Download Students list DRUGS

Students list DRUGS
http://www.mayohealth.org/usp/di/uspA-AM.htm
Common Name Generic Name
Prescription
OTC
Illegal
Aspirin
acetylsalicylic acid
OTC Rye’s syndrome/flu
Tylenol
acetaminophen
OTC liver damage
Advil ibuprofen
OTC
Aleve napercin
OTC
Anacin
Negative
Effects
Positive
Effects
painkiller
anti-inflammatory
pain killer
painkiller
anti-inflammatory
anti-inflammatory
acetylsalicylic acid and caffeine OTC
Excedrine acetylsalicylic acid and caffeine OTC
Alcohol ethanol
relaxing
anaesthetic addictive
methanol, isopropyl alcohol
blind, liver damage
OTC antiseptic
Percoset
codeine
analgesic
Darvoset codeine
analgesic
Tylenol III
(codeine)
cocaine
morphine
Botulism(bacteria)
found in canned food
small amts neck and muscle spasms face chemical peel inhibits release of
neurotransmitter, inhibiting activity at the effector site
Introducton: Unit 1
From Shelly’s “Pharmacology: Drug Actions and Reactions” by Ruth
Levine; “Murder, Magic and Medicine” by John Mann and “Tales of a
Shaman’s Apprentice” by Marc Plotkin
“Macbeth” passage p.1 of the introduction MMM
Read "Macbeth"
Potions – magic or just non-Christian, toxic parts of plants and reptiles –
Shake witches – poisonous brew
Primitive man identified edible and poisonous plants and animals
Therefore use for executions, euthanasia, murder and hunting
Even still food was in short supply so most cultures discovered plants that
would alleviate their misery by providing appetite suppressants, stimulants
and psychedelic
Opium 5000 years
Cocaine 2000 yrs
Egyptian remedy: colick: poppy pods (opium -> morphine) and fly dirt
Pharmacology is the study of chemical agents (xenobiotics – drugs
substances foreign to the body) and living organisms (different cell types)
and all aspects of their interactions i.e. a biological response. These
xenobiotics may include: pollutants, food additives, contaminants and
DRUGS.
These substances can be:
1. Absorbed in lungs skin GI
2. Metabolized in liver
3. Excreted skin lungs kidneys bowels
Physicians use drugs as therapeutic agents
Of interest or concern – some drugs are taken over long periods of time –
oral contraceptives, insulin, drugs of abuse, food additives, economic
insecticides, fertilizers, industrial pollutants of air or water. All these
substances foreign to the body are known as xenobiotics.
Medicines are as old as the human race: combat illnesses from the plants
(and sometimes animals) around them
Ex. Ease pain: alcohol, opium;, quinone (cinchona bark) to treat malaria,
ipecac to treat amoebic dysentery
Poisons: helped valuable discoveries to elucidate info. about
neurotransmitters, synapse etc. – curare (arrow poison), veratrine ,
ouabain (arrow poison), – curare, ouabain not absorbed in gut very well so
can eat animals killed this way
MAGIC: witches potions
Basic Pharmacology
200 x 106 years ago prim. Mammals
humans Homo sapiens
unique chemistry
cells – blood bone, nerve, muscle
nucleus
RNA & DNA – sugars , lipids and fats and N.A.
The body is composed of 45-75% water depends on age build and sex
NM: C H O N S P Cl
M: Na K Ca + 20 others
Atoms with chem. bonds –-> molecules
Water 3-D structure
Glucose 1x 10-9 m
RBC 1x 10-5 m
10,000 x larger
Human ovum 1x 10-4 m almost visible
Biochemical processes controlled by ez ; interconversions of chem.
