medicines and drugs

Substances that improve health (have therapeutic effect)Assist in body's natural healing process

Therapeutic effect of inert substance in the bodyPlacebo Effect

Medicines

Chemicals that affect body function

Alter physiological state (consciousness, activity level, coordination)Alter mood or emotionAlter sensory sensations

Effects of Drugs

Drugs

Pharmaceutical Products2015 4 14 11:52

Medicines and Drugs Page 1

Identification/Extraction of lead compoundsLead compounds are synthesized in the lab or isolated from existing speciesCompounds tested on animals to establish LD50

Discovery Research (0-3 years)

Dose testing for 50-100 healthy volunteersPhase I

Therapeutic testing for 100-300 patientsPhase II

Therapeutic testing (clinical trials with placebo) for 1000+ patientsPhase III

Development Research (3-9 years)

Tracks long-term effectsPhase IV

Regulatory Review (9-11 years)

Measures adverse reactions/efficacyTranslational research collected on data

Post-Market Monitoring (11+ years)

Stages of Drug Development2015 4 14 11:55


Method of Administration

Anatomical Entry Efficiency Descriptions Examples

Oral Taken by mouth Slow Absorption mainly in small intestine

TabletsLiquids

Inhalation Vapor breathed in Fast Enters the bloodstream in the lungs

Asthma inhalers

Intravenous Injected into bloodstream

Fastest Precise amount of drug administered

Local anesthetics

Intramuscular Injected into muscle Slowest Relatively safe Vaccines

Subcutaneous Injected into fat under skin

Moderate Works best in constant area (e.g. thigh)

Dental injections

Rectal (Suppository)

Inserted into rectum Moderately fast

Absorption through large intestine

Digestive illness treatment

Skin Patch Placed on skin Moderate Absorption from skin

Nicotine patch

Eye/Ear Drops Liquid delivered to opening

Fast Liquid directly targets area

Eye/ear infection treatment

Administering Drugs2015 4 14 11:58


Drug blood concentration between LD50 and ED50Range of safe drug administration

Therapeutic Index = LD50 / ED50

Therapeutic Window

Unintended physiological effect

Aspirin (lowers risk of heart disease, but increases risk of Reye's syndrome)Thalidomide

Can be beneficial or detrimental

Risk-Benefit ratio must be assessed

Side Effects

Increasing amounts of drug are needed to achieve original effect

Increased ability to metabolize drugLong-Term Depression (leading to habituation)Body adjusts to higher levels of drug

Possible Causes

Tolerance

Drug Terminology2015 4 14 12:09


Involves HCl (from gastric juices), and pH of stomach is 1.5 ~ 2.5

Alcohol, smoking, stress, anti-inflammatoriesCauses

Acid Indigestion (discomfort from excess HCl)Heartburn (acid rising to esophagus)Ulcer (damage to stomach lining, resulting in tissue loss/inflammation)

Effects

Excess Secretion of Gastric Juice

Digestion

Antacids neutralize excess acid

Al(OH)3 + 3HCl AlCl3 + 3H2OMg(OH)2 + 2HCl MgCl2 + 2H2OCaCO3 + 2HCl CaCl2 + H2O + CO2NaHCO3 + HCl NaCl + H2O + CO2

Reactions

Mg can cause diarrhea Al can interfere with phosphate absorption, leading to bone damageCO3 can cause bloating and belching due to CO2 production

Side Effects

Treatments to Excess Acid

Metal Carbonate/Hydroxide (active ingredient)

Forms a neutral layer on top of stomachPrevents acid reflux

Alginate

Prevents flatulence and belchingAntifoaming Agent (dimethicone)

Antacid Composition

Antacids2015 4 14 12:14


Pain receptor (stimulate by prostaglandins)Pain signal transmitted to brainBrain perceives pain

Pain Response

Inhibits prostaglandin release (reduce inflammation and fever)Non-narcotic, as they do not change functioning of brain

Mild Analgesics (Aspirin, NSAIDs, etc)

