prontosil sulfonamide - un.uobasrah.edu.iq

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Chemotherapy: this term is refers to treatment of disease by chemicals that

kill cells, specifically those of micro-organism (virus ,bacteria, fungi,

protozoa, and parasites) or cancer.

*1877: Louis Pasteur, discovered bacterial diseases .

*1900:Ehrlish was working on tissue dyes with in Arsenic derivatives

(salvarsan) which effective against trypanosoma (sphlis) ,but later they found

that arsenic causes hepatotoxicity or nephrotoxicity .

** selective toxicity ( S.T) :

The substance or drug which inhibit or kill the M.O selectively with no or

little effect on host .

*1929:Fleming discover penicillin

*1939:Domagk developed the prontosil from red tissue dye .

prontosil sulfonamide

*1940:Florey used the penicillin as drug .

*1942:Waksmas ,define the antibiotic substance produce from the living

M.O which inhibit or kill the another living M.O

Waksmas Streptomycin

Antibacterial not antibiotic.

Antibacterial include chemical drug and antibiotic .

*Antibiotic :is a substance or compound (made from a living source) that kill

or inhibit the growth of bacteria .

*Antibacterial : is a substance or compound that kills or inhibit the growth of

bacteria

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Classification of Antibacterials :

There are -4- ways to classify the antibacterial they are :

1-according to the nature:

a-synthetic chemical e.g. sulfonamide.

b-antibiotic e.g. penicillin G.

c-semi synthetic ( modified the antibiotic ) e.g. ampicillin, carbenicillin

2-according to the effectiveness:

a- Bactericidal : (agent that destroys or kills bacteria )

e.g. penicillin, amino glycoside , cephalosporin

(narrow spectrum)

b- Bacteriostatic: (agent that inhibits the growth or reproduction of bacteria)

. e.g. tetracycline , chloramphenicol ,erythromycin ,sulfonamide.

(broad spectrum)

3- according to the spectrum :

a- narrow spectrum : (agent acting only on single or limited group of

micro-organisms ) . e.g. penicillin G, amino glycoside like streptomycin

.

b- broad spectrum :(agent that effective against G+ also against G-

bacteria). e.g.ampicillin , chloramphenicol , tetracycline

c- extend spectrum : (agent that effect on a wide range arity of

M.O ) e.g. enrofloxacin , sulfa and trimethoprim .

4- according to the mechanism of action :

a- antibacterial which inhibit cell wall synthesis.

β – lactum ring

b- antibacterial which inhibit protein synthesis they effect on ribosome

which effect to 30s and 50s :

1- binding irreversibly to 30s, e.g. aminoglycosides , streptomycin

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2-binding reversibly to 30s , e.g. tetracycline

3- binding reversibly to 50s , e.g. chloramphenicol , macrolides ,

erythromycin , lincocins.

c- antibacterial which effect on permeability of cell membrane they act as

detergent cell membrane . e.g. polymyxins

d- antibacterial which inhibit synthesis of folic acid (antimetabolites) e.g.

sulfonamides and trimethoprim.

e- antibacterial which inhibit RNA synthesis e.g. rifampin ( (for

tuberculosis ).

f- antibacterial which inhibit DNA synthesis e.g. 1- fluroquinolone :

enrofloxacin ,flumequine 2- nitrofurans : furaltidone.

** Resistance of M.O to antibacterial :

- Drug resistance :temporary or permanent capacity of micro-organism to

remain viable or multiplying in presence of certain concentration of

antibacterial which would destroy another similar M.O.

- type of resistance :

1-intrinsic ( natural ) resistance :

It is naturally resistant to antibacterial without prior exposure to the

antibacterial because of the lack of receptor on the M.O.

e.g. mycoplasma . naturally resistance to penicillin because of lack the cell

wall .

2- acquired resistance :

It is resistance of M.O which due to prior exposure to certain antibacterial or

transferred from another M.O.

*acquired res. Consist by- 2- ways:

1-either from using sub lethal or sub inhibitory concentration for long time

and become resistance .

2-transfer from other resistance M.O (more common )

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*Transferable resistance :

It is an extra chromosomal piece of DNA which carry genes (code)for

resistance is called resistance factor .

Resistant factor consist of 2 parts :

1- resistance determent (RD)

2- resistance transfer (RTS)

*mechanism of resistance :

1-codes for enzymes which destroy or change the structure of antibacterial

-penicillinase only for penicillin .

-acetyl transferase for chloramphenicol.

-adenylase , phosforylase , acetylase for amino glycosides .

2-codes for decrease or prevent entry (uptake ) of antibacterial in side of M.O

e.g. aminoglycosides

3- decrease the affinity of binding of antibacterial to it is binding site e.g.

tetracycline

4-change the shape or structure of binding site .

*method of transfer bacterial resistance :

1-conjugation : transfer the R.F from R.M.O (donor) to non R.M.O by direct

contact through piles (bridge).

2-transduction : transfer of RD after multiplication by bacteriofage from

R.M.O to non R.M.O

3-transformation :transfer of RF from R.M.O after lyses to non R.M.O

4-transposon:part of plasmid which contain one gene cod which jumped from

plasmid to plasmid or from plasmid to chromosome or from chromosome to

plasmid inside the organism.

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Penicillin

-discovered by Fleming 1929 ,produced by penicillinum natatum , contain β

–lactam ring (6- amino pencillinic acid)

-mechanism of action :

Inhibit the cell wall synthesis by

inhibiting the rigidity of peptidoglycan layer by inhibiting the transpeptidase.

enzyme .

• Penicillins can be divided to four groups they are:-

1- Natural(Basic) Penicillins:

- They are narrow spectrum, bactericidal, and penicillinase sensitive

(Penicillinase is specific type of -lactamase, affect the penicillins by

hydrolysing the -lactam ring).

