoxycillin

Drugs for G.I. DisordersDrugs for G.I. Disorders

AntacidsAntacidsSodium hydrogen carbonateSodium hydrogen carbonate

Calcium carbonateCalcium carbonate

Magnesium hydroxideMagnesium hydroxide

Aluminium hydroxideAluminium hydroxide

Drugs for G.I. DisordersDrugs for G.I. Disorders

LaxativesLaxativesBulk laxatives (increase the volume of the Bulk laxatives (increase the volume of the

intestinal contents, stimulate peristalsis)intestinal contents, stimulate peristalsis) cellulose, methyl-cellulosecellulose, methyl-cellulose

Stimulant laxatives (increase gut motility)Stimulant laxatives (increase gut motility) anthraquinones (senna and cascera), anthraquinones (senna and cascera),

bisacodylbisacodylLubricants (softening and/or lubricating)Lubricants (softening and/or lubricating)

liquid paraffinliquid paraffin

Drugs for G.I. DisordersDrugs for G.I. Disorders

Anti-diarrhoea drugsAnti-diarrhoea drugsMorphine-like agentsMorphine-like agents

morphine, codeine, diphenoxylate, morphine, codeine, diphenoxylate, loperamideloperamide

AdsorbentsAdsorbents kaolin, chalkkaolin, chalk

Drugs for non-medical purposeDrugs for non-medical purposeDrugs which are rigidly controlled by law in their Drugs which are rigidly controlled by law in their

production, distribution and sale. Use of these production, distribution and sale. Use of these drugs is prohibited.drugs is prohibited.

Drugs which are potentially dangerous. Use of Drugs which are potentially dangerous. Use of these drugs is under vigilance: penalties for these drugs is under vigilance: penalties for misuse; taxes for sale of these drugs.misuse; taxes for sale of these drugs.

Drugs which may cause damage to individuals if Drugs which may cause damage to individuals if used in excess. Controls mainly by taxation.used in excess. Controls mainly by taxation.

Drugs in Everyday LifeDrugs in Everyday Life

Drugs for non-medical purposeDrugs for non-medical purpose alcoholalcohol caffeinecaffeine tobaccotobacco ““health products”health products”

Drugs in Everyday LifeDrugs in Everyday Life

““illegal” drugsillegal” drugs cannabiscannabis sedative-hypnotic drugssedative-hypnotic drugs opiumopium morphine and related drugsmorphine and related drugs cocainecocaine amphetamine and related drugsamphetamine and related drugs

SOME DRUGS OF ABUSESOME DRUGS OF ABUSE

DrugDrug Trade NameTrade Name ““Street Name”Street Name”

AmphetamineAmphetamine ------ 大力丸大力丸 安菲他命安菲他命BrotizolamBrotizolam LendorminLendormin 13A13A 屋仔屋仔CannabisCannabis ------ 大麻大麻 ““Grass”Grass”ChlordiazeproxideChlordiazeproxide LibriumLibrium 綠豆仔綠豆仔 利眠寧利眠寧CocaineCocaine ------ 可卡因可卡因 CokeCoke CrackCrackDiazepamDiazepam ValiumValium 羅氏五號羅氏五號 十號十號FlunitrazepamFlunitrazepam RohypnolRohypnol White CrossWhite Cross （十字架）（十字架）KetamineKetamine KetalarKetalar KK 仔仔

SOME DRUGS OF ABUSESOME DRUGS OF ABUSE

DrugDrug Trade NameTrade Name ““Street Name”Street Name”

LSD (Lysergic acidLSD (Lysergic aciddiethylamide)diethylamide)

------ 迷幻藥迷幻藥

MethaqualoneMethaqualone MandraxMandrax 忽得忽得Methylenedioxy-Methylenedioxy-methamphetaminemethamphetamine

------ MDMAMDMA “ “Esctasy”Esctasy”忘我忘我

MethamphetamineMethamphetamine ------ 冰冰MidazolamMidazolam DormicumDormicum 羅氏藍精靈羅氏藍精靈ScobarbitalScobarbital SeconalSeconal Lily 40Lily 40 莉莉四十莉莉四十TriazolamTriazolam HalcionHalcion 藍精靈藍精靈 藍瓜子藍瓜子