????? ?? Clinical Pharmacology

1
????? ??Clinical Pharmacology Mechanism of
Drug Action

• ? ? ?
• Natural Products Research Institute
• College of Pharmacy

2
?? (Scope)

• ????? ??? ??? ?? ? ???
• ???? ?? receptors(???) ??
• ?? (Effectiveness) ???
• ??? (Adverse Drug Reaction) ???
• ???? (Mechanism) ? ??
• ?????? (Drug interaction) ??
• ?? ? ?? ??
• Diseases vs Therapeutics

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?? (DrugTherapeutics) ??
??? ??? ??? ??? ?? ?? ???? ????? ???? ???? ?????.
?? ?? ??? ??? (Xenobiotics)? ???? ?? (Diseases)?
???? ?? ?? ?? ???? ? ??? ?? (Trauma)? ???? ??,
??, ? ??? ??? ?? ?? ??? ??? (Heavy metals), ???
(Poisonous gases), ? ???? ???, ?? (?. ??, ????
?), ???? ? ?? (Toxins)? ??? ???? ????
(Intoxication)? ???? ???? ????? ??? ??? ??? ???
??? ??? ????? ??? ? ??? ?? ??? ??? ?? ? ????.
??? ??? ?? ??? ??? ?? ???? (Malnutrition) ??? ???
??? ?? ? ??? ? ??? ??? ??? ?? ?? ???? (Abnormal)
??? ???? ???. ??? ???? ??? ????? ???? ??
(Substances)? ?? ??(Drugs) ???. ?? ???? ??????
??? ????? ???(Immunity)? ???? ??? ???? ??
(Vaccine) ? ??? ??? ?? ? ??? ??? ??? ??? ?? ???
??? ?? ??? ??? ????. ? ??(Drug) ? ??? ??
(Treatment), ?? (Prevention) ? ?? (Diagnosis)?
???? ?????. ??? ??? ??? ?? (Administration) ? ???
?? ? ?? (Effectiveness)? ????? ?? ?? ???
(Side-effects)? ??? ??? (Safety)? ?????? ???. ??
?????? ??? ?? ???? ????. ??? ??????? ?? ?? ???
???? ?? ?? ??? ?? ?? ?? ??? ????? ?? ??? ?????
?? ??? ??? ??? ?? ????? ???? ?? ????? ??? ?? ???
?? ??? ???? ?????? ??? ????? ??? ????. ??? ?
????? ???? ???? ??? ?? ????? ???? ??? ??? ????
??? ????? ????? ????.

• ? ?????
• ?? ???? ??? ??? ???, ??? ????, ???? ????? ????
  ??
• ????? ???? ?? (Terminology)? ??
• ??? ??? ??? ?? ? ??(??, ??, ??, ??)
• ?? ??? ???? ??? ??? ?? (Mechanism)
• ??-??? ???? (Drug-Drug Interaction)
• ???? ?? (Accurate reading of prescription)? ??
  ?? ?.

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• Origin of Life
• Primitive Earth Condition
• C, H. N. atmosphere (CO, CO2, CH4, H2, N2),
  minerals and H2O
• Temperature 0 100 C ??
• Ureys Experiment (Chicao Univ) amino acids
  formation with electric sparks and C, H. N.
• J. Oro and Kimball Purine synthesis with HCN

Evolution(more entropy energy inputless
entropy degradation---more entropy) Atoms and
molecules Macromolecules (DNA, RNA,
Polypeptides, Polycarbohydrates) Organells
(mitochondria) Cell Tissue ---Organs
---Systems (Circulatory, Digestive, Respiratory,
Excretory, Reproductive) Organisms
Living Entity??? ???? ??? ?????????

• ????? ?? (?????)
• ?? (??? ??) ??? ??
• ?? (yin yang) ???? ?? ?. ?-?, ?-? ?? ??
  dynamic state
• ?? (5 elements) ?, ?, ?, ?, ? (?? ?? ?? ??)
  ??? ??? ??

• ?, ?, ?, ?, ?
• ?, ?, ??, ??, ??, ??

?????, ?

