Pharmacology: Antibiotics

• These are finals notes from a Pharmacology lecture

Module 7 - Antibiotics

• Antimicrobials kill or inhibit microbes, including bacteria, viruses, protozoa, and fungi, can't be seen by the naked eye
• Doxycycline and tetracycline treat ehrlichia (protozoa) and E. coli
• Antibacterials are drugs that act specifically on bacteria
• Penicillin treats streptococcus, staphylococcus, E. coli, and salmonella
• Antibiotics are drugs produced from yeast or fungi with antimicrobial or antibacterial action
• Povidone iodine is a mineral used to disinfect wounds and kill bacteria
• Penicillin and sulfonamides are examples of antibiotics
• Parasiticides kill parasites, including ectoparasiticides (for external parasites) and anthelmintics (for worms)
• Antifungal drugs treat fungal infections
• Anti-cancer drugs treat tumors and cancer

Antibiotics Classified by Spectrum of Activity

• Narrow-spectrum antibiotics target a specific bacterium (either gram-positive or gram-negative)
• Broad-spectrum antibiotics act on all bacteria

Stains and Fixers in Gram Staining

• Crystal violet is the primary stain
• Iodine acts as a fixer
• Alcohol removes excess stain
• Safranin is the secondary stain
• Red or pink stained bacteria are Gram-negative

Why Gram-Negative Bacteria are Harder to Kill

• Gram-negative bacteria have a thinner cell wall compared to Gram-positive bacteria

Antibiotics Classified by Type of Action

• Bacteriostatic antibiotics inhibit bacterial growth in an additive fashion
• Examples of bacteriostatic drugs include tetracyclines, chloramphenicol, macrolides, lincosamides, spectinomycin, sulfonamides, griseofulvin, rifampin, and trimethoprim
• Bactericidal antibiotics kill bacteria in a synergistic fashion
• Examples of bactericidal drugs include penicillin, cephalosporins, aminoglycosides, TMP-S (trimethoprim and sulfonamides), nitrofurans, metronidazole, quinolones, amphotericin, bacitracin, and novobiocin

Antibiotics Classified by Mode of Action

• Some antibiotics inhibit cell wall synthesis
• Examples include penicillin, cephalosporins, vancomycin, bacitracin, and cycloserin
• Some antibiotics impair cell membrane function with cell membrane but can’t protect cell
• Examples include polymyxin, colistin, tyrocidine, amphotericin, and nystatin
• Some antibiotics inhibit protein synthesis
• Examples include tetracycline, aminoglycoside, chloramphenicol, macrolides, and lincosamides
• Some antibiotics inhibit DNA synthesis
• Examples include novobiocin and quinolones
• Some antibiotics inhibit DNA-dependent RNA polymerase
• Rifamycin (brand Rifampin)
• Some antibiotics inhibit folic acid synthesis
• Examples include sulfonamides and trimethoprim

Antibiotics and Their Sources

• Penicillin comes from Penicillium notatum and Penicillium chrysogenum
• Chlortetracycline comes from Streptomyces aureofaciens
• Oxytetracycline comes from Streptomyces rimosus
• Streptomycin comes from Streptomyces griseus
• Erythromycin comes from Streptomyces erythreus
• Bacitracin comes from Bacillus subtilis
• Tylosin comes from Streptomyces fradiae
• Vancomycin comes from Streptomyces orientalis
• Gentamycin comes from Mircomonospora purpurea
• Nevoblocine comes from Streptomyces niveus

Penicillin Types and Properties

• Narrow-spectrum B-lactamase sensitive (G+)/ natural penicillin
• Pen G (benzylpenicillin), Pen V and Pheneticillin
• Narrow-spectrum B-lactamase resistant (G+)/ antistaphylococcal penicillin
• Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Methicillin, and Temocillin
• Broad-spectrum B-lactamase sensitive/aminopenicillin
• Ampicillin, Amoxicillin, Hetacillin, Pivampicillin, Talampicillin, and Mecillinam
• Broad-spectrum B-lactamase sensitive with extended spectra (can handle Pseudomonas)
• Carbenicillin, Azlocillin, Mezlocillin, and Piperacillin
• B-lactamase protected broad spectrum (potential pen.)
• Clavulanate + potentiated amoxicillin (Clavamox- kilala as co amoxiclav), sulbactam+ potential ampicillin, ticarcillin+ clavulanic acid and piperacillin+tazobactam
• MOA of penicillin: Inhibit cell wall synthesis (affects growing cells/ combination with bacteriostat is inappropriate)
• Interferes with transpeptidase (enzyme responsible for crosslink between peptidoglycan strands)
• Penicillin binds (PBP) on the cell wall of susceptible bacteria and inhibits transpeptidation
• Prevents peptidoglycan synthesis, leading to cell wall-deficient forms (spheroplasts and filamentous forms) and autolysis, resulting in cell death (bactericidal action)

