Ms.

Reysa Gabilogon
PHARMACEUTICAL CHEMISTRY
INTRODUCTION

Organic Medicinal Chemistry

- the practice of medicinal chemistry that is devoted to the discovery
and development of new drugs.
we should learn the existing drugs how they develop it what disinte
part of their sturcture is responsible for that specific effect. gration is breaking down the dosage form into smaller pieces into finer
particles.
Drug After disintegration magundergo siya ng dissoution
- an agent intended for use in the diagnosis, mitigation, treatment, dissolution- madisolve siya. Should be turn to solution before
cure, or prevention of disease in humans or in other animals makamove on kay abrsoption.

Receptor
- a substance to which a drug needs to interact with to elicit a I. Absorption
pharmacological response. - the transfer of a drug from its site of administration to the systemic
- 90% proteins, 10%some are nucleic acids and lipids circulation (or to the bloodstream)

Affinity  Chemical structure

- ability of drug to bind to the receptor sila nagadictate if papasukin or hindi.
if the drug very big molecule (remember yung mga
Intrinsic activity methods mga absroption) cannot have the passive
- ability of a drug to exert a pharmacologic action diffusion. it will be difficult to pass in the cell membrane
(semi permable sila so di lahat makapasok)
Agonist  Variation in particle size – dictates the particle sizes
- Affinity + Intrinsic activity  Nature of the crystal form (Am orphous > Crystalline)
the drug able bind to the receptor, then after binding may amorphous - walang order, madaling mabreak. mabilis
pharmacologic effect maabsoption
crystalline- may order and formation. matagal ibreak down,
Antagonist/Blocker matagal maabsoption.
- Affinity only Sa insulin yang lente
the drug able bind to the receptor but no pharmacologic effect  Ultra-lente = 100% crystalline (long-acting) -matagal na
response whole day na, subcutaneously
 Lente insulin = 70% crystalline, 30% amorphous
(intermediate) Intravenous
 Semi lente = 100% amorphous (short-acting) yung gina 3x
day before magkaon para dili magshoot up ang sugar,
subcutaneously
 Type of tablet coating
sugar coating- para sa mga AI na bitter or dili pleaset. Ex.
ferric sulfate (lasang balak)
interecoated - design to disintergate and dissolution in the
Allosteric site intestine. For sensitive to acid na drugs.
- site other than the binding site film coated - not really affected sa gastric acid
 Blood flow to the absorption site
FOUR FUNDAMENTAL PATHWAYS OF DRUG  Total surface area available for absorption
PHARMACOKINETICS  Contact time at the absorption surface

LADMERT Bioavailability
L- liberation - the fraction of administered drug that reaches the systemic
A- Absorption circulation in a chemically unchanged form (f)
D- Distribution the amount of drug that reaches the blood. true of IV na 100%
M- Metabolism bioavailablilty sa iba hindi na.
E- Excretion (it involved metabolism and elimination)
R- Responce II. Distribution
T- Toxicity - the process by which a drug reversibly leaves the bloodstream and
enters the interstitium (extracellular fluid) and/or the cells of the
Lideration - release of the active ingredient from the dosage form. not tissues
all drug doesnt need liberation example sa IV. The one who really
need it is the oral tablets because it has AI + excipients. Plasma Protein Binding (parang magnet)
- serves as a reservoir
- Albumin - binds acidic drugs
- α-1-acid-glycoprotein - binds basic drugs
- may limit access to certain body compartments
- Prolongs drug duration of action
Awitan & Munar Noctureous, partial beneficial
GSDMSFI | BS Pharmacy 3
 - The CYP enzymes are heme proteins. The heme portion is an iron-
III. Metabolism containing porphyrin called protoporphyrin IX, and the protein portion
- converts drugs into polar form, water-soluble products that are is called apoprotein.
readily excretable
-involves detoxification process (kanang gina inactived ang drug) but Example
not all the time. Oxidation of Alcohols
Primary = Aldehyde = Carboxylic Acid
Prodrugs Secondary = Ketone
- compounds that are inactive in their native form, but are easily
metabolized to the active agent
Ex:
- Enalapril to Enalaprilat
- Chloramphenicol palmitate to Chloramphenicol
- Primidone to Phenobarbital
- Phenacetin to Paracetamol Always Asian ang mga mapula or redness. Kulang sila sa enzymes na
aldehyde dehydrogenase or slow lang.
First Pass effect
- drugs may be metabolized by hepatic enzymes to inactive chemicals
(drug is metabolized prior to absorption)
- only drugs administered orally and rectally undergo first pass
metabolism (CYP 450) Antidote: ethanol
- Ex: Nitroglycerin
Reduction
IV. Excretion - plays an important role in the metabolism of many compounds
- the main route of excretion of a drug and its metabolite is through the containing carbonyl, nitro and azo group
kidney (for LMW & polar drugs) - carbonyl compounds are converted to alcohol derivatives while nitro
- Other types: Biliary/Fecal, Breastmilk, Sweat (for HMW & lipophilic and azo are converted to amino derivatives
drugs) Baliktad ang reaction.

