Clinical Pharmacy Practical Handouts (PC 609)
Summer course 2016
Subject index
page
Subject
Intended Learning Outcomes of courses (ILO's)
3
Part 1: Drawing standards of chemical structures
4
Part 2: Physicochemical properties of drug action
34
 Acid/base properties
34
 Predicting degree of ionization of drug molecule
38
 Hydrophilic/lipophilic properties
42
 The hydrophobicity constant
46
 Case study
50
Part 3: Titrimetric determination of pharmaceutical preparations
58
 Penicillins: Benzylpenicillin
58
 Cephalosporins: Cephalexin
60
 Sulfonamides
62
 Determination of ZnSO4/Sulfacetamide sodium
64
 Assay of zinc undecenoate
67
 Propylparaben
69
 Betadine
71
 Isoniazide (INH)
73
 Busulphan
75
 Problems
77
Part 4: Case study
80
Evaluation sheet
100
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Medicinal Chemistry
Clinical Pharmacy Practical Handouts (PC 609)
Summer course 2016
Evaluation of the Practical pharmaceutical chemistry
PC609
 The 25 Marks of practical course will be distributed as following:
 The total degree of practical course
25 Marks
 ChemBioDraw exam
8 Marks
 Physicochemical exam
5 Marks
 Assay exam
5 Marks
 Case study exam
4 Marks
 Behavior and attendance
3 Marks
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Intended Learning Outcomes of courses (ILO's)
Upon completion of the course the student should be able to:
1. Draw chemical structures in two and three dimension using ChemDraw
program.
2. Draw diagrams and sketches of different equipment and glassware used in
chemical reactions using ChemDraw program.
3. Explore in detail some further useful application of ChemDraw program.
4. Understand the relationship between the chemical and physical properties of
related compound and their medicinal use and pharmacological activity.
5. Handle laboratory chemicals in a correct and safe way to obtain optimum
results without harmful effects.
6. Perform titrimetric techniques for determination of some pharmaceutical
compounds, handling data in term of graphical presentation.
7. Be familiar with the analysis of drugs and the laboratory techniques used for
that.
8. Analyze pharmaceutical dosage forms and determine their active constituents
by different analytical methods.
9. Identifying the drug impunities and different related substances and giving
possible explanation of their existence.
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PART 1
Drawing Standards of Chemical Structures
Overview
The information required to begin using Chem Draw includes how to do the following:
 Start Chem Draw.
 Create, open, and save documents.
 Identify the parts of the Chem Draw interface.
 Drawing the different chemical structures and showing the chemical properties,
stereochemistry, fragmentation pattern, 1H-NMR, …..etc..
 Drawing the synthesis, degradation and metabolic pathways of the drugs.
 Interpretation of the mode of actions of drugs and drug receptor interaction in
diagram form.
Basics drawing using Chem Draw
Starting Chem Draw
You can start the Chem Draw application in the following ways:
 From the desktop, double-click the Chem Draw icon, or:
 From the Start menu, choose Chem Draw, where a new document is created.
 The Work Area:
 The work area appears whenever you launch Chem Draw. By default, the work area
displays commonly used toolbars, the main menu, and document status bar. The
work area appears below:
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Optional Toolbars
ChemDraw provides a number of optional toolbars and information windows to
facilitate production of ChemDraw documents. These toolbars are accessed from the View
menu. They are divided into three basic groups:
 Standard Toolbars and Show Windows
 Tool Palettes
 Templates
Showing and Hiding Toolbars
To show or hide a toolbar:
 From the View menu, select a toolbar.
 A check mark appears next to the item when the toolbar is displayed.
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Docking and Undocking Toolbars
The standard toolbars, can be docked or undocked. Docked toolbars can attach to any edge
of the ChemDraw window. Undocked toolbars can float anywhere in the ChemDraw screen.
To dock a toolbar:
 Drag the toolbar to the edge of the ChemDraw screen where you want it to dock.
 Double-click the toolbar background. This wil dock the toolbar in the default
position.
To undock a toolbar:
 Drag the toolbar into the position you want.
The Main Toolbar
Most common tools are on the main toolbar. These include all tools necessary to draw
and edit structures, reactions, and shapes. Go to View>Show Main Toolbar.
The main toolbar has other toolbars extending from it. You can “tear off” these smaller
tool bars and place them anywhere on your screen. To tear off a toolbar:
1. Click the arrow on the lower right of a tool in the main toolbar.
2. While holding the mouse button down, point to the title bar, and release the button.
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Opening Documents
To open a document, do one of the following:
 Go to File>Open. In the Open dialog box, select the name and location of the file and
click Open.
 In the File menu, choose the document from the list at the bottom.
Saving Documents
 Go to File>Save; Choose a folder in which to store the file.
 Type a file name in the Save As text box.
 Select a file format then Click Save.
Selecting Objects
Use the Lasso or the Marquee tool to select any object. You use the Lasso for freehand
selection and the Marquee to select rectangular regions. When you select a structure or
object, the selection is displayed with a light blue frame around it with three types of
selection handles:-
A) Drag this handle to rotate the object.
B) Drag any corner to resize.
C) Drag any side handle to distort.
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The Lasso Tool
Use the Lasso tool to make freehand selection of irregular areas. To select objects using
the Lasso tool:
1. Select the Lasso tool.
2. Press the mouse button while the pointer is not over any object.
3. Drag around part of a structure or other object.
The Marquee Tool
Use the Marquee tool to select objects and structures within a rectangular area.
1. Select the Marquee tool.
2. Click and drag diagonally over the structures or other object.
As you drag, a rectangle appears that defines the selection area. Bonds and other objects
are selected only if they are entirely within the rectangle.
Selecting entire structures
To select an entire chemical structure, double-click a bond or atom in the structure
using a selection tool.
Character Map
The floating Character Map window displays the 256 characters in any font. The
default font is Symbol. Use it to add symbols or styled fonts to labels. The character map is
active only when a text box is open for editing.
With a text box open, mouse over the character map to view a larger version of the
characters in the top right corner of the window.
Click any character in the table to enter that character in the text box.
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Bonds
The Main toolbar and Multiple Bonds toolbar offer numerous options for drawing
bonds.
To draw the first bond of your structure, select the solid bond tool in the Main toolbar
and click in the document window.
 To draw another bond, point to an atom where a grey box appears then click.
 You can draw a bond in any direction. Using a bond tool, click and drag from an
existing atom or an empty area in the document window.
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There are several ways to draw a double bond:
 Draw a bond using the Double bond tool.
 Draw a single bond over an existing single bond.
 Using any bond or selection tool, point to an existing bond and type ‘2’
To draw triple or quadruple bonds:
 Draw a bond using the triple or quadruple bond tool.
 Using any bond or selection tool, point to an existing bond and type‘3’ or ‘4’.
Changing the Bond Order
You can reduce or increase the order of bonds in a structure by using the Bond
Properties dialog box or with the shortcut menus as follows.