- There are two types of natural penicillins they are:

a- Penicillin G: (Benzyl penicillin, Procain penicillin,

Benzathine penicillin): It was the first of the penicillins, and remains an important and useful

antibiotic,it is particularly active against Gram-positive bacteria, sensitive

micro-organisms include Gram positive streptococci, Gram-positive

Bacilli, Gram-negative cocci (Neisseria), most anaerobic bacteria

including Clostridium and Spirochetes.

-Staphylococcus aureus resist natural penicillins because of its ability to

produce penicillinase (β-lactamase)

Penicillin G is inactivated by gastric juice (Acid labile) so that it not

administrated orally but used via other routes like intravenous and

-

-

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Intramuscular.

b-Penicillin V: (Phenoxymethyl penicillin)

- Semi synthetic penicillin, it has similar bacterial effect to Penicillin G.

Penicillin V is acid stable in contrast to Penicillin G therefore it can be

administred orally.

2- Antistaphylococcal (penicillinase resistant) Penicillins:

They are semi-synthetic, narrow spectrum, acid stable (can be

administrated orally) and penicillinase resistant penicillins.

These antibiotics are effective against streptococci and most community-

acquired

Penicillin-resistant staph. infection (drug of choice).

Examples; Nafcillin, oxacillin, cloxacillin, and dicloxacillin

3-Aminopencillins (extended spectrum pencillins):

Semi –synthetic ,extended spectrum ,acid stable and penicillinase sensitive

penicillins .they have an antibacterial spectrum similar to penicillin G but

more effective against Gram-negative bacilli ,they have given orally and

paraenterally .

Examples : Ampicillin , Amoxicillin and Pivampicillin.

4-Antipseudomonal penicillins:

Semi-synthetic, broad spectrum, acid labile and penicillinase sensitive

penicillins.

Examples; Carbencillin, Mezlocillin, piperacillin, and ticarcillin.

Clinical problems with penicillins :

1- Narrow spectrum: it corrected by administration of extended or

broad spectrum penicillins instead of narrow spectrum penicillins

2- Acid lability: it corrected by administration of acid stable penicillins .

3- Short Half- life: it corrected by increase the half life of penicillins

by using of probencid which blocks the tubular secretion of penicillin .

thereby prolonging it is half-life.

4- Penicillinase sensitivity: it solved by using of Clavulanic-

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suitable penicillin .

Side effect of penicillins:

1-hypersensitivity : it range between skin rash to anaphylactic shock lead to

death.

2-oral penicillin it cause GIT disturbance (diarrhea) due to effect to normal

micro flora of the GIT , e.g. fungus and bacteria(E coli)and cause

diarrhea.

3-slight nephrotoxicity .

4-neurotoxicity :penicillins irritant to the neural tissues so that they induce

seizures .

Dose :

Penicillin G it is Biological I.U

Substance which measure in I.U(international unit) but it is not equal in all

time .

I.U for penicillin G = 0.6 µg

1667 I.U = 1mg

Cephalosporins:

-the cephalosporins are semi-synthetic antibiotic because of very toxic

,derived from products of various micro-organism ,including cephalosporium

and streptomyces.

-all cephalosporins have a7- amino cephalosporanic acid and composed of

dihydrothiazine ring fused to β – lactam ring

-the cephalosporin β – lactam ring is the chemical group associated with

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Mechanism of action :

It is the same like penicillin.

*cephalosporins can be divided into four generations they are:

1-First generation :

example –

oral (acid stable)

I.M ,I.V (acid lable)

The first generation drugs are active against of both G+ and G-

,pasteurella,E.coli ,actinobacillus actinomyces , haemophilus , clostridium

and salmonella spp.

2-Second generation:

Example

oral

I.V ,I.M

Second generation have good activity against G+ and G-

3-Third generation :

Third generation more active against the G-including β-lactamase producing

strains and drug choice for pseudomonas .

4-Fourth generation

-cefeprime . I.V

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They are extremely broad spectrum being highly active against G-.they are

not destroyed by the most common β-lactamase of klebsiella spp and

pseudomonas.

Side effect :

1-hypersensitivity (skin rash )

2-nephrotoxicity

3-oral cephalosporin cause G.I.T disturbance.

Other cell wall synthesis inhibitors include:

1-bacitracin:

Is a mixture of polypeptide antibiotics produced by bacillus substilis.

-Mechanism of action :

Inhibit cell wall synthesis .

-antibacterial activity:

Bactericidal ,narrow spectrum ,inhibit G+ cocci, including staph .aureus

,strept. , a few G- organism.

-pharmacokinetic:

-absorption : not absorbed orally and it is given orally for treatment of local

infection ,it is not given paranterally because nephrotoxic .

-uses:

1-for topical application in combination with polymyxin for human and

animal .

2-used mixed with feed a flow lable as growth promoter in poultry and

calves.

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2-Vancomycin :

-it is not commonly used in vet. Medicine.

-is aglycopiptide antibiotic produced by streptomyces orientalis.


The inhibit cell wall synthesis by preventing the polymerization of the linear

peptidoglycan synthtase .

-they are bacteriostatic and narrow spectrum agents that are active against

G+organism ,it is administered orally to control clostridium and to treat

resistant staph.and strept. Infection.

-side effect :

Nephrotoxicity ,ototoxicity and hypersensitivity .

**Inhibitors of cell membrane function :

This group of antibiotics will alter cell membrane permeability (cationic

detergents ) and this action will lead to loss the integrity of bacterial cell

membrane .

-polymyxins:

-the polymyxin are a group of antibiotics produced by bacillus polymyxa

Polymyxin B (Aerosporin) and polymyxin E (Colistin) are used in the

treatment of bacterial diseases .


Bacterial act as cationic detergent effect of the permeability of cell membrane

by dissolving lipid .

-antibacterial activity:

Active against G- bacteria,pseudomonas aeruginosa.

-polymyxins are not well absorbed from the gastrointestinal tract ,paraentral

administration of polymyxins results in high drug concentrations in the liver

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and kidney ,the polymyxins are slowly excreted by glomerular filtration ,the

slow elimination rate is due to binding in tissues .elimination is decreased in

patients with renal disease ,and drug accumulation can lead to toxicity

.therefore polymyxins are used topically only with few exceptions

- uses:

1-topical with bacitracin .