Penicillin Side Effects and Interactions

• Penicillin can biotransform into penicilloic acid, which tends to be allergenic and can lead to cross-sensitivity
• Guinea pigs, chinchillas, birds, and snakes & turtles are sensitive
• Penicillin interacts with salicylates, phenylbutazone, sulfonamides, and anticoagulants
• Penicillin + cephalosporin leads to pseudomonas
• Penicillin + streptomycin/gentamycin leads to Listeria
• Withdrawal times for penicillin: 7-30 days in meat and 2-3 days in milk

Cephalosporins and Their Properties

• 1st generation cephalosporins are narrow spectrum for G+, B-lactamase sensitive, and not effective for anaerobic bacteria
• Cephalothin, Cephaloridine, Cephairin
• Cefazolin, Cephalexin (most popular), Cephradine and Cefadroxil
• 2nd generation cephalosporins are broad-spectrum (G+G-), B-lactamase resistant, and not effective for obligate anaerobic bacteria
• Cefamandole, Cefoxitin, Cefotiam, Cefaclor (most popular), Cefuroxime (most popular) and Ceforamide
• 3rd generation cephalosporins are narrow spectrum (G-), B-lactamase resistant, and pass the blood-brain barrier
• Drugs: Ceftiofur, Ceftriaxone, Cefsulodin, Cefotaxime, Cefoperazone, and Moxalactam
• 4th generation are broad-spectrum (G+G-), B-lactamase resistant, and have extended spectra
• Cefepime
• Cephalosporins MOA: same as penicillin

Cephalosporins: Indications and Side Effects

• Used to treat Cephairin benzathine, Dry-cow mastitis Tx, Cephapairin sodium andmastitis
• Can also be used for Ceftiofur
• Ceftiofur treats pneumonia caused by Pasturella and cross-resistance with penicillin is possible (as well as among penicillin)
• Side effects of cephalosporins include nephrotoxicity, pain at the injection site, and phlebitis
• Cephaloridine can cause anemia in cats
• Cephalosporins interact with aminoglycosides, furosemide, and ethacrynic acid
• Withdrawal times for cephalosporins: 4-42 days in meat and 3-4 days in milk

Aminoglycosides Properties

• All are antibacterial and long-acting
• Narrow spectrum (G-/aerobic)
• Streptomycin and Dihydrostreptomycin
• Broad spectrum
• Neomycin, Framecetin (neomycin B), Paromycin (aminosidine), Kanamycin, Gentamicin, Tobramycin, Amikacin, Sisomicin, Netilimicin, and Paromonycin

Miscellaneous Aminoglycosides

• Aminoglycosides, Apramycin
• Specific action: for E. coli and salmonellosis
• Sometimes proteus, klebsiella, treponema, mycoplasma
• Toxic in cats
• Little cross-resistance
• Spectinomycin
• Only aminoglycoside that is bacteriostatic
• MOA: inhibit Protein/CHON synthesis at binding site (30s and 50s sub-ribosomal unit)
• Spectinomycin lacks the capacity to produce misreading of the m-RNA
• Functional integrity of cell membrane is lost

Aminoglycosides Side Effects

• Ototoxicity (cats loss righting/balance reflex), Convulsion and collapse, Neuromluscular blocking, Nephrotoxicity

Aminoglycosides Interactions and Withdrawals

• Muscle relaxants, Furosemide, Ethacrymic acid, Halothane anesthesia
• Withdrawal times: 20-30 days in meat (PO)
• 100-120 days in meat(parenteral) and 2-3 days in milk

Tetracyclines

• Short-acting Tetracycline and Oxytetracycline
• Intermediate-acting: Demethylchlortetracycline and Metacycline
• Long-acting: Doxycycline, Minocycline and Tigecycline
• All salts of tetracyclines are HCI, except doxycycline which is hydrate

Tetracyclines MOA

• inhibit CHON synthesis at binding site 30s sub-ribosomal unit
• block attachment of aminoacryl tRNA to acceptor site at mRNA-ribosome
• chlor: decrease conversion and glutamate into CHON
• more effective in multiplying organisms

Tetracyclines Spectrum, Action, and Indications

• These are broad spectrum, both aerobic and anaerobic organisms, even mycoplasma, rickettsia, chlamydiae and some protozoa
• Thru chemical manipulation, oxytetracycline can become long-acting (choice of carrier and increase magnesium content) and indication
• Specific condition such as pink eyes, chlamydiosis, heartworm, Anaplasmosis, Actinomycosis, actinobacillosis
• Nocardiosis, esp, minocycline
• Ehrlichiosis, esp, doxycycline
• Also for eperythrozoonosis and haemobartonellosis
• Minocycline and doxycycline are effective for resistant Staphylococcus aureus