To reduce the bond order:
1. Point to the bond to change and Right-click or Control-click.
2. Choose the appropriate bond type from the shortcut menu that appears.
To use the eraser tool for reducuing the bond order:
1. Click the Eraser tool.
2. Click a single, double, or triple bond. The bond order is reduced by one.
Bond Hotkeys
To modify a bond, place your mouse over the bond and select a key (K) listed below:
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Function
Summer course 2016
K
Function
K
Change to single bond
1
Change to bold bond
b
Change to double bond
2
Change to dashed bond
d
Change to triple bond
3
Change to hashed bond
H
Change to quadruple bond
4
Change to hashed-wedged bond
h
Center a double bond
c
Change to wedged bond
w
Double bond to the left
l
Change to wavy bond
y
Double bond to the right
r
Open a bond properties text box
/ or ?
Rings
You can draw aliphatic and aromatic rings of different sizes and types.
1. In the Main toolbar, select a ring tool.
2. Click and drag in the document window to orient the ring.
If you click an atom or bond with a ring tool in an existing structure, the ring is fused
to it.
Spiro and sprout rings
By default, clicking an atom in a ring using a ring tool forms a spiro link.
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You can change this behavior so that a sprout bond appears instead:
1. Go to File>Preferences.
2. On the Building/Display tab, check the box next to Sprout Rings Instead of Spiro
When Clicking.
Aromatic Structures
Delocalized rings: You can draw a resonance delocalized ring using any ring tool except for
the cyclohexane chairs.
1. Click a ring tool.
2. Press the Ctrl key and click in the document window.
Resonance structures: You can draw benzene in either of their two orientations:
1. Click a ring tool.
2. Press the Shift key and click in the document window.
Adding chains to structures
To add an acyclic chain to an existing structure, click an atom in the structure. Click
and drag in the direction you want to draw the chain.
Specifying chain length: To specify the exact length of a chain before drawing:
1. Select the Acyclic Chain tool.
2. Click an existing atom or an empty area in a document window. The attach Chain
dialog box appears type the numbers of atoms in the chain then click Attach.
3. Or click and drag in the document window in the direction you want the chain to
grow. The number at the end of the chain indicates how many atoms you have drawn.
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Changing Chain Direction
 To change the direction of the chain as you draw: Press Ctrl key while drawing
chains in the direction you want.
Moving Atoms
You can use any of the bond tools to move an atom within acyclic or cyclic structures.
You cannot use a ring tool.
To move an atom in a chemical structure:
1. Click a bond tool.
2. Point at the atom to move. A highlight box appears over the atom.
You can convert ring types by dragging one atom on top of an adjacent atom, e.g. if
you want to convert a 6-membered ring into a 5-membered ring perform the following:1. With a bond tool selected, point to an atom and Shift+Drag.
2. Release when one atom is on top of the other, the bond between the atoms
disappears.
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Captions and Atom labels
Chem Draw enables you to create the following types of text:
 Caption text: - Create annotations, chemical names, chemical formulas, page titles,
and information in tables.
 Atom label text: - Identify atoms and substructures by their chemical symbols and
formulas.
Tutorial: Drawing a chemical structure of Aspirin (acetylsalicylic acid):
To add the carboxylic moiety:
 Select the Text tool, click the end carbon on the methyl group, a text box appears.
 In the text box, type COOH, then click the entr key or click outside the text box.
To add the caption Aspirin: Acetylsalicylic acid:
 Select the Text tool, click below the drawing and type “Aspirin: Acetylsalicylic acid”
in the text box.
 Click outside the text box.
(To edit the caption or atom label, click in the text box with the text tool and begin
typing).
Shortcuts and Hotkeys
Hotkeys are organized into atom labels, bond types, and functions such as adding a
charge or displaying a bond.
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Atom Keys
Using Hotkeys, you can add functional groups to your structures with one keystroke.
For example, place your mouse over an atom and press ‘1’ (to add n-butyl group), ‘2’ (secbutyl group), ‘3’ (ter.-butyl group), ‘4’ (phenyl), b (Bromine) c (Carbone), e (ethyl), f
(fluorine), i (iodine), l or C (Chloride), n (nitrogen), N (sodium), O (oxygen), s (sulfur), and
…..
Deleting structures, bonds or atoms:
To delete the entire structure, do one of the following:
 Select the Eraser tool, double click on any atom or bond in the structure.
 Select the entire structure with the Marquee or Lasso tool and press Backspace
or Delete.
To remove any bond or atom, do one of the following:
 Click the bond or atom with the Eraser tool.
 Point to the bond or atom with the Marquee or Lasso tool and press Backspace
or Delete.
Atom Numbering
You can add sequential numbering indicators to atoms. The types of indicators are
(The default indicator is numbers):
 Numbers (1, 2, 3, and so on)
 Text ending with a number (atom1)
 Greek letters in the Symbol font
 Letters (a, b, c, and so on)
Showing Atom Numbers
1. Select one or more atoms to number.
2. While pointing to the selected atoms or structure, do one of the following:
 Right-click, point to Atom on the context menu, and click Show Atom
Number.
 Type the HotKey ‘ (single quote).
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Hiding atom numbers
1. Select the atoms or structure.
2. Right-click, point to Atom, and deselect Show Atom Number.
To remove an atom number indicator, do one of the following:
 Click the indicator with the Eraser tool.
 Point to the indicator with the Marquee or Lasso tool and press Backspace or
Delete.
Editing Atom Numbers
To edit the atom number text and style:
1. Select the Text tool.
2. Select the atom number indicator and type the changes.
3. To edit the atom number style, select the atom number indicator with the Text tool
and use the Text menu or Text formatting toolbar.
The Chemical Symbols Tools Palette
Use the Chemical Symbols tools to add chemical symbols to your structure. When you
click the Chemical Symbols tool, the following palette appears:
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When you attach a symbol (other than H-dot or H-dash) to an atom, it remains at a
fixed distance from the central character of the atom label. If you drag the symbol, it will
maintain that fixed distance as it moves around the atom.
 Lone Pair Symbol
It is used to indicate a lone pair of electrons common in Lewis structure
representations. To draw a lone pair:
1. Hold down the mouse button over the Chemical Symbols tool and drag to select the
lone pair from the palette.
2. Point to the atom where you want the lone pair located and drag in the suitable
direction to position it then release.
 Radical, Radical Cation and Radical Anion
 Radical symbol is used indicate a single non-bonded electron.
 Radical cation and radical anion symbols are used to represent radicals that are
charged.
To draw a radical, radical cation or radical anion symbol:
1. Hold down the mouse button over the Chemical Symbols tool and drag to select the
symbol from the palette.
2. Point to the atom where you want the symbol to appear then Drag from the charge
portion of the symbol to the radical portion of the symbol.
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 Charge Symbols
Charges are always assigned to a specific element in the atom label, whose acceptable
valences become those of the similar isoelectronic neutral element.
To draw a charge and associate it with a structure:
1. Hold down the mouse button over the Chemical Symbols tool
and drag to select
the charge symbol from the palette.
2. Click to the atom to which you want the charge to correspond.
The number of hydrogen atoms increases or decreases as appropriate for the addition
of the charge.