2-local for treatment of intestinal infection in poultry and young calves.

Side effect :

-nephrotoxicity and neurotoxicity if given paraenterally bacitracin in limited

to topical application because of nephrotoxicity.

**Protein synthesis inhibitors:

-this group of antibiotics has been exerting their effect by inhibition of

synthesis of bacterial protein by interfering with ribosomal subunits (30s or

50s ) of bacteria .

-this inhibition may be either reversible (bacteriostatic) or irreversible

(bactericidal) .

This group includes :

*Aminoglycosides:

-they are hydrophilic , polycationic ,amine containing carbohydrates .

-the major clinically important aminoglycosides are :

-gentamicin - derived from micromonosporium spp .

- derived from streptomyces spp.

-amikacin - semi-synthetic from kanamycin .

-netilmicin - semi-synthetic from gentamicin.

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*chemical structure:

This group it polycationic compound consist of 2- amino sugar connected by

glycosidic linkage hexose.


They inhibit protein synthesis by irreversible binding to 30s which lead to

misreading of genetic code and production of false protein.

-activity :

-All aminoglycosides are bactericidal and active against G-but not strept.

-amikacin , gentamicin . and tobramycin are active against pseudomonas

aeruginosa.

-streptomycin active against mycobacterium tuberculosis.

-side effect :

1-the main side effect ,nephrotoxicity like neomycin.

2-ototoxicity like streptomycin .

3-neuromuscular blocking effect.

Tetracyclines :

Are classified according to the duration of action into :

1- short acting tetracycline :

example – tetracycline semi-synthetic.

derived from streptomyces spp.

Dosage interval 6 hrs .

2-intermediate acting :

-

semi-synthetic.

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Dosage interval 12 hrs .

3-long acting tetracycline :

-doxycycline .

-minocycline.

Dosage interval 24 hrs.

- mechanism of action :

Inhibit protein synthesis reversibly by binding to 30s ribosomal subunit.

-activity:

Bacteriostatic ,broad spectrum , tetracycline are active against mycoplasma ,

Chlamydia , rickettsia and some protozoa ( theleria and anaplasma) they are

active against of G+ and G- bacteria but have little useful against E.coli ,

salmonella ,proteus and pseudomonas.

-pharmacokinetic:

-absorption : well absorbed from the stomach and upper gastro-intestinal tract

.but the absorption will decrease in case of presence of calcium (Ca) , iron

(Fe), magnesium (Mg) ,and aluminum (Al) due to chelating effect .

-distribution : well distributed throughout the body (depend on degree of lipid

solubility )even in CNS and placenta .

-metabolism: in the liver .

-excretion : they are excreted unchanged in both the kidneys (passive

filtration )and feces .

-side effect :

1-metal chelating : tetracycline chelate (Ca, Mg, Fe ,Al) so that they may

cause discoloration of teeth , decalcification of bone in developing fetus and

pregnant animals.

2-G.I.T disturbance : direct irritation to G.I.T (nausea ,vomiting ,anorexia)

3-photosensitivity .

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4-irritation at the site of injection .

5-nephrotoxicity , hepatotoxicity.

Chloramphenicol:

It is abroad spectrum antibiotic ,bacteriostatic ,derived from streptomyces

venzuelae .


Bind reversibly to 50s ribosomal subunit and cause inhibition to peptidyl

transferase enzyme lead to inhibition of protein synthesis.

-activity:

act against G- specially salmonella typhi. and G+ bacteria ,reckettsia and

chlymedia .

-side effect :

1-aplastic anemia (dose independent )

2-bone marrow depress lead to anemia (dose dependent )

3-G.I.T disturbance ( diarrhea).

Macrolides:

Include:

-erythromycin

-olendomycin

-

treatment and prevent mycoplasma in poultry(CRD)


Bacteriostatic , inhibit protein synthesis by binding reversibly to a site on the

50s subunit of the bacterial ribosome .

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-activity:

-broad spectrum , they are effective against G+ and G- bacteria ,

erythromycin is very irritant when given paraenterally , it is given orally.

-side effect :

-bone marrow depression .

-gastro intestinal disturbance (diarrhea).

-hepatotoxicity.

Lincosamides :

They are broad spectrum ,bacteriostatic .antibiotic derived from streptomyces

spp.

They are include :

-lincomycin .

-chlindomycin. (semi synthetic)


Inhibit protein synthesis in bacteria through binding to 50s ribosomal subunit

of bacterial reversibly.

Activity:

used to treat staph. and strept. Bacteria and some other anaerobes.

Side effect:

Include occasional vomiting and diarrhea.

Aminocyclitol:

Include

1-spectinomycin.

2-apramycin.

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-mechanism of action:

Bacteriostatic , inhibit protein synthesis ,reversibly by binding with 30s .

Activity :

It is effective against G-and some G+ bacteria and some mycoplasma.

Uses:

1-for treatment of CRD (chronic respiratory disease)in poultry (mycoplasma

and E.coli ) .

2-combination lincosamide and tylosin for treatment mycoplasma.

3-can be given paraenterally as alternative for treatment of nisseria

gonorrhea in penicillin allergic .

Bacterial metabolism inhibitors :

complete synthetic drug

Sulfonamides:

Original prontosil

the sulfonamide are classified into 3 groups :

1-absorbable sulfonamide :

Which divided according to the duration of action or (dose interval)into:

a-short acting sulfonamides:

-sulfonamide

-sulfisoxazol

it is called triple sulfa

Dosage interval 4-6 hrs.

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b-intermediate sulfonamides :

-sulfamethoxazol.

Dosing interval 12 hrs .

c-long acting sulfonamides:

-sulfamethoxypyridazine .

Dosing interval 24 hrs.

d-extra long acting sulfonamides :

-sulfamethylphenazole.

