Pharmacology

Rapid Revision

Dr. Priyanka Sachdev

 Pharmacology

• Pharmacokinetics • ANS

• CNS
• Pharmacodynamics
• GIT
• Antimicrobial drugs
• Endocrine
• Renal system
• Autocoides
• Respiratory sustem
• Blood
• CVS
• Anticancer drugs
 Pharmacology

• Pharmacokinetics • ANS

• CNS
• Pharmacodynamics
• GIT
• Antimicrobial drugs
• Endocrine
• Renal system
• Autocoides
• Respiratory sustem
• Blood
• CVS
• Anticancer drugs
Pharmacodynamics  What the drug does to the body
• Physiological and biochemical effects of drugs

• Their mechanism of action at organ system

Pharmacokinetics  What the body does to the drug

• Absorption

• Distribution

• Biotransformation (metabolism)

• Excretion of the drug

Pharmacodynamics deals with

a. Effect of drugs on body

b. Effect of body on drugs

c. Absorption of drugs

d. Metabolism of drugs
Pharmacodynamics deals with

a. Effect of drugs on body

b. Effect of body on drugs

c. Absorption of drugs

d. Metabolism of drugs
Pharmacokinetics includes study of all except -

a) Absorption

b) Distribution

c) Adverse effects

d) Excretion
Pharmacokinetics includes study of all except -

a) Absorption

b) Distribution

c) Adverse effects

d) Excretion
Pharmacodynamics includes -

a) Drug elimination

b) Drug excretion

c) Drug absorption

d) Mechanism of action
Pharmacodynamics includes -

a) Drug elimination

b) Drug excretion

c) Drug absorption

d) Mechanism of action
Factors affecting absorption

1. Aqueous solubility

2. Formulation

3. Concentration of drugs

4. Lipid solubility

5. Surface area

6. Motility of GIT

7. Presence of other substances in GIT

8. Vascularity of the absorbing surface

9. Ionization of drugs and local pH

• HA  H+ + A-

• BOH  B + + OH-

• Unionized form  Absorbed

• Ionised form  Excreted
For absorption  Same pH is required
• Weakly acidic drugs  unionize/absorbed more at  acidic Ph (Stomach)
• Weakly basic drugs  unionize/absorbed more at  basic pH (intestine)

For excretion  Opposite pHis required

• Weakly acidic drugs  ionize/excreted more at  basic pH (Alkaline urine)
• Weakly basic drugs  ionize/excreted more at  acidic pH (Acidic urine)
Remember

• Alkalinization of urine  done by IV infusion of sodium bicarbonate

• Acidification of urine  done by IV infusion of arginine hydrochloride followed by

ammonium chloride (NH4Cl)
Acetyl salicylate & phenobarbitone are better
absorbed from stomach because they are-
a) Weak acids remain non-ionic in gastric pH

b) Weak acids remain ionic in gastric pH

c) Strong acids fully ionised in gastric pH

d) Weak bases which are ionised at gastric pH

Acetyl salicylate & phenobarbitone are better
absorbed from stomach because they are-
a) Weak acids remain non-ionic in gastric pH

b) Weak acids remain ionic in gastric pH

c) Strong acids fully ionised in gastric pH

d) Weak bases which are ionised at gastric pH

Acidic drug is more ionized at –

a) Alkaline

b) Acidic pH

c) Neutral pH

d) None
Acidic drug is more ionized at –

a) Alkaline

b) Acidic pH

c) Neutral pH

d) None
About acidic drug true is -

a) Best absorbed in acidic medium

b) Best absorbed in alkaline medium

c) Not absorbed in acidic medium

d) Binds to alpha glycoprotein

About acidic drug true is -
a) Best absorbed in acidic medium

b) Best absorbed in alkaline medium

c) Not absorbed in acidic medium

d) Binds to alpha glycoprotein

Which is the best way to manage a patient present with aspirin
poisoning:

a. Make urine acidic with NH4Cl

b. Make urine alkaline with NaHCO3

c. Treat with N-acetyl cysteine

d. Do gastric lavage
Which is the best way to manage a patient present with aspirin
poisoning:

a. Make urine acidic with NH4Cl

b. Make urine alkaline with NaHCO3

c. Treat with N-acetyl cysteine

d. Do gastric lavage
• Aspirin is an acidic drug; it readily crosses any acidic medium. To treat this toxicity,
make the urine alkaline with NaHCO3.