Mimics body's painkillersTemporarily binds to opioid receptors in the brain

Narcotic

Sweating, diarrhea, anxiety, cramps

Symptoms that occur upon the discontinuation/decrease of intake of medications drugs

Weaker analgesic used to relieve withdrawal effectsMethadone

Potential for Withdrawal

Strong Analgesics (Opioids)

Analgesics2015 4 14 12:23


Aspirin (Salicylic Acid Derivative)

Paracetamol (Acetaminophen)

Structure

Functional Groups

Benzene RingEsterCarboxylic Acid

Benzene RingAmideAlcohol

Method of Function

Blocks prostaglandin synthesis in the body

Reduces production of prostaglandins in the brain

Advantages AnalgesicAntipyreticAnti-inflammatoryBlood coagulant (reduces risk of heart attack/stroke)

AnalgesicAntipyreticRare allergic reactionsNo irritation to stomach wall

Disadvantages Allergic reactions are commonStomach/duodenum irritationReye's syndrome possibilitiesAcidosis of blood caused by overdose

Blood disorder possibilitiesBrain/Kidney/Liver damage with chronic use or overdose

Mild Analgesics2015 4 14 12:24


Salicylic Acid Ethanoic Acid Aspirin Water

Derivation of Aspirin2015 4 16 11:24


Codeine Morphine Diamorphine (Heroin)

Structure

Functional Groups

Benzene RingAlkene3o AmineEther (2)Alcohol

Benzene RingAlkene3o AmineEtherAlcohol (2)

Benzene RingAlkene3o AmineEtherEster (2)

Therapeutic Uses

2nd step in pain managementCough medicationDiarrhea treatment

Severe pain managementDependence is possibleMedical professional required

Very severe pain managementMost rapid acting/strongestHigh potential for habituation, addiction and dependence

Strong Analgesics2015 4 14 12:24


Advantages Disadvantages

Short-Term Effects

EuphoriaDulling of painInhibition of cough reflexRelaxationAnxiety relief

Nausea/VomitingComa/Death (with overdose)

Long-Term Effects

ConstipationRenal issues/failureDisruption of menstrual cycleAddiction/Dependence

Social Effects HIV/AIDS from sharing needlesDangerous behavior to feed addictionSocial problems

Medical Wide therapeutic windowFast deliveryCodeine is not addictiveAntidiarrheal propertiesReduces coughing

Risks associated with intravenous injections

Advantages/Disadvantages2015 4 14 12:24


A drug that causes a decrease in brain activityIn turn, causes changes in function to rest of the body

Depressant

Effects of Depressants

Dosage Low - Moderate High Lethal

Effect CalmnessAnti-anxietyRelaxed muscles

Slurred speechPerception changeSleep induced

Respiratory depressionComaDeath

Description Tranquilizer Sedative-Hypnotic

Depressants2015 4 14 12:25


Antiseptic properties

Possible beneficial health effects (anti-clotting effect)

Social environments

Uses of Ethanol

Effects of Ethanol

Short-Term Effects Dilation of blood vesselsFeeling of relaxation and confidenceJudgement/concentration impairedSlurred speechLoss of balanceRisk-taking, violent behaviorDehydrationVomitingLoss of consciousness Respiratory depressionComa/Death

Long-Term Effects Dependence (alcoholism) and related withdrawal symptomsLiver disease (cirrhosis, cancer)Permanent brain damageHigh BPFetal alcohol syndrome

Effects on Society Family breakdowns due to alcoholismRoad accidents and violent behavior cost society

Two or more drugs amplifying the effect of one another

SynergySynergistic Effects of Ethanol

Aspirin Causes stomach lining bleeding/ulcers

Depressants Heavier sedation and coma

Tobacco Increases the incidence of cancer

Effects of Ethanol2015 4 14 3:02


CH3CH2OH (aq) CH3CH2OH (g)