• 17C ???? ??
• ????
• ?? (acupuncture Moxibustion)
• ?? (????, ????)
• ???? ?? (???)
• ?????? (complementary alternative medicines)

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• Eras of the Earth (Geological History) Divided
  into 4 eons
• 1) 45 ?? (Hadean), 38 ?? (Archean prokaryotic
  cells-blue green algae) 25?? (Profteozoic
  eukaryotes, animals)
• ------------and 11 periods (? 39 ?? ??? ??)
• 2) 6??2?4?5???? Paleozoic era includes
• Permian (2? 9????-mass extinction), Devonian
  (4???? ????, amphibians mass extinction),
• Silurians (4?4???? bony fishes animals and
  plants go on land)
• Ordovician (5??? jawless fishes, mass
  extinction)
• Cambrian (6??? many algae, animal phyla)
• 3) 2?4?5??6?5???? Mesozoic era (? 4 ??)
• Cretaceous (1?3?8????Dinosaurs extinction
  plants emerge)
• Jurassic (1?4?5???? birds, flying reptiles)
• Triassic (2?4?5???? giant reptiles, mammals)
• 4) 6?6???? Cenozoic era (? 1.5 ??)
• Quaternary (2???? humans)
• Tertiary (6?6???? primates)

• C, H, O, N, ? minerals
• Primary Metabolites ??? ?? ??(anabolism) ? ??
  (catabolism)
• carbohydrate ?, ----?? ??? ??
• amino acids----protein ??,?? ??, ? ?? ??
  enzyme, muscles, membrane, cells, hormones
• fatty acid---lipid??---??? ??
• purine, pyrimidine---nucleic acid---??-reproducti
  on- ??? ?? ? ??
• Secondary Metabolites ? ??? 2? ??? (? ? ??, ???,
  ????)

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• Basis of Life
• Essentials Carbon, Oxygen, Hydrogen, Nitrogen,
  Minerals (P, S. Fe, Mg, Mn, Co)
• Characteristics Metabolism(Anabolism
  Catabolism), Growth, Reproduction,
• Response to stimuli (Nerve),Movement

• Kingdom of Life
• Monera bacteria, Single-celled no nucleus
  (Prokaryotic-no nuclear membrane or
• membrane-bound organells)
• Prostista(????) Single-celled distinct nuclei,
  Motile simple nervous system
• Fungi Non-motile, no chloroplasts (???)Absorb
  nutrients, chitin cell wall
• Plantae Produce nutrients by photosynthesis
• Animalia Digest food from other organisms
  outside cells absorb products

Levels of Organization Biochemical Taxonomic
Ecological Organism Kingdom(?) Ecosystems Syste
ms Division(?) Phylum(?) Community Organs Class(
?) Population Tissues Order(?) Cells Family(?)
Organelles Genus(?) Macromolecules Species(?) Sma
ll molecules Sub-species(??) atoms
Disease (Mechanism) Malnutrition, Genetic,
Inflammation, Pathogenic organisms,
Physical(trauma/radiation)-Chemical agents,
Auto-immunity, Degeneration, Cancer, Nerve
dysfunction (emotion/stress)
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• Homeostasis ??? ??
• Blood pressure
• Body temperature ???? (CNS, Thoracic, ??, ????)
• Bio-rhythm(??, ?, ?, ??, ??, ??, ?? ?) ???? ???
  ??? ?? Jet Lag (1 ?? ?? ??? ? 1 ? ??)
• Stress ???(??, ??, ??, ???, ???) ??? (??, ??,
  ??, ??, ?? ?)
• ?? (fatigue)??? ?? ?? ??? ???,??? ?? ? ?????

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• Body
• body fluid 60 of body weight
• Intracellular fluid (????) 40 BW
• Extracellular fluid (????) 20 BW
• interstitial (???????) 15 BW
• Plasma 5 BW
• Blood 8 BW
• Plasma Blood cells (RBC, WBC, Platlets)
• Hematocrit RBC volume/Blood volume 35 45

