Katie Chan

MEDICINES AND DRUGS

PHARMACEUTICAL PRODUCTS

Natural Defense Systems of the Human Body

Human body can suffer breakdowns through injury, genetics or environment, age, ect.

Attacking microorganisms = invaders

Bodys responses = lines of defense Symptoms responses of the body to invading organisms Medicines work by supplementing our natural healing processes

Non-specific Defense Mechanisms First line of defense: barriers to prevent entry skin mucous membranes closures and secretions of natural openings such as lips, eyelids, ear wax, ect. Second line of defense: attack invaders white blood cells engulf invaders (phagocytosis) blood clotting to prevent blood loss and further invasions inflammatory response

Specific Defense Mechanisms Third line of defense: Immune system white blood cells produce specific proteins (antibodies) to recognize and destroy invaders memory cells enable the body to fight a repeat invasion of the same organism more effectively

Medicines vs. Drugs

Drug chemical that affects how the body

works Medicine substance that improves health

Can be natural or synthetic Synthetic medicines can contain non-active

ingredients that affect presentation of drug Therapeutic effect beneficial effect of medicine

Drug Effects on the Body

Alteration of the physiological state
Consciousness, activity level & coordination

Alteration of incoming sensory sensations Alteration of mood or emotions Most drugs have more than 1 effect, which make them hard to classify
Target nervous system & brain; including perception

of stimuli ((analgesics, stimulants, depressants)) Target metabolic processes ((anatacids)) Aim to supplement bodys ability to fight diseasecausing organisms ((antibacterials & antivirals))

Placebo Effect
Placebo effect patient receive therapeutic &

healing effects from pharmacologically inert medicines believe its the real drug Brain scans show that patients who believed they were taking pain meds release opiods/natural pain relief 1/3 of control group taking placebo show some improvements

Administration of Drugs
Drug delivery depends on chemical nature of

drug, condition of patient & most effective way of getting drug to target organ Ex. some chemicals (like insulin) decompose by digestive enzymes in gut cannot be administered as pills, but injected directly into blood

Method of Administrating Description Drug Oral Inhalation Taken by mouth Vapor breathed in; smoking

Example Tablets, capsules, pills, liquids Medications for respiratory conditions (ex. asthma); some drug abuses (nicotine & cocaine)

Skin patches Suppositories Eye or ear drops Parental by injection

Absorbed directly from the Some hormone skin into blood treatments, nicotine patch Inserted into the rectum Liquids delivered directly into opening Intramuscular Intravenous: fastest method of injection subcutaneous Treatment of digestive illnesses, hemorrhoids Treatments of infections of the eye or ear Many vaccines Local anaesthetics Dental injections

Physiological Effects of Drugs

Are complex because the drug can interact in

many ways Depend on dosage Therapeutic effect intended physiological effect Side effects - unintended physiological effect

Vary between different drugs Vary between same drug & different people Can be beneficial or benign or cause damage to organs Impact of side effects must be evaluated throughout drug treatment; patients must be aware

Physiological Effects (Cont)

Dosing regime amount of drug used for each dose

& frequency of administration

Variables: age, sex, weight of patient, diet, environment,

other drugs taken Ideally, dosage should result in constant levels of drug in blood (through continuous intravenous drip)

Therapeutic Window concentration in bloodstream

must be between therapeutic level & toxic level Tolerance repeated dose of drug result in smaller physiological effect
Need larger dose, which chance toxic side effects

Dependence/addiction patient becomes

dependent of drug in order to feel normal; suffers from withdrawal if without drug

Research and Development

Goal: develop drugs to be more effective & with fewer toxic side effects Very costly; large amount of research goes into drugs for obesity, depression, cancer, cardiovascular disease & ulcers b/c market can support cost Average development time for drugs: 10-12 yrs

Discovery Research (Yr 03)

Lead compounds compounds shown to have biological activity; first stage in drug

development is to identify and extract these

Often low levels of activity; often derived from plants

Analogues - chemically related compounds to

lead compounds; next step: synthesis of analogues combinatorial chemistry & high-throughput screening enable production & testing vast medicines in a short time Test on animals

Development Research(Yr 39)

Phase 1: 50-100 healthy volunteers Phase 2: 200-400 patients Phase 3: 3000+ patients; half are placebos Year 11: launch product; post-marketing monitoring: collect adverse drug reaction data

ANTACIDS

Acidity in the Stomach

Gastro-intestinal tract (gut) generates & maintains different pH environments
Plays an important role in controlling the activity of

digestive enzymes

Stomach generates a pH as low as 1-2

by producing hydrochloric acid from structure from

gastric glands (lining of the walls)

