option d: medicines and drugs
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Option D: Medicines and Drugs. Section D.1: Pharmaceutical Products pp 405-410 (Green and Damji ). Objectives. B.1.1: List the effects of drugs and medicines . B.1.2: Outline the stages involved in research , development and testing of new pharmaceutical products . - PowerPoint PPT PresentationTRANSCRIPT
Option D: Medicines and Drugs
Section D.1: Pharmaceutical Productspp 405-410 (Green and Damji)
ObjectivesB.1.1: List the effects of drugs and medicines.B.1.2: Outline the stages involved in research,
development and testing of new pharmaceutical products.
B.1.3: Describe the different methods of administering drugs.
B.1.4: Discuss the terms lethal dosage (LD50), tolerance, and side effects.
What exactly is a medicine? a drug ?
Any chemical (natural or synthetic) that does one or more of the following…
… alters mood or emotions… alters incoming sensory sensations… alters a physiological state including consciousness, activity level, or co-ordination
Why do people use medicines / drugs?
… improve health
… assist the body’s natural healing process
…‘placebo affect’
Medicines and drugs can be…
… helpful or harmful
… natural or synthetic
… legal or illegal
…
How are new drugs developed in USA?
(1) Research• Disease is selected
• Vulnerable targets are identified
• Potential lead molecules are considered
• Lead molecule is selected
How are new drugs developed?
(2) Preclinical trials–in vitro (lab environment)–in vivo (living organisms)• cell cultures / animals • usu 3 species )– rats, mice, guinea pigs
purpose – identify lethal dose, effective dose, potential side effects
How are new drugs developed?
(3) Phase 1 trials – initial clinical trials– small numbers•healthy volunteers• terminally ill patients (with their consent)
purpose: assess toxicity, effective dose, side effects
How are new drugs developed?
(4) Phase II trials – clinical trial– several hundred– ill patients– treated with drug or placebo• ‘blind’ test or ‘double-blind’ test
– statistical study purpose: determine dosage and
administration; eliminate bias
How are new drugs developed?
(5) Phase III trials – extended clinical trials
– thousands– ill patients– treated with drug and closely
monitoredpurpose: adjust dosage and monitor side
effects
How are new drugs developed?
(6) Drug launched
(7) Phase IV trials–Post-launching
purposes: new formulation, new dosage, new application, product extension
Drug Development…
• takes a long time and a lot of money…
Time – as much as 10-15 yearsCost – up to $800 million
Why does drug development require such an exhaustive process?...
• to protect users from harmful side-effects and/or death– drugs that make it through the approval process
have a reasonable risk/benefit ratio– most proposed drugs never make it through the
process
What is thalidomide and why was it such a problem?...
• non addictive sedative available in Europe
1958-1963
• given to pregnant women to treat ‘morning sickness’ – (which it did)
Structure of Thalidomide
Source: http://www.k-faktor.com/contergan/thalidomide.gif
Thalidomide exists as a racemic mixture of TWO stereoisomers – each with their own special impact on the body!
Why was thalidomide such a problem?...
• babies born dead or with birth defects:– no arms &/or legs, – short arms &/or legs– missing bones– Intestinal abnormalities
• 460 cases in UK• 3000 in former West Germany
What about thalidomide now?
As a result of the impact, thalidomide was initially banned, but
• is currently available (under another name)
to treat severe leprosy in Brazil, Mexico, USA– special warnings provided
• and is being considered for other applications (i.e. cancer treatment)
When are medicines/drugs considered hazardous?
When they pose a risk to the – Physical– Mental– Social
well-being of the user.
