ORGMED SUPPLEMENTAL NOTES

Medicinal Chemistry – incorporation of chemistry and biology in the research for the discovery and
design of new and better therapeutic chemicals and development of these chemicals into new
medicines.

Drug

• Any substance intended for use in diagnosis, cure, mitigation, treatment or prevention of
disease or to affect or alter the structure or function of the body of man or other animals
• Origin
o Natural: from plants and animals
o Synthetic: from pure synthesis of naturally occurringcompounds
o Semi-synthetic: natural intermediate of some drugs could be used for the synthesis
of a desired product
• Medicinal
o Chemotherapeutic: fight malignant/tissues and microorganisms
o Pharmacodynamic agents: acts on various functions of the body
• Types of disease treate
o Infectious: caused by microorganism may be person-to-person, or by outside
agents
o Non-infectious: diorders caused by genetic malfunction, environmental factors,
stress , or old age
o Non-disease:
▪ Alleviation of pain and symptom
▪ Prevention of pregnancy
▪ Anesthesia

IMPORTANT TERMS TO REMEMBER!!!

LIGAND – a chemical that binds to a receptor

• Affinity – ability to bind to a receptor

• Intrinsic activity – ability to exert a pharmacologic action

RECEPTOR – where the ligand binds

PHARMACOPHORE – The section of the structure which is responsible for its pharmacological
activity

ANALOG – synthetic compounds developed from a lead compound

NUCLEUS – Section of the structure which is responsible for its pharmacological activity

STRUCTURE-ACTIVITY RELATIONSHIP (SAR) – How a structure affects the effect of the drug

• Exhibited by compounds with similar structures to a pharmacologically active drug

DRUG DISCOVERY, DESIGN AND DEVELOPMENT

Goals

• To combat drug resistance, tolerance, tachyphylaxis

• Improve treatment of existing disease
• For treatment of newly identified disease
• Production of safer drugs by reduction or removal of adverse effects

Natural Product Screening

• Leads and natural sources from folklore medicine are assayed for their many types of
pharmacologic actions
• Costly, time-consuming

Rational Drug Design

• Focused approach on structural knowledge of the receptors or ligands to design, identify, or

create a lead
• Involves molecular modeling and QSARs

Drug Metabolism Studies

• Conducted for clinical candidates or drugs already in the market

• Metabolites are also isolated and assayed for biological activity

DDD Process – reduction of an undesirable pharmacologic response; obtain a better

pharmacokinetic response; alter drug metabolism; secure a more plentiful, less costly supply

• Discovery – IDENTIFICATION of new or previously biologically active compounds (can also

be called as hits)
• Lead optimization – hits are CONVERTED to lead compounds by the modification of
functional groups
• Toxicology and Clinical Development – RENDER the modified lead into a drug candidate
for clinical trials

DRUG-RECEPTOR INTERACTION

• Drug must BIND to the receptor in order to elicit an effect

• ONLY ONE LIGAND can bind to the site of the receptor
• DERIVED and OBEYS the Law of Mass Action
o When a drug combines with a receptor, it does so at a rate which is dependent
on the conc of the drug and the conc of the receptor.

Selectivity

• one chemical group can produce 2 different biologic effects

Ligand-Receptor/Enzyme-Substrate Hypotheses
 • Receptor Hypothesis
o By Paul Ehrlich = receptors, selective toxicity
o Side chains on the surfaces of cells were complementary to the dyes
• Lock and Key Theory
o Substrate and active site are completely complementary in shape to the active site
• Induced Fit theory
o “A Hand in a Glove Model”
o The substrate and active site are not completely complementary, but there is still
some complementarity
o The enzyme conforms to the shape of the substrate

RECEPTOR OCCUPANCY MODEL

Stresses the following:

• Potency - amount of drug needed to produce an effect; relates to affinity

• Efficacy - strength of Drug-Receptor complex in evoking a response; relates to intrinsic
activity

Hypothesis of Clark

• “Occupation Theory”
• Max pharmacologic effect can be obtained if ALL receptors are occupied
• Obeys Law of Mass Action: when a drug combines with a receptor, it does so at a rate which
is dependent on the conc of the drug and the conc of the receptor
• Only applies to full agonists