• Now, this acidic drug can't be reabsorbed from the basic medium, and it readily gets
excreted from the body.
Alkalinization of urine is done for:

(a) Weak acid drugs

(b) Weak basics drugs

(c) Strong acidic drugs

(d) Strong basic drugs

Alkalinization of urine is done for:

(a) Weak acid drugs

(b) Weak basics drugs

(c) Strong acidic drugs

(d) Strong basic drugs

 Bioavailability
• It is a measure of the fraction (F ) of administered dose of a drug that reaches the
systemic circulation in the unchanged form.
Route of General Bioavailiabilty
Administration characteristics
Intravenous Onset of action is fastest 100%
Intramuscular Painful 75-100%
Subcutaneous Lesser volumes can be given 75-100%
compared to intramuscular
route
Per oral Most convenient from patients 5% to <100% First pass
perspective MC used route metabolism limits blood
levels
Per rectal Less first pass metabolism than 30 to <100%
peroral
Transdermal Very slow absorbtion Lack of 80-100%
first pass effect Prolonged
duration of action
Bioavailability of drug injected I.V. is 100%

• Bioavailability after oral ingestion is lower because

(a) Drug may be incompletely absorbed.

(b) Absorbed drug may undergo first pass metabolism

• AUC tells about the extent of absorption of the drug.
• Tmax tells about the time to reach maximum concentration, i.e. rate of absorption
• Cmax is the maximum concentration of a drug that can be obtained
• It is calculated as Area under curve (AUC) of time and plasma
concentration.
 PRODRUGS
All – ACE inhibitors (except captopril and lisinopril
Prefer – Prednisone
– Proton pump inhibitors
– Proguanil

Doing – Dipivefrine
M – Mercaptopurine
– Methyldopa
– Minoxidil

D – Levo-dopa
In – Irinotecan
Clinical – Cyclophosphamide
– Clopidogrel
– Carbimazole

Subjects – Sulfasalazine
All are prodrug EXCEPT:

a. Aspirin

b. Levodopa

c. Dipivefrin

d. Captopril
All are prodrug EXCEPT:

a. Aspirin

b. Levodopa

c. Dipivefrin

d. Captopril
 Biotransformation (Metabolism)

• Biotransformation means chemical alteration of the drug in the body

• It is needed to convert nonpolar (lipid-soluble) compounds to polar (lipid

insoluble)

• So that they are not reabsorbed in the renal tubules and are excreted
Classification of Biotransformation
1. Nonsynthetic / Phase I / Functionalization reactions

2. Synthetic/ Phase II / Conjugation reactions

Phase I reaction (Non polar  polar)
• Convert parent drug to a more polar metabolite by introducing or exposing a
functional group (chemically reactive group), such as -OH, - NH7, -SH2, (hydroxyl,
amine and thiol respectively)

1. Oxidation

2. Reduction

3. Hydrolysis

4. Cyclization

5. Decyclization
Phase II reaction (Non polar  polar)
• It is coupling between drug and an endogenous hydrophilic substrate such as
glucuronic acid, sulfuric acid etc. to create more polar conjugates
• Thus conjugation enhances drug hydrophilicity.

1. Glucuronide conjugation

2. Glycin conjugation

3. Glutathion conjugation

4. Sulfate conjugation

5. Methylation

6. Acetylation
Acetylation

MNEMONIC- CHIPS – ABC

 Clonazepam (sedative)
 Hydralazine (anti HTN)
 Isoniazid (anti TB)
 Procainamide (anti-arrhythmic)
 Sulfonamides (dapsone)
 Acebutalol, Amrinone, ASA
 Benzocaine
 Caffeine
All drugs are metabolized by acetylation EXCEPT:

a. Phenytoin

b. Isoniazid

c. Procainamide

d. Hydralazine
All drugs are metabolized by acetylation EXCEPT:

a. Phenytoin

b. Isoniazid

c. Procainamide

d. Hydralazine
Mechanism of metabolism

• The drug metabolising enzymes are divided into two types:

