LECCTURE OF PHARMACOLOGY

MADE BY NURSING ZONE TEAM

L4. Chemotheraputic agents I

THIRD YEAR

@Nursing_Zone39
 Chemotherapy:Any Drug that take to treat infection.

Hmmmm
• Antibacterial antibiotics.
Classification

Team
• Antimyobacterium antibiotics.
of chemotherapy : • Antifungal antibiotics.
• Antiviral antibiotic.
• Anthelmithics.
• Anticancer drugs. • Antiprotozoa.
• Immunopharmacology drugs. All above Anti-infectives

Not Anti-infectives The use of drugs that are selectively toxic to invading “

because the infection is from inside the body. microorganisms “ but having minimal effects on the “ host “ or
human “

1- Antibacterial antibiotics.. C-Stationary

A-Lag (or adaptive
phase:
-Bacterial Growth Curve . phase):adaptation of
-Spectrum of the activity of antibacterial antibiotics.
nutrients
become less
so bacteria to new media,
“ what works and which of bacteria no growth
And waste
and Bacterial
microbes “ accumlates
-Step by step factors prescription of drugs. reduction of growth B-Logarithmic
growth. (or Static effect
-Patient Factor. curve exponential
-Drugs combinations. phase):
“ interfering with the medication “ D-Decline Bacteria
-Sites of antibiotics action phase: lack of doubles.
“ the site of working “. nutrients
-Classification of antibacterial antibiotics. Bacterial death

Step by step prescription of drugs. Spectrum of the activity of antibacterial

antibiotics
if there is no allergic to the drug we 1- Bacteristatic drug :
implemented the “ first line “ stops growth of bacteria
and if there is allergic to the drug we “ catches bacteria and then it delivers it to
move to “ second line “ immune system to get it rid of it “
and change the drug ( e.g : Chloramphenicol- Sulfonamides -
Tetracyclines )
2- Bactericidal drug :
Kills Bacteria
( e,g: Pencillin )
 • Patients factors
We must be attention when we select an antibiotics.

Hmmmm
Women:
Kidney, liver
Patient’s
pregnancy or
circulation.
immune liver
Age
breastfeeding system .

Safe in pregnancy
Can use
do we give

-Pencillin
( Bacteristatic drug or
- Cephalosporins Bactericidal drug )
- Erythromycins

Contraindicated in all trimester Contraindicated in lactating mothers Contraindicated in the last trimester
“ Not use in all months “ Not use “ 7 , 8 , 9 months “ Not use

Tetracyclines -Sulpha drug

- Tetracycline -Sulpha drug
- Quinolones
- Nitrofurantion - Nitrofurantion
- Streptomycin
- Quinolones
- Clarithromycin
- Chloramphenicol
- Metronidazole

Sites of antibiotics action..

Drugs Antibiotics can work in different places:
combinations

Cell Wall. Cell

membrane.

Disadvantages of drug
Tetrahydro-
• Advantages of drug
combinations combinations
folate Protein
Beta lactams and Bacteriostatic tetracycline may synthesis.
interfere with bactericidal of
aminoglycosides Gryrase-
Pencillin or cephalosporine
( synergism ) inhibitors
( Antagonism )
Nitroimidazotes
 Classification of antibacterial antibiotics
( Antibiotics can be classified according to )

Hmmmm
A-Spectrum
of activity
B-According to
mechanism of
action :

• Medically important microorganisms. • Cell wall synthesis: cycloserine - bacitracin - beta

• Isoniazid: a narrow-spectrum antimicrobial
drug.
“ their action limited”
• Ampicillin : an extended-spectrum
antimicrobial drug
“ their action is a little limited “.
• Tetracycline: a broad-spectrum antimicrobial
drug.
“ their action is not limited “
lactams - glycopeptides .
• Folic acid metabolism: trimethoprim - sulfonamides.
- sulfones
• Cell membrane : polymyxins.
• DNA replication: Quinolones - nitroimidazoles
• DNA dependent RNA polymerase: rifamycins
• Protein synthesis: aminoglycosides - macrolides
lincosamides - streptogramins -amphenicols -
tetracyclines- rhupirocin.

A-inhibitors of cell
wall synthesis
“ antibiotics inhibit
r
E-Inhibitors of DNA
gyrase.
z Classification of
formation of cell
wall “
antibacterial
antibiotics
according to r
mechanism of B-Inhibitors of cell

r action ( MoA) membrane.

D-Inhibitors of folate
synthesis .