Dosing interval 3-4 days.

2-non absorbable sulfonamides ( intestinal sulfonamide) :

They are non absorbable and they used in treatment of bacterial and protozoal

enteritis :

-sulfaguanidine .

-succinyl sulfa thiazole .

-phthayl sulfa thiazine.

3-topical sulfonamides:

-sulfacetamide : used as eye drops to treat ophthalmic infections.

-sulfathiazole : used for wound powders.


Sulfonamides are bacteriostatic inhibitor of folic acid synthesis ,it has similar

structure to Para amino benzoic acid so it inhibit the enzyme dihydropteroate

synthetase , trimethoprim is a selective inhibitor of bacterial dihydrofolate

reductase that prevents formation of the active tetrahydrofolic acid .

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PABA+ peteridine

↓ ←dihydropteroate synthetase )inhibit by sulfonamide

Dihydrofolic acid

(folic acid)

↓←dihydrofolate reductase )inhibit by trimethoprim

Tetra hydro folic acid

⁄ ↓ \

Thymidine purine methionin

↓ ↓ ↓

DNA DNA+RNA protein synthesis

NOTE: sulfonamides must not be used in case of presence of pus because

pus contains large amounts of Para amino benzoic acid (PABA)which

antagonized the action of sulfonamides .

-activity:

-bacteriostatic ( broad spectrum ).

-effective against G+ and G- except pseudomonas and proteus .

-effective against coccidia ,toxoplasma and clamydia.

-side effect:

1-crystal urea: sulfonamides can precipitate in the urinary tract at acidic PH

,which can result in hemat urea ,protein urea and tubular damage .

Steps to avoid crystal urea :

a-increase water intake .

b-use more water soluble sulfa like sulfisoxazole .

c-usage of triple sulfa (which is more soluble in water)

d-alkalinization of urine → give sodium bicarbonate .

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e-usage of sulfa – trimethoprim combination .

2-hypersensitivity.

3-the use of these drugs has been limited in food producing animals because

of residues of the drugs in meat , milk and egg .

Trimethoprim:

It differs from the sulfonamides is that it acts at a second step in the folic acid

synthetic pathway competitively inhibits dihydrofolate reductase .this is the

enzyme that catalyzes the reduction of dihydrofolic acid to tetrahydrofolic

acid , trimethoprim is bacteriostatic ,broad spectrum antibacterial ,it is weak

base and increase the activity of sulfonamide against resistance M.O against

proteus and treatment subclinical infection.

Trimethoprim sulfonamide

1 : 5 40 mg : 200 mg

80 mg : 400 mg

In veterinary medicine the combination is between trimethoprim and short

acting sulfonamide like sulfadiazine because of the half life of trimethoprim

in animal is arranged 2-6 hrs.

In veterinary preparation:

Sulfadiazine : trimethoprim

5 : 1

Side effect :

-anti-folate effect : megaloblastic anemia ,leucopenia, granulocytopenia these

effects can result from the drugs inhibition of mammalian dihydrofolate

reductase enzyme. These side effect can be treated with folinic acid which

given as adjuvant in order to prevent these side effects.

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Inhibitors of nucleic acid synthesis of function:

This group of antibacterial acts by inhibition of nucleic acids syntheses or by

interaction with their functions .

Nitrofurans:

-broad spectrum, antibacterial and synthetic antibacterial it has 2 types:

1-absorbable : including

a-furaltidone → for vet.med. (against G-used poultry of air sarculitis).

b-nitrofurntain.

2-non absorbable:including

a-furazolidone .

b-nitrofurazone

mixed with feed for treatment of coccidia.

Mechanism of action:

Inhibit DNA synthesis by causing damage of DNA after reduction .

Activity:

antibacterial spectrum of nitrofurans include ,G+ (including staph. Spp.)and

G- like salmonella spp. Also mycoplasma spp. Eimeria spp. And some other

protozoa.

Side effect :

1-G.I.T disturbance ( diarrhea)

2-inhibit spermatogenesis.

3-hepatotoxicity.

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Refampin :

Is abroad spectrum and bacterial antibiotic derived from streptomyces spp.

Mechanism of action:

it act by inhibition of RNA synthesis .

uses:

the ability of rifampin to penetrate into cells makes it an ideal drug for

treating intracellular infections it is used in the treatment of tuberculosis in

human and used in combination with erythromycin for the treatment of some

pneumonic condition in foals.

Side effect :

-enzyme induction : rifampin induces P450 in the liver and increases the

metabolism of many drugs like anticonvulsants and anticoagulants

-G.I.T disturbance .

Fluroquinolones :

They are broad spectrum , bactericidal and synthetic antibacterial .

-modification of nalidixic acid .

Types:

-flumequine → used for G-M.O.

-enrofloxacin

-norfloxacin

-ciprofloxacin

-danafloxacin→ used in poultry and ruminant.

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Inhibit DNA synthesis by inhibit DNA gyrase important for replication of

DNA .

Activity:

All these drugs act on G+,G-,mycoplasma ,pseudomomas .

Side effect :

-inhibition of articular cartilages growth and therefore should not be

administered to growing dogs or cats

-G.I.T disturbance.

Metronidazole:

Bactericidal , and antiprotozoal agent.


Works by disrupting DNA and nucleic acid and synthesis.

Activity:

has activity against most obligate anaerobes bacteria and against trichomonas

,giardia.

Side effect :

--neurologic disorder .

-G.I.T disturbance.

Basis of antibacterial combination :

In some cases antibacterial may be used in combination for the following

causes:

-to treat mixed infections .

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-prevention of resistance .

-reducing toxicity .

-for empiric purposes .

Types of antibacterial combinations are :

1-synergistic effect :

This type of combination happens when the antibacterial in combination exert

a greater antibacterial effect than either one alone (1+1>2) .

a-2drugs inhibit successive enzyme in metabolic pathway.