Enterohepatic Recirculation Example

- drugs emptied via the bile duct into the small intestine can be - Reduction of Aldehydes and Ketones to Alcohol
reabsorbed in the intestinal lumen back to systemic circulation - Chloral Hydrate --> Trichloroethanol (date rape drug or knock out
drop)
Metabolic Changes of Drugs and Related Organic Compounds
Hydrolysis
General Pathway of Drug Metabolism - for drugs containing the ester/amide functionality
Phase 1 Water ang nagreact. RCOOH - carboxylic
- also known as Functionalization reactions RCOOR -ester, RCONH2- amide. Drugs may ester ginametabolism
- Include: Oxidative, reductive and hydrolytic biotransformations sa body using hydrolysis.
- Purpose is to introduce a functional polar group(s) (Ex: OH, COOH,
NH2, SH) into the xenobiotic molecule to produce a more-water
soluble compound.
COOH- carbonyxl, NH2 - amino; SH- thiol or slfhydryl

Oxidation Example:
- Mixed Function Oxidase System
- Cytochrome P450 (wavelength) If may water mabreak ang beta lactam ring
- responsible for transferring an oxygen atom to the substrate
- contains iron and copper

Example
- CYP3A4 - most dominant isoform of Cytochrome P450 in the liver.
pinakamaraming klasing CYP450 sa liver. Daghan siya na drug na
pwede imetabolize
- CYP2D6 – antidepressants If ang betalactam ring sa penicillin and cephalosporin masira wala
Specific siya, responsible na enzymes na magmetabolise sa nang effect.
antidepressant
Phase 2
Cytochrome P450 Enzymes Nomenclature - also known as Conjugation Reactions
- CYP: Cytochrome P450 enzymes - Purpose is to attach small, polar, and ionizable endogenous
- Arabic Number: Family (CYP1, CYP2) compounds such as glucuronic acid, sulfate, glycine, and other amino
(Must have more than 40% identical amino acid sequence) acids to the functional handles of phase I metabolites or parent
- Capital Letter: Subfamily (CYP1A, CYP2C, CYP3A) compounds that already have suitable existing functional groups to
(Must have more than 55% identical amino acid sequence) form water-soluble conjugated products.
- Arabic Number: Individual enzyme in a subfamily (CYP1A2, Exception si INH (Isonazid) kasi mauna ang phase 2 sa phase 1
CYP2C9) but it has the same ending kay maging polar japon ang drug and
The CYP450 enzymes is mostly found in liver (produce in the readily excreted na siya.
liver) and you can also found them sa boung katawan. (small and - Conjugated metabolites are readily excreted in the urine and are
large intestine etc) bali main si liver. generally devoid of pharmacological activity and toxicity in humans.

