Pharmacology (1-24) Flashcards
what does rINN stand for
recognised international non-prprietary name
what does BAN stand for
British Approved Name
what does USAN stand for
United States Approved Name
this determines what the body does to the drug (Absorption, Distrbution, Metabolism, Excretion)
pharmacokinetics
name the 4 parts of pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
this is defined as what the drug does to the body / the relationship to drug concentration at the effect site
pharmacodynamics
name the pharmacokinetic model
helps understanding but is not directly relevant for clinical practice
one-compartment model
name the pharmacokinetic model
describes movement between compartments; drug is only removed from central compartment
two-compartment model
name the pharmacokinetic model
most commonly used to describe clinical scenarios
three-compartment model
name the pharmacokinetic model
drug is eliminated from the body, elimination occurs from central compartment
open model
name the pharmacokinetic model
drug is recirculated / drug is released into GIT via bile and then reabsorbed into plasma (enterohepatic recirculation)
closed model
reaction order?
rate at which drug concentration changes is constant and independent of drug concentration; rate of elimination is constant
zero order kinetics: 𝚫C/𝚫t = -K0
reaction order?
rate of drug elimination changes and is proportional to drug concentration; drug concentration decays exponentially; applies to most commonly used drugs
first order kinetics: 𝚫C/𝚫t = -KC
name 4 pH environments that may lead to ion trapping effect with drugs
- gastric pH
- fetal pH
- milk pH
- urine pH
what is the Henderson Hasselbach equation for acids
pH - pKa = log(ionized/nonionized)
what is the Henderson Hasselbach equation for bases
pH - pKa = log (nonionized/ionized)
how to find the pKa of a drug
pH at which 50% of the drug is ionized
this is the passage of a drug from site of administration to blood stream; influenced by solubility, physiochemical properties, site of administration, and bioavailability
absorption
name the 3 types of parenteral administration
- intravenous
- intramuscular
- subcutaneous
name the route of administration
most rapid onset of action, rate of administration usually slow
intravenous
name the route of administration
bypasses GIT, achieves sytemic levels more rapidly, advantageous when animal is inappetant or vomiting
parenteral
name the route of administration
often the only option for owners, influenced by speed of gastric emptying and presence of food
oral
this refers to the removal of a percentage of the drug as it passes through the liver via the portal vein before it reaches the systemic circulation and effect site
first pass effect
what effect does vasoconstriction have on absorption of agent from a site
reduces it
this is an indication of total exposure to the drug, used to define bioavailability, and used to calculate clearance
area under the curve (AUC)
this defines the extent to which an administered does of a drug enters the systemic circulation intact; referred to as F
bioavailability
what is the bioavailability of intravenous drugs
100%
this feature of pharmacokinetics is influenced by movement across membranes, blood flow to different organs, lipid solubility, and plasma protein binding
distribution
this is the main plasma protein drugs bind to
albumin
what is the equation for volume of distribution for a drug
Vd = Dose / C0
this is the peak plasma concentration after equilibrium is achieved and before elemination has begun
C0
this enhances drug access to sites of metabolism
lipid solubility
this enchances possibility of renal excretion of drug
water solubility
this part of drug elimination occurs mainly in the liver (but also in plasma, kidney, gut and lung); in phase 1 or phase 2 reactions
biotransformation
what are the 3 types of phase 1 biotransformation reactions?
- hydrolysis
- reduction
- oxidation
what are the 3 types of phase 2 biotransformation reactions
- acetylation
- glucoronidation
- conjugation to amino acids
what is the main organ for drug excretion?
kidney
what are the 3 main factors for drug excretion by the kidney
- water solubility
- GFR
- Active Transport
what are the 2 factors for reabsorption of a drug
- lipid solubility
- ionisation (ion trapping)
what are the 3 less common routes of drug elimination?
