Transcript 1-Introduction,Nomeclature & ROA(1,2&3)

Reading assignments:
Katzung’s Basic & Clinical Pharmacology ,
13th Edi ,Ch-1,p1-10;
Lippincott Pharmacology,6th Edi,Ch-1,p1-6;
Sanjib Das
M.B.B.S.,M.D.,P.G.D.H.A.
1
Learning Objectives

Discussing Pharm as a course for Step1 USMLE

Define the different terms presented

Identify sources of drugs, and recall their
nomenclature

Describe the different routes of drug administration
and list their merits and demerits

Describe the different phenomena of
pharmacokinetics such as Absorption and
Bioavailability
2
In current USMLE STEP 1 exams 2 types of
questions are asked
-straight recall
-integrated (horizontal/vertical)-mostly
2nd or 3rd order
Ref: www.nbme.org
PHARMACOKINETICS
GIT DRUGS
CNS DRUGS
PHARMACODYNAMICS
ENDOCRINE
CHEMOTHERAPY
CVS & RELATED DRUGS
Quiz1
5%
BL1
25%
TOXICOLOGY
Quiz2
5%
BL2
25%
Tested
in Shelf
CLINICAL
THERAPEUTIC
PRESENTATION
(10%)
External
Shelf Exam
(30%)
High yields topics are
1.General Principles of kinetics & dyanamics
(approx.10)
2.ANS ( mostly. physio-path vignetted Qs.)(approx.10%)
3.CVS (approx.20%)
4.CNS (approx.20%)
5.Antimicrobial & Anticancer (approx.20%)
6.Endocrinal drugs (approx.8%)
&
Low yield topics are
7.Miscell:GI drugs, Blood,Autacoids etc. (more number
questions are being asked these days) (approx.5%)
Scanning lecture notes
Text (while considering what lectures had emphasized)
Key study objectives
(Primary-know very well;Secondary-pretty well;Others-only familiarization)
Notes & review section with emphasis with key objectives
Qs. After every topic
Analyze mistakes
Review poorly understood areas
Subject practice tests
Prescribing the most appropriate
drug for a Clinical Scenerio?think like a physician

Introductory Information
 Integrative science
 Have to understand how the whole body works

Pharmacokinetics
 How the body affects Drugs?

Pharmacodynamics
 How Drugs affect the body?

Adverse effects
 Deals with Risks to the patient!

Pharmacotherapeutics
 How to use drugs clinically?

Penicillin G:









Beta-lactam ring
Penicillinase sensitive
Acid labile
Tubular secretion
Inhibits cell wall synthesis
Highest Chemottherapy Index
Hypersensitivity
Used mainly for gram positive bacteria
How others differ:
 Amoxicillin; acid stable; broad spectrum
 Oxacillin; acid stable; penicillinase resistant
 Nafcillin; biliary excretion; penicillinase resistant
Template for drug information
Pharmacokinetics-absorption
-distribution
-metabolism
-excreton
Pharmacodynamics-moa
-indication
-a/e
LEARN EACH PROTOTYPIC DRUG
INFORMATION USING THIS
TEMPLATE
MEMORIZE HOW THE OTHER DRUGS
FROM THE SAME GROUP DIFFERS
FROM PROTOTYPIC DRUG
D-D Interaction -both kinetic & dynamic level
Toxicity -both kinetic & dynamic level
-‘Prototype’
-most commonly used drugs clinically
-Drugs with atypical pharmacological attributes
-existing category wise
-common endings or common characteristics with in the
name.
-only a few pneumonic
Pre-read before every lecture
Good Luck!!
14
Greek words:
Pharmacon: an active principle (a drug or
poison)
Logos: Knowing
A science that deals with fate and the
mechanism of action of drug in body.
Pharmacology covers both aspects of basic and
clinical sciences
15
Molecular pharmacology
2. Pharmacogenetics
3. Drug metabolism
4. Toxicology
1.
Clinical Pharmacology
(pharmacotherapeutics)
16
2. WHO (1966) defined drug as “any substance or
product that is used or intended to be used
physiological
systems or pathological states

can also be defined as any substance used for the
purpose of
of a disease in human,
plants or animals.
17
Goodman&Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition, PP:75 18
A drug molecule should be safe and
effective (safety and efficacy)
 If drug is not safe it shows toxicity