GSDMSFI | BS Pharmacy 3
Example
- Methylation and Acetylation - terminate or attenuate biological Intestinal Mucosa
activity. Ang result mainactive ang biological activity sa drug. - important site especially for orally administered drug
- Glutathione (GSH) Conjugation - protects the body against contains CYP3A4 isozyme and P-glycoprotein that can capture drug
chemically reactive compounds and metabolites. and secrete it back into the intestinal tract.
Very beneficial, inactived the chemically active compounds and
metabolites sa drug or body. Purpose is protection from chemically First-Pass Effect
active substances. Produced by the liver, pampalinis, mga free - orally administered drugs pass through the liver and are susceptibe
radicals (O negative one). Ang free radicals mabuo depende sa to hepatic metabolism before reaching the bloodstream
kinakain and sa stress. If stress ka nagalabas ng free radicals can - can decrease oral bioavailability
cause sign of aging (eyebags, dark circle/wrinkles).
Purpose ni glutathione is linisan ang free radicals, Antioxidant. Drugs Metabolized Extensively by First-Pass Effect
Pwede din vitamins C and E. Ang C pagboost sa immune system
and E is for sign of aging like myra E. -Isoproterenol - Pentazocine
- Lidocaine - Propoxyphene
Reactions: - Meperidine - Propanolol
Glucuronidation - Morphine - Salicylamide
- Most common - Nitroglycerin
- Example drugs: Morphine, Paracetamol, Chloramphenicol (a
antibacterial antibiotic) (Gray Baby Syndrome). Life threating to Enzyme Induction Enzyme Inhibitors
babies. Antidote: Dialysis. Paracetamol is a safe drug and safe to Phenytoin Metronidazole
babies because it can be metabolism through a lot of ways. Phenobarbital Erythromycin
- Glucuronyl transferase Rifampicin Disulfiram
Chronic Alcoholism Isoniazid
Sulfate conjugation (Unang madevelop sa babies) Carbamazepine Cimetidine
- Well-developed in infants. Ketoconazole
- Ex: Paracetamol. Toxic dose: 4,000mg/day. Toxicity: sa liver Acute Alcoholism
(Hepatotoxicity). Every 4hrs ibigay 500mg x 6(Tablet) = 3000mg ang
pwede a day. Antidote: NAC - N-Acetyl Cysteine (Fluimucil) – source
of glutathione in the body, precursor, raw material para makaproduce BIOTECHNOLOGY AND DRUG DISCOVERY
og glutathione. Para macleanse ang sobra na paracetamol. Genetic Engineering
- the key techniques that unlocked the door to the biotechnology arena
Glycine & Glutamine Conjugation - also known as rDNA
- used to conjugate carboxylic acids - allows scientists to manipulate genetic programming, create new
- Ex: Benzoic acid to hippuric acid (More water soluble and more genomes, and extract genetic material (genes) from one organism and
excretable form of the drug) insert it into another to produce proteins.
Glutathione or Mercapturic Acid Conjugation RECOMBINANT DRUG PRODUCTS
- an important pathway by which chemically reactive electrophilic Hormones
compounds are detoxified - Human Insulin, Recombinant
- free radical scavenger - the first pharmacologically active biological macromolecule to be
Ex. Paracetamol produced through genetic engineering
- approved as treatment for Type 1 (Insulin-dependent) diabetes
Glutathione or GSH
- a tripeptide (glutamyl-cysteinylglycine) In history
- Insulin was isolated from bovine and porcine sources but their amino
Acetylation sequence differs from human insulin; thus, leading to immunological
- acetyl group utilized is supplied by acetyl CoA reactions in some patients.
- important for drugs containing primary amino groups
- Hydralazine (SLE), Isoniazid (Peripheral Neuropathy), Sulfonamides Examples of Recombinant Human Insulin
(crystalluria) Humulin® - produced using recombinant E. coli
- uses N-acetyltransferase enzyme Novolin® - S. cerevisiae, a yeast
- primary function is to terminate pharmacological activity and
detoxification GLUCAGON
- GlucaGen®
SLE (Systemic Lupus Erythematosus) - Approved for use in hypoglycemia (causes the liver to convert
- autoimmune disease; more common in female glycogen to glucose) and as radiological diagnostic aid (relaxes
- antigen and antibody complex smooth muscles in GIT, decreasing GI motility and improving the
- SLE-like symptom - "Malar Rash or Butterfly Rash" quality of radiological examinations).
- PIMCH - Procainamide, Isoniazid, Methyldopa, Chlorpromazine, - The rDNA drug has the benefit that there is no chance of acquiring
Hydralazine bovine spongiform encepalopathy from glucagon therapy.
- Mad Cow Disease - caused by a prion that was suspected to infect
Methylation animal pancreas tissues.
inactivation of physiologically active biogenic amines
does not lead to polar or water-soluble metabolites but are Human Growth Hormone, Recombinant
pharmacologically inactive - hGH - a protein that is essential for normal growth and development
in humans
Liver - Somatrem - the first recombinant preparation
- the most important organ in drug metabolism and detoxification of
endogenous and exogenous compounds.
GSDMSFI | BS Pharmacy 3
Follicle-Stimulating Hormone - Recombinant GM-CSF - produced in S. cerevisiae
- Causes increased spermatogenesis in men binds to specific receptors on target cells and induces proliferation,
- Concert with estrogen and luteinizing hormone (LH) in stimulating activation and maturation
follicular growth and development in women - Administration to patients causes a dose-related increase in the
peripheral white blood cell count
Recombinant Products - Used to reconstitute the myeloid tissue after autologous bone
- Follitropin Alpha marrow transplant and following chemotherapy in acute myelogenous
- Follitropin Beta leukemia
- Decreases the incidence of infection, decreases the number of days
Thyrotropin Alpha that antibiotics are required, and decreases the duration of hospital
Human TSH - Thyrogen® stays
used as a tool for radioidine imaging in the diagnosis of thyroid cancer
Becaplermin
- Regranex Gel
an endogenous peptide that is released from the cells that are
involved in the healing process
- a recombinant human platelet-derived growth factor
- formulated as gel recommended for topical use in the treatment of
ulcerations of the skin secondary to diabetes

INTERFERONS
- secreted by eukaryotic cells in response to viral infection
- MOA: bimodal -- recruitment of natural killer (NK) cells to kill the host
cell harboring the virus
- Interferons then induce a state of viral resistance in cells in the
immediate vicinity, preventing spread of the virus.
- cytokines that mediate antiviral, antiproliferative, and
immunomodulatory activities