Acid not only kills ingested bacteria from food

but also provides optimum environment for digestive enzymes

Acidity (Cont)
Excess acidity is potentially harmful Gastric juice acidic production
Excess production is caused by excess alcohol,

smoking, stress and some anti-inflammatory drugs

Problems with gastric juice:

Acid indigestion feeling of discomfort from too

much acid in the stomach Heartburn (acid reflux) acid from the stomach rising into the oesophagus Ulcer damage to the lining of stomach wall, resulting loss of tissue and inflammation

Antacids
Antacids excess acid
Drugs help combat antacids by neutralizing the

hydrochloric acid to relieve symptoms

Antacids are usually weak basic compounds

Often metal oxides or hydroxides, carbonates or

hydrogen-carbonates React with acid to produce salt and water Does not directly coat ulcers or induce healing but they do allow stomach lining to mend

Because antacids can change the pH in the stomach, they can alter other chemical reactions (including the absorption of other drugs)

Antacids (Cont)
Aluminum hydroxide Al(OH)3 Al(OH)3(s) + 3HCl(aq) AlCl3(aq) + 3H2O(l)
Dissolve more slowly and tend to provide longer

lasting relief (than magnesium) Linked to development of Alzheimers

Magnesium hydroxide Mg(OH)2 Mg(OH)2(s) + 2HCl(aq) MgCl2(aq) + 2H2O(l)

Magnesium salts tend to be faster acting

Antacids (Cont)
Antacids with metal carbonates and hydrogen carbonates react with acid to produce a salt, water and carbon dioxide Antifoaming agents are used to avert bloating Sodium hydrogen carbonate NaHCO3
NaHCO3(aq) + HCl(aq) NaCl(aq) + H2O(l) + CO2

Calcium carbonate CaCO3

CaCO3(s) + 2HCl(aq) CaCl2(aq) + H2O(l) + CO2

Alginates float to the top of the stomach, forming a

raft which acts as a barrier preventing reflux into esophagus

ANALGESICS

General
Analgesics painkillers d drugs to relieve pain Pain receptors nerve messages of the brain that

detect pain as a sensation Prostaglandins chemicals that stimulate the pain receptors
Released from cells damaged by thermal, mechanical

or chemical energy Inflammatory response cause dilation (widening) of blood vessels near site of injury; can lead to swelling and increased pain Fever prostaglandins have an effect on temperature regulation that can result in increased temperature

Mild Analgesics
Prevent stimulation of the nerve endings at the

site of pain Release prostaglandins from the site of injury; give relief to inflammation, fever & pain Non-narcotics analgesics that do not interfere with the functioning of the brain Includes aspirin and non-steroidal antiinflammatory drugs (NSAIDs) (ex. ibuprofen) Paracetamol (acetaminophen)
Reduces production of prostaglandins in the brain, but doesnt

affect prostaglandin production in the rest of the body

Different than other drugs
Safest analgesic

Mild Analgesics Aspirin

Works by blocking the synthesis of prostaglandins Aspirin analgesic that was an ester derived from

salicylic acid

More tasty & less irritable in the stomach than salicylic acid

(which was proved to be effective for pain) Widely used to treat headaches, toothaches & sore throats; reduces fever (antipyretic) & inflammation; provide relief from rheumatic pain & arthritis

Available in many formations w/ various coatings &

buffering components

Can delay activity of aspirin until it is in the small intestine to

alleviate some of the side-effects

Reduces ability of blood to clot

useful for patients who risk heart attacks & strokes risky for people whose blood does not clot easily or for

surgery when blood must clot

Aspirin
Analgesic properties (painkiller)
Antipyretic property (reduces fever) Reduces inflammation

Paracetamol
Yes
Yes No

Yes
Yes Yes

Side-effects

Stomach wall irritant, blood anti-coagulant, can reduce colon cancer

Reyes syndrome (rare
potentially fatal liver & brain disorder) in children

Does not irritate stomach wall

Severe side-effects (overdosage) Synergistic effect w/ alcohol Allergic reactions

Serious kidney, liver & brain damage Toxic-side effects can be increased Rare

Increased risk of stomach bleeding Relatively common

Recommended use for children

No; can cause Reyes syndrome (although baby aspirin is available)