Can be used to find concentration in bloodKc has specific values at varied temp

Ethanol Equlibrium

Uses acidified K2Cr2O7 crystals (orange), which turn green after reductionExtent of color change is measured using a photocell (limited accuracy)

Cr2O72- + 14H+ + 6e- 2Cr3+ + 7H2OReduction

CH3CH2OH + H2O CH3COOH + 4H+ + 4e-Oxidation

Breathalyzer

CH3CH2OH + 2[O] CH3COOH + H2OWith catalyst, ethanol oxidizes into ethanoic acid

Ethanol concentration can be measured accuratelyFuel cell converts energy from oxidation into detectable voltage

Fuel Cell

Sample of breath enters infrared spectrometer

C-H band used (2850 - 3100 cm-)O-H band not used because of its presence in water vapor

Absorption Bands

Compared with reference sample to determine concentrationAmount of IR absorption at peak depends on concentration of ethanol in breath

Infrared Spectroscopy

Blood or urine is vaporized

Passes over surface of non-volatile liquid (stationary phase), like long-chain alkanes

Vapor is carried by inert gas (N2 or H2)

VolatilityAttraction to phases

Components of vapor move at different rates

Determination of substanceRetention time is the taken to leave liquid column

Compared to relative standard in mixture (e.g. propan-1-ol)Area of peak determines concentration

Gas-Liquid Chromatography

Detection of Ethanol2015 4 14 3:20


Diazepam Nitrazepam Flouxetine Hydrochloride

Structure

Other Depressants2015 4 14 3:50


A drug that causes an increase in brain activityIn turn, causes changes in function to rest of the body

Stimulant

Effects of Stimulants

Short-Term Effects Long-Term Effects

Increased HR/BPArtery constrictionPupil dilationRelaxation of air passagesSweatingIncreased concentration

ConstipationWeight lossEmotional instability

Stimulants2015 4 14 3:53


Mimic the effect of neurotransmitter substances (e.g. adrenaline) on the sympathetic nervous system

Both compounds have phenylethylamine structureAmphetamines mimic epinephrine

Amphetamines are sympathomimetic

Amphetamines and Epinephrine Comparison

Adrenaline Amphetamine

Structure

Physiological Effects

Increase HR/BPIncrease blood flow to brain/musclesIncreased mental awarenessPupil dilationReduced appetite

Increase HR/BPIncrease blood flow to brain/musclesIncreased mental awarenessPupil dilationReduced appetiteEuphoriaToleranceDependence

Amphetamines2015 4 14 3:59


Effects of Nicotine


Increases HR/BPIncreases concentrationCounters fatigueRelieves tension/boredomDecreases urine output

High BPIncreases heart disease risk (e.g. coronary thrombosis)Increases level of fatty acids (increases stroke/thrombosis risk)Overstimulation of stomach acid leads to risk of peptic ulcers

Effects of Caffeine

Small Dosage Large Dosage

Increases alertness/concentrationCounters fatigueDiuretic

AnxietyIrritabilityInsomniaTolerance/Dependence

Nicotine and Caffeine Comparison

Nicotine Caffeine

Structure

Functional Groups Heterocyclic 6-member ringHeterocyclic 5-member ring3o AmineAlkene (2)

Heterocyclic 6-member ringHeterocyclic 5-member ring3o AmineAlkeneAmide (2)

Nicotine and Caffeine2015 4 14 4:13


Discovered the antibiotic properties of penicillinAlexander Fleming

Isolated, purified and mass produced penicillinFlorey and Chain

Penicillin Discovery and Development

Binds to transpeptidase, irreversibly inhibiting itBeta-lactam ring is responsible for antibacterial properties

Inhibition of transpeptidase prevents cell wall formationCell wall becomes porousSize and shape of cell cannot be maintained, and cell bursts

Effects on Bacterium

Mechanism of Action

Prevent resistance to penicillinase enzymeProvide resistance to breakdown by stomach acid

Side Chain Modification

Penicillin Function

Can also wipe out useful/harmful bacteria in alimentary canal, and can lead to harmful bacteria replacing it