19
SOURCE OF DRUGS
1-Natural resources (Including plants, animals, microorganisms,
minerals)
 Plants –Morphine, Atropine, Epedrine, Vincristine, Vinblastin,
Taxol, Caffein, Cocain
 Animals – Gelatin, Heparin, Insulin
 Human – GH, HCG
 Minerals – Iron, Al(OH)3, BaSO4
 Microorganisms – Penicillin, Amphotricin B, Gentamycin,
Doxorubicin, Vancomycin
2- Synthetic and semisynthetic
 –Aspirin, Acetaminophen, Oxycodone,
3- Genetic Engineering:
- Alcohol, GH, Insulin,
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Pharmacokinetics (PK) (The fate of drug
in body or what body does to drug)
 Pharmacodynamics (PD) (The effect of
drug on body or what drug does to body)
 Pharmacogenetics (PG): Different
genotypes in a population have different
receptors, different drug metabolizing
enzymes or transporters resulting to
different susceptibility to drugs

21
Movement (Kinetic) of drug in the body=
fate of drug in the body
 What body does to drug= what happens
to a drug in body

22
Greek words
pharmacon+ dynamis (power)
- action of the drug inside the body
- what the drug does to the body or
how the drug handles the body
physiological and biochemical effects of drugs, their
mechanism of action at macromolecular/ subcellular / organ levels
23
Use this slide to organize
your understanding of
Pharmacokinetics & Dyamics
Intramuscular >>>>>>>>>>>>>>>>>>>>>>>>
(Topical or subcutaneous) Skin >>>>>>>>>>
NBME

reservoir
Efficacy
Toxicity
Figure out step by step fate & D-R Interactions following administration of a drug by Oral
,Inhalational and IV route.
25
NBME
26
3 kinds of names
(a) Chemical name
Accepted as IUPAC name (International Unit of
Pure and Applied Chemistry nomenclature)
NBME
(b) Non-proprietary name (Generic)
Accepted by a competent scientific body such as
the United States Adopted Name (USAN) Council
(c) Proprietary name (Brand):
Name assigned by the manufacturer(s)
One drug may have multiple brand names
27
Chemical (IUPAC) name:
(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]
pyrrolidine-2-carboxylic acid
 Generic name: >>> used on examinations:
 Diazepam
Look for common endings
 Propranolol
 Doxazosin
 Captopril
 Brand Name: Capoten (Bristol -Myers Squibb)

NBME
28
Brand names are not tested in usmle exams –
but still you need to know for few most
Prescribed Drugs in USA because-----
29
The 10 Most
Prescribed Drugs in
USA 









Brand names are not tested in NBME exams
Hydrocodone (combined with acetaminophen) -- 131.2 million prescriptions
Generic Zocor (simvastatin), a cholesterol-lowering statin drug -- 94.1 million prescriptions
Lisinopril (brand names include Prinivil and Zestril), a blood pressure drug -- 87.4 million
prescriptions
Generic Synthroid (levothyroxine sodium), synthetic thyroid hormone -- 70.5 million
prescriptions
Generic Norvasc (amlodipine besylate), an angina/blood pressure drug -- 57.2 million
prescriptions
Generic Prilosec (omeprazole), an antacid drug -- 53.4 million prescriptions (does not
include over-the-counter sales)
Azithromycin (brand names include Z-Pak and Zithromax), an antibiotic -- 52.6 million
prescriptions
Amoxicillin (various brand names), an antibiotic -- 52.3 million prescriptions
Generic Glucophage (metformin), a diabetes drug -- 48.3 million prescriptions
Hydrochlorothiazide (various brand names), a water pill used to lower blood pressure -47.8 million prescriptions.
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THE NATURE OF DRUGS

Size and molecular weight (MW):
 Drugs in common use vary in size from MW 7(lithium) to over NBME
MW 50,000 (thrombolytic enzymes).
 The majority of drugs, however, have molecular weights between
100 and 1000.

Drug-receptor bonds:
NBME
 Drugs bind to receptors with a variety of chemical bonds.
 These include very strong covalent bonds (which usually result in
irreversible action), somewhat weaker electrostatic bonds (eg,
between a cation and an anion), and much weaker interactions
(eg, hydrogen, van der Waals, and hydrophobic bonds).
http://www.google.com/imgres?imgurl=http://thedrevilshow.com/wp-content/uploads/2013/11/routes-of-drug-delivery.jpg&imgrefurl
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Routes of Administration
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Merits:
Most common, convenient,
 Noninvasive
(No need for surgical procedure)
 self-medication possible
 economical
Demerits:
 cannot be used for uncooperative / vomiting patients.
 certain drugs are not absorbed or destroyed by the gastric
juices
 cannot be given in emergencies
 Drugs are more likely to undergo first-pass metabolism
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Low Bioavailability by oral route-why?
Destroyed
in gut
(1)
Dose
Not
absorbed
(2)
Destroyed
by gut wall
(3)
NBME
Destroyed
by liver
(4)
to
systemic
circulation
(3)+(4) are called Pre-systemic metabolism (1st Pass Metabolism)
What is the difference between 1st Pass Metabolism & real metabolism?
NBME
No first pass metabolism
 Fast onset of action
compared to oral route