Hypothesis of Ariens and Stephenson

• Effectiveness of a drug lasts as long as the receptor is occupied

• Intrinsic activity: ability of a ligand to activate the receptor; determines drug efficacy
• Response = # of drug receptor complexes formed

Hypothesis of Paton

• “Rate Theory”
• The effectiveness of a drug does not depend on the actual occupation of the receptor
but by obtaining proper stimulus
• Affinity: strength of attraction of the ligand to the receptor; determines drug potency

Hypothesis by Baker

• Active site-directed irreversible inhibition

• Formation of covalent bond between ligand and receptor

Easson-Stedman Hypothesis

• There is selective reactivity of one enantiomer with its receptor

 • Stereochemistry: A 3-point fit to the receptor makes one enantiomer more potent than the
other

BIOPHARMACEUTICAL PROPERTIES ON DRUG DESIGN

• Physicochemical properties: how functional groups in the molecule influence the

molecule’s characteristics
• Biopharmaceutics: study of the relationship between the physicochemical properties of a
drug and the effects observed after administration via dosage forms or drug delivery
systems
• Pharmacokinetics: LADME = what the body does to the drug
• Pharmacodynamics: what the drug does to the body = response

Based on acid-base polarity (PLEASE MASTER THIS BY HEART)

• Acid and basic functional groups = polar

o Hydrophilic, lipophobic, water soluble = ionized
• Neutral functional groups = nonpolar
o Lipophilic, hydrophobic, lipid-soluble = Unionized
Acidic Medium Basic Medium
Acidic Drug Unionized - ABSORBED Ionized – EXCRETED
Basic Drug Ionized – EXCRETED Unionized - ABSORBED

ACID + ACID = Absorbed and Unionized

BASE + BASE = Absorbed and Unionized
BASE + ACID = Excreted and Ionized
ACID + BASE = Excreted and Ionized
(so bale tandan niyo nalang na if same gani sila = absorbed dayon)
• Ionization constant (Ka)
o Negative log of Ka = pKa
o Indicate relative strength of an acid or base
o Dec pKa = inc Ka = inc acidity = dec basicity
(basta tandan jud ninyo nga kabaligtaran ni Ka sip Ka. So whenever taas si Ka meaning baba
sip Ka which leads us to the conclusion na increase ang acidity. So whenever baba man si
Ka, ibaligtad lang ninyo)
• Salt Formation
o Neutralization reaction between a base and acid; forms water and a salt
o Salt form of a drug is preferred = more soluble
▪ All salts are strong electrolytes EXCEPT Hg and Cd halides, Pb acetate
▪ Inorganic salt: drug + inorganic acid/base
▪ Organic salt: basic drug + acidic drug\

Based on Solubility

• Solubility
o Max amount of solute that can be dissolved in a solvent at equilibrium
o Saturation level – solvent cannot dissolve the solute anymore
 • Dissolution
o Process by which a substance forms a solution in a solvent
• Surface area, Particle size
o SA: how much exposed area of a drug molecule can interact with solvent
o Inc surface area = dec particle size
• Stability
o Maintain the physicochemical, therapeutic and microbial properties during the time
of storage and usage by the patient
• Log of the Partition coefficient (Log P)
o Calculate and predict hydrophilicity and lipophilicity of functional groups or
compounds
o Ratio of drug conc in octanol to that in water

o High logP = nonpolar/lipophilic

o Small logP = polar/Hydrophilic

Based on Stereochemistry

• Isomers differ in their pharmacokinetic and pharmacodynamic properties

• Enantiomers: have different potencies, receptor fit, biological activity, transport and
metabolism
o R-thalidomide (sedative) vs. S-thalidomide (teratogen)
o Levorphanol (analgesic vs Dextrophan (Antitussive)
• Diastereomers
o Ephedrine vs Pseudoephedrine
o Z-triprolidine (inactive) vs E-triprolidine (active)
• Geometric isomers (cis-trans, E-Z): have different physical and pharmacological activity
o Do not fit to the same receptor equally
o Ex. Diethylstilbestrol