Example : sulfa +trimethoprim .

b-one drug promote (facilitate) the entry of second antibacterial .

example :

+ aminoglycosides

c-first drug inhibit the enzymes which destroy the second drug .

example : clavulanic acid + penicillin

amoxicillin

2-addative effect :

This type of combination occurs when the antibacterial in combination exert

an equal antibacterial effect for each one of them alone (1+1=2)

Example : bactericidal + bactericidal

Penicillin + cephalosporin

Bacteriostatic + bacteriostatic

Tetracycline + chloramphenicol

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3-antagonistic effect:

This type of combination occurs when the antibacterial in combination exert a

lesser effect than each antibacterial acting alone (1+1<2=0)

Example:

+ any bacteriostatic

-chloramphenicol + macrolides .

Because macrolides prevent binding of chloramphenicol

on 50s.

-aminoglycosides + tetracycline

-penicillin + sulfa

Reasons of failure of treatment with antibacterial:

1-incorrect diagnosis

2-incorrect antibacterial uses.

3-inadjuvant dose and duration .

4-presence of closed abscess.

5-presence of foreign body .

6-supra infection .

7-presence of resistance M.O

General uses of antibacterial :

1-treatment of disease .

2-prophylaxes.

3-growth promoter.

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Characteristic of antibacterial used as growth promoter:

1-should not be used in therapy .

2-should not be absorbed orally .

3-used in low amount.

e.g. flavomycin ,virginomycin ,bacitracin .

Chemotherapy of parasitic disease:

The most common drugs which used for treatment of parasitic infection either

Endoparasites or Ectoparasites

1-drugs used in the treatment and control of endoparasites:

Anthelmintic:

a-drugs for round worms (antinematodes ).

b-drugs for tape worms (anticestodes).

c-drugs for flukes (antitrematodes) .

A-drugs for round worms (antinematodes):

This group is used for treatment of nematodes and the main used drug groups

for purpose are :

1- avermectins and milbemycins :

Natural or semi synthetic agents derived from streptomyces avermitilis and

streptomyces cyanogriseus .


Includes interfering with parasite nerve transmission.

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Activity :

-they are effective against a wide range of nematode species and a

developmental stages, but have no activity against trematodes and cestodes.

-avermectin and milbemycin prevent pre-infection for a period after

treatment.

-effective against warble flies , lice , mite (ectopatasite)

-given systemic s/c and orally .

Avermectins include abamectin , doramectin ,ivermectin and selemectin .

Restriction :

Should not be used in milking cows because the drug is lipid soluble and can

pass to milk , so milk should not be used until 28 days of treatment .

2-benzimidazoles (B2) :

Examples: albendazole , fenbendazole , flubendazole , mebendazole

,oxfendazole , cambendazole , thiabendazole, parbendazole .


B2 binding to tubular which is protein necessary for the formation of

microtubules in the absorptive cell in the intestine .this will cause lyses of

absorptive cells leading to a death due to starvation.

Characteristic of B2:

1-they are broad spectrum .

2-they are insoluble in water (slowly absorbed ).

3-given orally as a drench .

4-are effective against larval and adult round worms .

5-some of benzimidazoles are contraindicated in case of pregnancy because

of their ability to penetrate the blood – placental barrier , consequently they

cause teratogenic problem .

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Pro-benzimidazoles :

-thiophanate .

-febantel .

3-imidazothiazoles :

They act by interfering with parasite nerve transmission causing muscular

spasm and rapid expulsion .

e.g. : levamisole :

broad spectrum and anthelmintic , it is given orally as a drench , tablet ,s/c ,

i/m .

side effect :

-colic , diarrhea , salivation .

-drug is toxic to horses → treated by atropine sulphate .

4-organophosphorous compound :

Examples :haloxan , dichlorvos ,metrifonate .

-they act by inhibiting choline esterase enzyme there by interfering with

neuromuscular transmission in the parasite ..

-they are effective against adult gastro-intestinal round worms but ineffective

against migrating larvae , tape worms or flukes .

-clinical signs of toxicity such as salivation and diarrhea may occasionally

occur , particularly in foals .

5-tetrahydropyrimidines :

Example : morantel ,oxantel and pyrantel .

They interfere with parasitic nerve transmission as cholinergic stimulants

,leading to neuromuscular spastic paralysis , this mode of action is similar to

that of the imidazothiazoles .

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6-piprazine :

-it modifies neurotransmission in parasites causing expulsion of the parasite .

-piprazine is used for treatment of some gastro- intestinal round worms such

as toxocara in dogs and cats .

-given orally as a dipate ,citrate , hydrate or phosphate .

7-diethylcarbamazine :

-the mechanism of action of this drug is similar to piprazine .

-is active against adult ascarids but is more frequently used as a heart worm

prophylactic .

8-phenothiazine :

-mechanism of action , inhibit egg production .

-mainly used in horses for treatment of stronglus also used in cattle and sheep

.it is use prophilactically because is produce contamination of pasture of

parasitic infection .

-side effect :

-red discoloration of urine and milk .

-photosensitization lead to ulceration → blindness.

Drug effect on lung worm:

1-piprazine .

2-levamisole .

3-ivermection.

4-benzimidazole ( febendazole , oxfendazole ,albendazole ).

B-drugs for tape worms ( anticestodes ).

This group is used for treatment of cestodes and the main used drug groups

for this purpose are :

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1-praziquantel :

Mode of action : it act by increasing ion influx across the parasite tegument

leading to immediate muscle spasm .

-praziquantel is effective against all tape worms in dogs and cats and is

preferred in most echinococcus control programs .

It is very safe even in pregnant animals .

2-niclosamide :

-mode of action : act by interfering with adenosine triphosphate (ATP)

production .

-it has a little efficacy against echinococcus and variable activity against

dipylidium .

3-benzimidazole :

-albendazole , fenbendazole , mebendazole and oxfendazole are effective for

tape worm control in ruminant . fenbendazole and mebendazole also control

some tape worms in dogs and cats .

4-arecoline hydrobromide :

-mode of action :stimulation parasympathetic activity and intestinal secretion

in the host and direct action on the worm .