- biliary
- skin
- pulmonary
this is the time taken for the plasma drug concentration to fall by 50%
half-life of elimination
what is the equation for half-life in terms of K (slope of the PDC/time curve)
t 1/2 = 0.693 / K
name 3 factors affecting half-life of a drug
- access to sites of biotransformation or elimination
- interaction with other drugs
- physiologica/pthological states
what is the equation for the relationship between half-life and clearance?
t 1/2 = 0.693 x Vd / Cl_B
this is defined as the volume of blood cleared of the drug by all elimination processes per unit of time (mL/min) - encompasses biotransformation and excretion processes
clearance
this is where the levels of drug remain stable or consistent from dose to dose
steady state
how many half-lives does it take to reach 95% steady state
5
how many half-lives does it take to reach 99% steady state
7
name the 3 ways steady state can be achieved
- intravenous continuous infusion
- loading dose followed by a regular dose at fixed intervals
- fixed interval of a regular does
what is the fluctuation within steady state if the dose interval is the same as the half-life
50%
what is the fluctuation within steady state if the dose interval is twice the half-life
75%
name the formula for acids
(pharmacology summary of Formulae)
pH - PKa = log[ionized/non-ionized]
name the formula for bases
(pharmacology summary of Formulae)
pH - PKa = log[non-ionized/ionized]
name the formula for bioavailability
(pharmacology summary of Formulae)
F = AUC oral / AUC IV
name the formula for volume of distribution
(pharmacology summary of Formulae)
Vd = dose/C_0
(where C_0 = concentration at time 0)
name the formulas for half-life
(pharmacology summary of Formulae)
t 1/2 = 0.693/K
t 1/2 = 0.693 x Vd/Cl
name the formula for clearance
(pharmacology summary of Formulae)
Cl = Vd x K
name the formula for dose
(pharmacology summary of Formulae)
Dose = [Cmax] x Vd
this is a macromolecular structure with which the drug reacts; may be a protein, enzyme, nucleic acid, or less specific
drug receptor
this is a drug that binds to a physiological receptor and mimics the effect of the endogenous ligand
agonist
this type of agonist can achieve maximal response even if not all the receptors are occupied
full agonist
this type of agonist is incapable of achieving maximal response even if all the receptors are occupied
partial agonist
this is the tendency of the ligand (drug) to bind to the receptor
affinity
this is a term used to describe how good the drug is at eliciting a response
efficacy
this is a relative term that is often used to compare two drugs - comparing the concentration required to elicit the same response
potency
this is the concentration of the drug required to produce 50% of maximal response
EC 50
these drugs habe affinity but have no instrinsic activity & block the effect of the agonist
antagonist
name the type of antagonist
most important, effects are reversible/surmpuntable by increasing amount of agonist
competitive antagonist
name the type of antagonist
cannot be overcome by increasing amount of agonist; ex: Aspirin
non-competitive antagonist
at equilibrium, the number of receptors occupied by the drug is related to the concentration of the drug & described by this equation
Hill-Langmuir equation
this defines the capacity of a drug to preferentially produce one particular effect
selectivity
this is an absolute term; a drug with this tends to only act on one particular receptor type
specificity
this is the ratio of the dose giving an undesirable effect over the dose required to give the desired effect
therapeutic index
name 4 types of drug receptors
- ion chanell cell surface transmembrane receptor
- G protin couple receptor
- protein kinase
- cytosolic receptor
this type of drug receptor mediates action of a variety of proteins such as insulin
protein kinases
this is when a receptor is exposed to a ligand and the response reaches a peak then begins to fall off (despit the continued presence of ligand)
receptor desensitization
this is when receptors become internalized and degraded within the cell
receptor down-regulation
this is a term used to denote the rapid loss of responsiveness to a drug following intial dosing
tachyphylaxis
what are drug dosing regimens based on?