What are main vs side effects?• Main effect = desired response• Side effect = the unwanted response to the
use of a medicine or drug
Ex: Morphine – prescribed for painMain impact = pain reliefSide effect = constipation
Ex: Morphine – prescribed for diarrheaMain impact = induced constipationSide effect = pain relief
What are side effects?• NO drug is free of side effects… – range from trivial to serious – even death– allergies (over-reaction of immune system)• Mild skin rashes… to fatal shock• penicillin
– damage to liver &/or kidney• often long term• alcohol damages liver• users of one drug over a long time… or of multiple
drugs often have periodic liver / kidney function test
What is toxicity?• TOXICITY: – LD50 value
– Lethal dose of a substance that kills off 50% of a population• Not humans – numbers extrapolated from animal
studies
– Molecules with small LD50 numbers are the most toxic
Some interesting LD50Substance Animal, Route LD50
Vitamin C (ascorbic acid) rat, oral 11,900 mg/kg
Paracetamol (acetaminophen) rat, oral 1,944 mg/kg
Aspirin (acetylsalicylic acid) rat, oral 200 mg/kg
Some interesting LD50
Substance Animal, Route LD50
Grain alcohol (ethanol) rat, oral 7,060 mg/kg
THC (main psychoactive substance in Cannabis) rat, oral
730 mg/kg females; 1,270 mg/kg males
Caffeine rat, oral 192 mg/kg
Nicotine rat, oral 50 mg/kg
Some interesting LD50
Substance Animal, Route LD50
Metallic Arsenic rat, oral 763 mg/kg
Arsenic trisulfide rat, oral 185 mg/kg - 6400 mg/kg
Strychnine rat, oral 16 mg/kg
Arsenic trioxide rat, oral 14 mg/kg
Some interesting LD50Substance Animal, Route LD50
Aflatoxin B1 (from Aspergillus flavus) rat, oral 0.048 mg/kg
Venom of the Inland taipan (Australian snake)
rat, subcutaneous 0.025 mg/kg
Dioxin (TCDD) rat, oral 0.020 mg/kg
VX (nerve agent) human, oral 0.0023 mg/kg (est)
Batrachotoxin (from poison dart frog)human, sub-cutaneous injection
0.002-0.007 mg/kg (est)
Botulinum toxin (Botox) human, oral, injection 0.000001 mg/kg (est)
What is tolerance?• User needs increasing amounts of a drug to
get the same physiological effect. – Due to use over time and with regular use
• Maximum daily tolerance– amount that can be taken into the body without
undesirable symptoms occurring
Why is tolerance a problem?• Body may become tolerant to the positive
effect, not NOT to the harmful effect(s)– User needs more of the drug… and this intensifies
the harmful effect(s). – Barbituates – users develop a tolerance to
sedative but not to its effect on breathing (slows it down) – so they take so much of the drug their breathing stops.
Why is tolerance a problem?• Tolerance changes after the user stops using…– Body’s tolerance decreases with time and non-use– User begins using again… but at former dose (which was increasingly higher with time…)• User experiences more intense side effect(s)• Overdose may occur
What is dependence?• A person is ‘drug-dependent’ when an individual
continues to use a drug because s/he does not feel ‘right’ without it
• Dependence can be – Physical
• Without the drug, user experiences physical symptoms – Mild discomfort…. Convulsions– ‘withdrawal’
– Psychological• Intense craving for the drug and its effects
– difficult to stop using
–Drug Addiction
What is a therapeutic window?
• Measure of the relative margin of safety of the drug for a particular treament.
• Ratio of LD50 to ED50 – ED50 is the therapeutic dose – the effective dose
for 50% of the population.• If the window is WIDE, the effective dose is below
toxicity – so there is a safe margin• If the window is NARROW, small doses need to be
administered for successful treatment.
How are medicines/ drugs administered?
(1) Oral– Through the mouth• Tablet / capsule• Syrup
– adv: self-administer, easy– disadv: must be able to survive the digestive
system
How are medicines/ drugs administered?
(2) Rectal– suppository– adv: self-administer, efficiency– disadv: yuck factor
How are medicines/ drugs administered?
(3) Inhalation– by breathing (i.e. via an inhaler)– adv: rapid– disadv: drug must be for the lungs – or able to be
absorbed through the lungs
How are medicines/ drugs administered?
(4) Injections– intravenous – into blood stream (quick, but spreads
out dose)– subcutaneous – into body fat (good for fat-soluble
molecules)– intramuscular – into muscle tissue– adv: put directly where it is needed, requires reduced
dose, reduces chance of altercation by body– disadv: requires trained person, people don’t like
shots
How are medicines/ drugs administered?
(4) Injections– intravenous – into blood stream (quick, but spreads
out dose)– subcutaneous – into body fat (good for fat-soluble
molecules)– intramuscular – into muscle tissue– adv: put directly where it is needed, requires reduced
dose, reduces chance of altercation by body– disadv: requires trained person, people don’t like
shots
How are medicines/ drugs administered?
• Patches– Molecules absorbed through the skin barrier –
gradually – Adv: continuous and controlled rate; people like
them; can receive a strong medication without IV– Disadv: patch may come off; takes up to 72 hours
for drug to saturate the body; heat (from fever or use of heating pad) may increase side effects