3 Classes of IFN
Alpha
CYTOKINES
Beta
- Interleukin-1 - maturation and proliferation of B cells; activation of
Gamma
NK cells, inflammation, fever
- Interleukin-2 - stimulates growth and differentiation of T-cell
Alpha-Interferon
response; use to treat cancer or transplant patients
are glycoproteins derived from human leukocytes
- Interleukin-3 - differentiation and proliferation of myeloid stem cells
- Interleukin-4 - switches B cells from IgG to IgE
Beta-Interferon
- Interleukin-5 - activates eosinophil
are glycoproteins derived from fibroblasts and macrophages
- Interleukin 6 & 7 - controls differentiation of T Lymphocytes
- Erythropoietin - stimulates red cell production
Gamma-Interferons
- Interleukin-9 - potentiates IgM, IgG and IgE; stimulates mast cells
- share a receptor with alpha-IFN
- are glycoproteins derived from human T lymphocytes and NK cells
Hematopoietic Growth Factors
- acid-labile and used to be called "type 2 interferon"
- Hematopoiesis - process of blood cells production
- Pluripotent Stem Cell - parent hematopoietic stem cell that can
Interferon Alfa-2A
differentiate into any other cell by proper stimulation.
- Roferon A®
- expressed in an E. coli system and purified by using high affinity
Erythropoietin Alfa
mouse MAb chromatography
- Recombinant Epoetin Alfa - Epogen®, Procrit®
- used in the treatment of hairy cell leukemia and AIDS-related Kaposi
- a glycoprotein produced in the kidney that stimulates red blood cell
sarcoma in selected patients older than 18 years of age
production
- Also used to treat chronic hepatitis C, and in patients with this
disease, it can normalize serum alanine aminotransferase (ALT)
- indicated to treat anemia of chronic renal failure patients, anemia in
levels, improve liver histology, and decrease viral load.
ZDV-treated HIV-infected patients, and in cancer patients taking
chemotherapy
Pegylated Interferon Alfa-2A
- Pegasys®
Filgrastim
a covalent conjugate of recombinant interferon alfa-2A with a singly
- G-CSF, Neupogen
branched bis-monomethoxy PEG chain
- stimulates the proliferation of granulocytes (especially neutrophils) by
- approved in the treatment of adults with chronic hepatitis C who have
mobilizing hematopoietic stem cells in the bone marrow.
compensated liver disease and who have not been previously treated
- Used in patients receiving chemotherapy with drugs such as
with interferon alfa.
doxorubicin, cyclophosphamide, doxorubicin, etoposide -- high
incidence of neutropenia and fever
Interferon Alfa-2B
- Intron A®
Sargromastim
- indicated for hairy cell leukemia, condyloma acuminata (genital
- Granulocyte-Macrophage- Colony-Stimulating Factor (GM-CSF),
venereal warts), AIDS-related Kaposi sarcoma, and chronic hepatitis B
Leukine
and C infections
- endogenous form is produced by T lymphocytes, endothelial
fibroblasts and macrophages
Interferon Alfa-n1
GSDMSFI | BS Pharmacy 3
- Wellferon® - TNF - first cytokine to be produced upon infection -- can cause
- a mixture of alfa-interferons isolated from human lymphoblastoid cell cytotoxicity and inflammation; and serves as a signal to adaptive
after induction with mouse parainfluenza virus type 1. immune response.
- indicated in the treatment of chronic hepatitis C in patients 18 years - indicated for reducing signs and symptoms and inhibiting the
of age or older who have no decompensated liver disease. progression in patients with moderately to severely active rheumatoid
arthritis
Interferon Alfacon-1
- Interfegen ENZYMES
- used in the treatment of chronic hepatitis C virus infection in patients
18 years of age or older with compensated liver disease and who Blood-Clotting Factors
have anti-HCV serum antibodies or HCV RNA Tissue Plasminogen Activator
- Alteplase (Activase) - rtPA
Interferon Beta-1a - used to improve ventricular function following an acute myocardial
- Avonex infarction, including reducing the incidence of CHF and decreasing
- indicated for the treatment of relapsing forms of MS mortality
- used to treat acute ischenic stroke after CT scan or other diagnostic
Interferon Beta-1b imaging has ruled out intracranial hemorrhage
- Betaseron - used in cases of pulmonary thromboembolism and is being
- administered SC to decrease the frequency of clinical exacerbation investigated for unstable angina pectoris
in ambulatory patients with relapsing-remitting multiple sclerosis
(RRMS) Reteplase
-Retavase
Interferon Gamma-1b - considered a third-generation thrombolytic agent and has a
- Actimmune mechanism of action similar to that of alteplase
- indicated for reducing the frequency and severity of serious - acts directly by catalyzing the cleavage of plasminogen and initiating
infections associated with chronic granulomatous disease, an thrombolysis
inherited disorder characterized by deficient phagocyte oxidase
activity Tenecteplase
tPA produced by recombinant CHO cells
THE INTERLEUKINS
Factor VIII
Aldesleukin - Antihemophilic factor VIII (recombinant) - Recombinate, Kogenate,
- indicated for the treatment of metastatic renal cell carcinoma in Bioclate, Helixate
adults; acute myelegenous leukemia and adjunct therapy in the - used in the treatment of Hemophilia A (congenital disorder
treatment of Kaposi sacrcoma characterized by bleeding)

Denileukin Diftitox Clotting Factor IX

- indicated for the treatment of persistent or recurrent cutaneous T-cell - Christmas Factor
lymphoma whose malignant cells express the CD25 component of the - indicated for the control and prevention of hemorrhagic episodes in
IL-2 receptor persons with hemophilia B (Christmas disease), including the control
and prevention of bleeding in surgical procedures
Oprelvekin
- indicated for the prevention of severe thrombocytopenia; Anticoagulant
- it reduces the need for platelet transfusions after myelosuppressive Lepirudin
chemotherapy in patients with nonmyeloid malignancies who are high - from leeches (Hirudo medicinalis)
risk for severe thrombocytopenia - used to prevent thrombosis in the microvasculature of reattached
digits
Tumor Necrosis Factor
- Etanercept, Enbrel
ANTI-INFECTIVE AGENTS