Cpds
Cell membrane: separate processes
Lipid bilayer 7.5 – 10 nm
Semipermeable: nutrients and waste
Biol. systems in constant interaction with environment any external
change can affect exquisitely controlled biochemical process – to live
and function normally
Unit 2
History Medicines and religions intertwined over the years
Egypt and Babylonia 1600 B.C. Papyrus listing and characterizing 700
diseases
India: Sushruta (500B.C.) Hindu Prof. Of medicine: 1st aseptic surgery,
1st skin graft – he described 1100 diseases: smallpox vaccination
All this unknown in Europe for 2000 years
Greece: medicinal pharmacy "History of Plants" 300 B.C.
Dioscorides: Nero’s surgeon described 600 plants This was the chief
source of pharmacological knowledge till 16th century "Father of Materia
Medica" (later in Europe)
1st ethics Hippocrates 400B.C.
Anatomy & Physiology
Sensory and motor nerves
Erasistratus 0 AD antiquity, function of arteries – physiologist
Herophilus: anatomist 19 centuries before Harvey "Circulation of Blood"
Roman Era: Galen "described humors" blood phlegm yellow and black bile
and earth air fire, water
Middle Ages: no significant developments in Europe till 1500 AD
Paracelsus
Greeks (B.C./A.D.)
Advances with Arabs/Jews
Crusades later brought their discoveries to Europe
p.6 Arabs contributed: precision in observation
control in experimentation
meticulous record keeping
dev. The Exp. Method
Moslems: 1st apothecary shops
1st pharmacy school
1st standards regulations
standards storage and preparation of drugs
1st consumer protect
punish by law if deceptive
13th century medicinals come to Europe
15th century alchemy of Arabs – Europe relatively pure substances for
medical use S, Fe, As
Paracelsus: "Grandfather of Pharmacology"
"the dose is the poison"
The body is composed of chemicals
Laudanum "tincture of opium" active part morphine
Hg to treat syphilis
Rise of Pharmacology:
Wm. Harvey 1600 "circ. of blood"
Toxicity of drugs/poisons in animals
Crude drug –> active principal –> characteristic Effect (Separation
of parts)
Controlled studies – DOSE --> RESPONSE
Amt. of drug --> biologic effect or response
1806 1st isolation active principal
white crystalline morphine from opium (poppies) Columbia overrun
study of natural drugs (organic chem. Synthesis
Site of Drug Action
1856 curare acts at junction of nerve-muscle
Cellular Mech. Of Drug Action – receptor (composed of chemicals)
Fate of Drugs in Body
Chemical conversion in body or excretion
Modern Era
Ether Morton 1819 – 1868
Antiseptic Lister 1827-1912
Chemotherapy Ehrlich 1854-1915 p. 15
Insulin Banting & Best 1921
"Basis for Rational Therapy of Disease"
"Murder, Magic and Medicine"
Humans concerned with digestive organs specifically bowels
17th cent. England – bimonthly purging for good health
many substances used for murder, magic, and folk medicine – clinically
acceptable drugs today
Unit 3
Cell Intercommunication
1. neurotransmission: chem. Signal
structure of nerve
2. . Hormonal: chem. Messengers from glands
3. Autacoid: local hormones that act locally
Nerve width 5-100um (10-6)
Axon less than 1 mm -> 1.0 m (spinal column 1-25 um diameter)
Synapse
Synapse
muscle
nerve
Myelin sheath: electrical insulator
Na+ ClAt rest ++++++++++++ Passage of nerve impulse: ++++++++++++
-------------------------------------K+
AK+
A--------------------------------------++++++++++++
++++++++++++
These thin membranes of primarily lipids are selectively permeable to
K+ and Cl- and 50-100 less permeable to Na+ At rest there is an
electrical potential difference of up to –85 mV. The difference
between a nerve cell and other cells is the excitability. When
depolarized the potential difference is +40 mV all occurs within a
millisec. The nerve impulse is a series of depol. and repolarizations.
Synapse is between nerves and neuroeffecter junctions are between a
nerve and any other cell types.
Neurotransmitters bind to specific receptor site like key and lock.