1. Microsomal enzymes

2. Non Microsomal enzymes

 Microsomal enzymes

Induction Inhibition
 Microsomal Enzyme Inhibition
• One drug can competitively inhibit the metabolism of another if it utilizes same
enzyme

• Occurs by direct effect on the enzyme  fast (within hours)

• Precipitate toxicity of object drug

Microsomal Enzyme Induction

• Increase the synthesis of microsomal enzyme protein (cytochrome P-450 and

glucuronyl transferase)

• Many drugs interact with DNA  Slow

• Decreased intensity and duration of action of object drugs

 Hofmann elimination

• Inactivation of the drug in body fluids by spontaneous molecular rearrangement without

the agency of any enzyme

• e.g. Atracurium
All are enzyme inhibitors EXCEPT:

a. Carbamazipine

b. Cimetidine

c. Valproate

d. Ketoconazole
All are enzyme inhibitors EXCEPT:

a. Carbamazipine

b. Cimetidine

c. Valproate

d. Ketoconazole
Which of the following drug is an enzyme inducer:

a. Rifampicin

b. Isoniazid

c. Ketokonazole

d. Erythromycin
Which of the following drug is an enzyme inducer:

a. Rifampicin

b. Isoniazid

c. Ketokonazole

d. Erythromycin
Which is Cyt. P450 inhibitor -

a) Ketoconazole

b) Rifampicin

c) Phenytoin

d) INH
Which is Cyt. P450 inhibitor -

a) Ketoconazole

b) Rifampicin

c) Phenytoin

d) INH
Hofmann elimination is -

a) Inactivation of drug by metabolizing enzyme

b) Unchanged excretion by kidney

c) Excretion in feces

d) Inactivation by molecular rearrangement

Hofmann elimination is -

a) Inactivation of drug by metabolizing enzyme

b) Unchanged excretion by kidney

c) Excretion in feces

d) Inactivation by molecular rearrangement

 Excretion

• Excretion is the passage out of systemically absorbed drug

Rate of Elimination

• Rate of Elimination is the amount of drug eliminated per unit time

Clearance (CL)
• The clearance of a drug is volume of plasma from which the drug is completely
removed in unit time

• Clearance is the measure of the body's ability to eliminate the drug

• It is the ratio of rate of elimination to the concentration of drug.
Order of Kinetics

Rate of Elimination α (Plasma Concentration) order

1. Zero order kinetics

2. First order kinetics

Zero order kinetics

Rate of Elimination α (Plasma Concentration)0

(Plasma Concentration) 0 = 1

• Rate of elimination is independent of plasma concentration

• Rate of elimination is constant.

• CL decreases with increase in concentration

• A constant amount of the drug is eliminated in unit time

First order kinetics
• Rate of Elimination α (Plasma Concentration) 1

• Rate of elimination is proportional to plasma concentration for drugs

• CL remains constant

• A constant fraction of the drug present in the body is eliminated in unit time.
 First order kinetics
Zero order kinetics

(Plasma Concentration) 1
(Plasma Concentration) 0 = 1
• Rate of elimination is proportional to plasma
• Rate of elimination is constant. concentration for the drugs

• CL remains constant

• CL decreases with increase in

concentration

• A constant fraction of the drug present in the

body is eliminated in unit time.
• A constant amount of the drug is
eliminated in unit time
MNEMONIC

Zero - Zero order kinetics shown by

W - Warfarin
A - Alcohol and Aspirin
T - Theophylline
T - Tolbutamide
Power - Phenytoin
True about zero order kinetics:

a. Rate of elimination is independent of plasma concentration

b. Rate of elimination is dependent on plasma concentration

c. Clearance of drug is always constant

d. Half-life of drug is constant

True about zero order kinetics:

a. Rate of elimination is independent of plasma concentration

b. Rate of elimination is dependent on plasma concentration

c. Clearance of drug is always constant

d. Half-life of drug is constant

 Pharmacology

• Pharmacokinetics • ANS

• CNS
• Pharmacodynamics
• GIT
• Antimicrobial drugs
• Endocrine
• Renal system
• Autocoides
• Respiratory sustem
• Blood
• CVS
• Anticancer drugs
All receptors have 2 properties 

• Affinity
• Intrinsic activity
 Affinity
• Ability of a drug to combine with the receptor

• If a drug has no affinity, it will not bind to the receptor.