Using hotkeys to draw a charge and associate it with a structure:
1. Select the atom to which you want the charge to correspond.
2. Press the key board bottom "-" to add a negative charge or "+" to add positive
charge.
Rotating a Symbol
All symbols are rotated around the same end from which they were originally drawn
To rotate a chemical symbol:
1. Select the chemical symbol with a selection tool.
2. Drag the Rotation handle on the chemical symbol.
Coloring Text or Structure:
You can color captions, atom labels and structure as a whole or in part by select the
captions, atom labels and structure by the lasso tool then:.
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1. From the Color menu, choose a color.
2. Or right clink then selecting the color from the menu and choose a color.
3. Or selecting the color tool from style toolbar
Rotating Objects
1. Select an object to rotate. The Rotation handle is at the top of the selection rectangle.
2. Drag the Rotation handle clockwise or counterclockwise.
To rotate a selected object by a specified angle:
1. Select an object to rotate, right click over the object, select rotate from the menu.
2. The Rotate Objects dialog box appears, enter a number and click either degrees CW for
a clockwise rotation or degrees CCW for counterclockwise rotation [(Optional) to rotate
the atom label text, select Rotate Atom Labels].
3. Click Rotate. Objects are rotated around the center of the selection rectangle.
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Moving Objects
To move an object:
1. Select the object using a selection tool.
2. Point within the border of the Selection rectangle.
3. Click and drag the object.
To constrain the movement to the horizontal or vertical direction: Shift+drag the
selected objects.
Copying Objects
1. Select one or more objects.
2. Ctrl+drag or Option+drag the object(s) to create a copy and position it.
To constrain the copy to move only vertically or horizontally while positioning it, hold
down the Shift+Ctrl or Shift+Option keys.
Deleting Labels
To delete an atom label, leaving the underlying bonds unchanged, do one of the
following:
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 Select the Eraser tool and click the atom label.
 With a selection, bond, or ring tool selected, point to the atom label and press the
space bar, Backspace, or Delete key.
Deleting Objects
To delete selected objects, do one of the following:
 Press the Delete key.
 Go to Edit>Clear.
Also you can delete the whole structure through selecting the Eraser and double
clicking on any part of the structure.
Drawing Arrows and Shapes
Use the tools and tool palettes on the main toolbar to add shapes to your documents.
Overview: Chem Draw provides four tools that enable you to add shapes to your
documents:
Orbital tools palette
Draw orbitals
Chemical Symbols tools Draw charges, radicals, and other
palette
symbols.
Arrow tools palette
Draw arrows.
Drawing Elements tools
palette
Brackets tools palette
Draw boxes, circles, and lines
Draw brackets, braces, parentheses,
and daggers.
Arc tools palette
draw arcs
Pen tool
Draw freehand shapes.
Selecting Tools from the Palette
 The Arrow, Arc, and Drawing Elements tools each contain a palette with different
types of that tool.
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 When you choose a tool type from the palette, it becomes the default. To use a
different tool type, select it.
 To select a tool and use its default tool type Click the tool’s icon to select it.
 To choose a different tool type from the palette:
1. Point to the tool’s icon and hold down the mouse button. The palette appears.
2. Drag to select a tool type from the palette.
3. Release the mouse button over the object you want to select.
Framing Objects
You can enclose your drawings or group structures with a rectangle, brackets,
parentheses, or braces. To enclose your object:
1. Select one of the box tools.
2. Point where you want a corner of the box to be located.
3. Drag from one corner of the box diagonally to the opposite corner.
Also you can enclose your object by another method:
1. Select the drawing to enclose.
2. Right click, Add Frame and select the frame type.
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Drawing Circles and Ovals
To draw a circle or oval:
1. Select one of the circle or oval tools.
2. Point where you want the center of the circle to be located.
3. Drag outward from the center.
Drawing Paired Brackets
Paired brackets can only be placed in a vertical orientation. A rectangle or box defines
their position. To draw paired brackets:
1. Select a paired bracket tool.
2. Point where you want a corner of the bracket to be located.
3. Drag from one corner of the box diagonally to the opposite corner.
Note: while selecting the bracket tool, double clickin on the bracket will change its direction.
Arrows:
There are many arrows types available (e.g. such as crossed (no-go) arrows,
equilibrium arrows of unequal lengths, and elliptical arcs.), letting you add a wide variety of
reactions and annotations to your drawings.
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You can customize arrows not only for length and angle, but for arrowhead width and
shape. You can also drag an arrow from its middle to create an arc of any length.
When you mouse-over an arrow with the Lasso, Marquee, or an Arrow tool selected,
the application switches to edit mode and adjustment handles appear on the arrow.

Arrows are used do outline diferent metabolic and synthetic pathways.

While selecting the arrow, double cliking on the arrow will revese its direction.
Working with Structures
1- Automatic Error Checking (Checking Chemistry)
 Chem Draw automatically checks for correct chemical syntax as you draw. If Chem
Draw finds an error, a red box is displayed around the erroneous object. The red box
is display only and does not print.
 To view a description of the error, do one of the following:
o Right-click on the error and choose Explain This Warning.
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To check the valences of all selected atoms in a structure:
1. Select a structure, part of a structure, or caption with a selection tool.
2. From the Structure menu, choose Check Structure.
Each label in the structure is checked, sequentially. When a label is incorrect, a
message window appears.
To continue checking the structure when a message appears:
 Click Ignore: - To ignore all subsequent errors in a structure:
 Click Ignore All: To stop checking a structure when a message appears:
 Click Stop:-The check ends and the atom that is causing the problem are selected.
To disable the automatic error checking:
o On the Tools menu, deselect Show Chemical Warnings.
 This setting applies to all documents.
To disable the automatic error checking on a specific object:
o Right-click the object and choose Display Warnings.
When Display Warnings is deselected for an object:
o Red boxes are not displayed for errors.
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o Errors are not reported by the Analyze Structure or Check Structure commands.
2- Structure Clean Up
The Structure Clean Up command is used to neaten the appearance of molecules by
regularizing bond lengths and angles. Graphic objects such as arrows and aromatic circles
are not affected. Use Structure CleanUp to redraw structures that you may have drawn
freehand or to neaten structures that you may have imported from another application.
Structure CleanUp may not create the best structure.
To clean up the structure:
 Select the structure and from the Structure menu, choose Clean up Structure.
3- Viewing Analysis Information
 The Analysis window displays the chemical formula, exact mass, molecular weight,
m/e, and elemental analysis for the entire document, a structure, part of a structure, or
a caption in Formula style.
To view information about a selected structure:
1. Select structure.
2. From the View menu, choose Show analysis window, the Analysis window
appears.
To paste information about a structure as a caption:
1. Click the check boxes for the information that you want to paste.
2. Click Paste.
Formula: The molecular formula showing the exact number of atoms of each element in the
molecule and charges, radicals, and isotopes.
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Exact Mass: The exact molecular mass of the structure, where atomic masses of each atom
are based on the most common isotope for the element.