-effect against most cestod in dog (echinocochus granulosus )

-toxic in cat , arecoline should never be administered to cat as in this species

the gastro-intestinal stimulation is particularly sever and may cause death .

-side effect :diarrhea and vomiting .

Vomiting after dosing only reduces the efficiency of the drug if it takes places

with in the first few minutes after administration . should be fast the animals

over night .

5-dichlorophen:

-effected in dogs and cats but not against echinococcus .

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-given orally as tablet (coated).

6-bunamidine hydrochloride:

-effect in dog and cat , sheep and birds .

-it is irritant ,it is administered orally in compression – coated tablet form .

7-nitroscanate :

-effective against cestod and nematodes .

-it is given orally .

C-Drugs for flukes (anti trematodes):

(drug effective against liver flukes , fasciola hepatica ,fasciola gigantica)

Activity of these drugs :

-activity against immature flukes 4-6 weeks of flukes , immature flukes it is

in liver parenchyma.

-activity against mature flukes 12 weeks and fluke it is in bile duct .

Drug acting in mature flukes:

1-carbon tetrachloride (CCL4):

Mode of action : through excretion of metabolite in the bile .

-toxicity:

1-acute toxicity :hypocalcaemia . treated by calcium.

2-chronic toxicity :it is cause liver damage ,fatty degeneration ,necrosis

,hemorrhage .

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2-benzimidazole :

albendazole and netobimin (probenzimidazole )are active against fasciola ,

they are effective against adult stages , triclabendazole is highly effective

against all liver stages of fasciola.

3-clorsulon:

-it is a sulfonamide and competitive inhibitor of important enzymes for

energy metabolism in flukes.

-it is used in cattle for control of liver flukes.

4-oxyclozanide and rafoxanide :

-they act by interfering with adenosine triphosphate (ATP) production .

-oxyclozanide is mainly active against adult flukes , while rafoxanide is

active against adult and immature flukes .

5-nitroxinil:

-mode of action :uncoupling oxidative phosphorylation .

-administration : S/C

Drug acting mainly on immature flukes :

1-diamfenetide:

-mode of action : through metabolites .

-activity : effective against immature flukes is used for treatment of acute

fascioliasis resulting from activity of immature forms of fasciola hepatica in

liver parenchyma .

Antiprotozoal drugs :

They are a class of pharmaceutical used in treatment of protozoal infections .

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Anticoccidial drugs :

This group of antiprotozoal is used for treatment or prophylaxis or both

against coccidal infections which caused by eimeria spp.

A- Miscellaneous anticoccidial agents :

1-sulfonamides :

The first effective drugs used in the treatment of coccidiosis in chicken (E.

tenella).

-it is only drugs effective against all species of eimeria .

-they are coccidiostatic at low doses and coccidiocidal at higher doses.

Example :- sulfadimethoxine .

-sulfachlorpyridazine .

-

given as sodium salt in the

drinking water


-antagonist to folic acid (similar to bacterial infection ).

-sulfaquinoxaline usually combine with amprolium or diaveridine to get :

a-synergism effect .

b-broad spectrum .

c-decrease dose required .

d-less toxicity .

2-nitrofurans :

-used for prophylaxis .

-they are active against eimeria and histomonas .

-mode of action :inhibit the synthesis of DNA.

Example : furazolidone , nitrofurazone .

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3-vitamine antagonists (thiamine antagonist):

a-amprolium:

-a structural analogue of thiamine (vitamin B1) competitively inhibit thiamine

utilization by the coccidia .

-act in the day (4) in the life cycle .

-not effective against all species of eimeria .

-amprolium is used prophylactic to prevent coccidiosis in chicken and turkeys

so that mixed in feed as continuous medication .

b-diaveridine :

it is coccidiostatic agent used to prevent coccidiosis in poultry , it is given

togather with sulfaquinoxaline .

c-ethopabate:

example : monensin , narasin , salinomycin , lasalocid .

-the mechanism of action of this group is illustrated by forming complex as

with ions such as Na , K ,Mg ,and Ca, then this ionophores carrying these

ions to inside of the schizont . there by effect on the balance of the schizont ,

consequently rupture of the schizont .

-widely used for prophylaxis .

-promote weight gain especially in ruminant .

5-quinolates :

Example :clopidol , methyl benzoquate , decoquinate .

This group acts by disruption of mitochondrial cytochrome system of

coccidian in the sporozoite stage .

6-robenidine:

-coccidiocidal .

-mode of action :by complete suppression of oocyst production .

7-aprinocid :

-mode of action : inhibition nucleic acid formation (purine synthesis) .

Antibabesial drugs :

a group of drugs are used to treat babesia spp. Infections .

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(babesia are protozoal parasite multiply in the blood cells cause

disease in domestic animal , horse , dog, transmitted by ticks .

1-quinuronium sulphate .

-effective against all species of babesia .

-mode of action :more potent anticholine esterase activity .-given by

s/c.

-accumulation Ach new symptoms (salivation, defecation , may

stagger and fall ).

-quinuronium release histamine and depresses cellular oxidation

.this drug causes fall in blood pressure .

-antidote of toxic sign by given a large dose of atropine sulphate

before administration of drug s/c .

2-amicarbalide :

-replaced quinuronium to a large extent for treatment of babesiasis .

-mode of action : anticholine esterase activity .

-is effective against babesia app. Infection .

-can be given s/c and I/m .

-cause release of histamine , so that causes reaction in site of

injection .

3-imidocarb:

-mode of action :anticholine esterase activity .

-this drug is highly effective to all spp. of babesia .

-it is given s/c and I/m .

-it is given as prophylactic and treatment .

-drug residues up to 3 month .

-it is safe drug.

4-diminazene :

-mode of action :inhibition DNA synthesis .

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-it is active against babesia ,trypanosoma and some bacteria like

(brucella ,streptococci).

-it is given s/c .

-less toxic .

-drug residues up to 3 weeks .