Heart-Artery-Arteriole-blood capillary-Venule-Vein
Capillary----GI duct----Portal vein------Liver
Capillary-tissue -------- Interstitial fluid
Lymph capillary Thoracic duct Lymph Trunk
Vena cava
BW 50 kg, Body fluid 30 Kg, (bone, muscles,
organs20 Kg) 20 kg ??? ??(fat)? ??????? ?? H2O
?? Aristolochic acid (???) diureticsKidney
cancer ??
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Drug Transport Across Membrane (?? ???
??) Passive Diffusion energy (no) Carrier (no)
Rapid(lipophic, nonionic, small molecules)
Slow (hydrophilic, ionic, large
molecules) Facilitated Diffusion No
Yes bind to carrier by
noncovalent. Chemically similar
drugs compete for carrier Aqueous Channels
No No Small hydrophilic drugs (lt200
mw) diffuse along concentration gradient by
passing through aqueous channels (pores) Active
Transport Yes Yes Identical to
facilitated diffusion except that ATP
powers drug transport against concentration
gradient
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• Mole ???/liter molar ??? ?? 1 ??? 1 mole? ???
  ??? Molarity ? ?? ?? 1 ??? ??? mole ?
• Molal ?????? ?? 1 kg? 1 mole? ??? ???
  Molality ??? ??, ?? ?? 1 kg? ??? ??
• Molarity??? ??? ?? Molality-??? ??? ??

• Osmosis????? ???? ?? ??? ?? Osmolaity total
  molality of a solution
• 1mole glucose 1m fructose2 osmol/L-360 g/L
• 0.3m glucose (0.3osm, 300 milli osm) has same
  osmolality and osmotic pressure as blood has.
• 180(mw) x 0.3 osm 5.4 g ? 5 glucose ???(50
  g/1000cc)
• Isotonic? ??? ?????0.9
• ?????(NaCl)(0.9 at isotonic)(9 g/1000cc) Na
  Cl-9/40mw
• 0.225 m x20.25 osm
• KCl 1.19 (isotonicity)

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• Mole ???/liter molar ??? ?? 1 ??? 1 mole? ???
  ??? Molarity ? ?? ?? 1 ??? ??? mole ?
• Molal ?????? ?? 1 kg? 1 mole? ??? ???
  Molality ?????, ?? ?? 1 kg? ??? ??
• Molarity??? ??? ?? Molality-??? ??? ??

• Osmosis????????? ???? Osmolaity total
  molality of a solution
• 1mole glucose 1m fructose2 osmol/L-360 g/L
• 0.3m glucose (0.3osm, 300 milli osm) has same
  osmolality and osmotic pressure as blood has.
• 180(mw) x 0.3 osm 5.4 g ? 5 glucose ???(50
  g/1000cc)
• Isotonic? ??? ?????0.9
• ?????(NaCl)(0.9 at isotonic)(9 g/1000cc) Na
  Cl-9/40mw0.225 m x20.25 osm
• KCl 1.19 (isotonicity)

• ISOTONIC Osmosis does not occur in cell through
  plasma membrane
• Hypotonichemolysis RBC burst
• Hypertonic Shink cells
• Dehydration of human total blood volume ??,
  osmolality, osmotic pressure ??, ????, ??? ? ??
  Drink water--??

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• Drug Administration (??)
• Formulation (Preparation Form Dosage Form)
• ?? ?? ???? (??? ???? ? ?? ??? ???)
• Barrier Route ??? ?? Barrier ??
• ? ??? ?? (???, ???)? ?? Barrier ?? ??? ??? ? ??
  ?? ??
• ?? ??? ??? Barrier ?? Brain Barrier
• ???? Route? ?? IV, PO ? Barrier ?? ??
• Setting ?? ?? ??? IV??, ???, Tablet (PO) ???,
  ?? ?? ??
• Urgency ?? ??? ???IV ??? ?
• Stability ? ??? ??? ??(pH2)? ?? ?? ? ???
  (enteric coating) ? ??? ?? ?? ????--??
• First Pass Effect ? ??? ?? ?? (??)? ??
  ??/?? (?)?? ??? ? ??, IV ??

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• Routes (????) ??, ??, ??
• P.O. (Oral)(per os) ???- ? ??? ??? ??? ??
• capsule, tablet(?), powder(?), pill (?), fluid
  extract, elixir ?
• ?? ?? (percutaneous route)
• sublingual (??) troche (???)
• rectal (PR) ?? ??-?? (suppository)
• Inhalation ?? spray
• Topical ???? ointment (?,?,?,?, ??)
• Transdermal ?? patch (delayed-drug delivery)
  ??--Capillary blood vessel? ??
• ??? (Parenteral) (??-Injections)
• Intravenous (IV) ??
• Intramuscular (IM) ??
• Subcutaneous (SubQ, SC) ??
• Intraperitoneal (IP) ??