Molecular Weight: The average molecular mass of the structure, where atomic masses are
based on the natural abundance of all isotopes of the element.
Elemental Analysis: The percent by weight of each element in the structure.
m/e: Mass/charge, where charge =1. The weights of the most common isotopes and a
graphical representation of the isotopic abundance is shown.
4- Viewing Chemical properties
To view information about the chemical properties of selected structure:
1. Select an entire structure, part of a structure, or a caption (in Formula style).
2. From the View menu, choose Show chemical properties window.
To paste information about a structure as a caption:
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1. Click the check boxes for the information that you want to paste.
2. Click Paste.
5- Viewing the Stereochemistry:
When the Show Stereochemistry option is selected, Chem Draw calculates the absolute
stereochemistry for tetrahedral atoms and double bonds according to the Cahn-IngoldPrelog (CIP) priority rules.
Chem Draw calculates and displays the following stereochemical terms:
 (R), (S)-Standard tetrahedral stereochemistry
 (E), (Z)-Standard double-bond stereochemistry.
To show the stereochemistry of a structure:
1. Select an entire structure.
2. From the Object menu, choose Show Steriochemistry.
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6- Drawing-Structures from Chemical Names
One of the most significant and useful features in Chem Draw is Struct=Name. Draw
or open a chemically correct structure and Chem Draw displays the IUPAC name.
In Chem Draw only, you can draw a structure automatically from a chemical name, by
using the Convert Name to Structure feature.
 Chem Draw recognizes most organic nomenclature.
 Most inorganic chemistry is recognized, especially when the rules closely match
those for organic chemistry.
Converting Names to Structures
 Inserting Names: For example, to insert Acetyl salicylic acid:
1. From the Chem Draw Structure menu, choose Convert Name to Structure. The
Insert Structure dialog box appears.
2. Type Acetyl salicylc acid.
3. Click OK.
The molecular structure and name appear in the drawing area.
Converting Structures to Names
1. Select the chemical strucure
2. From the Chem Draw Structure menu, choose Convert Structure to Name.
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NMR- prediction
Chem draw has the ability to predict proton and carbon-13 NMR, i.e. Chem NMR estimates
and displays proton and carbon-13 chemical shifts in ppm for a selected molecule.
To view 1H or 13C NMR information:
1. Select the target chemical structure.
2. From the Structure menu, choose 1H-NMR Shifts or 13C-NMR Shifts.
Chem NMR redraws the molecule with the estimated shifts and displays the
information and line spectrum in a new window.
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Drawing with Templates
 Template documents are collections of structures organized by structural type or
functionality.
 A structure in a Template document is named a template. Use an existing template
instead of drawing the structure to shorten the time required to create documents.
The Templates Tool:
 The Templates tool contains a palette from which you can select different types of
structures or objects. The Templates tool has two levels:
o The first level displays the available Template documents.
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o The second level displays the templates within each Template document.
Drawing a Template
 To draw a template: Click in a document window. The template is drawn centered
around the pointer in the orientation that it appears in the Templates palette.
Fusing a Template with an Existing Structure
To draw a template and fuse it with an existing structure:
 Click an existing bond in a document window.
 To deposit a template and create a spiro-linkage with an existing structure:
Guided by the Chem Draw program, draw the following structures
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Guided by the Chem Draw program, draw the following pathways:
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PART 2
Physicochemical Properties of Drug Action
Acid/base properties
Different types of functional groups commonly exist in drugs are listed in the following
tables:
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35
Summer course 2016
Medicinal Chemistry
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Summer course 2016
 Identify the functional groups of each of the following drugs and determine whether they
are acidic, basic and/or neutral.
Answer:
For aspirin:
For fluoxetine:
For chloropromazine:
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Medicinal Chemistry
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For amlodipine:
For fexofenadine:
For ciprofloxacin:
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Predicting the degree of ionization of drug molecule
1. Calculate the percentage of ionization of amobarbital (its pKa: 8.0) in the stomach (pH ~
2.0), duodenum (pH ~ 5.5), and ileum (pH ~ 8.0). Discuss the effect of pH on its
ionization.
Answer
In the stomach (pH ~ 2.0):
pH = pKa + log([A-]/[HA])
2 = 8 + log([A-]/[HA])
-6 = log([A-]/[HA])
[A-]/[HA] = 0.000001
As shown above, (pH ~ 2.0) amobarbital is in the unionized form (~100%)
In the duodenum (pH ~ 5.5):
In the ileum (pH ~ 8.0):
Comment:
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Medicinal Chemistry
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2. Calculate the percentage of ionization of phenylpropanolamine (its pKa: 9.4) in the
stomach (pH ~ 2.0), duodenum (pH ~ 5.5), and ileum (pH ~ 8.0). Compare these results
with those obtained with amobarbital.
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Medicinal Chemistry
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3. Calculate the percentage of ionization of sulfacetamide in the stomach (pH ~ 2.0),
duodenum (pH ~ 5.5), and ileum (pH ~ 8.0). Draw the structure of the predominate form
of the drug in each site.
Sulfacetamide has the following structure and pKa values:
Answer:
In the stomach:
In the duodenum:
In the ileum:
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Medicinal Chemistry
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4. For the following organic functional groups, name each one, and show all possible
hydrogen bonds with water.
Answer:
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Medicinal Chemistry
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Hydrophilic/lipophilic properties
(Water and lipid solubility)
Guided by the following table which represents water-solubilizing potential of organic
functional groups in a polyfunctional molecule, predict the water solubility for each of these
compounds using the empiric method of Lemke:
Functional Group
Alchohol
Monofunctional
Molecule
5-6 Carbons
Polyfuncational
Molecule
3-4 carbons
phenol
6-7 Carbons
3-4 Carbons
Ether
4-5 Carbons
2 Carbons
Aldehyde
4-5 Carbons
2 Carbons
Ketone
5-6 Carbons
2 Carbons
Amine
6-7 Carbons
3 Carbons
Carboxylic acid
5-6 Carbons
3 Carbons
Ester
6 Carbons
3 Carbons
Amide
6 Carbons
2-3 Carbons
Urea, carbonate,
carbamate
2 Carbons
N.B:

Each charge on a molecule, anionic or cationic contributes to the solubility of 20-30
carbons.
1-Aspirin:
Funtional Group
Value
1 Carboxlic acid
3
Total
6
1 Ester
3
Number of carbon atoms
9
So the drug is water insoluble because the carbon solubilizing potential is
less than carbon number.
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Medicinal Chemistry
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2-Betaxolol
3-
Funtional Group
Value
1 Amine
3
Total
10-11
1 Alcohol
3-4
Number of carbon atoms
18
2 Ether
4
So the drug is water insoluble because the carbon solubilizing potential is
less than carbon number.