E
C-Inhibitors of protein
synthesis.
A- inhibitors of cell wall synthesis
i-B-lactams..
Hmmmm
1-penicillin..
-MoA: inhibit transpeptidases wich is responsible for assembly , maintenance , regulation
of bacterial wall . Thus bacterica get lysed The penicillin non toxic to human (selectivity)
2-B-lactamase inhibitors..
-Enzymes produced by G+ & G- bacteria,
wich can inactivate B-lactem antibiotic , this
develops resistance to the antibiotic
Clavulanic acid : add to other antibiotics
(penicillin) to enhance thire activity and
give Augmentin reaction
A) amoxicillin + clavulanic acid=
co-amoxiclav
B) Ticarcillin +clavulanic acid =
co-ticarclav
-Clinical uses of penicillin:
1) streptococcal infection. 2)meningococcal
infl ation. 3) gonorrhea 4)syphilis
5)diphtheria. 6)tetanus and gas gangrene
-Prophylactic uses of penicillin:
1) rheumatic fever. 2)gonorrhea & syphilis.
3) bacterial endocarditis. 4)agranulocytosis
patient
-Adverse effects of penicillin:
1) hypersensitivity. 2)nephritis.
3) neurotoxicity , seizures. 4)platelet
dysfunction
3-Sephalosporins
Now ara semisyntheticlly produced , you
shouldn’t mixed with Cephamycins.
-Classification according bacterial
susceptibility & B-lactamases
resistance:
1st : cefradin , cephalexin , cefradoxil.
2nd : cefuroxime , cefalcor, cefprozil.
3rd : cefotxime , ceftazidime , ceftriaxone.
(Replaced 1st).
4th : cefi pime , cefpriome.
-Pharmacokinetics (ADME) :
• Administered IV & IM.
• 3rd generation good concentration in CSF.
• Eliminate by tubular secretion.
• Ceftriaxone & cefoperazone excreted in
bile (use in renal insuffi ciency)
-Clinical use :
Alternative to penicillin in : respiratory
& urinary infection , staphylococcal infection,
meningitis , typhoid fever
-adverse effects : hypersensitivity,
nephrotoxicity. , diarrhea. , bleeding ,
disulfi ram like reaction , neutropenia
 4- Carbapenems (imipenem) 5- Monobactam (Aztreonam)
• Broad spectrum B-lactam antibiotics & resist • inhibit G- rods . No activity against G+ .

Hmmmm
most lactamases.
• low immunogenic potential; less cross-
• limiting use because dehydropeptidase
linking & hypersensitivity so penicillin
toxicity inactive metabolite , but if we add
allegic patient tolerate it .
enzyme inhibitor like Cliastatin will give
• main indication :Hospital Aquired
prolonged antibacterial action .
• use for patient with : neutropenia or Infl ation, Only given IM&IV.
esinophilia

ii-Glycopeptides (Vancomycin )
-MoA : inhibit bacterial cell wall synthesis it’s bactericidal ,except streptococci it’s bactristatic.
-pharmacokinetics: poor absorbing orally , given slowly IV for 60-90 min.
-clinical uses : 1)drug of choice for infection. 2)restricted to serious infection .
-adverse effects: 1) flushing, hypotension, shock (red man syndrome ) after rapid IV injuction.
2) neurotoxicity & ototoxity.

B- inhibiting of cell membrane (polymixin).

-MoA : have cationic detergent properties, which distribute cell

membrane phospholipids and lead to bacterial death.
-pharmacokinetics (Abs,Disturb,Elim) : not absorbed from GIT ;
only used topically (ointments, cream , drops)
-Clinical use : selectivity rapid bactricidal action on G- bacilli, use
limited for thire toxicity, also use for eye , ear , skin infections
treatments
-adverse effects: serious and include sever neurotoxicity &
nephrotoxicity
 Classification of Protein synthesis inhibitors..
Drugs that a ect 30S ribosomes

Hmmmm
1.Tetracycline:
MoA: act by inhibiting bacterial
protein synthesis, via targeting
2. Glycylcyclines:
MoA:
• Tigecycline is the first available
3.AMINOGLYCOSIDES:

bacterial ribosomes. Selectively:-
usually they spare (do not affect)
mammalian ribosomes at the dose
used regularly.( Ca+2, Mg+2,
Fe+2, Al+3) .
Pharmacokinetics: Absorption:
• Oral bioavailability of tetracycline
~ 50%.
• Oral absorption is impaired by
chelation with cations
( Ca+2, Mg+2, Fe+2, Al+3) and
milk.
Distribution:
• Crosses the placenta.
• Tetracyclines concentrate in liver
and kidney and bind to tissues
which have high calcium content
(bone & teeth).
Excretion:
Excreted in both faeces and urine.
Clinical antimicrobial uses:
Rickettsiae / Chlamydia Cholera /
Plague Acne vulgaris. Pneumonia
Aminoglycosides "irreversibly"
member of this class.
bind to 30S subunit.
• Is a derivative of minocycline,
is structurally similar to the Pharmacokinetic:
tetracyclines. Single daily dose: is more
Action and MoA: e ective and less ototoxic and
It has a broad spectrum nephrotoxic.
activity against : multidrug- Clinical uses:
resistant Streptococcus • Urinary tract infections UTI.
pneumoniae, vancomycin- • Plague.
resistant enterococci, & MRSA , • Tuberculosis.
some gram-negative organisms, Adverse e ects of
and anaerobic organisms.
aminoglycosides:
Clinical use:
• Tigecycline is indicated for • Ototoxicity (could lead to deaf).
• Nephrotoxicity
treatment of complicated skin
and soft tissue infections & • Neuromuscular blockade.
complicated intra-abdominal • Paralysis: rarely.
infections. • Contact dermatitis – Neomycin