Based on GIT Physiology

Parts

• Stomach (Body and Pylorus): acidic

• Small intestines (Duodenum, Jejunum, Ileum + villi, microvilli): basic

Intestinal Digestion

• Final preparation for absorption

• Hydrolysis of large molecules
• Conversion to an aqueous solution or emulsion

Absorption
 • Physiologic: rate and extent of disappearance of drug from the site of administration
• Pharmacologic: rate and extent of drug entry into the systemic circulation
• Factors
o Surface area: ↑surface area, ↑ absorption
o Degree of perfusion: ↑ perfusion, ↑ absorption
o Dose size administered: ↑ dose size, ↑ absorption
o pH of absorbing environment
o Gastric Emptying Time (GET)
✓ ↑ GET, ↓ GER, ↓ Absorption
✓ ↓ GET, ↑ GER, ↑ Absorption

PRODRUGS

• Bioreversible derivatives of drug molecules that undergo an enzymatic/chemical

transformation in vivo to release the active parent drug, which can then exert the desired
pharmacologic effect
• Optimize ADME or improve oral BA
• Types
o Hard prodrug: biologically active with inc water/lipid solubility
o Soft prodrugs: biotransformed in a rapid and predictable manner into nontoxic
moieties
o Carrier-linked: active drug + carrier group that can be removed enzymatically
o Mutual prodrugs: two synergistic drugs attached to each other
o Bioprecursors: inert molecules obtained by chemical modification
▪ Without a carrier; bioactivated via redox

PHASES OF METABOLISM

Phase 1: Functionalization

• Non-synthetic reactions
• Provide a polar functional group or “handle” to the drug molecule via direct introduction of
the functional group or modifying or “unmasking” existing functional groups
• CYP 450 Oxidation
o Microsomal mixed oxidase system
o Mixed function oxidases/monooxygenases
o Found in lungs, intestines, skin
o Requirements:
▪ Heme protein with iron (Fe3+: rest/oxidized, Fe2+: active/reduced)
▪ NADH/NADPH cofactors
▪ H2 atom to be abstracted from the substrate
▪ Oxygen
o Results in activation of O2 as electron acceptor
▪ Oxidation of substrate
▪ Formation of one molecule of H2O
 Oxidation Inc O
Dec electron
Inc unsaturation
Dec H
Reduction
Inc H
Reduction Inc H
Inc electrons
Dec unsaturation
Dec O

Phase 2: Conjugation

• Aka synthetic reaction

• Attach small, ionizable, endogenous compounds to functional handles
• Drug conjugation reactions MAKES the drug inactive and water-soluble, easily excreted
via urine/bile
• Each reaction uses a specific transferase enzyme
• Usually attaches to -OH groups except Acetylation, which attaches to N
• Produces polar and active compounds EXCEPT acetylation and methylation