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• Doseing Regimens(???) route, amount-dose-frequenc
  y ??
• Dosage
• Posology
• Single dose (IV or PO)
• Continuous infusion (IV)
• Intermittent dose

??? ?? state-state ?? ??
2)
1)
Onset? ???-??? ??? Half-life? ???
3)

• Half-life
• ???? ?? ? plasma ? ???? ½ ? ?? ??
• Distribution Half-life 1? ??? ?? ? ???
• ??? ????? ??? ????? plasma
• ??? ½ ? ?? ?? (t ½ a)
• Loading dose initial dose- ?? ???? ?? ??
• Maintenance dose State-state ??? ??

Peak (????-????) Troughs(????) ??? ??? morphine
?? ? ? ??? ? 2 ?? ?? ?????? ??? ?? ??
Onset ???? ????? ??? ?? Duration ??? ????? ??
??? ??
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• Metabolism (Phase I II)
• Phase I (oxidation, reduction, hydrolysis)(Cyt
  P450, Mixed Function Oxidase)

CH3COOH
Hydroxlation
NADPH, O2
Dealkylation
OC2H5
OH
Microsomes
Oxidation
Reduction
NADPH
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Non-microsomal oxidation and reduction
Alcohol oxidation
NAD
CH3CH2OH
CH3CH2O
Alcohol reduction
NADH H
R-CH2-OH NAD H2O
Phase II Rx-synthetic carried out by specific
enzyme

• Glucuronide conjugation drug(-OH) UDPGA
  -OC6H9O6 UDP
• (glucuronyl transferase)
• 2. Ethereal sulfate conjugation (sulfokinase)
  -OH PAPS -OSO3 PAP
• 3. Acetylation (acetyl transferase) -NH2
  CH3CO-CoA -N-COCH3 CoA
• 4. Transulfuration (in mitochondria) CN-
  S2O3-- -- CNS- SO3-
• Glutathione conjugation --CH2Cl GSH
  -CH2-S-SH2-CHCOOH
• NHCOCH3
• UPGA Uridine diphosphoglucuronic acid
• PAPS 3-phosphoadenosine-5-phosphosulfate
• GSH glutathione (g-glutamyl-cysteinyl-glycine)

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Drug Clearance

• Clearance Elimination rate (mg/hr)/Drug
  concentration (mg/L) Liter/hr
• Or Clearance k x Vd k elimination rate
  constant, Vd apparent volume of distribution
• Hepatic clearance and Enterohepatic Cycling
  (biliary elimination of drug)
• Hepatic clearance rate of drug removal by
  liver/ conc. Of drug in portal vein
• Enterohepatic Cycling reabsorbed from GI tract
  and returned to the systemic circulation
• Renal clearance
• Glomerular filtration drug in blood pass into
  the nephron diffusion process small, nonionic
  molecules (drug bound to plasma protein can not
  pass) rate of filtration depends in part on BP
• Tubular secretion drug secreted into nephron
  from efferent arteriole Active transport (drug
  bound to carrier are transported)
• Tubular reabsorption drug re-absorbed into blood
  stream from nephron tuble diffusion process
  (small and nonionic molecules) More ionic
  metabolized drug products are readily, easily
  passed to urine, and eliminated.

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?? (Terminology)

• ??? ?? (Definition) ? ??? ??
• Drugs, Medicine(s), Therapeutics
• Drug (droog-dry-??? ??)
• Generic/nonproprietary drugs ??? ?? vs ??? vs
  ???(??) vs ???(official name ??? ???FDA ??
  ??-pharmacopoeia ? ???-compendium/NF,
  ???-standard ?)
• OTC ???/??? over-the-counter
• Ethicals ??? ??? ??
• Adverse Action (Reaction), Side-effects
• Pharmacodynamics, Pharmacokinetics
• Receptors, Drug-Drug Interaction
• Cure, Treatment
• Administration, Route, Dose, Dosage, Regimen
• Elixirs, Extracts, Tincture, Injection
• ??? (Abbreviation Terms) ???? (Med Pharm terms)
• ???? ??????? ??? ??

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Abbreviation in Pharmacology-(??????? ????)

• -ology study, Pharm- drug
• Rx take Recipe
• PO per os (orisora) ??
• SC subcutaneous??(sub-??)
• Sub-lingual ??
• PR ?? per rectal
• IM Intra-muscular (????)
• IV Intra-venous (????)
• IP intra-peritoneal (????)
• AM ante meridiem (before noon)
• PM Post meridiem (after noon)
• d die (day) ?
• h hour, ??
• hs ?? ?