 Intrinsic activity
• After binding to the receptor, the ability of drug to activate the receptor is called its
intrinsic activity

• It varies from -1 through zero to +1

• Based on their intrinsic activities  Drugs may be divided into 4 types

1. Agonist

2. Partial agonist

3. Antagonist

4. Inverse agonist
• Agonist  IA is +1  Bind to the receptor and activate it maximally similar to that of
physiological signal molecule

• Partial agonist  IA between 0 and +1  It bind with receptor and activates it

submaximally similar to that of the physiological signal molecule 

• Antagonist  IA is 0  Binds to receptor but produces no effect  But now agonist

is not able to bind to the receptor because these are already occupied by the antagonist
 it decreases the action of the agonist but itself has no effect.

Inverse agonist  IA is -1 bind to receptor and produce opposite effect

Dose Response Curve (DRC)

• It is a graph between the plasma concentration of drug (on X-axis) and the
effect/ response produced by the drug (on Y-axis)

• Generally, the intensity of response increases with increase in dose and the dose-
response curve is a rectangular hyperbola
• DRC is usually hyperbola in shape.

• As curved lines cannot give good

mathematical comparisons, so usually the
dose is converted to log dose to form log
DRC, which gives a sigmoid shaped
curve
Important parameters determined from DRC

1. Potency

2. Efficacy

3. Slope

4. Therapeutic index and Therapeutic range

 Potency

• Measure of amount of a drug needed to produce the response (x axis)

• Drugs producing the same response at lower dose are more potent whereas drugs
requiring large dose are less potent

• In DRC, more a drug is on left side of the graph, higher is its potency and a drug is on right
side of the graph, lower is its potency
Efficacy

• It is the maximum effect produced by a drug (y axis)

• In DRC  More peak of the curve greater is the efficacy.

Which is more important???
• Efficacy is clinically more important
than potency

• Efficacy is a more decisive factor in the

choice of a drug
 Remember

• The position of DRC on the dose axis (X axis)

is the index of drug potency which refers to
the amount of drug needed to produce a
certain response

• The upper limit of DRC (Y axis) is the index

of drug efficacy and refers to the maximal
response that can be elicited by the drug
QUESTIONS???
Question 1
Compare Drug A and C ?
• POTENCY 'A' is more is potent than 'C’

• EFFICACY Drug 'A' and 'C' have equal efficacy

Compare Drug A and B ?
• POTENCY Drugs 'A' and 'B' are equipotent

• EFFICACY  A is more efficacious than B

Compare Drug B and C ?
• POTENCY Drug ‘B' is more potent than C

• EFFICACY  Drug ‘C’ is more efficacious than B

Question 2
Compare Drug A and B ?
• POTENCY Drug B is less potent than drug A

• EFFICACY  Drug B equally efficacious as drug A.

Important parameters determined from DRC

1. Potency

2. Efficacy

3. Slope

4. Therapeutic index and Therapeutic range

 Slope

• Steep slope indicates that a little increase

in dose will markedly increase the
response (dose needs individualization)

• Flat slope implies that little increase in

response will occur over a wide dose
range
Important parameters determined from DRC

1. Potency

2. Efficacy

3. Slope

4. Therapeutic index and Therapeutic range

 Therapeutic index/Safety margin
• Gap between the therapeutic effect DRC and the adverse effect DRC
• Median Effective Dose (ED50): It is the dose that will produce the half of the maximum
(50%) response. More is ED50, lower is the potency and vice a versa.

• Median Lethal Dose (LD50): It is the dose that will result in death of 50% of the animals
receiving the drug. More is LD50 safer is the drug.
• Therapeutic Index (T.I) is a measure of
the safety of a drug.