4-
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5-
6-
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7-
8-
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The hydrophobicity constant (π)
Hansch constant
Guided by the following table that represents hydrophilic/lipophilic values of different
atoms and functional groups. Calculate logP value for each of the following compounds:
1-Aspirin:
Fragment
π value
Fragment
π value
1 Carboxylic acid
-0.7
1 Aliphatic Carbons
+0.5
1 Ester
-0.7
LogP
+1.1
1 Phenyl
+2.0
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2-
3-
4-
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5-
6-
7-
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8-
9-
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Case Study
Case 1
Each of these drug molecules interacts with different biological targets and elicits a unique
pharmacologic response. For each of these molecules, point out and name the sites of
different types of non-covalent bonding that could be formed with the target receptor.
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Case 2
When you look at any drug molecule, there are a number of functional groups that
contribute to the properties of that drug molecule. Analyze the following structures and
assign the different hydrophilic and lipophilic parts in the structure.
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Case 3
A long-distance truck driver comes into the pharmacy complaining of seasonal allergies. He
asks you to recommend an agent that will act as an antihistamine but that will not cause
drowsiness. He regularly takes an antacid for indigestion because of the bad food that he
eats while on the road.
1.
a) Calculate log P value of each drug guided by the previous table that represents
hydrophilic/lipophilic values of different atoms and functional groups?
b) Based on your answers, provide a rational for whether the truck driver should be
taking cetrizine or clemastine?
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2.
Summer course 2016
The pKa value of cetrizine is 2.9 and its % ionization is 11.2% in the stomach (pH ~
2). The antacid neutralizes stomach acid to pH = 3.5. Determine whether the truck driver
will get the full antihistaminergic effect if he takes his antihistamine with the antacid at the
same time. Provide a rational for your answer?
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Case 4
The nurse in the hospital pharmacy gets an order for a patient that includes the two drugs
drawn below. She is unsure if she can mix the two drugs together in the same IV bag and is
not certain how water soluble the agents are.
1.
What is the chemical consequence of mixing aqueous solutions of each drug in the
same IV bag? Provide a rationale that includes an acid base assessment?
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Case 5
A 24-year-old man comes into the pharmacy and asks you to recommend a treatment for the
itching and burning he has recently noticed on both feet. He indicates that he would prefer a
cream rather than a spray or a powder. Your recommendation to this patient is to use
terbinafine, a very effective topical antifungal agent that is sold over-the-counter.
1.
Identify the structural characteristics and the corresponding properties that make
terbinafine an agent that can be utilized topically?
2.
The biological target of drug action for terbinafine is squalene epoxidase. Consider
each of the structural features of this antifungal agent, and describe the type of interactions
that the drug will have with the target for drug action. Which amino acids are likely to be
present in the active site of this enzyme?
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Case 6
A mother presents a prescription for her 6-month-old daughter for pediatric drops that
contains:
Phenylephrine (decongestant)
Chlorpheniramine (antihistamine)
Guaifenesin (expectorant)
She wants to know if this medication will have an effect on her daughter's alertness.
1.
Identify the structural features/functional groups of phenylephrine and guaifenesin
that contribute to improved water solubility (medication given as drops). List the type(s) of
interactions that these groups have with water, and draw an example of these interactions
(with appropriate labels) below.
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2.
Summer course 2016
a) Determine the functional groups that will allow the drug to cross the blood-brain
barrier (have an effect on this child's alertness)?
b) Calculate log P value for each drug (guided by the previous table that represents
hydrophilic/lipophilic values of different atoms and functional groups)? Determine which
agent is likely to have the most significant effect on the alertness?
3.
Identify the binding interactions that chlorpheniramine and guaifenesin could have
with their respective targets for drug action?
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PART 3
Titrimetric Determination of Pharmaceutical
Preparations
Penicillins
Benzylpenicillin
Principle: (iodimetric assay)
Benzylpenicillin doesn’t react with iodine in neutral aqueous medium. In alkaline
medium, the alkaline penicillin is decomposed giving penicilloic acid which can be oxidized
by known excess standard iodine and the excess unused is back titrated against standard
sodium thiosulfate using starch as indicator.
Procedure:
 Reconstitute one vial of benzylpenicillin with water, transfer the solution into 200
mL measuring flask, wash the bottle three times with water, transfer the washing
into the measuring flask and complete to the mark with water.
 Transfer 5.0 mL into glass stoppered conical flask, add 5.0 mL 1.0 M NaOH and
stand for 30 minutes over a boiling water bath.
 Cool, and then add 7.0 mL 1.0 M HCl followed by 25.0 mL 0.02 M iodine.
 Allow to stand for 15 minutes then titrate the excess iodine against 0.02 M sodium
thiosulfate (Na2S2O3) using starch as indicator (starch is added when solution color
becomes straw yellow).
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:-
4 Moles iodine = 1 mole benzylpenicillin
iodine =
E.P =
1 mL
M iodine 
1
Benzylpenicillin
4
mL
M Na 2S2O 4
M.wt of benzylpenicillin x Molar ratio  Molarity
1000
1Mole of iodine = 2 mole Na 2S2O 4
%Purity  (25-
x Ep
100
)  factor  Dilution factor 
2
weight of vial
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Cephalosporines
Cephalexin
Principle:
Cephalexin doesn’t react with iodine in neutral aqueous medium. In alkaline medium,
the alkaline decomposition product can be oxidized by known excess standard iodine and
the excess unused iodine is back titrated against standard Na2S2O3 starch as indicator.
Cephalexin Oral Suspension (Ceporex 250 mg)
Procedure:
 Reconstitute the powder of the oral suspension with water to the mark of the bottle
(60.0 mL), transfer 5.0 mL into 250 mL measuring flask and dilute to mark with water.
 Transfer 5.0 mL into glass stoppered conical flask; add 5.0 mL 1.0 M NaOH then
stand for 20 minutes.
 Add 20.0 mL acetate buffer solution (to adjust pH at 4.6), 5.0 mL 1.0 M HCl followed
by 25.0 mL 0.01 M iodine and stand for 20 minutes.
 Titrate the excess unused iodine against 0.02 M Na2S2O3 using starch as indicator
(starch is added when solution color becomes straw yellow).
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:4 moles iodine  1 mole cephalexin
E.P =
1 mL
M iodine 
mL
M Na 2S2O 3
M.wt of cephalexin  Molar ratio x Molarity of iodine
1000
1 mole iodine  2 mole Na 2S2O3
% Purity  (25-
x Ep
100
)  Factor  Diltution factor 
2
weight taken
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Sulfonamides
Group I :
Acidic NH which can be assayed argentometrically
Group II :
Primary aromatic amino group can be assayed diazometrically,
bromometrically (direct or indirect)
1- Principle of Argentometric assay:
Sulfonamides have acidic properties as they contain acidic hydrogen thus react with
excess standard silver nitrate with the precipitation of silver salt and release of nitric acid.
The excess unused silver nitrate can be back titrated against ammonium thiocyanate
using ferric alum as indicator (Volhard method) or the released nitric acid can be titrated
against NaOH (acid-base titration).
(Excess unused)
Or
2- Principle of Indirect Bromometric Assay:
Sulfonamides react with excess standard bromine solution giving dibromo derivatives.
The excess unused bromine was reacted with potassium iodide to give equivalent amount of
iodine which can be titrated against sodium thiosulphate solution using starch as indicator.