1. Glucuronide conjugation
• Most common conjugation reaction
• Requires Glucuronic acid (from the oxidation of glucose)
• Glucose-1-P + UTP → UDP Glucose → [UDPG-DH, 2 NAD] → UDP-Glucuronate
o O-glucuronidation: APAP
o Acylglucuronidation: Ibuprofen
o N-glucuronidation: p-aminosalicylic acid
• Enzyme: UDP-glucuronosyltransferase
• Activated cofactor: uridine-5’-diphospho-a-D-glucuronic acid
• Not yet developed in neonates - Less expressed in <28 days
• Ex. Chloramphenicol, APAP, Morphine
o Morphine-3-glucuronide – convulsant
o Morphine-6-glucuronide – analgesic
2. Sulfate conjugation
• Most important for steroid hormones, heparin, chondroitin, catecholamines,
thyroxine, bile acids and phenolics
• Metabolites have low pKa, almost totally ionized, highly soluble and excretable via
urine (sa madaling salita, tanan drugs naa diri kay highly excretable)
• Transfer of sulfone from 3’-phosphoadenosine-5’-phosphosulfonate by
sulfotransferase
• PAPS is formed from inorganic sulfate and STP
• Sulfate + ATP → [ATP Sulfonylase; APS Phosphokinase] → PAPS + ADP + PPi
• Sulfate pool is limited and easily depleted/saturated
• Major process in neonates
3. Amino acid conjugation
• Forms an amide with aromatic or alkyl carboxylic acids
o Glycine, glutamate (major); aspartate; taurine, serine
o Glycine: mammals
▪ Reduced in infants and elderly
▪ Benzoic acid + glycine = hippuric acid
▪ Salicylic acid + glycine = salicyluric acid
• Glutamine: Humans and other primates
o Liver and kidney
• Minor pathway
4. Glutathione conjugation
• For detoxification of chemically reactive electrophilic compounds
• Tripeptide: glutamylcysteinylglycine
• Does not require activation; -SH readily attacks electrophilic centers
o Conjugation by Glutathione-S-transferase
o Removal of glutamate by Glutamyl transferase
o Removal of glycine by Cysteinylglycinase
o Forms a mercaptopuric derivative, that is easily excreted in urine
5. N-acetylation
• Transfer of acetyl CoA to primary and aliphatic and aromatic amines, amino acids,
hydrazines, sulfonamides
o Sulfonamides, hydralazine, isoniazid, procainamide
o Isoniazid undergoes phase 2 before phase 1 metabolism
• Secondary and tertiary amines are not acetylated
• Catalyzed by N-acetyltransferase – a liver mitochondrial enzyme which uses Acetyl
CoA as coenzyme
o Polymorphism leads to fast and slow acetylator phenotypes
o FAST acetylators: prone to drug-induced toxicities
▪ Eskimos, Asians
o SLOW acetylators: eliminate the drug rapidly
▪ Europeans, Caucasians, Egyptians
• Ex. Sulfonamide, Hydralazine, Isoniazid, Procainamide (SHIP)
 • May cause activation – acetylcholine
6. Methylation
• Occurs on O/N/S atoms on endogenous or drug molecules
• Leads to less polar and active metabolites
o Ex. Norepinephrine to Epinephrine
• Catalyzed by methyltransferase, which transfers a methyl from S-adenosyl
methionine (SAM)
o ATP + Methionine = [methionine adenosine transferase]=> S-AM
• Minor pathway: Does not enhance water solubility but is able to deactivate the drug
o Ex. NE, DA, 5HT, Histamine

STRUCTURE AND DRUG MECHANISMS OF ANTIBIOTICS

ANTIBACTERIAL AGENTS – substances produced by microorganism which has the capacity to

inhibit growth and cause the destruction of other microorganisms; can be -static (inhibit) or -cidal
(kill)

General mechanism of action of antibacterials/antibiotics:

1. Inhibition of CELL WALL SYNTHESIS

• MOA: Binds with one or more PBPs (penicillin-binding protein) causing selective inhibition
of transpeptidase/transamidase , carboxypeptidase and endopeptidase reactions required
for cross linkage between peptide chains in the synthesis of mucopeptide
• EXAMPLES

UNDER BETA-LACTAMS (Penicillins, Beta-lactamase inhibitors, Cephalosphorins,

Carbapenems and Monobactams)