• q ?? (quaque)
• q.d ??, quaque die
• q.h ???, quaque hora
• q2h ? 2????
• bid 1? 2 ?(bis in die)
• tid ter in die (1? 3 ?)
• qid quater in die (1? 4 ?)
• q.s ???, quantum satis
• repetat ????
• stat ??,
• AA aa ?? ??(2 ???? ??) ana
• m m dict ?????,
• S.O.S ????, si opus sit
• (if it is necessary)

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• AD?? ? (auris dextra)
• AS auris sinistra(? ?)
• OD oculus dextra (dexter)
• OS oculus sinistra (sinister)
• bin ??? 2? bis in noct
• tin ter in noct ??? 3?
• BT ????
• D ???, dispense
• cap capsule
• tab tablet (??)
• pil pill (??)
• elix elixir
• ext extract, ???
• tr tincture ??
• comp compound, ???

• pc ??, postcibal, postprandial
• ac ante cibum, before meal ??
• p.r.n ???, pro re nata
• Ungunguentum, ??, ointment
• aq ?, aqua
• fl fluid, ??
• M ????, mix
• dil ????, dilute
• div ????, divide
• dos ??
• gm gram ??
• gr ???
• Oz ??, ounce. 1/16 pound, 28.4 ??

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Abbreviation in Pharmacology-1

• -ology study, Pharm- drug
• Rx take Recipe
• PO per os (orisora) ??
• SC subcutaneous??(sub-??)
• Sub-lingual ??
• PR ?? per rectal
• IM Intra-muscular
• IV Intra-venous
• IP intra-peritoneal
• AM ante meridiem (before noon)
• PM Post meridiem (after noon)
• d die (day) ?
• h hour, ??
• hs ?? ?
• q ?? (quaque)
• q.d ??, quaque die
• q.h ???, quaque hora
• q2h ? 2????
• bid 1? 2 ?(bis in die)

• AD?? ? (auris dextra) (Anno Domini ??)
• AS auris sinistra(? ?)
• OD oculus dextra (dexter)
• OS oculus sinistra (sinister)
• bin ??? 2? bis in noct
• tin ter in noct ??? 3?
• BT ????
• D ???, dispense
• cap capsule
• tab tablet
• pil pill
• elix elixir
• ext extract, ???
• tr tincture ??
• comp compound, ???
• pc ??, postcibal, postprandial
• ac ante cibum, before meal ??
• p.r.n ???, pro re nata
• Ungunguentum, ??, ointment

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Pharmacokinetics (??? ??/??/??/?? ADME)

• Absorption ??
• Drug-associated factor ??? ??
• Patient-associated factor ??? ??? ??
• Distribution ??
• Membrane permeability blood-brain barrier
  blood-testes barrier blood- placenta barrier
• Plasma protein binding albumin binding
  (decrease of free drug conc.)
• Depot storage
• lipophilic drugs (sedative thiopental) accumulate
  in fat. The obese patients got more effects.
• Calcium-binding drugs tetracycline accumulates
  in bone and teeth.
• Vd apparent volume of distribution (??? ??)
  ??? ??? plasma? ????? ?? ????? ???? ??? ??. Vd3
  L (plasma ?? ??, plasma ??? 3 L), Vd16 L ? ??
  (3L extracellular fluid 3L plasma 1013 L
  interstitial fluid), Vd gt 46 L ??, ?? ??? ??(??,
  4046 L) (?? 6070 Kg ?? ??)

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??-ADME

• Metabolism?? (Phase I II reactions)
• ???? water-soluble, more polar??? ??? ??? ??????
• Active drugs? less active or Inactive form??
  transformation
• Prodrug (Inactive)? ????? Active form?? ??
• Phase I reaction (nonsynthetic) ?? ?? ????? more
  polar form?? ?? Microsomal enzyme? cytochrome
  P450 (hepatocytes ? endoplasmic Reticulum? ??
  inducible enzyme) ,???? oxidation or reduction?
  ??
• Phase II reaction(synthetic) a polar group
  (glutathione) conjugates to the drug phase 1 ?
  ?? ?? ?? conjugation? ? ?? ??
• Excretion??
• ?, ??, ??
• ??? ??? ?? (?, enterohepatic circulation ? ???
  ??)