• Drugs having high T.I are safer

whereas those having low T.I are more
likely to be toxic.
Therapeutic range / Therapeutic window
• Dose which produces minimal therapeutic effect and the dose which produces
maximal acceptable adverse effect
Drugs which have low Therapeutic range / Therapeutic window

Plasma concentration has to be monitered regularly

Therapeutic Dose Monitoring (TDM)

MNEMONIC

TDM is required for

A - Aminoglycosides (e.g. gentamicin)
Drug - Digitalis
Possessing - Phenytoin (anti-epileptics)
Low - Lithium
Therapeutic - Tricyclic antidepressants
Index - Immunomodulators
 Pharmacology

• Pharmacokinetics • ANS

• CNS
• Pharmacodynamics
• GIT
• Antimicrobial drugs
• Endocrine
• Renal system
• Autocoides
• Respiratory sustem
• Blood
• CVS
• Anticancer drugs
Antimicrobials  Based on Mechanism of action

1. Inhibit cell wall synthesis

2. Cause leakage from cell membranes

3. Inhibit protein synthesis

4. Interference with nucleic acid synthesis

Antimicrobials  Based on Mechanism of action

1. Inhibit cell wall synthesis

2. Cause leakage from cell membranes

3. Inhibit protein synthesis

4. Interference with nucleic acid synthesis

Antimicrobials  Based on Mechanism of action

1. Inhibit cell wall synthesis

2. Cause leakage from cell membranes

3. Inhibit protein synthesis

4. Interference with nucleic acid synthesis

 Beta-Lactam Antibiotics
• Antibiotics having a β-lactam ring.

1  Thiazolidine ring
2  Beta lactam ring
Classification

1. Penicillins

2. Cephalosporins

3. Carbapenems

4. Monobactam
Mechanism of action

• Interfere with synthesis of bacterial cell wall

Cell wall consist of

1. UDP-N-acetylmuramic acid (NAM) pentapeptide

2. UDP-N-acetyl glucosamine (NAG)
 Normally
UDP- NAM and UDP- NAG

Peptidoglycan residues linked together forming

long strands and UDP is split off

Final step is cleavage of terminal D-alanine of

peptide chains by transpeptidases

Energy so released is utilized for establishment

of cross linkages

This cross linking provides stability and rigidity

to cell wall
 β-lactam antibiotics
β-lactam antibiotic

Inhibit the transpeptidases

cross linking does not take place

cell wall deficient (CWD) forms produced

CWD forms swell and burst

Bacterial lysis

Bactericidal action
• Bactericidal

• Active against multiplying organisms only

• Penicillin  higher susceptibility for gram-positive bacteria

1. In gram-positive bacteria  cell wall consists of thick layer of

peptidoglycan and extensively cross linked

2. In gram-negative bacteria  cell wall consists of thin layer of peptidoglycan

with little cross linking
Gram-positive bacteria Gram-negative bacteria
Mechanism of Antimicrobial Resistance
1. Decreased Permeability across the Cell Wall  by
modifying their cell membrane porin channels

2. Efflux Pumps  expulsion of the drugs from

the cell, soon after their entry  preventing
intracellular accumulation of drugs
 3. By Enzymatic Inactivation  Eg . β-lactamase,
penicillinase
Most common mechanism

β-lactamase enzymes

Hydrolyze β-lactam rings (active site) of β-lactam

antibiotics

Deactivate their antibacterial properties

4. Altered PBPs that lacks the binding affinity for
penicillin  MRSA 

Target site of penicillin i.e. penicillin binding

protein (PBP)

Gets altered to PBP-2a

Do not sufficiently bind to β-lactam antibiotics

Prevent them from inhibiting cell wall synthesis

Classification

1. Penicillins

2. Cephalosporins

3. Carbapenems

4. Monobactam
 Penicillins

• First antibiotic to be used

• Discovery of penicillin  Alexander Fleming

• Natural penicillin is obtained from a fungus Penicillium notatum and Penicillium

chrysogenum.
 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
Benzyl Penicillin or Penicillin G
Limitations in its clinical use