Yes

Strong Analgesics
Bind opioid receptors in the brain; which then blocks the

transmission of pain signals between brain cells Alters perception of pain Narcotics analgesics act on the brain and may cause drowsiness & change in behavior/mood Most effective painkillers for severe pain Side-effects: suppressing cough reflex, constipation, constriction of pupil in eye, narcotic effects Codeine, morphine & heroin (diamorphine)
Morphine heroin: etherification reaction; both OH groups

converted into ethanoate (ester) groups by reaction w/ ethanoic acid CH3COOH; loss of 2 polar OH groups means heroin is less polar & more lipid-soluble; enables heroin to cross blood-brain barrier quickly & why its faster acting Brain hydrolysis the heroin to morphine by reversing esterfication reaction

Codeine Effectiveness Increasing strength as

analgesics

Morphine
Increasing narcotic effects Benzene ring, ether, alkene, alcohol (2), tertiary amine Raw opium (10%)

Diamorphine
Increasing side-effects Benzene ring, ether, alkene, ester-ethanoate (2), tertiary amine Found in opium but usually obtained by reaction of morphine (semi-synthetic drug) Used medically only in a few countries legally for relief of severe pain Most rapidly acting and most abused narcotic Initially produces euphoric effects, but very high potential for causing addiction & increasing tolerance Dependence leads to withdrawal symptoms & many associated problems

Functional groups Obtained form

Benzene ring, ether (2), alkene, alcohol (1), tertiary amine Raw opium (0.5%)

Therapeutic uses

Preparation w/ a nonnarcotic drug (aspirin or paracetamol) in 2nd stage of pain management ladder Cough medications; Short-term treatment of diarrhea

Management of severe pain (& advanced cancer) Habit forming can lead to dependence use must be regulated by medical professional

Narcotic Effects
Heroin induces feeling of euphoria, as it causes a

dulling of pain & a lessening of fear & tension Long-term regular use leads to constipation, reduced libido, loss of appetite & poor nutrition Heroin users show dependence relatively quickly; cannot function properly w/o drug; suffer from withdrawal (sweating, anxiety); tolerance Drug taken by injection infections (HIV/hepatitis from unclean needles) Methadone alternative analgesic

Helps heroin addicts break their dependence Taken orally & longer duration of action Reduce drug craving & prevent symptoms of withdrawal Most effective treatment for opioid dependence, reducing death rates of addicts to ~1/10

Different analgesics work by blocking pain at different sites

Could be argued that mild analgesics seek to eliminate pain at the source Strong analgesics only alter our ability to perceive pain Analgesic ladder pain management as pain persists or increases 1. Use mild analgesics 2. Add a weak opioid (ex. codeine or tramadol) 3. In severe intractable pain, use strong opioids (ex. morphine, fentanyl or methadone)

DEPRESSANTS

General

Act on brain and spinal cord Neurotransmitters concentration/activity of chemicals

Altered to change communication between brain cells Result: cause a depression or decrease in brain activity

that influences functions of other body parts

Include drugs classified as tranquilizers, sedatives & hypnotics

Dosage Dosage effect Low Moderate Calmness Relief from anxiety Very relaxed muscles Tranquilizer High Slurred speech Staggering gait Altered perception Sleep induced Extremely High Respiratory depression Coma death Lethal Dose

Description

Sedative

Hypnotic

Increasing dosage

Ethanol (C2H5OH) Uses

Most widely used psychoactive drug Has some antiseptic properties
Used on skin before injection or to clean small wounds

Effect of hardening on skin

Rubbed on feet to prevent blisters

Ethanol in alcoholic drinks

Low doses can create mild excitement; users become

more confident, talkative & relaxed

Low doses might have beneficial effect

Help circulation & diminish cardio-vascular diseases Anti-clotting effect

Ethanol (C2H5OH) Abuses

Change in behavior; more adverse as dose increases

Short-term effects

Long-term effects
Dependence: alcoholism Liver disease (cirrhosis), liver

Loss of self-restraint; concentration, memory & insight are impaired Loss of balance & judgment Violent behavior associated w/ domestic abuse & family breakdown Dangerous risk-taking behavior leading to many accidents involving motor vehicles & machinery Dehydration caused by increased urine output leading to hangover & loss of productivity High doses can cause vomiting, loss of consciousness, coma & death

cancer
Coronary heart disease

High blood pressure

Fetal alcohol syndrome Permanent brain damage

Ethanol (C2H5OH) Metabolism

Polar OH group enables it to form hydrogen bonds w/ water readily soluble in aqueous solution

Dissolvable in lipids b/c small organic molecule

Can cross cell membrane easily Indigestion: C2H5OH passes quickly from gut to blood

& circulates to all tissues of the body

90% is broken down in the liver; remainder eliminated by kidneys & lungs Readily passes across placenta to fetus when consumed during pregnancy