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• Drug Action-1 (3? Levels)
• 1. Cellular Level (?? ????? ????)
• ??? ??? ?? ????? (Cellular receptos)? ??
• Receptors protein (??, enzyme ??), glycoprotein
  DNA
• ??? ???? ?? ??? ??? ??? macromolecules? ??? ???
• ???? ? ?? ??? ??
• ion channel ? open ?? close
• 2nd messengers ? ??? activation
• (cAMP, cGMP, inositol phospante ?)
• initiate biochemical reactions in cells Signal
  Transduction
• (?? Kinase? ??)
• normal cellular function is inhibited
• DNA, ???, RNA ????,
• bacteria cell wall ?? ??-??? ?
• ??? Cellular function is turned on (??)
• steroid ??? DNA ? ?? ?? DNA transcription-
• ? RNA ??-? ?? ?.
• ??? receptor ??? strength ? Affinity?? ?

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• Receptor Theory (????? ??? ??)
• - Langley and Ehrlich drug action? receptor? ???
  mediate ??.
• Clarks theory ?? ???(??? receptor ??? ?? ????)
• (receptor ? ??? reversible)
• Stephensons modified theory ??? receptor??
  ???? ?? ??
• affinity (?? ??? receptor ???? ???? ??)

• ???? ?? ??? ??? ? ??? ??(?, ???, ?? ?) ??
• ?? ??????? ???? (Target cells) ???? ??????
• ???? ????? ?????? ?? ???? ?? ????? ????.
• ?? ??? ???? ?????? (???? ? affinity? ???
• ?? ?????? ?? ??) ??? ????. ??? ???
• ???? ???? ? ???? ??? ?????? (Signal
  Transduction)
• ??? ??? ?? ??????? ???? ????? ?.
• ??? ??????? ??? ?? ????.
• Endocrine ???? ??? ??? ?????? ??? ????? ??
• Paracrine ???? ?????? ??? ??? ?????
• ??? ????? ??
• Autocrine ?? ????? ??????? ???? ? ??? ??.

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• 2. Drug Action at the Organism Level
• Efficacy ?? ??? ?? ??? ?? ??? ?? ? ?? ????
• ? ??? ?? greater efficacy
• Potency ?? ??? 50? ???? ? ???
• ?? ?? morphine 10 mg gt Codeine 20 mg (morphine
  is more potent)
• Potency? ?? ?? ???? ?? ???? ?? ??? ???,
• Efficacy? ?? ??? ?? ?? ???? ?? ??
• ? ?? ??? ??.

• Graded Dose-Response Curve (???? ??? ??? ??)
• ????? ?? ??, ??? ??? ???? ???? ?? vs ???
• ???
• receptor affinity, ADME, ? ??? ??? ??.

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• 3. Drug Action at the Population
• ?? ?? ?? ?? ?????(????-GLP) ?
• ???? (GCP)?? ??? Efficacy ? Safety? ???
• ??? ??
• EC50 (Effective concentration 50 ) ?? ?? ?? ?
• ???? 50 ? ??? ???? ??? ??
• LD 50 ( Lethal dose 50) ?? ?? ?? ? ????
• 50 ? ???? ???
• TI (Therapeutic Index) a measure of the safety
  of a
• drug (LD 50/ED 50).
• Margin of Safety The margin between therapeutic
  and
• lethal doses of a drug (???? margin? ??? ?? ?)

Phase IV post-marketing clinical survey
(pharmaco-vigilance)
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• Types of Drug Action
• 1.Agonist Receptor ?? ? ???? ?? ? ??
• (one acetylcholine binds to nicotinic
  receptor----Muscle cell does not depolarized)
• Strong-, Weak-, Partial agonists
• 2. Antagonist (???) agonist? ?? ????? ??, ?? ?.
• Competitive, Noncompetitive, Irreversible
  antagonists

• Feedback Inhibition/control ?? Product Inhibition
  ???.
• ???? ??? ???? ?? Feedback ????? ??(allosteric
  enzyme) ???? ???? ??? ????? ???
• ?????? (6-mercaptopurine, methotraxate ?) ??
  ????? ??? ??? ??? allosteric ??? ???? ??? ?? ?