Tetracyclines Side Effects, Interactions, and Withdrawals

• GIT disturbance
• Decrease B complex and K vitamins availability
• Chelates Ca in teeth and bones
• Decrease fracture healing
• Hypotension and collapse
• Nephrotoxic
• Swelling and necrosis at injection site
• Phototoxic dermatitis in human
• Drug fever in cat
• Decrease WBC chemotoxic and phagocytosis
• Milk, Antacid, Kaolin, Iron, Glucocorticoids, B-complex
• Ca in ringers solution, Methoxyflurance, Phenobarbital, Phenytoin, Food except minocycline and doxycycline
• Withdrawal: 7-28 days in meat, 4 days in milk
• Oxytetracycline = don't use in lactating dairy cow

Chloramphenicol

• Unique antimicrobial agent, Related drugs: Thiamphenicol and Florfenicol
• Chloramphenicol (not thiamphenicol and florfenicol) should not be given in animals that are eaten by humans because it causes irreversible anemia
• Blood dysgenesis
• GIT disturbances
• Suppress anamnestic immune response
• Delays wound healing
• Affects structure and fx of gonads
• Hemolysis and collapse

Chloramphenicol Interactions and Withdrawals

• Phenobarbital
• Codein
• Phenytoin
• NSAID
• Coumarin
• Sulfamethoxypyridizine
• Iron
• Folic acid
• B12
• Penicillin
• Aminoglycoside
• Cephalosporin
• Macrolide and Lincosamide
• Withdrawal
• 2 weeks in meat and 2-3 days in milk

Macrolides

• 12-membered ring and None
• 14-membered ring and Erythromycin
• 16 membered ring and Spiramycin, Josamycin and Tylosin
• 20- membered ring and Tilmicosin
• 15-membered ring (new and can penetrate lungs)
• Tulathromycin (used only in animals) and Azithromycin (used only in humans)

Macrolides MOA

• Inhibit CHON synthesis which binds to 50s sub-ribosomal unit
• Prevents translocation necessary to keep the peptide chain growing
• Affects rapidly dividing
• At high concentration
• erythromycin is bactericidal
• Good for anaerobic and aerobic G+ bacteria
• Good for mycoplasma and rickettsia
• Synergist: Macrolide + cefamandole = Bacteroides fragiles, Macrolide + ampicillin = Nacardia asteroides
• Macrolide + rifampin = Rhodococcus equi
• Good alternatives for penicillin staph and strep infection

Macrolides Side Effects, Interactions and Withdrawals

• Pain and swelling at injection site
• Hepatotoxic (cholestasis) (erythromycin) and GIT disturbance
• In pig, tylosin may cause rectal prolapse
• Chloramphenicol, Lincosamide
• The Acid preparation
• Withdrawal
• 7-21 days in meat and 36-96 hours in milk

Lincosamides

• Drugs: Lincomycin and Clindamycin
• MOA: inhibit CHON synthesis which binds to 50s sub-ribosomal unit
• Lincomycin + spectinomycin = Mycoplasma gallisepticum

Lincosamides Side Effects and Interactions

• Clindamycin - induce pseudomembranous enterocolitis (clos. Difficile)
• The skeletal muscle paralysis
• Muscle relaxants and anesthetics
• Kaolin and Pectin
• Chloramphenicol
• Macrolide
• Withdrawal
• 2 days in meat and 36 hrs in milk

Polymyxin and Colistin

• Oral drugs
• Polymyxin B/polymyxin, Parenteral drugs and Polymyxin E/Colistin
• Colistimethane

Polymyxin and Colistin MOA and Indication

• Impair cell membrane fx
• Combine and disorganize structures respiratory for maintenance of osmotic equilibrium within the cell attached to phospholipids/polyphosphate
• As a result, cell permeability is altered, cell constituents escape from the protoplasma, esp. Purine and pyrimidine

Sulfonamides More Effective in G-/narrow spectrums

• Act synergistically with TMP'S and tetracyclines and beneficial in endoxemia
• Main indication is life-threatening infection due to G-bacilli or pseudomonas resistant strain
• Side effect
• Nephrotoxic, Muscle blockage, neurotoxic, paint at injection site and hypersensitivity

Sulfonamides interactions and withdrawals

• Divalent cations, unsaturated fatty acid and Quaternary ammonium
• Withdrawal: 2 weeks

Sulfonamides

• The standard use has sulfathiazole, sulfamethiazine, sulfamerazine, sulfapyridine, sulfadimethoxine and sulfamethoxypyridazine
• Highly soluble (UTI): is sulfasoxazole
• Poorly soluble (GIT) are sulfaguanidine, bacterial hydrolysis and Phthalylsulfathiazole