 Example
○ NG
○ Lorazepam (Ativan)
(3)+(4) are called Pre-systemic metabolism (1st Pass Metabolism)
37
Roach’s Introductory Clinical Pharmacology, 9th Edition
38
NBME
Merits
 Immediate action, so useful in
emergencies
 Avoids gastric juices / first pass
metabolism
 Can be used in unconscious
patients
 Irritant drugs
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Demerits
 Painful
 Risk of thrombophlebitis
 Expertise required
 Aseptic condition needs to be maintained,
hence costly
 Attains high concentration in plasma &
tissues
 If administered very rapidly – can cause
organ toxicity
40
Basic methods for
delivering iv therapy
Making the right
choice!
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Continuous Infusion
42
Intermittent Infusion
43
Direct Injections
44
45


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
Mild irritant drugs can be given
Absorption is quick
Volume injected is max. 10 ml
No first-pass metabolism
46
Roach’s Introductory Clinical Pharmacology, 9th Edition
47
Absorption is slow and
constant -produce
sustained effect
 Max 2 ml can be
injected
 Self-administration
possible – e.g.,
Insulin



Absorption is slow
Drug volume should
be small (e.g. BCG
vaccination, drug
sensitivity testing)
48
e.g. Steroids in Rheumatoid arthritis
http://www.rheumatologynetwork.com
49
Used where drugs (lipid insoluble/ highly polar) do
not cross blood brain barrier but required action in
brain or spinal space.
 strict aseptic precautions should be taken.

pedagogyeducation.com
50
 Examples:
1.
2.
3.
4.
Amphotericin B in cryptococcal
meningitis
Spinal anesthesia
Opioid analgesics
EPIDURAL
51

Application of drugs to skin or to the mucus
membrane like eye, ear, mouth, airways,
rectum and vagina
52
Relatively little first pass metabolism due to the
high vascularity of rectum
 Used in patients with vomiting /or where drug
induces vomiting
 Larger amount and drugs with unpleasant taste
can be administered
 Examples: Diclofenac, Acetaminophen

http://nursing-knowhows.blogspot.com
53
Absorption to blood circulation
Protection of Skin, No absorption
Color Atlas of Pharmacology, Editted by: Heinz Lüllmann, Thieme, 2005 54
NBME
TRANSDERMAL DELIVERY
 Administration of drugs to skin
for systemic effects
 Provides uniform plasma
concentration
 Follows zero order absorption
 Less inter-individual variations
 No first pass metabolism
 Convenient – better
compliance
 e.g, Estradiol, Nitroglycerin,
Scopolamine
 In Transdermal patch delivery
polymers control the release of
drugs
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56
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
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



Delivery of drug to respiratory tract
Alveolar epithelium offers good surface
area for lipid soluble drugs
Very rapid onset of action due to large
surface area and more vascularity
Drugs administered in gases or aerosol
form
Rapid action
No/less systemic toxicity
dose required is less
e.g., inhalational anesthetics (Nitrous
oxide, ether, halothane), Albuterol,
Steroids – Beclomethasone in Asthma
57
Demerits

training for use (skill required); so difficult in
children and geriatric patients

Expensive

Can not be given to unconscious patients
58
It can be used for either
local or systemic
administration of drugs
 Example of local effects:
Decongestive effect
(Oxymethazoline)
 Example of systemic
effects: Antimigraine drugs
(Rizatriptan), insulin or flu
vaccine

59
The nasal cavity is covered by a thin mucosa
which is well vascularised. Therefore, a drug
molecule can be transferred quickly across the
single epithelial cell layer directly to the systemic
blood circulation without first-pass hepatic and
intestinal metabolism. The effect is often reached
within 5 min for small drug molecules
 Drugs with poor absorption or extensive first pass
metabolism can be given in this way
 Small dosage of administration is most important
pitfall in using these drugs

60
61
Dose (Dosage): The amount of Drug
given to a patient (e.g. 200 mg of
Ketoconazole or 10 units of Insulin)
 Dosage form: The physical form of a
drug given to a patient (e.g. Tablet,
Capsule or Ampoule)

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Oral Dosage forms: Tablet, Capsule,
Suspension, Emulsion, Sachet (powder,
granules), Syrup,…..
Topical dosage forms: Creams, Ointments,
Lotions, gels, Suppositories, Aerosols, Foams,
Douch, pastes,…..
Parenteral Dosage forms: Injectables (Ampoule,
Vial, Infusions,…..)
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Greek words
Pharmacon (drug)+ kinesis (movement)
- movement and alteration of the drug inside the body
- what body does to the drug or
how body handles the drug (ADME)
- Absorption (A),
- Distribution (D),
- Metabolism or Biotransformation (M)
- Excretion (E)
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- Passage of drugs from the site of administration to
the systemic circulation (plasma , serum or blood)
- Intravenous (IV) administration does not involve
absorption, and there is no loss of drug
Processes of absorption
NBME
1. Simple or Passive diffusion
2. Carrier-mediated facilitated diffusion
3. Active transport
4. Pinocytosis
66
NBME
The rate of Absorption of drug from site of
absorption to central compartment (Blood) is
proportional to drug concentration gradient
across the barrier, the surface area of the
absorption and the thickness of barrier (Fick’s
first law).
 Based on Fick’s first law the diffusion goes from
high concentration to low concentration