History
-Joseph Lister (1876) introduced antiseptic principles for use in -Heavy metals were also used but had severely limited
surgery and posttraumatic injury usefulness because of toxicities
-He used PHENOL (Carbolic Acid) as wash for the hands, as a
spray on an incision site, and on bandages applied to wounds Selective Toxicity
-Paul Ehrlich - worked with a set of antibacterial dyes and -the property of certain chemicals to kill one type of organism
antiparasitic organic arsenicals while not harming the other
-His goal was to develop compounds that retained antimicrobial
activity at the expense of toxicity of human host - "Magic Germicides
Bullets" -anti-infective agents that are used locally
-Paul Ehrlich discovered Compound 606 (also known as
Antiseptics
arsphenamine, salvarsan), an antisyphylitic agent
-are compounds that kill (-cidal) or prevent the growth (-static)
-Dyes such as Gentian Violet and Methylene blue were used
of microorganisms when applied to living tissue
as anti-infectives

GSDMSFI | BS Pharmacy 3
Ideal Properties of Antiseptic • Alcohols and aldehydes - used as antiseptics and
-Low-enough toxicity that it can be used directly on skins and disinfectants
wounds • Antibacterial potencies of the primary alcohols (against
test cultures of Staphylococcus aureus) increase with
-Exert a rapid and sustained lethal action against
molecular weight until the 8-carbon atom (octanol)
microorganisms • Increased primary alcohol chain length increases =
-Low surface tension so that it will spread into the wound Van der waals interactions increase = increased abilitiy
-Should retain activity in the presence of body fluids, including to penetrate microbial membranes (more potent)
pus • Water solubility decreases = apparent antimicrobial
-Non-irritating, non-allergenic, lack systemic toxicity when potency diminishes with molecular weight.
applied to skin or mucous membranes and does not interfere • Branching of alcohol chain decreases antibacterial
potency (weaker Van der Waals forces brought about
with healing
by branching do not penetrate bacterial cell
membranes)
Disinfectant • Primary > Secondary > Tertiary
-an agent that prevents transmission of infection by the
destruction of pathogenic microorganisms when applied to NOTE
inanimate objects • Isopropyl alcohol is slighlty more active than ethyl
alcohol against vegetative bacterial growth but both are
Ideal Disinfectants ineffective against spores
-Exert rapidly lethal action against all potentially pathogenic
microorganisms and spores MOA
-Have good penetrating properties into organic matter. • Denaturation of important proteins and carbohydrates
-Share compatibility with organic compounds (particularly
Alcohol, USP
soaps)
• Ethanol, Ethyl Alcohol, Wine Spirit, Spiritus vini
-Not inactivated by living tissue
rectificatus, Grain Alcohol
-Noncorrosive • Contains 95% ethanol by volume
-Aesthetically pleasing (nonstaining and odorless) • Fermentation product from grain and other
carbohydrates sources
Antisepsis • "Alcohol" - substance known as ethyl alcohol, hydrated
-application of an agent to living tissue for the purpose of oxide of ethyl, or spirit of wine, from whatever source
preventing infection or whatever process produced, having a proof of 160
or more and not including the substances commonly
known as whiskey, brandy, rum or gin.
Decontamination
• the most widely abused of all recreational drugs
-destruction or marked reduction in the number of activity of • widely used in pharmaceutical preparations
microorganisms • undergoes a series of oxidation reactions in vivo
• antidote: DISULFIRAM
Disinfection
-chemical or physical treatment that destroys most vegetative Denatured Alcohol
microbes or viruses, but not spores, in or on inanimate objects • ethanol that has been rendered unfit for use in
intoxicating beverages by the addition of other
Sanitation substances
-reduction of microbial load on an inanimate surface to a level • completely denatured alcohol contains added methanol
considered acceptable for public health purposes (wood alcohol) and benzene and is unsuitable for