Many drugs and other xenobiotics also fit into various types of
receptors and elicit a response – agonists. Those that block the
receptor site are antagonists. All due to changes in cell membrane
permeability to Metal ions. The nt. is destroyed by ez or reabsorbed
into the neural cell
Xenobiotics prevent or increase release of nt. by
1. binding to receptors, thus denying access
2. changing membrane permeability
3. mimicking action of nt.
4. or by altering re-uptake of nt.
NEUROTRANSMITTERS
Acetylcholine:: interacts with 2 types of receptors
1. muscarinic (fly agaric mushroom Amanita muscaria)
2. nicotinic (Nicotiana tabacum)
Catecholamines:
1. noradrenaline: gut lungs and heart
2. adrenaline: adrenal glands on kidney
These nt. bind to 3 main types of receptors in the ANS
ANS flight or fright
1. Sympathetic: catecholamines act on heart lungs, gut and peripheral
blood vessels ( eyes dilate hair stands on end
2. Parasympathetic: acetylcholine predominates heart rate falls blood to gut
for digestion
Any xenobiotic can wreak havoc in this finely balanced system
Hormones: chemical cpd released by endocrine glands to reach distant
cells – to effect e.g. oxytocin (peptid hormone from a) from pituitary to
uterus and mammary glands and birth and testosterone a steroid a type of
lipid like cholesterol
Local hormones (autacoids) histamine and serotonin
1, histamine: gastric to release HCL for digestion
allergic response bronchioles tighten, runny nose respond to rid body of
allergens
3. Serotonin: CNS brainstem, mood, satiation vomiting reflex A deficiency –
migraine and depression.
Signal Transduction: these are all chemical messengers, now translate
to an event i.e. open a channel and allow ions like sodium and chloride and
calcium to pass.
Steroid hormones: pass through cell membrane since nonpolar (lipid
soluble) and bind to receptors inside the cell – nucleus-DNA – triggers
growth or differentiation i.e. production of new proteins and ez.
Therefore for our purposes all xenobiotics exert effect by affecting a cell
receptor with subsequent changes in cellular biochemistry.
Stimulants, Hallucinogens and Inebriants
Stimulants, p.56: xanthines: caffeine, theobromine and theophylline
contained in tea, coffee, chocolate caffeine.
Stronger stimulants of abuse include: amphetamines and cocaine.
These stimulants were either consumed in a beverage or chewed in a quid.
Tea 1st probably Confucius (500 B.C.) 1st documented 350 A.D.
China, then Japan, then 1500’s Europe India 1800’s – 100 mg caffeine/cup
and theophylline for asthma a bronchodilator
coffee 250 mg caffeine / cp
Coffee p. 57 originated from Ethiopia, unknown in Europe till 16th
century, South America in the 18th century and Sao Paolo now 1/2 world
supply
Theobroma cacao (from Mexico)– Cortez 1519 – Mayan young Dona
Marina chocolatl reserved for Montezuma and Aztec nobility for
aphrodisiac properties
1550 nuns – coca + vanilla + sugar in water by 1700 – 2000
chocolate house in London, Now from Brazil Nigeria Ghana
Theobromine active ingredient in chocolate with similar activities to
caffeine. Addiction due to pleasure. However withdrawal of caffeine –
headaches, fatigue, lethargy and nervousness
Hallucinogens, p.66: Chemicals which, in non-toxic doses, produce
changes in perception, in thought and in mood, but which seldom produce
mental confusion, memory loss, or disorientation for person, place and
time.
Mushroom’s (Amanita muscaria) – red with white spots often in
children’ books – common name fly agaric used as an insecticide i/e.
poison peeing story
In Siberia, the wealthiest person brings the mushrooms to eat the
mushroom he gets small high, then pees thc others drink more muscarine
in each successive 5 times each time more intense and faster high acts at
muscarinic acetylcholine site. This is due to chemical reactions that modify
the weaker hallucinogen to the more potent form each pass through the
body.