1. Not effective orally  because of

breakdown by acid in stomach

2. Susceptibility to penicillinase 
Penicillinase hydrolyze β-lactam
rings (active site) Deactivate
their antibacterial properties

3. Narrow spectrum of activity 

covering mainly gram positive
bacteria.
Adverse effects
1. Local irritancy

2. Hypersensitivity reactions

3. Jarisch-Herxheimer reaction 
Penicillin injected in a syphilitic patient

sudden release of spirochetal lytic products

Produce shivering, fever, myalgia, exacerbation of lesions, even vascular collapse.

Lasts for 12–72 hours

Does not need interruption of therapy, Aspirin and sedation for relief of symptoms.
Uses

• Theuraptic Uses  LAST MAN DP

• Prophylactic uses  RAB

 Theuraptic Uses

LAST MAN DP
• L - Leptospira
• A - Actinomyces
• S – Streptococcus, Staphylococcus (non-penicillinase-producing)
• T – Treponema, Tetanus (and Gas gangrene)
• M - Meningococcus
• AN – Anthrax, Actinomycosis
• D – Diptheria
• P _ pnemococcus
 Prophylactic uses

RAB

1. Rheumatic fever  Benzathine penicillin 1.2 MU every 4 weeks till 18 years of age
or 5 years after an attack, whichever is more.

2. Agranulocytosis patients

3. Bacterial endocarditis  Dental extractions, endoscopies, catheterization, etc. cause

bacteremia which in patients with valvular defects can cause endocarditis.
 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
Semisynthetic Penicillins

• Aim  to overcome the shortcomings of PnG,

1. Poor oral efficacy due to acid succeptibility

2. Susceptibility to penicillinase.

3. Narrow spectrum of activity

 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
Phenoxymethyl penicillin (Penicillin V)
• It differs from PnG only in that it is acid stable.

• Oral absorption is better

• Peak blood level is reached in 1 hour
• Plasma t½ is 30–60 min.
Acid-resistant penicillins

V - Penicillin V
O-Oxacillin
D- Dicloxacillin
K-Cloxacillin
A - Amoxycillin and Ampicillin
 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
 Penicillinase-resistant Penicillins

• Have side chains that protect the β-lactam ring from attack by penicillinase
Methicillin

• Highly penicillinase resistant ie. resistant to β- lactamases

• But it is not acid resistant  must be injected

 MRSA
• MRSA have emerged in many areas.

• MRSA have altered PBPs which do not bind penicillins.

• These are insensitive to all penicillinase-resistant

penicillins

• All MRSAs  multidrug resistance

• DOC  vancomycin, linezolid and teichoplanin

 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
Extended Spectrum Penicillins

1. Aminopenicillins

2. Carboxypenicillins

3. Ureidopenicillins
1. Aminopenicillins

• This group has an amino substitution in side chain

• Ampicillin is the prototype

• Acid stable
• Not resistant to penicillinase or β-lactamases

• Spectrum It is active against all organisms sensitive to PnG.

• In addition, many gram-negative bacilli  e.g. H. influenzae, E. coli, Proteus,
Salmonella , Shigella and Helicobacter pylori are inhibited.
 2. Carboxypenicillins

• This group has an carboxy substitution in the side chain

• Carbenicillin is the prototype

• It is not acid resistant (inactive orally)

• It is not penicillinase-resistant

• Spectrum  Active against Pseudomonas aeruginosa and Proteus which are

not inhibited by PnG or aminopenicillins.

• Platelet aggregation affected

3. Ureidopenicillins

• Piperacillin is the prototype

• Spectrum  8 times more active for pseudomonas than carbenicillin.

• Activity against Klebsiella, many Enterobacteriaceae and some Bacteroides.