Sodium tetrathionate
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3- Principle of Direct Bromometry:
It depends on direct titration of the sample with standard potassium bromate (KBrO3)
solution in the presence of potassium bromide in acidic medium (Conc. HCl).
In acidic medium, KBrO3 oxidize bromide into bromine which reacts with
sulfonamides and at the end point the first excess of bromine oxidize the indicator (methyl
red or methyl orange).
4- Principle of Diazometric Assay:
The free basic amino group in sulfonamides can be diazotized with nitrous acid
produced in situ using mixture of NaNO2/HCl to give the corresponding diazonium salt. The
end point can be detected using either external indicator such as potassium iodide starch
paper or internal indicator such as metanil yellow.
Notes:
 This titration must be carried out in ice bath to achieve stability of nitrous acid.
 The tip of the burette must be kept under the surface of the solution to prevent escaping
of nitrous acid.
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Determination of ZnSO4/Sulfacetamide sodium
A- Sulfacetamide sodium (Molecular weight of sulphacetamide sodium = 254)
Procedure:
 Transfer 10.0 mL sample into a glass conical stoppered flask, add 25.0 mL 0.05 M
Br2 and 2.0 mL Conc. HCl.
 Stand for 15 minutes then add 10.0 mL 10% potassium iodide solution.
 Titrate the liberated iodine against 0.05 M Na2S2O3 using 1 mL starch as indicator.
B- Zinc Sulfate
(Molecular weight of ZnSO4.7H2O = 287)
Procedure:
 Transfer 10.0 mL sample solution to a glass conical flask, add 10.0 mL distilled
water and 2.0 mL ammonia buffer solution (pH = 10.0)
 Titrate against 0.05 M EDTA (Ethylene Diamine Tetraacetic Acid) using few
specks of Eurochrome Black T (E.B.T.) indicator
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
A- Sulfacetamide sodium
Results and calculations:2 moles Br2  1 mole sulfacetamide sodium
Br2 
1
sulfacetamide sodium
2
E.P.=
1 mL 0.05 M Br2 
mL
Na 2S2O3
M.wt of sulfacetamide sodium  Molar ratio x Molarity
1000
1mole Br2  1mole I 2  2 moles Na 2S2O3
Na 2S2O3 
Concentration  (25-
1
Br2
2
x Ep
100
)  factor 
2
volume taken
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
B- Zinc Sulfate
Results and calculations:-
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Assay of zinc undecenoate
Product formula C22H38O4Zn
Molecular weight 431.9
Action and use
Zinc undecenoate is used topically in treatment of fungal infections.
Zinc undecylenate is an antifungal agent with uses similar to those of
undecenoic acid. It is used to treat or prevent athlete’s foot. It usually used in
combination with undecenoic acid to kill the fungus and the germs that lead to the
symptoms of athlete’s foot.
Definition: Zinc di(undec-10-enoate).
Content: Zinc undecylenate contains not less than 98.0 per cent and not more than
the equivalent of 102.0 percent of zinc di(undec-10-enoate), calculated with reference
to the dried substance.
Solubility: Practically insoluble in water and in ethanol (96 per cent).
Assay: Carry out the complexometric titration of zinc.
Procedure:
 Transfer 10.0 mL sample to a glass conical flask, add 10.0 mL distilled water
and 2.0 mL ammonia buffer solution (pH 10.0).
 Titrate the mixture against 0.01 M EDTA solution using few specks of
Eurochrome Black T (E.B.T.) indicator till pure blue color was obtained.
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Calculation:
1 mole EDTA  1 mole Zinc undecenoate
1 mL
M EDTA =
M.wt of Zinc undecenoate x Molar ratio x Molarity
1000
=
g Zinc undecenoate
E.P =
mL
% Conc. = EP x Factor x
=
EDTA
100
Volume taken
g%
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Propylparaben
 Used as preservative.
Principle:
It depends on hydrolysis of the ester using known excess of standard alkali and the
excess unused alkali is back titrated against standard acid using phenolphthalein indicator.
NaOH+ HCl
NaCl + H2O
Procedure:
 In a beaker, 0.5 g propylparaben powder is heated with 25.0 mL 1.0 M NaOH over a
boiling water bath for 30 minutes.
 Transfer the contents of the backer into a 100 mL measuring flask, wash the beaker with
few mL of water and transfer the washing to the measuring flask and complete to the
mark with water.
 Transfer 10.0 mL of the solution into a conical flask, add 10 drops of phenolphthalein,
and titrate against 0.2 M HCl.
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:-
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Betadine
(Povidone iodine)
2-Pyrrolidinone-1-ethenyl polymer compound iodide
It’s a complex of iodide with povidone. It is used as antiseptic solution and used preoperation to prevent wound infection.
Advantages: Non-staining and non-irritant.
Principle:
a) Determination of total iodide:
 By adding drops of sodium bisulfite (NaHSO3) till the brown color of the iodine
disappears where iodine is converted into iodide.
 Then the total iodide is treated with known excess standard AgNO3 and the excess
unused AgNO3 is back titrated against standard NH4SCN using ferric alum as
indicator.
b) Determination of available iodine:
 Stirring of betadine sample for 1 hour then titrated against standard Na2S2O3 using
starch as indicator.
Total I2-available iodine = iodide in the complex (officially not more than 6.6%)
Determination of available iodine in betadine sample:
Procedure:
 Transfer 10.0 mL betadine sample into glass stoppered conical flask, add 10.0 mL water
and titrate against 0.05 M Na2S2O3 using 1.0 mL starch as indicator.
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:-
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Isoniazide (INH)
It is used for treatment of tuberculosis
Principle: (Indirect Bromometry)
Oxidation of INH with known excess standard Br2 will give isonicotinic acid and the
excess unused Br2 can be determined by adding 10% KI to liberate equivalent amount of
iodine which can titrated against standard Na2S2O3 using starch as indicator.
Excess unused
Procedure:
 Transfer 10.0 mL of the sample into glass stoppered conical flask, add 25.0 mL
0.05 M Br2 and 2 mL conc. HCl.
 Stand for 15 minutes then add 10.0 mL 10% KI solution.
 Titrate the liberated iodine against 0.05 M Na2S2O3 using 1.0 mL starch as
indicator.
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:-
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Busulphan
(Anticancer alkylating agent)
1,4-Butanediol dimethanesulfonate ester
Principle:
Busulphan undergoes hydrolysis by heating with water to give two molecules of
methanesulfonic acid and one molecule of 1,4-butanediol. The produced methanesulfonic
acid is highly acidic and could be titrated against standard sodium hydroxide.
Procedure:
 Transfer 10.0 mL busulphan sample into a glass conical flask; add 10.0 mL water
and warm gently for 5 minutes.
 Cool and titrate against 0.1 M NaOH using 10 drops phenolphthalein indicator.