Anti theileriosis :

a group of drugs are used to treat theileria spp. Infection .

1-chlortetracycline and oxytetracycline :

-they are used for prophylaxis and may reduce parasitaemia by a

arresting schizogony .

-it is given by I/m or I/v injection .

2-hydroxynapthoquinones :

Example :buparvaquone ( and parvaquone .

-they are used for the treatment of theileriosis in cattle .

-are thought to interfere with protozoa mitochondria .

3-gloxanane :

-very effective drug for theileria 100%.

-given I/v.

Antitrypanosomal drugs :

A group of drugs are used to treat trypanosoma spp. Infection .

1-quinapyramine:

-they are effective against most spp. of trypanosoma.

-mode of action : anticholine estrase .

-when toxic sings appear can be given the antidote (atropine sulphate) .

-drugs is formulated as ( chloride & methyl sulphate )salt .the difference in

solubility is reflected in the rates of absorption ,the methyl sulphate being

quickly and the chloride slowly absorbed from sites of s/c or I/m .

2-phenanthridinium compound :

Example: dimidium , homidium ,metamidium , prothidium .

-mode of action : block DNA synthesis.

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-homidium is used because quickly absorbed than other drug .

-given s/c and I/m .

3-diminazine :

-these drugs appear to bind to parasite DNA and block DNA and RNA

synthesis.

-they are may be used therapeutically ,or for prophylaxis or both .

4-suramin:

-used against T.evansi infection in camels .

-suramin is not absorbed orally ,therefore it administrated I/v route only

because it is irritating nature through I/m or s/c , routes.

-mode of action : preventing cell division .

-Suramin binding or combine with plasma protein and persist for many weeks

in the body . since quinapyramine , phenanthidinium and diminazine are basic

substances ,the acidic suramin will combine with them to form an insoluble

complex. these complexes when injected form depots from absorption

proceeds very slowly .

-drug residues up to 3 month .

Antitoxoplasmosis drug:

a group of drugs are used to treat toxoplasma spp. Infection

-sulfonamide and trimethoprim .

-clindamycin and clarthromycin .

Antitrichomonal drug :

a group of drugs are used to treat trichomonas spp. Infections.

-nitroimidazole derivatives :

Example :metronidazole , ronidazole and carnidazole .

They act by interaction with protozoal DNA activities .

Antihistomoniasis drugs :

a group of drugs are used to treat histomonas spp. Infections.

-dimetridazole:

-it is one of the nitromidazoles and it appears to interfere with RNA synthesis.

-also it can be used as antitrichomonal agent too.

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Drugs acting on cardiovascular system:

The heart a vital organ used to pump blood around the body in the blood

vessels . it has an intrinsic rhythmic contraction which is due to electrical

activity in the sino-atrial (S.A) node .this spreads over the atria to the

atrioventricular (A.V)node then through the bundle of His and Purkinje fibers

into the ventricles this electrical activity gives rise initially to the contraction

of the auricles followed by the ventricles after a brief delay . this delay allows

filling of the ventricles .the heart rate (chrontropic )slowed by vagal activity

involving stimulation of muscarinic receptors by acetylcholine ,the

stimulation of β1 receptor adrenergic lead to increase the force of contraction.

Inotropic drug:

alter the strength of the heart beat ,as well as stimulate heart rate involve to

increase contraction and shorten the refractory period .pathological alteration

in the refractory period , excitability and rate of propagation of electrical

activity can lead to ectopic beats of auricular or ventricular origin , the

abnormal contraction give rise to a trial flutter or fibrillation .

cardiac stimulation *Inotropic drugs *:

these drugs which increase the force of contraction . they are include :

A- Cardiac glycosides (digitalis )

B- Sympathomimetics .

C- Parasympatholytics .

D- Xanthenes' derivatives.

A-cardiac glycosides :

They are derivatives from plant origin .

1-Digitalis purpurea → the main active principle is Digitoxin.

2-Digitalis lanata , → the main active principle is Digoxin .

The chemical structure is steroid like (aglycone) and sugar (glycone ) such as

Digitoxin . this sugar is important and fixation on heart muscle as well as it is

action.

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mode of action :

-indirectly : by inhibition of vagus nerve and that lead to increase the force of

contraction , and the excitability of the heart muscle and increase the

refractory period .

-directly :act on the heart through inhibition of muscle bound ATPase which

responsible for sodium ,potassium transport leading to increase in the

intracellular .

Pharmacokinetic :

-absorption :is mainly from small intestine but depend on :

1-polarity of glycoside : more polar →less absorption like Ouabain glycoside

5-10%

Digitoxin → 80%

Digoxin → 43%

2-form of preparation : fine powder → high absorption

Tablets → less absorption

-in the blood they bounded to plasma protein .

-metabolism : in the liver by conjugation and can go through the

enterohepatic circulation and also metabolized in the intestine by intestinal

bacteria.

-they are not given to ruminant because of microbial activation .

-excretion : is mainly by kidney and liver through bile where it may be

reabsorbed after activation by M.O. leading to long t 1/2 or excreted in feces.

There is species variation in duration of action .

t1/2 digoxin → 26 hrs in dogs .

t1/2 digitoxin → 21 hrs

in cats the t1/2 is longer because of the deficiency of conjugation in this spp.

Dosing :

Often an initial loading dose is followed by a lower maintenance dose to

achieve digitalization .

Therapeutic uses:

-effective in left ventricular disease and also treatment of congestive heart

failure .

-atrial flutter .

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-atrial fibrillation .

Other cardiac glycosides :

-Strophanthin – K :

from strophanthus kombe and strophanthin –G from strophanthus gratus

(ouabian) they are chemically and pharmacologically similar to digitalis .

Ouabian destroyed by intestinal enzyme ,it is usually given I/V . it

metabolized rapidly with short duration of action .

-used in cat because no vomiting as digitalis .

-scillarin –A and B:

derived from red squill (rat poison ) it is pharmacologically same as digitalis

but less potent.