either internal or external use (eye toxicity and bone
Sterilization marrow toxicity/ leukemia, respectively)
-a process intended to kill or remove all types of
Specially Denatured Alcohol
microorganisms, including spores, and usually including
• ethanol treated with one or more substances so that its
viruses with an acceptably low probability of survival
use may be permitted for a specialized purpose
• Ex: iodine in alcohol for tincture of iodine, methanol,
Pasteurization
and other substances in mouthwashes and aftershave
lotions, and methanol in alcohol for preparing plant
-a process that kills nonsporulating microorganisms by hot
extracts.
water or steam at 65 - 100°C
Primary Uses of Alcohol
Evaluation of the Effectiveness of a Sterilant
• external as an antiseptic, preservative, mild
counterirritant, or solvent.
Alcohols & Related Compounds
Rubbing Alcohol
GSDMSFI | BS Pharmacy 3
 • usually contains 70% ethanol
• astringent, rubefacient, refrigerant, mild local Formaldehyde Solution (Formalin)
anesthetic (results from the evaporative refrigerant • contains not less than 37% of formaldehyde with
action of alcohol when applied to skin) methanol added to retard polymerization
• has been injected near nerves and ganglia to alleviate • disinfectant, embalming fluid
pain • MOA: direct and nonspecific alkylation of nucleophilic
• has low narcotic potency and has been used internally functional functional groups of proteins
in diluted form as mild sedative, a weak vasodilator
and a carminative
• Low dose - CNS stimulant Glutarol/Glutaraldehyde (Cidex®)
• High dose - • sterilizing solution for equipment and instruments that
• Acetaldehyde - causes N & V, and vasodilatory cannot be autoclaved (for 30 mins)
flushing
Phenols and their Derivatives
Alcohol….
• used in pharmacy for the preparation of:
Phenol, USP
Spirits - preparations containing ethanol as the sole solvent • the standard to which most germicidal substances are
compared
Tinctures – hydroalcoholic mixtures • Phenol Coefficient - defined as the ratio of a
Fluidextracts - contain alcohol as cosolvent disinfectant to the dilution of phenol required to kill a
• 70% - acceptable bactericidal concentration given strain of bacterium Salmonella typhi - under
• 60 - 95% - does not have any significant difference in carefully controlled conditions over a given period
bactericidal action
• 60% - also effective but requires longer contact time MOA
• 70% - can be used safely for preoperative sterilization • Denature bacterial proteins at low concentrations (dose
of the skin dependent) hindi pa mag grow ang bacteria
• Lysis of bacterial cell membranes occurs at higher
Dehydrated Alcohol concentrations (bacricydal)
• or Absolute alcohol
• contains not less than 99% ethanol by weight Phenol
• Carbolic Acid
Isopropyl Alcohol • was introduced as a surgical antiseptic by Joseph
• primarily used to disinfect the skin and surgical Lister
instruments • its use as either an antiseptic or disinfectant & is
• rapidly bactericidal in the concentration range of 50% largely obsolete not in use (Phenolated Calamine
to 95% Lotion)
• a 40% concentration is considered to be equal in • exhibits germicidal action, caustic to skin, exerts local
antiseptic power to a 60% ethanol anesthetic effects
• 2-propanol
Liquefied Phenol
Ethylene Oxide • simply phenol containing 10% water
• C2H4O
• used to sterilize temperature-sensitive medical p-Chlorophenol
equipment and certain pharmaceuticals that cannot be • used in combination with camphor in liquid petrolatum
autoclaved as an external antiseptic and anti-irritant
• MOA: ALKYLATION of functional groups in nucleic
acids and proteins by nucleophilic ring opening
• forms explosive mixtures in air at concentrations
ranging from 3% to 80% by volume
• explosion hazzard is eliminated when gas is mixed with
sufficient concentrations of carbon dioxide -
Carboxide® p-Chloro-m-xylenol
• Carcinogenic • a non-irritating antiseptic agent with broad-spectrum
• Disinfectant only antibacterial and antifungal properties
• marketed in a 2% concentration as shampoo
• used topically for tinea infections such as athlete's foot
and jock itch.