Overprescription

Adherence to treatment is necessary to prevent resistanceProblems arise from allergic reactions to penicillin

Patient Compliance

Antibiotic use in animal feedstock

Factors Contributing to Antibacterial Resistance

Antibacterial Drugs2015 4 14 4:25


Viruses and Bacteria Comparison

Viruses Bacteria

Size 100 nm 100m

Complexity Not very complex Complex

Cell Central DNA/RNACapsid (protein coat)No cellular features

Single DNA StrandHas cellular features

Life Functions Non-livingNo metabolism/growth/excretionNeeds other cells to reproduce

LivingHas metabolism/growth/excretionCan reproduce by itself

Block reverse transcriptase activity with host cellBecome part of viral DNA, preventing viral replicationPrevent viruses from leaving host cell after replicationChanges cell membrane of host cell, preventing viral entry

Antiviral Mechanisms

As metabolism of both are closely linked, treatment is difficultHIV binds to T-cells

Mutations are commonHIV destroys immune helper cells, weakening the immune system

Problems with treatment

Sociocultural Issues

Sociocultural Issue Related Points

Condom Use Availability/Cost, cultural resistance

Cultural Factors Ignorance, misinformation, wishful thinking, stigmatization

Illicit Activities Drug use, prostitution, impact of war

Resources Availability of medical services, cost of drugs, condom use

Orphans Resources/Cost, family devastation

AIDS Problem

Antiviral Drugs2015 4 14 5:00


Geometrical IsomerismChiralityRing-strainPolarity

Factors Affecting Drug Action

Drug Action2015 4 14 5:12


Cisplatin is an anti-cancer drug, while transplatin has no effects on the bodyCis- and Trans- forms of drugs can have different effects

Cl- leaves Pt2+Dative bond forms between Guanine and Pt2+Prevents proper replication

Cisplatin Mechanism

Cl- are on opposite sides of Pt2+

Thus, cannot bind to DNA, and cannot prevent replicationTransplatin cannot attach to 2 bases on DNA chain

Transplatin

Cisplatin and Transplatin

Geometrical Isomerism2015 4 14 5:18


Two mirror image forms of a compoundOccurs when carbon is bonded to four different groups

Enantiomers

Differences in Enantiomer Behavior

Active Enantiomer Inactive Enantiomer

Only one enantiomer is producedIn Vivo

Mixture of enantiomers produced (racemic mixture)Both enantiomers need to be studied separately

In Vitro

Enantiomer Production

R-Thalidomide S-ThalidomideR-Thalidomide is sleep inducing and relieved morning sickness in pregnant women

S-Thalidomide is teratogenic, causing birth deformitiesIn human metabolism, however, both are formed, regardless of which one is administered

Thalidomide Example

Chirality2015 4 14 5:35


Penicillin Mechanism of Action

sp2 hybridization (in Carbons with 3 bonds) desire 120o anglesp3 hybridization (in Carbons with 4 bonds) desire 109.5 angleAs ring has 90o bonds, bonds are weakened, and breaks relatively easily

Ring strain in Beta-lactam ring

Thus, due to the high reactivity of Beta-lactam ring, transpeptidase binds to penicillin

Prevents binding to active sitePrevents penicillinase from destroying beta-lactam ring of penicillin

Protects penicillin from being broken down by stomach juices

Side Chain Modification

Ring Strain2015 4 14 6:11


Membrane-bound structure that resists the entry of chemicals into the brainHydrophobic/non-polar, and thus, not easily crossed by polar molecules

Blood-Brain Barrier

Morphine Diamorphine (Heroin)

Esters in heroin are less polar than alcohols in morphine

As a result, heroin has greater potency, side effects, and risks of tolerance/dependence

Thus, heroin can cross the blood-brain barrier more easily

Morphine vs. Heroin

Heroin is metabolized by esterases (hydrolyze ester links)Thus, heroin is a pro-drug (drug that is converted into an active form through normal metabolic process)