Synergistic effect of ethanol

Synergy potential to increase activity of other drugs when taken at the same time Can lead to fatal results Examples
W/ aspirin stomach bleeding & risk of ulcers W/ depressants heavy sedation, possibly coma W/ tobacco cancers

Ethanol Detection
Ethanol analysis of breath
At body temp in lung, ethanol is dissolved in the blood

& is released into the air in exhaled breath Breathalyzer - orange potassium dichromate (VI) turns green chromium (III) Cr3+ as they oxidize the ethanol to ethanal & ethanoic acid; color change measured on photocell

Infrared spectroscopy; intoximeter more accurate breath analysis

Different molecules have different absorption bands in

infrared part of spectrum; cause vibrations Ethanol has absorption of 2950 cm-1 b/c of C-H bonds Size of peak can be used to measure ethanol concentration compared to reference of air

Ethanol Detection(Cont)

Fuel cell different version of intoximeter

W/ catalyst, ethanol is oxidized in air first to ethanoic

acid and then to water & carbon dioxide Fuel cell converts energy released when oxidation occurs into detectable electrical voltage & measure concentration

Ethanol analysis in blood & urine: Gas-liquid chromatography

Blood/urine is vaporized & injected into stream of inert

gas over surface of non-volatile liquid Components of the vapor (including ethanol gas) move at different rates depending on boiling pt. & relative solubility Peak of retention time corresponding to ethanol can confirm presence in vapor

Other Depressants
Benzodiazepines Depresses activity in part of the brain that controls emotion
used as tranquilizers in treatment of anxiety disorders

& related insomnia Used as sleeping pills & muscle relaxants Dependence; mostly used for short term-treatments Contain benzene rings & diazepine structure (7 membered heterocyclic ring w/ C & 2 N atoms); largely non-polar high lipid solubility cross blood-brain barrier

Anti-depressant fluoxetine hydrochloride (Prozac)

Increase levels of serotonin (important

neurotransmitter) used to treat depression and eating & panic disorders

STIMULUS

General
Affect nervous system Functions opposite to depressants increase

activity of brain & state of mental alertness Prevent excessive drowsiness & allow greater concentration Physiological effects
Help facilitate breathing by relaxing air passages;

treatment of respiratory infections (ex. bronchitis) May reduce appetite; treatment of obesity May cause palpitations or tremors Used in excess: cause extreme restlessness, sleeplessness, fits, delusions & hallucinations

Neurotransmitters chemicals that act as

messengers in nervous system

different stimulants function in different ways but most

commonly they alter levels of neurotransmitters

Amphetamines
Adrenaline (epinephrine) hormone released in times of stress & enables body to cope w/ sudden demands imposed by pain, shock, fear, cold, ect.
Increase heart rate & blood pressure Increase blood flow to brain & muscles Increase air flow to the lungs

Increase mental awareness

Noradrenaline (norepinephrine) a neurotransmitter responsible for communication

in part of nervous system known as sympathetic nervous system

Very similar structure & physiological effects to

adrenaline

Amphetamines (Cont)
Amphetamine stimulant that mimics & enhances adrenaline & noradrenaline effects
Similar structure to adrenaline & noradrenaline Dervied from

CH2CH2NH3
Phenyl ethyl amine

Sympathomimetic stimulating sympathetic nervous system; apply to amphetamines In small doses, amphetamine increase mental alertness & physical energy

Amphetamines
Side-effects
Dilation of pupils of they eyes Decreased appetite Possible blurred vision & dizziness Long-term: depression & reduced resistance to

infection

Regular use leads to tolerance & dependence

Designer drugs modifications to the amphetamine structure are very powerful &

dangerous
Methamphetamine (crystal meth) & ecstasy Long term effects: serious brain damage & fatal

Nicotine
Most widespread & abused stimulant Obtained from tobacco plants; also found in tomato,

potato, green pepper & eggplant Taken by inhalation (or chewing) of smoke from cigarettes, cigars & pipe tobacco
Contain noxious components: tar & carbon monoxide

Lipid soluble molecule can cross blood-brain

barrier & bring rapid effects on brain activity Increases levels of adrenaline & alters concentrations of certain neurotransmitters in the brain Quickly leads to dependence & addiction Withdrawal symptoms: nausea, weight gain, drowsiness, inability to concentrate, depression & craving for cigarettes

Nicotine (Cont)
Adverse effects on pregnancy and cancers of the lung, mouth & throat

Short-term effects of Nicotine Consumption

Increases concentration

Relieves tension and

boredom Helps counter fatigue Increases heart rate & blood pressure Decreases urine output

