The Journal of Clinical Pharmacology

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The Journal of Clinical Pharmacology
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Clinical Pharmacology

• Pharmacokinetics and pharmacodynamics
• Drug metabolism
• Drug interactions
• Therapeutic review

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• ????????
• 20
• ????(80)
• ????(40)
• ????(40)

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Orientation to Pharmacology

• Lu-Tai Tien, Ph.D.

Department of Medicine School of Medicine Fu-Jen
Catholic University
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Ready to study pharmacology?

• Pharmacology is a science that draws on
  information from multiple disciplines, including
  anatomy, physiology, psychology, chemistry, and
  microbiology etc.

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Four basic terms

• Drug
• Pharmacology
• Clinical pharmacology
• Therapeutics/pharmacotherapeutics

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Drug

• A drug is define as any chemical that can affect
  living processes.
• All chemicals can be considered drugs, since,
  when given in large enough amounts, all chemicals
  will have some effect on life.

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Pharmacology

• Pharmacology can be defined as the study of drug
  and their interactions with living systems.
• the physical and chemical properties of drugs as
  well as their biochemical and physiologic effects
• knowledge of the history, sources and uses of
  drugs as well as knowledge of drug absorption,
  distribution, metabolism, and excretion

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Clinical pharmacology

• Clinical pharmacology is defined as the study of
  drugs in humans.
• This discipline includes the study of drugs in
  patients and in healthy volunteers.

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Therapeutics

• Therapeutics, also known as pharmacotherapeutics,
  is defined as the use of drugs to diagnose,
  prevent, or treat disease.
• Alternatively, therapeutics can be defined simply
  as the medical use of drugs.

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Properties of an ideal drug

• Effectiveness
• Safety
• Selectivity

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Additional properties of an ideal drug

• Reversible action
• Predictability
• Ease of administration
• Freedom from drug interactions
• Low cost
• Chemical stability
• Possession of a simple generic name

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No drug is ideal

• No drug is safe.
• All drugs produce side effects.
• Because medications are not ideal, all members of
  the healthcare team must exercise care to promote
  therapeutic effects and minimize drug-induced
  harm.

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Pharmacokinetics

• ?????
• ???????????????????????????????

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?????????

• ????? (Absorption)
• ????? (Distribution)
• ????? (Metabolism)
• ???? (Excretion/elimination)

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?? (Absorption)

• ??????????????????, ??????????????????
• ??????????
• pH ?????????
• ???????????

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??????????

• ????
• ?????? ? ???
• ???????
• ??????
• ????
• ???????????
• ????
• ???? Adenosine triphosphate (ATP)
• ?????? ? ???
• ?????

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pH ?????????

• ????? (HA) ????????????????
• HA H A-
• ????? (BH)??????????????? (B)
• BH H B

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??????????
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?????????????????
Henderson-Hasselbalch equation
????????
pH pKa

log
???????
A-
log
pH pKa

For acids
HA
B

For bases
pH pKa
log
BH
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???????????

• ???????
• ?? gt ?
• ?????????
• ?? (???)gt ?
• ???????????
• ????????????

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????? (Bioavailability)

• ????????????????
• ?? ?? 100 ??????????????, ?? 70 ????????????,
  ??????? 70

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????????

• ??????????????? 100 ??
• ??????? (????)?????????????????????????
• AUC area under curve ??????

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??????????

• ???????
• ????????????????????
• ??????
• ???? No
• ???? No
• ???? ????? Yes
• ??????
• ?? Penicillin G ??? pH ???????????
• ?????
• ????,????,??????

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?? (Distribution)

• ?????????????????????(????)???????????
• ???
• ???????
• ????????

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???????

• ????????????????????????, ?Vd??
• C D/Vd or Vd D/C
• C ?????????
• D ???????

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?? (Metabolism)

• ??????? (biotransformation)
• ?????(????)?????????????????
• ??????????? (prodrugs), ???????????????????
• ??????????????

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?????

• Michaelis-Menten kinetics
• V ???????

Vmax C
Km C
C ?????
Km Michaelis-Menten ??
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V ???????
Vmax C
C
Km

????
C gtgt Km
VmaxC
V
C
????
Vmax
C ltlt Km
VmaxC
V
Km
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???????

• ????????????????????????????
• ?????????????????????????????????

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?????

• ?????????????
• ????????, ??, ???
• P-450 ???? (major)
• ??????, ????? (minor)

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?????

• ????
• ???????????????????????

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?? (Excretion/elimination)

• ????????????????????
• ????????????????????????

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Study question I

• ???????, ??????????
• (A) ????
• (B) ????
• (C) ??
• (D) ????
• Answer (C)

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Study question II

• ??????????? 100 mg ????????????
  20µg-ml???????????????????????????????????,??????
  
• (A) 0.5 L (B) 1 L (C) 2L (D) 5 L (E) 10 L

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Answer D

• Vd D/C
• D ???????
• C ????????

D 100 mg 1 ? 10-1 g
C 20 µg/ml 2 ? 10-5 g/ml
1 ? 10-1 g
0.5 ? 104 5 ? 103 ml 5 L
Vd D/C

2 ? 10-5 g/ml