o Penicillin
▪ Old Source: Penicillium notatum
▪ New: P. chrysogenum, P. rubens
▪ MOA: Interfere with transpeptidation or cross-linking or peptidoglycan
chains
▪ STRUCTURE: Beta lactam ring with a thiazolidine ring (Para matandaan ang
iyahang structure, bahay siya na may garage)
▪ NUCLEUS: 6-aminopenicillanic acid (6-APA)
▪ WOF: penicillins can cause allergies that’s why before giving it to the px, you
need to ask first. IF PX IS ALLERGIC = give MACROLIDES
TYPE OF PENICILLIN EXAMPLE REMARKS
NATURAL PENICILLINS Penicillin G • IV form – AQUEOUS Pen G
• IM form – Benzathene Pen G
(gives depot effect; given if
compliance is an issue;
RAPIDLY excreted)
• DOC for syphilis
• DOC susceptible Gram +
cocci
• TAKE NOTE: Pen G is ini-
inGect, parenteral
Penicillin V • Acid stable
• For minor infections only due
to RESISTANCE
• TAKE NOTE: Pen V = V is for
Vunganga, oral route
ANTISTAPHYLOCOCCAL/ Methicillin • Prototype
PENICILLINASE-RESISTANT • Acid-labile
PENICILLINS (Narrow- • Phased out in the market
spectrum) because of high incidence of
nephrotoxicity; interstitial
nephritis
• Oldest penicillin used in
MRSA infection along with
(remember CONDOM)
C – loxacillin
O – xacillin
N – afcillin
D – icloxacillin
O - xacillin
M - ethicillin
Nafcillin • Alternative to methicillin
• Can be given to patients with
renal problems
ISOXAZOYL Penicillins • Halogenated analogs
(remember OCD) • DICLOXACILLIN is best
ABSORBED ORALLY
Oxacillin • Treatment of
Cloxacillin staphylococcal infections
Dicloxacillin (e.g. impetigo)
AMINOPENICILLINS (Broad- Ampicillin • Prototype (BCH:
spectrum) Bacampicillin, Cidacillin,
Hetacillin)
• POOR GI absorption
• Mostly given IV
• DOC for L. monocytogenes
Amoxicillin • better GI absorption = given
PO
• For respiratory infections
• Prone to resistance
ANTIPSEUDOMONAL Carboxypenicillin (may • Increase Gram (-) activity
PENICILLIN ‘car’ sa name) • Used in combos for
Pseudomonas aeruginosa
Carbenicillin
Ticarcillin
Ureidopenicillin • Piperacillin – most potent
(remember PAM) • Piperacillin + Tazobactam
(has the broadest
Piperacillin spectrum of all the
Azlocillin pencillins
Mezlocillin

o Beta-lactamase inhibitors
▪ DO NOT HAVE significant antibacterial activity, instead they bind to and
inactivate beta-lactamases
▪ Little to no antimicrobial activity
▪ Potentiates the activity of B-lactams against Gram + cocci (bale
ginatabangan lang niya ang other drug na antibiotic para madeliver iyang
effect; POTENTIATION ANG MAHITABO 1+0=2)
▪ EXAMPLE PREPARATIONS IN THE MARKET:
✓ Augmentin, Co-amoxiclav: Amoxicillin + clavulanic acid
✓ Timentin: Ticarcillin + Clavulanic acid
✓ Tazocin, Piptaz, Zosyn: Piperacillin + Tazobactam
✓ Zerbaxa: ceftolozane + tazobactam
✓ Avycaz: Ceftazidime + avibactam
✓ Unasyn: ampicillin + sulbactam
o Cephalosphorins
▪ Old source: Cephalosporium acremonium
▪ Cephalosporin C – first cephalosporin
▪ New: Acremonium chrysogenum
▪ Classified into 5 GENERATIONS
▪ NUCLEUS: 7-aminocephalosporanic acid (7-ACA)
▪ STRUCTURE: B-lactam + dihydrothiazine ring (take note para dili malimtan:
Piattos + box + Sulfur na atom)
 ▪ Habang tumataas ang generation, lumalawak ang Gram (-) coverage nya,
nawawala naman ang positive