Aldehydes
Hexachlorphene
GSDMSFI | BS Pharmacy 3
 • used in concentrations 2 to 3% in soaps, detergent
creams, lotions, and shampoos for various antiseptic
uses.

Hexylresorcinol
• 4-Hexylresorcinol
• an effective antiseptic, possessing both bactericidal
Cresol and fungicidal properties
• a mixture of three isomeric cresols • has surfactant properties, local anesthetic activity
• an inexpensive antiseptic and disinfectant • formulated into throat lozenges because of its local
• Example- Lysol anesthetic and antiseptic properties

Chlorocresol
 Only useful as preservatives

Oxidizing Agents

Oxidizing agents
Thymol
• Isopropyl m-cresol • their value as germicides depend upon the liberation of
• extracted from oil of Thymus vulgaris (Thyme, of the oxygen in the tissues (peroxides) and their ability to
mint family) denature proteins (permanganates)
• has mild fungicidal properties and is used in alcohol • especially effective against anaerobic bacteria and can
solutions and in dusting powders for the treatment of be used in cleansing wounds
tinea (ringworm) infections Hydrogen Peroxide 2-3%
• bubbles that form during the liberation of oxygen help
to dislodge debris
• effectiveness is somewhat limited by its poor
penetrability and transient action

Carbamide Peroxide
Eugenol • Gly-Oxide
• 4-Allyl-2-methoxyphenol • a stable complex of urea and hydrogen peroxide
• obtained primarily from clove oil- Eugenia caryophyllus • liberates hydrogen peroxide when mixed in water
and Caryophyllus aromaticus- toothache drop • used as both antiseptic and disinfectant
• possesses both local anesthetic and antiseptic activity • preparation is especially effective in the treatment of
and can be directly applied on a piece of cotton to oral ulcerations or in dental care
relieve toothaches
• also used in mouthwashes because of its antiseptic Hydrous Benzoyl Peroxide
property and pleasant taste
• Panoxyl® 2.5%, 5%, 10%
• most effective topical OTC agent for the control of acne
• both keratolytic and keratogenic agent
• MOA: induces proliferation of epithelial cells, leading to
sloughing and repair
• S/E: dryness
Resorcinol
Halogen Containing Compounds
• m-Dihydroxybenzene (resorcin)
• a weak antiseptic
Iodine
• used in 1% to 3% solutions and in ointments and
pastes in concentrations of 10% to 20% for the • one of the oldest known germicides in use today
treatment of skin conditions such as ringworm, • the following are iodine preparations official in the USP
eczema, psoriasis, and seborrheic dermatitis Iodine Tincture: 2% solution of iodine in 50% alcohol with NaI-
• a keratolytic agent (causes the stratum corneum of the water only
skin to slough, opening the barrier to penetration for
antifungal agents Lugol's Solution/ Strong Iodine Solution: 5% iodine in water
with KI
Iodine Solution: 2% iodine in water with NaI
GSDMSFI | BS Pharmacy 3
 • inorganic iodide salts are present to solubilize the Methylbenzethonium Chloride
iodine and reduce its volatility • Diaparene®
• MOA: probably acts to inactivate proteins by iodination • used specifically for the treatment of diaper rash in
of aromatic residues and oxidation infants caused by Bacterium ammoniagenes (causes
liberation of ammonia in decomposed urine)
Iodophors
• complexes of iodine and non-ionic surfactants Cetylpyridinium Chloride
• such complexes retain the germicidal properties of • used as a general antiseptic
iodine and also reduce its volatility and essentially • available form: throat lozenges and mouthwashes
remove its irritant properties • FDA approved for the treatment of gingivitis

Povidone-Iodine Chlorhexedine gluconate

• Bactidol®, Chlorhex®, Hibiclens®
• Betadine® • in RP - Bactidol® is Hexetidine
• Polyvinylpyrrolidone(PVP)-Iodine • used as irrigation solution and as mouthwash
• used as an aqueous solution for presurgical • not absorbed through skin or mucous membrane and
disinfection of the incision site does not cause systemic toxicity
• used to treat wounds and damage to the skin and
effective for local bacterial and fungal infections
Dyes
Chlorine-Containing Compounds
• cationic dyes are active against gram-positive bacteria
MOA and many fungi
• release of hypochlorous acid (HClO): chlorination of • gram-negative bacteria are generally resistant
amide nitrogen atoms and oxidation of sulfhydryl • Can either be disinfectant or antiseptic
groups in proteins Gram staining
• V-iolet
Halazone • I-odine
• used to disinfect drinking water • A-lcohol
• S-affranin
Chloroazodin
• used to disinfect wounds, as packing for dental caries Gentian Violet
and for lavage and irrigation • Crystal violet, hexamethyl-p-rosaniline chloride, methyl
• a glyceryltriacetate solution is used as wound dressing violet, methyl-rosaniline chloride
• primary dye in gram-staining
Oxychlorosene Sodium • available as vaginal suppositories for the treatment of
• used to treat localized infections to remove necrotic yeast infections (pessaries)
tissue from massive infections or radiation necrosis, to • available as topical solutions for the treatment of
counteract odorous discharges, to act as an irritant, cutaneous Candida albicans infections
and to disinfect cysts and fistulas • used orally as an anthelmintic for strongyloides and
oxyuriasis

