Pharmacodynamics / pharmacokinetics

PK meaning

Action of animal on drug - absorption, distribution, metabolism, excretion

PD meaning

Action of drug on animal

Clinical efficacy takes data from

In vitro sensitivity, PK, PD

Amoxicillin as semi synthetic anti microbial features

Penicillin with large spectrum of activity, not acid labile = oral

Synthetic antimicrobial example

Fluoroquinolone

Main MOA of antimicrobials

Prevent growth + survival of invading organisms while causing minimal damage to the host (selective toxicity to prokaryotes)

How antibiotics work - main MOA

Disrupt cell wall production + function

Disrupt cell membrane function

Distrust dna function

Disrupt protein synthesis

How antibiotics work - examples with MOA Disrupt cell wall production + function

Beta lactams, penicillins, cephalosporins

How antibiotics work - examples with MOA Distrust cell membrane

Ionophores

How antibiotics work - examples with MOA With dna disruption

Sulphonamides, fluoroquinolones, aminocoumarins

How antibiotics work - examples with MOA Distrust protein synthesis

Aminoglycosides, tetracyclines, macrolides, florphenicol

Antibiotic classifications - bacteriostatic vs bacteriocidal + eg

S- prevent replication, don’t kill susceptible (tetracyclines, macrolides)

C- kill susceptible (fluoroquinolones, beta lactams, trimethroprim)

CFU meaning

Colony forming units

Antibiotic classifications - Conc + examples

Gentamicin cidal at high conc

Tetracyclines used at static dose

Antibiotic classifications - Bacteriostatic needs what from host as slow onset of action

Good immune response

Antibiotic classifications - Bacteriocidal need what cells

Active growing

Antibiotic classifications - Spectrum of activity + examples

Broad - don’t need to diagnose (penicillins, aminoglycosides, macrolides)

Narrow (sulphonamides, cephalosporins, tetracyclines, fluoroquinolones)

Is penicillin good against gram - or + (+why)

Gram +

Doesn’t cross outer membrane

Empiric therapy

Infecting organism not identified - broad spectrum use

Definitive therapy

Organism identified - narrow spectrum use

Prophylactic therapy

Prevent initial infection of recurrence (before CS)

Curative treatment

Treating sick animal/group following diagnosis + clinical disease

Regulation of prophylactic use

Ensure welfare, no routine use, ensure hygiene, not to increase production

metaphylaxis treatment

Treating group after diagnosis of infection + disease in part of group → prevent spread to those in close contact

Categories of antibiotic use

A - avoid

B- restrict

C- caution

D- prudence

Categories of antibiotic use - classes in category a

Sulfones, amdinopenicillins

Categories of antibiotic use - classes in category b

3+4 cephalosporins, quinolones

Categories of antibiotic use - classes in category c

Aminoglycosides, 1+2 cephalosporins

Categories of antibiotic use - classes in category D

Penicillins, steroids, sulfonamides

Length of treatment MOA - time over MIC dependent examples

Penicillins, cephalosporins, tetracyclines, macrolides

Length of treatment MOA - conc dependent examples

Aminoglycosides

Length of treatment MOA - area under curve dependent examples

Fluoroquinolones

Post antibiotic effect (PAE) meaning

Ability of drug to suppress/kill bacteria after drug conc has dropped below MIC

What affects systemic availability of drug

Dose, route of administration, dose rate, access to site of infection

Route of administration - injection features (pros+cons)

Severe infection

+for poor absorption, no GI absorption, quicker onset (IV)

-client training, compliance, pain, cost, aseptic technique, higher initial conc in other places, soluble prep

Route of administration - IV features (pros+cons)

Enters cells via passive diffusion

+total dose enters circulation

-high conc quickly declines (give slowly)

Route of administration - IM,SC features (pros+cons)

+rapid absorption

-pain, scar, withdrawal period, no large vol

What needs to be good for route of admisnitatrion to have no effect

Absorption

Route of administration - oral features (pros+cons)

-need to take GI tract into account (rumen dilutes), less bioavailability, hepatic portal vein (first pass metabolism), affected by food

What affects systemic drug distribution

Blood flow, cell barrier penetration, diffusion/perfusion, binding to plasma proteins (available to kill bacteria, urine excretion, long acting), selective location binding

Vol of distribution def

Reflection of amount left in blood after drug absorbed (large = doesn’t remain in blood)

Half life def

Time required for plasma conc to half after reaching pseudo-equilibrium distribution

Synergism def + what affects it

potentiation of 1 drug action by another (preventing drug or bacterial metabolism)

Conc, bacterial life cycle phase, L-form inhibition

Half life vs clearance

C- ability to eliminate drug

HL- overall elimination during terminal phase (depends on clearance + distribution)

Methods of drug elimination

Kidney, liver, bile, sweat, milk, faeces

Methods of clearance

Liver metabolism, unchanged excretion in kidney

Fraction unchanged (fu) meaning

Proportion of drug cleared by kidneys

Fraction unchanged (1-fu) meaning

Fraction of drug cleared by metabolism

What affects drug elimination by liver

Blood flow, enzyme activity (inactive + active metabolites), liver damage, other drugs (enzymes)

What affects drug elimination by milk (acidic)

Dose, lipid soluble, ionisation at blood pH (alkaline), disease (mastitis)

Best classes for udder + lung infection

Macrolides

Which groups are beta lactams

Penicillins, cephalosporins

Beta lactams - groups + examples

Simple penicillins = penicillin G, penethamate

Broad spectrum penicillins - ampicillin, amoxicillin, cloxacillin

Cephalosporins

Beta lactams MOA

Interferes with cross links in cell wall in growth → weaken cell wall → lyses

Classes of penicillins 5 + examples

Natural - penicillin G, penicillin V

Beta lactamase resistant - cloxacillin

Aminopenicillins - amoxicillin, ampicillin

Extended agents - ticarcillin, carbenicillin

Augmented agents - amoxicillin + clavulanate

form of penicillin for farm animals (reduces pain)