Heroin in the Brain

Polarity2015 4 14 6:50


Collection of stored chemicals

Contains information on purity, chemical structure, quantity, and properties

Expensive/time consumingNo need to synthesize/evaluate drugs individually

Large numbers of related compounds can be produced

Advantages

Compound Libraries

Method for synthesizing compound libraries simultaneously

Automated process reacts small number of compounds with reagents, but produces large number of products

Starting materials covalently bonded to resin beadsReagents mixed together, then split into portionsMixed/split again to react with new reactantsProcess is repeated until combinatorial library is created

Purification is easy, using isolation by washing/filtrationCompounds are separated/purified and then tested for biological activity

Solid-Phase Chemistry (Mix-Split)

Individual compounds are reacted with reagents in separate vesselsProduces smaller and more focused compound libraries

Structure-activity relationshipsDrug optimization

Uses

Parallel Synthesis

Combinatorial Chemistry

Molecular-modelling software predicts/analyzes interaction between drug and receptor site

3-D modelling of drug

Facilitates rational drug development/design

Evaluates biological effects of new drugs

Computer-Aided Design (CAD)

Drug Design2015 4 14 7:04


% of dose reaching bloodstream

Making drugs more polar will make drug delivery more efficientReacting drug's acidic/basic group to form an ionic salt increases efficiency

Improving Bioavailability

Bioavailability

Aspirin (Carboxylic Acid and Sodium Hydroxide)

Fluoxetine (Primary Amine and Hydrochloric Acid)

Polarity Modification2015 4 14 7:05


Enantioselective synthesis only produces one enantiomer

Reactant becomes optically activeChiral auxiliary (which is chiral itself) attached to reactant

Creates stereochemical conditions necessary to follow specific reaction pathway

Blocks reaction site by steric hindrance (large size of auxiliary prevents chemical reaction)

Once desired enantiomer is formed, chiral auxiliary is removed

Process

Chiral Auxiliary2015 4 14 7:05


Lysergic Acid Diethylamide Mescaline Psilocybin

Structure

Functional Groups

Indole Ring1o AmineAmide

Benzene Ring1o AmineEther (3)

Indole Ring3o Amine IonPhosphate Ion

Solubility in Nonpolar Membrane

Large non-polar moleculeVery soluble

Polar due to N-H in amineNot very soluble

Contains ionic groupsLeast soluble

Duration of Response

Takes effect in 20 minutesLasts 12 hours

Takes effect almost immediatelyLasts 6 hours

Takes effect rapidlyShorter lasting than mescaline

Short-Term Effects

HallucinationsMood swingsImpaired judgmentIncreased BP/HRDilated pupilsChanges to body temperature

HallucinationsAnxietyTremorsAbdominal pain/nauseaIncreased HR

HallucinationsCompulsive movementDizzinessLaughterMuscle weaknessDrowsiness

Long-Term Effects

FlashbacksPsychological dependenceHPPD

Psychological dependenceHPPD

FlashbacksHPPDTolerancePsychological dependenceRisk of psychological disorders

Mind-Altering Drugs2015 4 14 7:40


Structure of Tetrahydrocannabinol

Effects


Feelings of relaxation/euphoriaLoss of time perceptionEnhanced auditory/visual perceptionsHallucinationsConfusion/emotional distressIncreased risk of sedation with depressants

DependenceAnxiety

Legalization

Arguments For Arguments Against

Analgesic effectsMedical uses (glaucoma, Parkinson's, MS)Personal freedom argumentReduced costs with prosecutionReduced risks to users (due to better control)

Increased risk of accidents/crimesIncreased risk of lung cancerMay suppress immune systemIncreased number of drug addictsGateway drug hypothesis

Cannabis2015 4 14 7:40


medicines and drugs

Documents

drugs page

hcl mgcl2 2h2ocaco3

hcl alcl3 3h2omgoh2

drug blood concentration

excess acidaloh3

excess hclheartburn

slow absorption

phosphate absorption