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Laboratory Report
Results and calculations for ….…………………………………
Group: ……………….………
Student Name: ……………………………….…………………………………
Student No.:- ………………
Results and calculations:-
1 mole busulfan  2 mole methane sulfonic acid  2 mole NaOH
1 mole NaOH 
1 mL
M NaOH =
1
mole busulfan
2
M.wt of busulfan x Molar ratio x Molarity
1000
=
g busulfan
E.P=
mL
% Conc. = EP x Factor x
=
NaOH
100
Volume taken
g%
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Problems
a. Calculate the number of grams of sulfacetamide sodium equivalent to 1.0 mL of 0.02 M
KBrO3. (M. wt. of sulfacetamide sodium = 254).
b. Calculate the number of mL of 0.1 M Br2 consumed by 10.0 mL of sulfacetamide
sodium sample (0.7 %). (M. wt. of sulfacetamide sodium = 254).
c. Calculate the number of grams of busulphan equivalent to 1.0 mL of 0.1 M H 2SO4. (M.
wt. of busulfan= 246).
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d. Calculate the number of mL of 0.01 M silver nitrate consumed in the assay of 10.0 mL
of sulfacetamide sodium (0.45%). (M. wt. of sulfacetamide sodium= 254).
e. In the determination of a sample of propylparaben powder, a weight of 0.5 g of the
powder was heated with 25.0 mL 1.0 M NaOH, then transferred to a 100.0 mL
measuring flask and completed to the mark with water. A volume of 10 mL of the latter
solution was titrated against 0.2 M HCl and 9.5 mL were consumed in the titration. What
is the %purity of propyl paraben powdered sample (M. wt. of propyl paraben= 180).
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f. In the assay of cephalexin oral suspension (99% w/w purity), 5.0 mL equivalent to 250
mg cephalexin were hydrolyzed and determined iodimetrically. Calculate the number of
mL of 0.2 M iodine consumed in the assay. (M. wt. of cephalexin= 347).
g. In the determination of sulfacetamide sodium eye drops by the indirect bromometric
method, a volume of 10.0 mL of the eye drops was completed to 100.0 mL with water,
and 10.0 mL of the diluted solution were treated with 25.0 mL of 0.05 M Br2. If 8.0 mL
0.1 M Na2S2O3 was consumed, find the % concentration of the eye drops. (M. wt. of
sulfacetamide sodium= 254).
h. Calculate the number of mL of 0.5 M iodine consumed by penicilloic acid produced
after alkaline hydrolysis of 0.5 g of benzyl penicillin sodium (99 % w/w purity). (M. wt.
of benzyl penicillin sodium = 356).
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PART 4
"Antifungal drugs"
Case 1
MJ is a 67-year-old male heart transplantation patient receiving immunosuppressive
therapy (cyclosporine and corticosteroids) who was readmitted to the hospital 2 months
after his surgery, complaining of fever, malaise, joint pain and painful oral lesions (white
plaques). Cardiac output and renal function tests were normal, indicating that there were no
signs of tissue rejection. A chest radiograph revealed diffuse lung infiltrates. Blood and
throat cultures yielded Candida albicans. Therapy was initiated for MJ with amphotericin B
by slow IV infusion. After 20 hours, severe thombophlebitis developed near the injection
site. Although miconazole (4) is available for IV administration, the cardiologist was
reluctant to use it.
Structure (1)
Structure (2)
Structure (3)
Structure (4)
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Question 1:
Describe the injectable form of miconazole (4). What is the basis for the physician’s
reluctance to administer it to this patient?
The correct answer is:
Question 2:
Select, from the imidazole antifungal structures (1-3) given, the most appropriate one
for IV administration to this patient. Justify your choice based on structure/solubility
properties.
The correct answer is:
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Case 2
W.U is 5 years old, she complained from skin infection. Her mother took her to
dermatologist. She told him that infection started week ago. The doctor diagnosed her taenia
pedis.
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Question 1:
Identify and comment on mode of action for different drugs.
The correct answer is:
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Question 2:
Suggest one of the provided drugs which could be used as drug of choice and which of
them could be used orally for treatment of topical infection?
The correct answer is:
Question 3:
Select, from the imidazole antifungal structures (1-3) given, the most appropriate one
for IV administration to this patient. Justify your choice based on structure/solubility
properties.
The correct answer is:
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Tetracyclines
Case 1
JS visits his physician complaining of a fever, stiffness of the neck and other joints, a
low-grade headache, and general fatigue. He further states that the symptoms started about 2
week ago and have been constant during that time. He states that he initially thought he
might have caught a cold or the flu during his annual camping trip with his old army
buddies; however, since the symptoms have not dissipated, he is now concerned that these
symptoms could be associated with recently diagnosed problems with his kidneys. A routine
examination 4 months before this visit revealed abnormal creatinine levels and a low
glomerular filtration rate, along with other laboratory results indicative of the early stage of
renal failure. At present, his renal status is being monitored monthly, and he has been placed
on Amphogel (aluminum hydroxide suspension), 15 ml po with meals. JSʼs physician
suspect that his current symptoms are unrelated to his renal problem but could be due to
lyme disease, which could have been contracted during his company trip. The use of
tetracycline to treat early stage of lyme disease has been shown to decrease the duration of
symptoms and to prevent any major complication.
Tetracycline (1)
Doxycycline (2)
Question 1:
What is the mechanism of action of the tetracyclines in the treatment of lyme disease?
The correct answer is:
Question 2:
Which of the two tetracyclines shown (1-2) would be the best choice for this patient?
Explain your answer based on the chemical differences between these two compounds
The correct answer is:
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Question 3:
What is the purpose of using Amphogel in this Patient?
The correct answer is:
Question 4:
Why does the addition of either drug (1) or drug (2) to this patient’s drug regimen
require the pharmacist to help the patient establish a proper dosing schedule?
The correct answer is:
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Case 2
Rk a15-year-old adolescent girl, with a severe case of acne, come to your community
pharmacy with a prescription for oxytetracycline (1). After consulting her patient profile
card, you find she also has a gastric hyperacidity disorder that causes intermittent distress
sever enough to warrant medication with an antacid: Mylanta (aluminum hydroxide and
magnesium hydroxide). Mylanta is her OTC drug of choice. Compliance has been a
problem with this woman when taking medication in the past, and she claims she ‘’just does
not remember to take her pills when she is supposed to’’. You check your inventory and
find tetracycline product 1 to 4 on hand.
Structure (1)
Structure (2)
Structure (3)
Question 1:
Discuss the antibiotic potency and duration profile of each of this molecules based
upon their chemical structures.
The correct answer is:
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Question 2:
Discuss the potential drug-drug interaction between any of tetracycline structure and
the Mylanta taken intermittently by this patient. What professional advice would you
provide if both drugs needed to be taken?
The correct answer is:
Question 3:
Which tetracycline structure (1- 3) would be most stable in this patient stomach during
hyperacidity ‘flare-up’? For one molecule not selected, diagram the mechanism of acidcatalyzed drug decomposition and show the final inactive product that could form.
The correct answer is:
Question 4:
Based on all of the preceding, would you dispense the original agent or call the
physician to discuss substituting one of the alternative agents?