B-: Sympathomimetic :

It is include β adrenoreceptor agonist .e.g. Isoprenaline , Epinephrine .

They cause increase the force and rate of muscular contraction of the heart

(increase in cardiac output ) .

C-Parasympatholytic :

Example : Atropine .

D-xanthine derivatives :

Example : caffeine , theophylline , theobromine . are mild myocardial ,

vasomotor ,and respiratory stimulant and bronchodilators ,there for it is useful

in treatment of the cardiac failure in combination with glycoside .

Antidysrhythmic agent :

The term antidysrhthmic drugs refer to the agents that suppress abnormal

beats or restore normal cardiac rhythm by depressing various properties of

the myocardium (heart muscle ) .this is general mechanism of action for all

these drugs .

-Quinidine :

-Quinidine is an antiarrhythmic agent used in treatment of atrial fibrillation

and ventricular arrhythmias .

-from plant origin known by Cinchona .

-the side effect : include hypersensitivity reaction , gastrointestinal

disturbance .

-procainamide :

-is used in the treatment of atrial and ventricular arrhythmias .

-side effect :anorexia , nausea and vomiting , and drug hypersensitivity .

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-Lidocaine :

-Lidocaine is an agent that may be given I/V in the treatment of ventricular

arrhythmias (similar to quinidine) .

-large I/V doses may produce convulsions , coma and respiratory depression

Vasodilators :

A vasodilator is a drug that dilates blood vessels with a resultant increase in

blood flow , this type of drugs are used mainly for treatment of hypertension

and angina pectoris .

-Glyceryl trinitrate ( Nitroglycerin) :

-it is the most common smooth muscle relaxant vasodilator used in the

treatment of acute angina pectoris .

-side effect : headache , dizziness .

-Isosorbide dinitrate:

-Isosorbide dinitrate is thought to be effective in the prophylactic , treatment

of angina pectoris ,as well as the treatment of acute angina attacks .

-side effect : headache and dizziness .

-Hydralazine and minoxidil :

-are direct acting peripheral vasodilators used in the treatment of

hypertension.

Coagulants and anticoagulant : Coagulants : preparation help in suppressing traumatic and surgical

hemorrhagic . these includes:

a- Physiological coagulants :

natural or synthetic preparation of clotty substances .

Example : thromboplastin , thrombokinase , thrombin ,fibrinogen and fibrin.

b-surgical haemostatic :

these include , oxide cellulose , calcium alginate .

c-parenteral coagulants :

efficient haemostatic which can be given parenterally .

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1-amixture of Na malonic and Na oxalic acid of 5% from each .

2-vit K :it is fat soluble vit. Sources mainly in food , it is important for

prothrombin synthesis in liver .it is absorption from intestinal depend on the

presence of bile and fat in the intestine , storage in liver and excretion in via

the mainly system . lack of vit. K lead to hypoprothrombenia and the

formation of blood clot .

Uses: -in veterinary medicine ,vit k is used for the treatment of rodenticide

toxicity .

-in sever disease of hepatitis and gastroenteritis when vit k absorption and

prothrombin synthesis a restricted .

c-local haemostatic :

are used to control capillary bleeding or bleeding from other small vessels .

astringent metals and plant substances act as haemostatic .

example: ferric chloride ,alum , tannic acid (tea).

Anticoagulant :hey are compounds used to prevent blood from clotting .

a-in vitro anticoagulant :

they are compounds or substances used to prevent coagulant in test tube for

research or laboratory purposes .

common mode of action :is that they make ionic calcium it is not suitable to

give to living animals .

-sodium florid and oxalate .

-sodium edentate (EDTA) or citrate cause chelation of calcium .

b-systemic anticoagulants :

Heparin :

It is polysaccharide naturally found in the most cell and it is prepared from

bovine lung and porcine intestinal mucosa it can be used in vivo and in vitro .

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Action :

Heparin act as an anticoagulant by preventing the conversion of prothrombin

to thrombin ,without thrombin , fibrinogen is not converted to fibrin and a

clot dose not form .

Uses :

-used in blood transfusion .

In case of surgery to prevent formation of thrombus .

Protamine:

It is protein taken from fish sperms used as anticoagulant .

Warfarin:

It is coumarine derivatives present naturally in some plants like sweet clover.

Fibrinolytic:

Drugs that promote fibrinolysis , it is mainly used to :

-control plasmin production .(by stimulating conversion of plasminogen to

the enzyme plasmin ).

2-removed of thrombus and pus or necrotic tissues like :

a-streptokinase and staphylokinase :has both pyrogenic and antigenic effect .it

is derived from bacteria .

b-urokinase :plasmogen activator derived from urine .it is not pyrogenic or

antigenic .

c-amino caprice acid .

clinical uses:

1-treatment of pulmonary embolism .

2-treatment of arterial thrombosis and emboli .

3-treatment of coronary thrombosis.

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Antithrombosis:

Aspirin and some NSAIDS :have ability to prevent platelets aggregation

through inhibition of prostaglandin synthesis (inhibition of thromboxin

synthetase).

Hematinics or antianaemics :

Drugs used in treatment of anemia .like :

-iron :

It is important for hemoglobin synthesis ,the form of iron in these products

may be iron dextran , ferrous sulphate , peptonized iron , ferric hydroxide and

others .

Absorption :

Mainly in the duodenum . diet component like as carbonic acid , citric acid ,

phosphate and pancreatic secretion facilitate absorption.

Paranteral preparation :

Iron dextran usually given by deep iron to treat anemia .

-cobalt :

Cobalt deficiency associated with anemia, it treated with cobalt sulphate,

cobalt chloride .

-copper :

Essential for the normal utilization of iron in hemoglobin synthesis , treated

by copper sulphate , copper glycinate .

Note:

Vitamin deficiency anemia treated by cyanocobalamine (vit. B12 ) , folic

acid.

-androgens :

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The treatment for anemia associated with chronic renal failure has

traditionally been androgen therapy .

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