Sulfonamides and Topicals

• Sulfathiazole, Succinylsulfathiazole, Salicylazosulfapyridine (active sulfapyridine)
• Potentiated sulfa, Trimethoprim + fulfadiazine, Trimethoprim +, sulfamethoxazole, Trimethoprim + sulfadoxime and Ormetoprim + sulfadimethoxine
• Topicals have Mafenide, silver sulfadiazine, Sulfacetamide, Sulfathiazole and silver sulfadiazine

Sulfonamides MOA and Side Effects (With Crystalluria)

• Inhibition of folic acid
• PABA + 2 = dihydropteroic acid
• Dihydrofolate syntase acid (folic acid), decrease dihydrofolate reductive
• Tetralydrofolic acid (folinic acid), TMP: inhibit dihydrofolate reductase
• Cause inhibition of growth and multiplication of org
• Crystalluria with hematuria, hypersensitivity, GIT disturbances, blindness, collapse, Anemia, Hepatitis, Conjunctivitis, Keratitis sicca, Thyroid. Decrease growth and egg production

Sulfonamides Indications, Interactions, and Withdrawals

• Most effective at early stages of acute infect & when organisms are rapidly multiplying
• Ca-containing fluids, Acidic drugs -antacid, Urinary acidifier, Phenytoin
• Withdrawal
• 7-15 days in meat and 60-96 hrs in milk

Quinolones

• Quinolone carboxylic acid (Enrofloxacin, Norfloxacin, Ciprofloxacin, Pefloxacin, Danofloxacin, Rosaoxacin, Acrosocacin, Oxolimic acid), Naphtyridine, Cinnolone and Pyridopyrimidine
• Inhibits bacteria
• The excessive drug use in an immature animal, interaction

Quinolones MOA, Indications, and Side Effects

• inhibit DNA, inhibit synthesis. supercoiling and exposure, cross-resistance.
• Side effects: Neurotoxic, GIT, Anemia. Erythrocytes, and cartilage

Nitrofurans

• Drugs: nitrofurazone
• inhibit bacterial, and blocking translations
• Can be inhaled or ingested
• The withdrawals and effects can be varied

Pleuromutilins

• The Tiamulin, and Valnemulin and affects certain mycolpasmas, swine, interact

Coccidiosis

• In poultry, tiamulin, interferes with monensin and salinomycin metabolism
• Tiamulin + salinomycin or monensin = produce toxic effect

MODULE 8: Antiviral and Antifungal Drugs

• Rarely used and affects our own cells

Viruses

• Can have DNA and RNA types, replication dependent

Antivirals

• Early site, AMANTADINE
• RIMANTADINE: Derivative of amantadine, effects primary transcription

Pyrimidine

• Analogs prevent amino acid and nucleic acid synthesis, affects forming nucleosides. Interferes with protein synthesis like iodoxuridine. Is effective in the herpes’

Anti-Virals

• Inhibit nucleotides and is effective to herpes

Maturation

• affects the process and the body by increasing the resistance of antibodies
• Interferon (Protein substance released from mammalian cells with the ability to cause other cells to resist viral infection)
• Host modulators are antivirals modulate to help antibody production

Module 9 - Antiprotozoals

• Antiprotozoals are classified according to protozoan infection, may be coccidiosis, or isosporic

Anticoccidials

• Dilute airway mucus after systemic administration
• Drugs, schedules

Aminprolium

_ Competes with thiamine, structurally looks like thiamine so it can be competitive _ Structurally

Anticoccidials

• Monensin
• Affective against trophozoites and schizonts and effective for certain cycles _ Have ability and effective

Treatments

• Anti-trypanosones _ Treat with

Large Animals

• Treat with OP compounds _ Avermectin treats all the animals

Module 10 - Anthelmintics

General Info

• Anthelmintic and External Parasitacide
• By impairment
• Inhibitors of glucose
• Disruption that’s transferred

Treatments of Glucose Imbalance

• Causes paralysis. Has cholinergic and causes inhibitors
• Mabilis Na ang contraction

Benzimidazole

_ Most dewormers kill adults

Treatments of infections in species

Treatment is used on Avermectics

Internal Paraciticides

• Are used for OP and Pyrethroids. Contains an avermectin and are effective

Methylene Blue

• Module 11
• The neoplastic diseases that can be treated by adjusting drugs.

Neoplastic Drug

• Some are cell, some induce hormones, others can prevent reproduction. Are both antiseptics and disinfectants with toxicity
• Need certain care

Toxicodology

• Module 12
• Some substance that effect

Avert and Remove

• Use fluids and induce cathartics
• Administer fluid
• Administer antidotes
• Symptoms include reactions to all
• And the compounds should be taken. Use saline drips, activated charcoal for poisoning