Basic Fuchsin
Cationic Surfactants • ingredient of carbol-fuchsin solution (Castellani's paint),
used topically in the treatment of fungal infections,
Cationic Surfactants such as ringworm and athlete's foot.
• quaternary ammonium compounds that ionize in water
and exhibit surface-active properties Mathylene Blue
• MOA: adsorb onto surface of the bacterial cell, at • antidote for cyanide poisoning
which they cause lysis • in high concentrations, it promotes the conversion of
• inactivated by soaps and other anion detergents hemoglobin to methemoglobin (less affinity to oxygen),
• tissue constituents, blood, serum, and pus tend to which because of its high affinity for cyanide ion diverts
reduce the effectiveness of these substances it from inactivating cytochrome C oxidase
• in low concentrations, it is used to treat drug-induced
Benzalkonium Chloride methemoglobinemia
• Merthiolate® - New • used for the treatment of cystitis (inflammation of the
• used as detergent, emulsifying agent and wetting bladder) and urethritis
agent • Bacteriostatic- used to prevent the growth of the
• used with sodium nitrate as a preservative bacteria
• Old Merthiolate- Thimerosal (Mercury)
Mercury Compounds Mercurials
GSDMSFI | BS Pharmacy 3
 commonly used as preservative in vials of injectable drugs in
• MOA: reacts with SULFHYDRYL (-SH) groups in concentrations of 1% to 4% in water or saline solution;
enzymes and other proteins has local anesthetic action
• this is reversible by thiol-containing compounds such • PHENYLETHYL ALCOHOL
as CYSTEINE and DIMERCAPROL occurs naturally in rose oil and pine-needle oil; used primarily
in perfumery
Uses • BENZOIC ACID
o Antiseptic, disinfectant and preservatives
used externally as an antiseptic for lotions, ointments and
Mercuric Chloride mouthwashes; more effective as a preservative in foods
• Corrosive sublimate and pharmaceutical products at low pH
• HgCl2 • SODIUM BENZOATE
used as preservative in acidic liquid preparations in which
Mercurous Chloride
benzoic acid is releases
• Calomel • SODIUM PROPIONATE
• Hg2Cl2
effective antifungal that is used as preservative
Ammoniated Mercury • SORBIC ACID
• HgNH2Cl an effective antifungal preservative; used to preserve syrups,
• White precipitate elixirs, ointments, and lotions containing components
• used for skin infections such as sugars that support mold growth
• Minamata and mad hatter's disease- caused • POTASSIUM SORBATE
by mercury
used as the same way as sorbic acid
Nitromersol • PHENYLMERCURIC NITRATE
• was once a very popular antiseptic for skin and used to preserve injectable drugs but bacteriostatic efficacy is
ocular infections reduced in the presence of serum
• PHENYLMERCURIC ACETATE
Thimerosal
used as preservative
• Merthiolate® - old
• weak bacteriostatic antiseptic that is applied Anti-Tuberculae Agents
topically in ointments or aqueous solutions
Mycobacterium tuberculosis
• Acid fast bacteria
Preservatives • Rod shaped, aerobic bacteria that does not form
spores
• used to prevent microbial contamination • facultative intracellular, obligate aerobe
• Ideal Characteristics: effective at low concentrations • causes Koch's disease
against all possible microorganisms, nontoxic, • Lowenstein-Jensen medium (serpentine growth
compatible with other constituents used in the colonies)
preparation, stable for the shelf-life of the preparation
• Increased the shelf life of products ISONIAZID (INH or H)
• Isonicotinic acid hydrazide
Parabens • Nydrazid®
• p-hydroxybenzoic acid • MOA: inhibits the synthesis of mycolic acid, an
• useful as preservative for liquid dosage forms important component of the cell wall of mycobacteria
• have ANTIFUNGAL properties • Principal adverse effect: Peripheral neuritis due to the
• preservative effect tends to increase with molecular competition of INH with pyridoxal phosphate for the
weight enzyme apotryptophanase
• Methyl paraben- effective for molds (lipophilic) • co-administration of pyridoxine (antidote) (Vit. B6)
• Propyl paraben- effective for yeast (more soluble to oil) prevents peripheral neuritis
VITAMIN Bs
Other Preservatives B1- Thiamine
B2- Riboflavin
• CHLOROBUTANOL B3- Niacin
B5- Pantothenic Acid
employed as a bacteriostatic agent in pharmaceuticals for
B6- Pyridixine
injection, ophthalmic use, and intranasal administration
B9- Folic Acid
• BENZYL ALCOHOL (Phenylcarbinol, Phenylmethanol)
B12- Cyanocobalamin

Ethionamide
GSDMSFI | BS Pharmacy 3
 • Ethambutol
• Trecator SC® • Streptomycin
• structural analogue of isoniazid
• used in the treatment of isoniazid-resistant tuberculosis PTB = 2 mos (RIPE w/ or w/o S)
S/E: GI irritation, hepatotoxicity, peripheral neuropathies, 4 mos - maintenance phase (R + I)
optic neuritis

Pyrazinamide (PZA or Z) Cycloserine

• Pyrazinecarboxamide • Seromycin®
• MOA: unknown • isolated from different species of Streptomyces: S.
• used in combination with other agents because orchidaceus, S. garyphalus, S. lavendulus
resistance develops rapidly • MOA: prevents the synthesis of cross-linking peptide in
• S/E: hepatotoxicity (inc. ALT/AST) the formation of bacterial cell walls
• must be enzymatically hydrolyzed to pyrazinoic acid
(active form) Capreomycin
• isolated from Streptomyces capreolus
Ethambutol (EMB or E)
Streptomycin
• E for the eyes • only aminoglycosides used for tuberculosis
• Myambutol® • the first antibiotic effective in the treatment of TB (1944
• S/E: Optic neuritis by Waksman)
• loss of ability to discriminate between red and green
• MOA: inhibits the incorporation of mycolic acids in the
cell walls of the bacteria

Para-Aminosalicylic Acid (PASA/PAS)

• MOA: acts as a competitive inhibitor for p-
aminobenzoic acid (PABA) in folate biosynthesis
• S/E: severe gastric irritation
• second-line treatment for TB

Clofazimine
• Lamprene®
• MOA: unkwown
• basic red-dye used in the treatment of leprosy,
including dapsone-resistant forms
• S/E: Colored-maroon urine
• Second line drug

Antitubercular Antibiotics

Rifamycins
• obtained from Streptomyces mediterranei- fungus we
get the Refampicin
• Most active against tuberculosis
• includes Rifampin and Rifabutin

Rifampin

• Rifadin, Rimactane, Rifampicin

• the most active agent against TB
• enzyme INDUCER
toxic effects are relatively infrequent
• when it is taken in combination with INH or ethambutol,
incidence of HEPATOTOXICITY is significantly higher
• S/E: reddish color of body secretions, hepatotoxicity

First Line Treatment for TB

• Rifampin
• Isoniazid
• Pyrazinamide
GSDMSFI | BS Pharmacy 3