Effective against Remarks

1 GENERATION
ST
Remember PECK • All “CEPH-“including cefaZOLIN,
Proteus cefaLEXIN, except cefadroxil and
E. coli cefamandole (the only ‘cef’ na
Klebsiella dili 2nd generation)
• Excellent agents for skin and soft
Effective against tissue infections due to S.
Gram (-) coverage aureus and S. pyogenes
• CEFALEXIN: used for UTI in
pregnant women
• CEFAZOLIN: used for pre-surgical
prophylaxis
2nd GENERATION Remember • The only generation that has
HENPECK coverage for anaerobes
H. influenzae • All “CEF” + vowel letter (a, e, I, o
Enterobacteriaceae ,u) including pro and meta and
Neisseria loracarbef (remember TETA,
META, FOX = cefoTETAn,
cefMETAzole, ceFOXitin)
• For respiratory tract infections
3RD GENERATION Remember • DOC for many Gram (-) bacteria
HENPECKSSS • “CEF” + consonant including
Salmonella money (cefoPERAzone), taxes
Shigella (cefoTAXime), and fixers
Serratia (cefixime) including also
moxabactam
• CEFOTAXIME, Ceftriaxone: tx of
community-acquired pneumonia;
antibiotic of first choice for the
tx of brain abscess and meningitis
 • CETRIAXONE (Rocephin): new
DOC for Typhoid fever, Neisseria
gonnorrhea, severe forms of Lyme
disease
• CEFOPERAZONE, Cefotaxime,
CEFTAZIDIME, Ceftriaxone,
MOXOLACTAM: antipseudomonal
• CEFTAZIDIME: DOC for
Pseudomonas aeruginosa
meningitis
• Ceftibuten, Cefdinir, Cefixime,
Ceftidoxime, Cefditoren
4TH GENERATION Remember • For nosocomial infections
HENPECKSSS + • Usually given oral
pseudomonas • Remember “Pi-pi” = cefePIme,
cefPIrome
• More resistant to beta -lactamase
5TH GENERATION Remember • Remember “ROL-ROL” =
HENPECKSS + ceftaROLine, ceftobipROL,
pseudomonas + including ceftolozane
MRSA

o Carbapenems
▪ For ESBL infection (extended spectrum beta lactamase
▪ Epileptogenic = most epitoleptic class (can cause seizures)
▪ Synthetic derivatives of the natural product Thienamycin (from
Streptomyces cattleya)
▪ THIENAMYCIN – unstable prototype
▪ EXAMPLES:
▪ IMIPENEM
• N-formimidoyl thienamycin
• Added with cilastatin (brand name: Thienam, PRIMAXIN) to
inhibit DHP-1
• Broadest of all beta lactams
• MOST EPILEPTOGENIC
▪ DORIPENEM
▪ MEROPENEM
• 2nd gen carbapenem
• DHP and B-lactamase resistant
• Therapeutically equivalent to imipenem
▪ ERTAPENEM
▪ With benzoic acid = high protein binding = inc half-life
▪ DOC for Extended-spectrum beta-lactamase-producing G (-) bacteria
▪ ONLY CARBAPENEM that has NO coverage for Pseudomonas
 o Monobactams
▪ Works on Gram (-), Pseudomonas
▪ Only available in IV form; poorly absorbed orally
▪ Excreted in the urine
▪ EXAMPLES:
▪ Aztreonam
• From Chromobacterium violaceum
• Not orally active => parenteral
• For Gram (–) aerobes, including P. aeruginosa, nosocomial
infections
• Magic bullet for Pseudomonas
• Last line

UNDER POLYPEPTIDE ANTIBACTERIALS

• Inhibits cell wall synthesis by binding to the D-ala-D-ala terminus

• Inhibits transglycolase (prevents elongation and cross-linking)
• Most lack systemic activity (only used topically), except Vancomycin (systemic)

o Vancomycin
o From Streptomyces orientalis/Amycolaptosis orientalis
o DOC for infection caused by MRSA (including pneumonia, bacteremia and
endocarditis)
o DOC for Pseudomonas colitis caused by oral form of Vancomycin
o Susceptible to penicillin
o Target trough: 15-20 ug/mL (if maglampas within these values =
NEPHROTOXIC)
o ADR: flushing (Red Man Syndrome); nephrotoxicity

2. Inhibition of PROTEIN SYNTHESIS

• Inhibit protein synthesis at the 30s ribosomal subunit
• Synergistic with beta-lactam antibiotics
• Inhibits either 30s or 50s
• 30s – Aminoglycosides, Tetracyclines
• 50s – Macrolides, Chloramphenicol, Clindamycin (Lincosamides) (To remember:
buy AT 30, CELL @ 50)
• All are STATIC (inhibit) EXCEPT AMINOGLYCOSIDE
• EXAMPLES
o Aminoglycosides
▪ -micin: from Micromonospora spp
• GENTAMICIN: from M. purpurea
▪ -mycin: from Streptomyces spp.
• STREPTOMYCIN: S. griseus
o 1st aminoglycoside discovered
o 1st effective agent vs. TB
o DOC for tularemia
• TOBRAMYCIN: S. tenebravius
• NEOMYCIN: S. fradiae
• KANAMYCIN: S. kanamyceticus
• AMIKACIN: semisynthetically derived from Kanamycin