e 2 is allosteric enzyme
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• ?? ?? ? ???
• ??? ?? ?? ?? ? ??? ?
• ??? ??? ?? ???, ? ????? ???? ????? 500 mg, 250 mg
  ??? ??? ????. ???? ?? amoxacillin 500 mg PO stat,
  100 mg bid x 5 days, ? ??? ???? 500 mg capsule ?
  ??? ??? ?? 100 mg ??? ??? ???? ?? ??? ??? ???
  ????? ??.
• ??, ?? ? ????? ?? ??? ?
• ?? ? ??? ?? ?? ???? ?? ???? ???? (flow rate)?
  ????. ? ??, ??? ??? ?? ??? ????? ?? ??? drop
  factor ? ????? ??. Drop factor(??mL ? drop ?)?
  ??, ? ????? ?? ???? ??, ?? label? ??? ?.
• ?? 1 mL 10 15 drop ??.
• Drop factor X mL/min flow rate
• ?? ??, ???(?????, Normal Saline, NS) 1000 mL? 5
  ?? ?? ??? ?? drop factor ? 15 ? ????
• ??? ??/???(min) X drop factor flow rate
  (drops/min)
• 1000 mL/300 min X 15 50 drops/min ? ??.

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??!! ????

• ?? ??? ??(Apothecaries System)
• ?? ??? ?????? ?????? ??
• ???(Metric System) ?? ???? ??
• ?-??? ?????? ??? ?? ?? ?? ??
• ??, ?? ??? ?? ? ??
• ? ??? 100 ??? ??? 100 ???? ?? ????
• ?? ? 100 ??? ??? 100 ????.
• ?? ?? ?? ? ???? ?? (???), ?? ??? ???
• ????? ??, ???? ?? ?? ???? ???.
• ??? ???? ?? ???? ??? ??? ????
• 1 pint16 floz, fl fluid (??)
• 2 pints1quart(qt), 4 qt 1 gallon(gal)
• ?????? 12oz1pound(lb) ??

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• ???
• 1gallon 4 L
• 1 qt ?? 32oz 1.0L
• 1pt (32oz) 500 mL
• 1 oz (8 dram) 30 32 mL (?? gm)
• 1 grain 0.6 gram

??? ??? ??? 1 teaspoonful (???) 45 mL 1
tablespoonful(?????) 15 16 mL 1 teacupful
(??) 180 mL 1 glassful (???) 240 mL ?? ???
??? ???.
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• Patient Profile on Drug for Prescription
• Age ??(metabolizing enzymes ?? ??) ?? ??
• (body weight/body surface)
• Pregnancy status ??? ?? ??
• Smoking and Drinking habits Cytochrome P450
  induction
• Liver Kidney diseases ?? ??? ??, ?, ?? ????
• Pharamcogenetics ??? ???, ???? ??, ???? ??? ??
• Bridging Test (??? ?? ?? ???, ?? ????? ??
• ?? ??)
• Drug interaction
• Psychological factors ??? ??? ????-??? ?

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• ??, ??, ??, ??? ?? ??? ?
• ?? ??? ??? ??? ??, ??, ??? ??
• ????/???? X ???? ?? (??) ??
• ??? ??? ?? ? ???? ???? (Body Surface Area) ??
• ????? ??? pp. 138 ? ?? Nomogram? ???? ??
• ?? BSA (m2)/?? BSA(?? 1.73 m2) X ???? ?? ??

??? ?? Vial ?? ????? ?? ????? ?????
????. Ample ??? ??? ???? ???? ???? ??? ?? ? ???
???? ?? ?? ?? ?? ????? ?? ?? ???? ?? ?? ?????
??? ????? ?? ? ??? ?? ?? ?? ?? ?? ????? ????
??? ? ??? ??? ??.
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• Tolerance, Depedence, and Withdrawal
• Tolerance ?? ??? ??? ?? ?. (??? ?? ??)
• Metabolic ??? ???? ??? ????? ??
• Cellular Receptor ?? (??? ??? ??)Downregulation
  (??? ??)
• Dependence ???? ??? ??? ??? ???. ??? ????
• ?? (Withdrawal Symptoms)
• Withdrawal ??? ???? ? ??? (?,???? ?? ??? ?? ?
  ????) (?? morphine, ? ??? ??? ?? ??? ??? ???
  ????? ??)
• Cross tolerance/ cross dependence ??? ??? ???
  ????
• ??(???)?? ??? ?? ?? ??---methadone ? heroin
  ? ???? ??? ?? tolerance/dependence ? ?? ?? ????
  ??? ???? ??