The correct answer is:
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Macrolides
Case 12
Tw is a 14-year-old boy diagnosed in a local emergency room with ‘’walking
pneumonia’’ and prescribed erythromycin (1) 250 mg po qid. His father is concerned about
cost, as the family has no prescription plan and must pay for all drugs. He is additionally
troubled when you explain that nausea, vomiting, abdominal cramps and diarrhea are
relatively common side effects of therapy with erythromycin (1), because his son has a
sensitive stomach. you mention two expensive alternatives, clarithromycin (biaxin) (2) and
azithromycin (zithromax) (3) that produce minimal to negligible gastrointestinal upset. as
you prepare to dispense erythromycin (1),you ask whether TW has any other medical
problems. As Mrs. W supervises TW’s other medication, Mr. W only know that his son has
asthma and ‘’hayfever‘’ treated with prescription prescribed by his pediatrician. A computer
check show TW receives cromolyn sodium (nasalcrom) 2 puffs bid, albuterol (ventolin) 2
puffs qid prn, terfenadine (seldane) 30 mg qhs, and theophylline (theo-dur) 200 mg bid.
Structure (1)
Structure (2)
Question 1:
Discuss structural changes and mechanism of action of these three macrolides (1-3)
relative to antimicrobial potency under acidic conditions and gastrointestinal side effect.
The correct answer is:
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Question 2:
Is the cost differential significant enough for the three agents to warrant a trial of
erythromycin (1) as prescribed?
The correct answer is:
Question 3:
What problems can you foresee from this limited medication history? of what
significant, if any, are the concurrent drugs?
The correct answer is:
Question 4:
Give another derivative to overcome the side effect of erythromycin.
The correct answer is:
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Sulfonamides
R.M is a 45-years old woman with Ocular pain. She complains from irritation, redness
in eye. She asks the physician to recommend for her the suitable drug. From the medicinal
chemistry point of view, select the most suitable sulfa drug for this case from the following
list of drugs and justify your selection.
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Question 1:
From the medicinal chemistry point of view, select the most suitable sulfa drug for this
case from the previous list of drugs and justify your selection.
The correct answer is:
Question 2:
Classify other drugs according to duration of action.
The correct answer is:
Question 3:
Discuss the mechanism of action of sulfa drugs.
The correct answer is:
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Penicillins
A 56-year-old male chemistry professor, who has recently had a squamous cell
carcinoma removed from his upper torso at the university dermatology clinic, returns to the
clinic complaining that surgical wounds has become infected. The wounds is tender red and
swollen and on manipulation releases large amount of creamy yellow pus. A grams stain
reveals large No. of gram-positive cocci in clumps. Culture and sensitivity results will be
available in 48 hours. Since the professor is otherwise healthy and insists that, he has classes
to teach, the attending dermatologist decides to treat him on an outpatient basis using a
penicillin derivative.
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Structure (5)
Structure (6)
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Question 1:
What is the likely causative organism in this case?
The correct answer is:
Question 2:
What is the initial treatment should be instituted? Select the more appropriate
penicillin from the structures (1-6) provided. Justify your choice based on the properties of
each.
The correct answer is:
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Anticancer drugs
Case 1
A 45-year old woman with ovarian cancer was treated every 21 days with the
following chemotherapy regimen:
Cyclophosphoramide (1) 1000 mg/m2 IV
Cisplatin (2)
50 mg/m2 IV
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Question 1:
What are the mechanisms of antitumor action for cyclophosphoramide (1) and
cisplatin (2)? Explain why transplatin is inactive as an antitumor agent even though it binds
to DNA in vitro.
The correct answer is:
Question 2:
After the third course of chemotherapy, the patient develops renal complications. Her
oncologist decides to use another related compound in place of cisplatin (2) which of the
drugs (3 or 4) should be used, and why?
The correct answer is:
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Question 3:
The patient’s tumor progress despite completion of the previously described
chemotherapy regimen. Her physician decides to initiate drug (6) therapy, 135 mg/m2 every
21 days. What is the mechanism of action of drug (6)? How does it differ from using drug
(5) as anticancer agent?
The correct answer is:
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Case 2
IR, a 65-year-old woman new to your community, has a history of mild congestive
heart failure being controlled with quinapril. She has recently been diagnosed with breast
cancer, and she is about to start a course of intravenous therapy at an outpatient clinic. One
of the antitumor agents in her regimen is the anthracycline molecule as shown in structure
(1). IR is taking a holistic approach to her treatment, and she has purchased several OTC,
vitamin supplements, one of which contains ferrous sulfate (structure (2)).
Structure (1)
Structure (2)
Question 1:
What are the mechanisms by which anthracyclines, like structure (1), exert their
antineoplastic activity?
The correct answer is:
Question 2:
What problems are inherent in this clinical situation?
The correct answer is:
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Question 3:
Can you suggest an alternative anthracycline-based antitumor agent that would be less
cardiotoxic?
The correct answer is:
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Case 3
JM, a 86-year-old woman, was recently diagnosed with non-Hodgkin's lymphoma.
Immediately after diagnosis, she was treated with the following therapeutic regimen known
as M-BACOD:
Methotrexate, Leucovorin, bleomycin, adriamycin-doxorubicin, cyclophosfamide,
oncovin-vincristine, dexamethasone
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Question 1:
What is the target enzyme for the action of methotrexate (1)? Encircle the part
responsible for the binding.
The correct answer is:
Question 2:
What effects are produced in cancer cells because of the action discussed in 1?
The correct answer is:
Question 3:
What is leucovorin (2) rescue? Why it is appropriate in this particular case?
The correct answer is:
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Case 4
KO, a 37-year-old premenopausal mother of 3, has recently been diagnosed with
breast cancer. A biopsy revealed that the mass detected by routine mammography was
malignant. Through further testing, it was also determined that several lymph nodes were
involved. Her oncologist suggested surgery to remove the primary tumor and affected
lymph nodes, followed by systemic chemotherapy. The chemotherapy prescribed included a
combination of 5-flurouracil (1) and cyclophosfamide (2). The patient was educated about
the side effects of this type of drug therapy and a given series of appointments for the
chemotherapy.
Structure (1)
Structure (2)
Structure (3)
Structure (4)
Question 1:
What is the mechanism of action for each of these chemotherapeutic agents? Include
in your answer the appropriate chemical steps relevant to the activation and mechanism of
action of each drug.
The correct answer is:
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Question 2:
In the primary literature, it has been shown that drug (3) increases intracellular folate
concentrations. If drug number (3) was added to this combination, would this affect either of
the drugs prescribed? If so, describe how each drug might be affected.
The correct answer is:
Question 3:
The oncologist decided to add drug (4) to the original 5-flurouracil/cyclophosphamide
combination. What is the purpose of using 5-flurouracil and leucovorin in combination? In
your answer be sure to include the mechanism of action of leucovorin.
The correct answer is:
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Evaluation Sheet
Student's name: ....................................................................................................................................
Student's number: ....................................................................................................................................
Lab
Date
Lesson
Mark
Signature
1
2
3
4
5
6
7
8
9
10
11
12
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