normal healthy individuals
name 4 things that may cause a dosing regimen to need individualization
- age
- species
- health status
- concurrent treatment
certain states of the animal may cause drug dose regimens to need individualization bc they may result in these 3 changes
- changes in Vd
- changes in plasma protein binding
- changes in metabolism
name 4 routes of ectotoxicity for ectoparasiticides
- incorrect disposal
- leakage from fish farms
- excretion in feces or urine
- topical products washed off
name the 5 points of the BSAVA/BVA/BVZA 5-point plan for responsible ectoparasiticide use
- educate clients to check & prevent parasites
- understand the risks
- risk-based prescribing
- ensure appropriate use & disposa
- record & monitor use
what is the mode of action for systemic macrocytic lactones?
(ectoparasiticide)
bind to glutamate & GABA-activated chloride channels
(leading to paralysis and death)
do systemic macrocytic lactones have repellent or knock-down activity?
no
name the two main groups of systemic macrocytic lactones
- Avermectins
- Milbemycins
what are the 2 main parasites that systemic macrocytic lactones act against
- Mites (Sarcoptiforms & Demodex & other)
- Fleas
(NOT ticks)
what species are systemic macrocytic lactones used clinically for?
range of species
these are licensed for flea control in dogs and cats in the US; derived from Saccharopolyspora spinosa; selective for insects
Spinosyn macrocytic lactones
(Spinosad and Spinetoram)
what type of pyrethroid is Permethrin
type 1 (non alpha-cyano)
what type of pyrethroid is Cypermethrin, Deltamethrin, and Flumethrin?
type 2 (alpha-cyano)
what is the mode of action of Pyrethrins & Pyrethroids?
(ectoparasiticides)
affect voltage-gated sodium channels
(causing hyper-exciitability and death)
what species are Pyrethrins & Pyrethroids used clinically on?
dogs, small mammals, horses, farm animals, poultry
do Pyrethrins & Pyrethroids have repellent or knock-down activity?
yes, good
what adverse effects can type 1 Pyrethroids have?
- excitation
- tremors
- hyperthermia
what adverse effects can type 2 Pyrethroids have?
- salivation
- extensor tone
- incoordination
- seizures
- apnea
what is the mode of action for oxadiazines?
blocks neuronal sodium channels
(causing paralysis and death)
do oxadiazines have repellent or knowck-down activity?
no
what species are oxadiazines used for clinically?
dogs and cats
what is the mode of action for phenylpyrazoles?
(ectoparasiticide)
bind to GABA & glutamate-activated chloride channels
(leading to hyper-excitability and death)
name two types of phenylpyrazoles
(ectoparasiticide)
- fipronil
- pyriprole
what species are phenylpyrazoles used for clinically?
dogs and cats
does phenylpyrazoles have repellent or knowck-down activity?
no
which ectoparasiticide is topical and spreads in sebum?
phenylpyrazoles
what two species are phenylpyrazoles highly toxic to?
rabbits and fish
what is the mode of action for neonicotinoids?
(ectoparasiticide)
bind to nicotinic acetylcholine receptors
(leading to hyper-excitability, paralysis and death)
do neonicotinoids have repellent or knock-down activity?
no (except nitenpyram has knock-down effect)
what species are neonicotinoids used for clinically?
dogs, cats, small mammals
name 3 types of neonicotinoids
- nitenpyram
- imidacloprid
- dinotefuran
what is the mode of action for isoxazolines?
(ectoparasiticide)
bind to GABA and glutamate-activated chloride channels
(causing hyper-excitability and death)
what parasites are isoxazolines efficient on
- fleas and other insects
- Sarcoptes, Demodex & other mites
- ticks
do isoxazolines have repellent or knock-down activity?
NO
what species are isoxazolines used to treat clinically?
dogs, cats, poultry
what percent are isoxazolines passed out unchanged in feces?
80-90%
what is the mode of action for formamidines?
(ectoparasiticide)
- monoamine oxidase inhibitor
- octopamine receptor agonist
- Alpha2 receptor agonist
(causing increased nerve activity and death)
what parasties are formamidines effictive against?