Flux (molecule per unit time)  dc / dt  (c1  c2 )
Surface area  Diffusion coefficient
thickness
67
Non-permeable membrane
68
Semi-permeable membrane
69
Semi-permeable membrane
Equilibrium
70
NBME
71
NBME
72
NBME
-
Majority of drugs are absorbed by this
phenomenon
-
Transfer of drugs from the region of higher
concentration to the region of lower
concentration (along the concentration gradient)
-
No energy, no carrier required
Not saturable and not inhibited
-
lipid soluble drugs readily move through the lipid
bilayer by this process
-
-
Driving force: concentration gradient
73
74
NBME
Movement occurs along the concentration
gradient
- Carrier needed; but no energy required
- highly selective (specific), competitive and
saturable
-
-
Examples: absorption of Vit B12 from the gut,
uptake of Glucose through the membrane of
red blood cells
Mostly water soluble molecules pass through
this process
75
NBME
76
NBME
-
Movement is against the concentration gradient
Carrier and energy (both) are required
Highly selective (specific), competitive and
saturable
examples: Glucose absorption from gut lumen
into intestinal epithelial cells, Levodopa
absorption
77
NBME
Primary Active Transport
 Secondary Active transport

78
NBME

Directly using of metabolic energy to
transport molecules across the membrane by
coupling of carrier to ATP (e.g. Na+-K+
ATPase)
79
NBME
 The
sodium ions and ATP bind to the
protein. Then the hydrolysis of ATP
causes the protein to change
conformation and transport the
sodium ions to the other side of the
cell membrane. As the potassium ions
are bound to the protein on the
outside of the cell, the sodium ions
are released and the potassium ions
are moved to the inside of the cell
80
NBME
81
NBME
 The
transport across a biological
membrane of one solute (s1) against
its concentration gradient is
energetically driven by the transport
of another solute (s2) in accordance
with its concentration gradient.
82
NBME
 Secondary
active transporters are
classified as either symporters or
antiporters. Symporters, also termed
cotransporters, transport S2 and S1 in
the same direction, whereas
antiporters, also term exchangers,
move their substrates in opposite
directions
83
NBME
 The
driving force for this type of
transport therefore is stored in the
electrochemical potential created by
the concentration difference of S2
across the plasma membrane,
Depending on the transport direction
of the solute.
84
85






A mode of endocytosis used for extracellular fluids
Small particles coming into the cells by forming an
invagination
The formed vesicles will fuse with lysosymes and the
enzymes release their contents
The hydrolysis needs energy through ATP but at the
end due the usage of energy from engulfed liquids
(lipids) a surplus amount of energy will produce
It is non specific and if it is specific it is called
Receptor Mediated Endocytosis
It has small role in drug transport however some
medical proteins are use this method for their
transport
86
87
Qs








Visualize the interrelationships between various
processes/steps of Pharmacokinetics &
Pharmacodynamics following administration of a drug by
oral route.
Relationships betweenPharmacokinetics ,
Pharmacodynamics & Pharmacogenetics
Drug Nomenclature
Merits & demerits of various routes of drug
administration with an emphasis on oral,s/l,
intravenous,im,s/c & TDD routes
Why s/l routes of cyclobenzamine is preferred over oral
in the treatment of fibromyalgia?
What is the diff.between dose & dosage
Know various processes of drug absorption through
various routes.
What are the basic differences between Simple or
Passive diffusion,Carrier-mediated facilitated diffusion &
Active transport
88
PowerPoint Slides

Several of the PowerPoint slides are Copyright © 2002-04,
the American Society for Pharmacology and Experimental
Therapeutics (ASPET). All rights reserved.

Some of slides in this session are from the above mentioned format
and are free for use by members of ASPET.

Some others are from various sources like text book, recommended
books, slides of Drs. Anooshirvan Shayeganpour (professor, SABA
school of Medicine),S.Kacker (professor, Clinical Pharmacology &
Therapeutics, MUA)& S. Akbar (ex. professor, Pharmacology ,MUA)

Core concepts of various USMLE High yield review series like
Kaplan ,BRS etc. are thoroughly explored & integrated whenever
necessary