 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
Beta-lactamase Inhibitors
• Three inhibitors of β-lactamases enzyme 

1. Clavulanic acid (combined with amoxicillin)

2. Sulbactam (combined with ampicillin)
3. Tazobactam (combined with piperacillin)
 Mechanism of action

β –lactamase enzyme produced by various

organisms

Hydrolysis of β-lactam ring of penicillins (β -

lactam antibiotics)

Reduces their effectiveness

β - Lactamase inhibitors have a β -lactam
ring

It binds to β - lactamase

Inhibits them

Protect β -lactam antibiotics from

destruction

Increase the effectiveness of β -lactam

antibiotics
Remember

• β-lactamase inhibitors themselves are not antibacterial

• But augment the activity of penicillins against β-lactamase producing organisms

 Penicillins

Natural penicillin Semisynthetic Penicillins β-lactamase inhibitors

CST
Benzyl
Benzyl penicillin
penicillin Clavulanic
Clavulanic acid
acid
(Penicillin
(Penicillin G)
G) Sulbactam
Sulbactam
Tazobactam
Tazobactam
Acid resistant Penicillinase Extended spectrum
Alternative to resistant Penicillins
Penicillin G Penicillin
CONDOM Amino Ureido
Phenoxymethyl
Phenoxymethyl Penicillins Penicillin
Penicillin
Penicillin Cloxacillin
Cloxacillin AA MAP
(Penicillin
(Penicillin V)
V) Oxacillin
Oxacillin Carboxy
Nafcillin Ampicillin
Ampicillin Penicillins Mezlocillin
Mezlocillin
Nafcillin
Dicloxacillin Amoxycillin
Amoxycillin CT Azlocillin
Azlocillin
Dicloxacillin
Methicillin Piperacillin
Piperacillin
Methicillin Carbenicillin
Carbenicillin
Ticarcillin
Ticarcillin
The following is not a penicillinase resistant penicillin-

a) Methicillin

b) Ampicillin

c) Oxacillin

d) Nafcillin
The following is not a penicillinase resistant penicillin-

a) Methicillin

b) Ampicillin

c) Oxacillin

d) Nafcillin
Acid Labile penicillin is-

a) Cloxacillin
b) Ampicillin
c) Methicillin
d) Phenoxy Methyl penicillin
Acid Labile penicillin is-

a) Cloxacillin
b) Ampicillin
c) Methicillin
d) Phenoxy Methyl penicillin

Acid-resistant penicillins

V - Penicillin V
O-Oxacillin
D- Dicloxacillin
K-Cloxacillin
A - Amoxycillin and Ampicillin
Which among the following is not a beta lactamase resistant Penicillin?

a) Methicillin
b) Carbenicillin
c) Nafcillin
d) Oxacillin
Which among the following is not a beta lactamase resistant Penicillin?

a) Methicillin
b) Carbenicillin
c) Nafcillin
d) Oxacillin
All of the following are therapeutic uses of penicillin G, except

a) Bacterial meningitis
b) Rickettsial infection
c) Syphilis
d) Anthrax
All of the following are therapeutic uses of penicillin G, except

a) Bacterial meningitis
b) Rickettsial infection
c) Syphilis
d) Anthrax
All of the following are beta lactamase inhibitors except-

a) Clavulanic acid
b) Sulbactam
c) Tazobactam
d) Aztreonam
All of the following are beta lactamase inhibitors except-

a) Clavulanic acid
b) Sulbactam
c) Tazobactam
d) Aztreonam
True regarding clavulanic acid is

a) Deactivates beta lactamase

b) Decreases renal excretion of amoxycillin
c) Potentiates action of penicillin
d) Decreases the side effects of amoxicillin
True regarding clavulanic acid is

a) Deactivates beta lactamase

b) Decreases renal excretion of amoxycillin
c) Potentiates action of penicillin
d) Decreases the side effects of amoxicillin
Some gram-negative bacteria produce an enzyme that blocks the action of
beta lactam antibiotics in periplasmic space. Which arrow in the structural
diagram of Penicillin G denotes the site of action of this enzyme?

a) A
b) B
c) C
d) D
Some gram-negative bacteria produce an enzyme that blocks the action of
beta lactam antibiotics in periplasmic space. Which arrow in the structural
diagram of Penicillin G denotes the site of action of this enzyme?

a) A
b) B
c) C
d) D
THANK YOU

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