Long-term effects of Nicotine Consumption High blood pressure Increases risk of heart disease (including angina) Chronic lung disease Coronary thrombosis Increases the level of fatty acids in the blood which can lead to atherosclerosis & stroke Over-stimulation of stomach acids which can lead to increased risk of peptic ulcers

Caffeine

Worlds most widely used stimulant Present in coffee, tea, chocolate & colas Reduce physical fatigue & restore mental alertness Acts as a respiratory stimulant increasing rate of energy release within cells Intensifies & prolongs effects of adrenaline
Effect of small consumption Enhancement of mental energy, alertness & ability to concentrate Acts a diuretic, increasing volume of urine; can cause dehydration Effect of large consumption Can cause anxiety, irritability & insomnia Can cause dependence Withdrawal: headaches & nausea

Intake of more than 4 cups per day may be

considered non beneficial

Pregnant women should limit caffeine intake

Helps body absorb some analgesics Included in formation of headache pills & other meds

ANTIBACTERIALS

 Penicillins - antibacterial agent Antibiotics chemicals that act against other

General

microorganisms; usually produced by microorganisms Penicillin G

Inhibits development of cross-links in bacterial cell walls,

so weakening walls & causing bacteria to rupture & die during reproductive phase Effective against wide range of bacteria
Including ear, nose, throat, mouth, wound infections

Disadvantage of penicillin G: broken down by stomach

acid & has to be injected directly into the blood; also digested in pill form

Antibiotic Resistance
Bacterial resistance major problem w/ use of penicillin; penicillin proved to be ineffective against some populations of bacteria Penicillinase enzyme produced by resistant bacteria
Can open pencillins 4-membered ring & render inactive

Arises by genetic mutation in bacteria

# of resistant organisms increases dramatically w/

increased exposure to antibiotic

Superbugs bacteria which carry several resistant genes; serious problem

Antibiotic Resistance (Cont)

Responses to challenge of antibiotic resistance:
Developing different forms of penicillin, w/ modified

side chains able to withstand action of penicillinase Controlling & restricting use of antibiotics by legislation to make them prescription-only drugs; encourage doctors not to over-prescribe Patient Compliance: education & encouragement of patience is important to complete the full course of treatment w/ antibiotic

ANTIVIRALS

Viruses
Viruses take over functioning of other cells
Small & simple structure; no cellular structure Contain only protein & nucleic acid Only capable of reproducing inside another living cell Viral diseases: measles, meningitis, polio, AIDS, avian flu

Treating viral infections is a challenge b/c viruses live w/in cells & cannot be easily targeted Cannot be attacked by antibiotics: lack cell structure of bacteria Spreads rapidly: by the time symptoms appear, it has already spread throughout the body Mutate rapidly: changes their susceptibility

Viruses (Cont)
Antibodies vaccination for a virus
Helped w/ cholera, polio, measles, smallpox

Some antivirals work by altering the cells DNA so virus cannot use it to multiply Antivirals could also block enzyme activity w/in host cell (prevents reproduction) Just because virus halted & relieved from

symptoms doesnt mean it hasnt completely eradicated from body Amantadine antiviral that causes changes in the cell membrane that prevent entry of the virus into the cells
Used as preventative treatment before infection has

spread

AIDS: a viral pandemic

AIDS (acquired immune deficiency syndrome) failure in immune system
caused by virus HIV (human immunodeficiency virus) Infection spreads at alarming rate through global

population

CD4+T cells vital white blood cells in immune system HIV; primarily infects by binding to specific

receptor proteins on surface & then penetrating the cell Retrovirus having its genetic material in form of RNA rather than DNA (HIV is a retrovirus) Reverse transcriptase controls synthesis of viral DNA from the RNA

AIDS (Cont)
HIV is a retrovirus, it releases its RNA in the cell and enzyme reverse transcriptase HIV DNA integrates into the cells own DNA and replicates with it when the cell divides Viral particles are produced w/in the host cell and are released in large numbers when cell dies 3 main reasons why its so hard to target:
Virus destroys T helper cells (cells in immune system that

defend the body against it) Virus tends to mutate very rapidly even w/in a patient Virus often lies dormant w/in host cells, so immune system has nothing to respond to

AIDS (Cont)
Antiretroviral drugs drugs that help fight HIV
Inhibits the enzyme reverse transcriptase so virus does

not affect host cell Does not destroy HIV infection but delays progression Prevent mother to child transmission of HIV during pregnancy Block the binding of HIV to cell membranes or to inhibit the assembly of new viral particles w/in cell

These also produce side effects