• ADVERSE EFFECTS:
▪ Most OTOTOXIC (SA)– Streptomycin, Amikacin
▪ Most COCHLEOTOXIC (KAN) – Kanamycin > Amikacin =
Neomycin
▪ Most VESTIBULOTOXIC (SG) – Streptomycin >
Gentamicin
▪ Most NEPHROTOXIC (NTG) – Neomycin > Tobramycin =
Gentamicin
▪ Least ototoxic and nephrotoxic – Netilimicin

o Tetracyclines
• Reversible inhibitors (bacteriostatic) of protein synthesis
• Binds to rRNA at 16s of 30s subunit = inhibits binding of aminoacyl-tRNA
to the acceptor site on the mRNAribosome complex
• DOC for Rickettsia
 • CHLORTETRACYCLINE: From Streptomyces aureofaciens -
OXYTETRACYCLINE: from S. rimosus
• BROADEST SPECTRUM but no spectrum for Pseudomonas
• STRUCTURE: 4 fused rings

• Side effects
▪ Permanent brown discoloration of tooth enamel via
calcium tetracycline precipitation
▪ Photosensitivity when patient is exposed to sunlight
(esp DEMECLOCYCLINE, DOXYCYCLINE)
▪ Fanconi-like syndrome: due to expired tetracycline

SHORT-ACTING 6-8 hours Tetracycline

Chlortetracycline
Oxytetracycline
INTERMEDIATE-ACTING 12 hours Demeclocycline - can be used
for SIADH
Methacycline
LONG-ACTING 16-18 hours Doxycycline - DOC for
cholera
Minocycline - Effective
alternative to rifampin for
eradication of meningococci
from the nasopharynx

DoMino
VERY LONG-ACTING 36 hours Tigecycline - for MRSA and
Acinetobacter baumani

o Macrolides
• STRUCTURE: a large lactone ring
 • Treatment for community-acquired pneumonia
• EXAMPLES (remember macroCARE)
▪ Clarithromycin
• More potent than erythromycin
• For ulcers caused by H. pylori
▪ Azithromycin
• once a day dosing
• Rapidly absorbed and well tolerated orally
• For nongonococcal urethritis (chlamydia, LRTI,
PID, pharyngitis, Legionaiire)
▪ Roxithromycin
• DOC for Legionaiire’s disease (Legionella
pneumophila)
• Potent CYP inhibitor
▪ Erythromycin
• From Streptomyces erythreus
• Former Ilotycin
• Alternative to penicillin if allergic ang px
o Chloramphenicol
• From Streptomyces venezuelae
• Reversible binding to 50s ribosomal subunit
• For typhoid fever (OLD DOC), Haemophilus, rickettsia
• Gray baby syndrome
• NEVER A DOC!!!

3. Inhibition of NUCLEIC ACID REPLICATION AND TRANSCRIPTION

• DOC for infxn caused by Streptrohomonas maltophilia
• DOC for Pneumocystic jirovecii pneumonia (PCP)
• Alternative tx for Toxoplasma gondii
• Adverse effects: (CHRANKS)
o Crystalluria
o Hemolytic anemia
 o Rashes
o Agranulocytosis
o Nausea/vomiting
o Kernicterus
o Steven’s Johnson Syndrome
• EXAMPLES
o Sulfonamide – inhibit DHPS (dihydropteroate synthase)
o Trimethoprim – inhibit DHDR (dihydrofolate reductase)

Quinolones/Fluoroquinolones
o Irreversible inhibitors of DNA Gyrase and Topoisomerase IV, which are involved
in DNA-dependent RNA polymerase activity
o Alters the conformation of the DNA via DNA supercoiling
o No supercoiling = no genetic information = no bacterial growth
o Habang gataas ang generation, gataas ang spectrum niya for Gram positive
bacteria

4. Injury to PLASMA MEMBRANE

5. Inhibition of SYNTHESIS OF ESSENTIAL METABOLITES