Procain penicillin

Penicillins + cephalosporins main properties

Kidney excretion, not enter CNS, weak acid, 50% plasma protein bound

Penicillins + cephalosporins side effects

Immune mediated reactions - haemolytic anaemia, thrombocytopenia (type 2 hypersensitivity), anaphylaxis (type 1 hypersensitivity)

Procaine reactions- CNS stimulation

Aminopenicillins - examples

Ampicillin, amoxicillin

Aminopenicillins - Treats

Gram - aerobes (salmonella, E. coli)

Which species is oral admiration of penicillin not used

Rabbits, Guinea pigs, hamsters, gerbils, small herbivores

Augmented amoxicillin - treats (better than aminopenicillins)

Gram - and gram +

1st gen cephalosporins - treats + examples

Gram + Aerobes, gram - aerobes

Cephapirin, cephalexin, cephalonium

2nd gen cephalosporins - treats

Some gram + aerobes, gram - aerobes, gram - anaerobes

3rd gen cephalosporins - treats + examples (not for general practice)

Mainly gram - aerobes, some gram + aerobes, pseudomonas

Ceftriaxone, cefotaxime

4th gen cephalosporins - treats + examples (cattle, horse, pigs only)

Gram + aerobes, gram - aerobes, pseudomonas

Cefquinome

Protein synthesis inhibitors - bind to what

Bacteria ribosomes

Protein synthesis inhibitors - Example groups

Aminoglycosides, tetracyclines, macrolides, lincosamides

Protein synthesis inhibitors - Aminoglycosides examples

Gentamicin, amikacin

Protein synthesis inhibitors - Aminoglycosides features

Polar, water soluble → can’t cross lipid cell membranes → synergistic with beta lactams

Need active oxygen carrier to enter cell → not for anaerobes

Protein synthesis inhibitors - Aminoglycosides MOA

Irreversibly bind to 30S ribosomes → disrupt initiation of protein synthesis, misread mRNA → bacteriocidal

Protein synthesis inhibitors - Aminoglycosides treats

Gram + aerobes, gram - aerobes

Protein synthesis inhibitors - Aminoglycosides distribution

Extra cellular fluid (not CSF)

Protein synthesis inhibitors - Aminoglycosides elimination

Kidney

Protein synthesis inhibitors - Aminoglycosides side effects

Nephrotoxicity (PCT damage) → azotaemia

Ototoxicity → CN8 damage

Protein synthesis inhibitors - tetracyclines MOA

Enter bacteria with active transport → Bind to 30S ribosomes → bacteriostatic

Protein synthesis inhibitors - tetracyclines treats

Gram +, gram -, mycoplasmas

Protein synthesis inhibitors - tetracyclines excretion

Kidney (doxycycline intestine), bile,

Protein synthesis inhibitors - tetracyclines examples

Doxycycline

Protein synthesis inhibitors - tetracyclines distrubition

In tissues (not CNS), pneumonic lung tissue

Protein synthesis inhibitors - tetracyclines side effects

Discolour bone, inhibit foetal bone growth, tubular necrosis, chelate calcium

Protein synthesis inhibitors - macrolides examples (synthetic = broader spectrum, better)

Erythromycin, clarithromycin, azithromycin

Protein synthesis inhibitors - macrolides MOA

Reversibly bind to 50S ribosome → inhibit RNA dependent protein synthesis → bacteriostatic, bacteriocidal at high conc

Reduced activity at low pH (pus)

Protein synthesis inhibitors - macrolides Treats

Gram + aerobes, gram - aerobes, anaerobes, atypical bacteria

Protein synthesis inhibitors - macrolides Absorption (erythromycin, azithromycin)

E- destroyed by GI acid

A- acid stable

Protein synthesis inhibitors - macrolides Distribution

Extensive, minimal CSF

Protein synthesis inhibitors - macrolides Elimination (erythromycin, azithromycin)

E- bile, enterohepatic recycling

A- bile

Protein synthesis inhibitors - macrolides Example used in farm animals (feed)

Tylosin

Protein synthesis inhibitors - macrolides Side effects

GI motilin agonists → stimulate motility, diarrhoea

Hyperthermia, hepatoxicity

Protein synthesis inhibitors - lincosamides examples

Lincomycin, clindamycin

Protein synthesis inhibitors - lincosamides Vs macrolides

L- not for gram - aerobic

M - gram - aerobic

Protein synthesis inhibitors - lincosamides MOA

Reversibly bind to 50S ribosome → inhibit RNA dependent protein synthesis → bacteriostatic, bacteriocidal at high conc

Protein synthesis inhibitors - lincosamides treats

Gram + aerobes, gram + anaerobes, gram - anaerobes, mycoplasma

Protein synthesis inhibitors - lincosamides side effects

Colitis (herbivores)

Bacteriostatic example of dna metabolism inhibitor

Sulfonamides

Bactericidal examples of dna metabolism inhibitor

Potentiated sulfonamides, fluoroquinolones, metronidazole

Bacteriostatic example of dna metabolism inhibitor - sulfonamides MOA

Block production of pyrimidines + purines (PABA) for dna synthesis

Doesn’t affect mammalian cells (folate)

Bacteriostatic example of dna metabolism inhibitor - sulfonamides example

Trimethoprim

Bacteriostatic example of dna metabolism inhibitor - sulfonamides absorption

GI tract (binds to feed)

Bacteriostatic example of dna metabolism inhibitor - sulfonamides distribution

Tissues, lung, CSF, protein bound