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• Drug Interaction (??????)
• Altered Absorption ??? ?? ??? ??? ?? antiulcer
  agent? ??
• ? ??-? ??? GI ?? ??
• Altered Metabolism Cytochrom P450 microsomal
  enzymes ? Induce ???
• ?? ??? (smoking) ? ?????? ?????.
• Plasma protein competition 2 ?? ??? ?? ? plasma
  protein ?
• ???? binding
• Altered Excretion ???? ? ??? ????? ??? ??
• probenecid? sulfonamide? same carrier
• Addition ? ??? ??? ?? 1 1 2
• Synergism ? ??? ??? ?? ?? ?? ? ?? 1 1 3
• Potentiation ? ?? ? ??? ??? ??? ? ??? ???? ?
• ?? ?? 0 1 2
• Antagonism ? ??? ???? ? ?? ?? 1 1 0

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• ???? ?? (Steps of New Drug Development with
  Efficacy/Safety Aspects
• ???/???/? ?? (??, ?? ? ? ??? ?? ??)
• ????? (Non clinical test Good Laboratory
  Practice) Efficacy ? Safety
• in vitro, organ, whole animals ??
• 3. IND (Investigational New Drug)??
• 4. ???? (Clinical Test)(Phase 1 3 ? Phase 4 ??0
• ? 1 ? (???) ??? ?? ? 2 ? (?? ??) ? 3 ?
  (pharmacokinetic/safety test)
• Double-blind, Randomized Controlled Trial
• ? 3 ? ?? ?? NDA (New Drug Application) ??? ??
• ?? ?? Monitoring? ??? ??? Population? ?? ?? ? ???
  ??

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• Peripheral Nervous System ?????
• ????? ? ????? ??
• ????? (Autonomic Nervous System) ?? ??(Cardiac)
• ? ??? (Smooth muscle)? ??
• ?????(Sympathetic Nervous System)
• catabolic action-??? ??
• ????, ?????, ????
• Stress ? ??
• ?????? (Neurotransmitter) Acetylcholine (Ach),
• norepinphrine and epinephrine
• ??????(Parasympathetic Nervous System)
• anabolic action-??? ??-
• ????, GI ????
• ?? ? ?? ??
• ???? (Somatic Nervous System) Skeletal muscle

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???? Nurons
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• ???? Process
• 1) ??????? ??? 2) presynaptic ??? ???? ??
• 3) ??? ??? presynaptic ?? ?????? ?? 4) ??? ???
• ???? Postsynaptic? ???? ??
• 5) ???? ?? (ion channel opening, 2nd messenger
  ???)
• ????? ????? ???? ??
• Receptor agonists
• ?????? ??? ???? ??(??)
• ??????? ?? (degradation)? ???? ??
• ????? ????? ???? ??
• Presynaptic nerve BLOKER
• ??? ??? (receptor antagonists)
• ??? (Gangliion) BLOKER

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Ganglion ???
Sympathetic and parasympathetic Nerve
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• Acetylcholine (Ach) ? ?? ???? ??
• Ganglionic transmission and block ?, ??? ?? ?
  ??? ????? ??? (ganglion)?? ???? ??? ??
  postsynaptic neurond ? nicotinic ???? ???? ????
  ???Cholinergic drugs? Ach ??? Ganglion ?? block
  block ?? ??? ??? ?? ?? ?? ???????? ????.
• Neuromuscular transmission Ach? nicotinic muscle
  (Nm) ???? ?? ? ?? ??, Ca ?? ? ??(influx)
• Central neurotransmission Ach ? ???? ??????
  muscaric ???? ??

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Sympathetic nerve
Brain, CNS ? ?? ?? (impulse) ? ??????
(Neurotransmitter) ??? ?? ? ???? ???? ?? ??
??(organs)? ????? ????. ?????? 1) ?????
(autonomic) (?? ? ??????? ????? ??? ??? ?? ????
??? ???) ? 2) ????(Somatic nerve system)(
skeletal muscle ? ??? ??)? ????.
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Brain signal ? release of acetylcholine at the
presynaptic neuron ? Ach binds to Receptors
(muscarinic, M ) ? Effects on heart and lung, etc
(Parasympathetic nervous system)
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MAOmono-amine oxidase
Diffuse
Catecholamines ?????? norepinephrine,
epinephrine diffuse and bind to adrenergic
receptor (?1. ?2.ß1, ß2) at the postsynaptic
cell, and effects on heart, and stomach, etc
(Sympathetic nervous system)
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