- Sarcoptes, Demodex & other mites
- ticks
do formamidines have repellent or knock-down activity?
yes, good
what species are formamidines used to treat clinically?
small animals, farm animals
what 3 animals are formamidines contraindicated for?
- cats
- horses
- chihuahuas
what is the mode of action for carbamates and organophosphates?
form complexes with acetylcholinesterases
do carbamates and organophosphates have repellent or knock-down activity?
yes, rapid
name 5 adverse effects of muscarinic overstimulation from organophosphate poisoning
- Salivation
- Lacrimation
- Urination
- Defecation
- GI cramps
- Emesis
(SLUDGE)
name 4 adverse effects of nicotinic overstimulation from organophosphate poisoning
- Mydriasia Tachycardia
- muscle Weakness
- Twitching
- Fasciculation
(high BP, paralysis)
(MT WTF)
which ectoparasiticide can cause irreversible chronic neurotoxicity from long term sub-clinical exposure (ataxia, paresis, paralysis)
carbamates and organophosphates
what species are calcium polysulfides and thiosulphates (lime sulphur) used to treat clinically
cats, horses, SA camelids
what parasites are calcium polysulfides and thiosulphates (lime sulphur) effective against in cats?
- Demodex gatoi
- Lynxacarus
- Notoedres
- Cheyletiella
- Trombicula
- lice
what parasites are calcium polysulfides and thiosulphates (lime sulphur) effective against in horses?
- Chorioptes
- lice
what parasites are calcium polysulfides and thiosulphates (lime sulphur) effective against in SA camelids?
- Chorioptes
- Sarcoptes
do calcium polysulfides and thiosulphates (lime sulphur) have repellent or knock-down effects?
NO
name 4 adverse effects of calcium polysulfides and thiosulphates (lime sulphur)
- skin irritatio
- malodorous
- yellow stains
- oral ulcers if ingested
name the topical ectoparasiticide formulation
hydrophobic polymers (resist wetting and degradation);
silicons oils and fatty acids (gradual release and diffusion);
can cause physical injury or skin irritation
collars
name the topical ectoparasiticide formulation
raid systemic absorption/diffusion through skin and coat; sebum may be important for diffusion;
can have aversion or irritation, effects on furniture and surfaces, and environmental impacts
spot-on or pour-on
name the topical ectoparasiticide formulation
good application and distribution, but more difficult to apply;
vulnerable to wetting and bathing;
disliked by animals;
increased risk of eye exposure, inhalation, and ingestion as well as human exposure
sprays and dips
this is an agent that kills microbes or inhibits their growth without damaging the host
antimicrobials
these are microbial products that kill or inhibit other micro-organisms
antibiotic
these are synthetic agents with activity against bacterial
antibacterial
name the type of resistance
lack of acticity due to inherent phenotype (e.g. lack of target, failure to penetrate cell wall, etc.)
inherent
name the type of resistance
mutations that confer resistance
chromosomal
name the type of resistance
resistance genes on mobile genetic elements (e.g. plasmids)
transferable
what are mycoplasmas resistant to?
beta-lactams
what are anaerobes resistant to?
aminoglycosides
what are aerobes resistant to?
metronidazole
this is the biggest driver of antimicrobial resistance
antimicrobial use
name 3 methicillin resistant staphylocci (MRS) organisms of concern
- S. pseudointermedius (MRSP)
- S. schleiferi (MRSS)
- S. aureus (MRSA)
name 2 multidrug resistant (MDR) cocci organisms of concern
- Streptococcus
- Enterococcus
name 2 other multidrug resistant (MDR) organisms of concern
- Pseudomonas
- Salmonella
what does nosocomial mean?