"Those who are rich among them, lay up large provisions of these
mushrooms, for the winter. When they make a feast, they pour water upon
some of the mushrooms, and boil them. They then drink the liquor, which
intoxicates them. The poorer sort … post themselves, on these occasions,
round the huts of the rich, and watch the opportunity of the guests coming
down to make water; and then hold a wooden bowl to receive the urine,
which they drink off greedily …, and by this way they also get drunk." P. 68
and 69. M M and Medicine
- the urine appears more powerful with each successive urine preparation –
- Alice in wonderland "Through the looking glass"
Psychoactive ingredient (muscimol and ibotenic acid) acts at GABA site.
The acid can be processed to be muscimol, which is the best-fit sub for
GABA receptor. GABA is active at 40 % of brain synapses p. 71 – also
muscarine is in the mixture - fly agaric. In 1869 Schmiedeberg muscarine
excitation of vagus nerve in frog – lead to discovery of acetylcholine.
Muscarine mimics ACh at parasympathetic nerve endings with muscarinic
receptors.
Inebriants, alcohols p.102
Plant extracts 6000-8000 yrs ago fermentation of fruits and cereals.
Beer from yeast fermentation 5000-6000 yrs ago Babylonians
Pharmacology of alcohol
Mild intoxication 30-50 mg of alcohol / 100 ml of blood, garrulity and
uncharacteristic silly behavior
100 mg/ 100 ml blood – more serious neurological disturbance – slurred
speech and staggering gait. (Silliness and aggressive behavior)
200 mg/ 100 ml blood vision and movement are impaired,
400 mg/ 100 ml coma results at twice conc.
Death usually due to respiratory distress with coma
Kava brew of Polynesia: from roots and shrubs
Drug Biotransformation (2 reactions for alcohol)
Enzymes that oxidize vitamin A are used to oxidize alcohols and
aldehydes
Methanol ‡formaldehyde ‡ formic acid
CH3OH
HCHO
HCOOH
Ethyl alcohol --‡ acetaldehyde ‡ acetic acid
CH3CH2OH + NAD+
CH3CHO
CH3COOH
Alcohol dehydrogenase
aldehyde dehyrogenase (high activity to
remove)
(low activity to remove – this is the limiting factor to remove alcohol)
Aldehydes are nasty toxic substances
Inherent ability of the liver to get rid of compound is limited by zero order
kinetics – no matter how much substrate the enzyme is saturated with the
alcohol and can only dispose of alcohol at set rate – Le Chatelier’s principle
Why can’t one pee out alcohol. Because the molecules are so small they
stay in the blood and do not go out through the kidneys, until processed by
the liver.
Calculate how much one can drink and still drive legally (CH3CH2OH M.W.
60 g)
Liquid soluble and lipid soluble therefore penetrate the blood brain barrier
and the placenta ‡ get CNS effects.
Alcohol can go everywhere there is water The body is 60% water
average wt 70 kg = 154 # therefore 40 kilogram of water
Sweden the law .02 %, N.C. .08% wt/vol. .08g/ml
Rate of metabolism 0.11 g/Kg body wt/hr
Women have 20 % higher level for same intake
Asians and Native American drink less higher level
Eskimos can process more
Men also have in their gut an additional enzyme that processes alcohol.
12 oz. Beer 350 ml x 5% = 14 g alcohol in 42 l
legal 34 g alcohol; 2 drinks ok 28 g, 3 drinks ok not 42 g ‡ wait 1 hr ‡ 34 g
alcohol
70 kg 2.5 drinks then 1 drink every 2 hours
full stomach increase by 1 hour
Brain not passive brain learns how to deal with drugs adapts if remove
alcohol you will experience withdrawal.
The way you feel is not right, over time your brain adapts to the alcohol in
your blood such that the same amount of alcohol in your blood now feels
like less alcohol, so you go ahead and drive but still have too high an
alcohol content.