Drugs that a ect 50S ribosomes

• These group of anti-microbials contains a

lactone ring.
• These are used in patients allergic to beta-
5.Macrolides.
lactam antibiotics.
• Now many in use including Erythromycin, ..‫ﻳﺘﺒﻊ‬
clarithromycin and azithromycin.
 MoA:
Inhibits the translocation of the newly synthesized peptides.

Hmmmm
Clinical uses:
• Regarded as safe drugs, and used as alternatives in penecillin patients.
• Mycoplasma infections. • Chlamydia infections.
• Corynebacterium diphtheriae infections.• Atypical mycobacterium infections.

Kinetics:
• Erythromycin is inactivated by gastric acid.
Adverse e ects:
•Epigastric distress: more with erythromycin.
• Cholestatic jaundice.
• Ototoxicity: erythromycin at high dose.
Drug - drug interactions:
Erythromycin, Clarithromycin and Telithromycin inhibit the cytochrome
P450 system, and so potentiate the activity of some drugs.

6. Chloramphenicol
MoA: It binds to the 50S subunit of the bacterial Ribosome, preventing the transpeptidation reaction.
Pharmacokinetics: Good concentrations in the CSF.
Clinical uses: Used only for life threatening: Haemophilus influenzae infections (resistant to other drugs);
and meningitis (achieves high concentration in CNS) in patients in whom penicillin cannot be used. For
typhoid fever; and for bacteroides infections
Adverse e ectopic:
• Pan-cytopenia.
• Reversible hemolytic & aplastic anemia (due to suppression of bone marrow)
• Gray baby syndrome (mainly in premature neonates): New born lacks an e ective glucuronide conjugation and
detoxification mechanism, consequently.
• Super-infections with Candida albicans • Optic neuritis in children.
Drug-drug interactions:
• Chloramphenicol inhibits cytochrome P450 enzymes so prolonging the half- life of several drugs including phenytoin,
coumarins and tolbutamide.
D-Targeting the synthesis or action of folate E-Targeting DNA gyrase (DNA topoisomerase)

Hmmmm
Clinical uses:
-Sulfonamides+trimethoprim= co-trimoxazole: for
Pneumocystis carinii (cause life threatening
pneumonia especially in HIV patients).
Adverse effects:
-Nausea, vomition, headache, mental depression.
Cyanosis caused by methaemoglobinaemia (not
serious).
Serious effects:
hepatitis, hypersensitivity reactions
(rashes: Stevens-Johnson syndrome, sensitivity to
the sun which may lead to extensive sun-burn,
fever, anaphylactoid reactions)
The enzyme gyrase (topoisomerase II)
permits the orderly accommodation of a
~1000 μm long bacterial chromosome
in a bacterial cell of ~1 μm.
Within the chromosomal strand, double-
stranded DNA has a double helical
configuration.
The former, in turn, is arranged in loops
that are shortened by supercoiling. The
gyrase catalyzes this operation: by
opening, underwinding, and closing the
DNA double strand such that the full loop
need not be rotated.

Clinical use

1-Fluoroquinolones
-Norfloxacin:
Include the broad spectrums: ciprofloxacin,
Bacterial prostatitis
levofloxacin, ofloxacin, norfloxacin and
-Ofloxacin:
moxifloxacin; as well as a narrow spectrum drug
Cervicitis
used in urinary tract infections: nalidixic acid -Anthrax
Low toxicity. (the first quinolone and not fluorinated).
Mild side e ects: Mode of Action:
frequent GIT Interferes with the supercoiling of bacterial DNA
(Nausea, diarrhea, ,Bacteriocidal.
liver abnormalities)
and skin rashes.

Adverse e ects
MADE BY NURSING ZONE TEAM

Pharma references

A- Basic and Clinical Pharmacology 13 E Paperback

Bertram Katzung (Author), Anthony Trevor (Author) Publisher: McGraw-Hill Medical; 13 edition
(December 23, 2014)
Language: English
ISBN13:97 0071825054
ISBN 10:0071825053
B. Lippincott Illustrated Reviews: Pharmacology 6th edition (Lippincott Illustrated Reviews Series)
Paperback
Karen Whalen PharmD BCPS (Author) Edition: Sixth, North American.
Edition Language: English. ISBN-13: 978-1451191776 ISBN-10: 1451191774
2. List Essential References Materials (Journals, Reports, etc.) British National Formulary (BNF)