healthcare-acquired
name the 3 most common problems of vet-visiting dogs, cats and horses that tend do get antimicrobials but do not always require systemic antimicrobial treatment
- pruritis
- diarrhea
- respiratory conditions
name the 3 most important drivers for antimicrobial use in practice which should be addressed to change the practice culture and improve antimicrobial stewardship (AMS)
- vet prescribing behaviors
- interactions with clients
- practice norms
this describes the drug-host interaction
(bioavailability, penetration and clearance)
pharmacokinetics (PK)
this describes the drug-target interaction
(mode of action)
Pharmacodynamics
name 6 factors affecting PK/PD drug models
- poor bioavailability
- hypovolemic shock/poor perfusion
- renal/liver failure
- increased minimum inhibitory concentration (MIC)
- biofilm
- pus, debris, foreign material
this type of drugs are largely restricted to extracellular fluid (ECF);
fluid retention, IV fluid therapy, and/or increased renal clearance may necessitate higher doses to ensure therapeutic concentrations at the site of infection
hydrophilic (water soluble)
this type of drug penetrates tissues effectively and are less affected by changes in fluid dynamics and clearance
lipophilic (fat-soluble)
excellent, good, or poor tissue penetration?
Chloramphenicols
Fluoroquinolones
Minocycline
Doxycycline
Metronidazole
Rifampin
excellent
excellent, good, or poor tissue penetration?
Trimethoprim-sulfonamides
Lincosamides
Macrolides
Tetracyclines
good
excellent, good, or poor tissue penetration?
Beta-lactamase inhibitors
Penicillins
Cephalosporins
Aminoglycosides & aminocyclitols
poor
name 3 concentration dependent antimicrobials
- most fluoroquinolones
- aminoglycosides
- metronidazole
name 2 time dependent antimicrobials
- penicillins
- cephalosporans
name 3 antimicrobials with mixed effects for mode of action
- some fluoroquinolones
- lincosamides
- tetracyclines
what is the efficacy of concentration dependent antimicrobials
ratio peak concentration (Cmax) to MIC
what is the efficacy of time dependent antimicrobials
time above MIC
what is the efficacy of antimicrobials with mixed effects
total 24h exposure (area under curve)
what is the dosing for concentration dependent antimicrobials
max dose every 24h
what is the dosing for time dependent antimicrobials
appropriate dose every 8-12h
Bacteristatic or Bactericidal?
Lincosamides
Macrolides
Chloramphenicols
Tetracyclines
Trimethoprim
Sulphonamides
bacteriostatic
Bacteriostatic or Bactericidal?
Penicillins
Cephalosporins
Fluoroquinolones
Trimethoprim-sulphonamides
Aminoglycosides & aminocyclitols
Metronidazole
bactericidal
Bacteriostatic or Bactericidal drugs?
may be more effective in seriously immunocompromised patients
Bactericidal drugs
Bacteriostatic or Bactericidal drugs?
may result in less toxin release and toxic shock in staphylococcal and streptococcal infections
Bacteriostatic drugs
Bacteriostatic or Bactericidal drugs?
minimum bactericidal concentration (MBC) is much higher than the MIC
bacteriostatic drugs
Bacteriostatic or Bactericidal drugs?
minimum bactericidal concentration (MBC) is close or identical to the MIC
bactericidal drugs
what is the most serious adverse drug reaction (ADR)
hypersensitivity reactions
what breed has a bred-specific risk of adverse drug reactions to sulphonamides
Dobermans
name the main route of excretion for these drugs
Fluoroquinolones
Rifampicin
Doxycycline
Chloramphenicols
hepatic (liver)
name the main route of excretion for these drugs
Tetracyclines
Lincosamides
Macrolides
Fluoroquinolones
Metronidazole
mixed hepatic-renal
name 5 circumstances where cuture and ASTs (antimicrobial sensitivity tests) are necessary
- deep or complex infections
- unusual cilinal signs/cytology
- Rod bacteria
- if empirical treatment fails
- if AMR is more likely
in these tests: the zones of inhibition around each antimicrobial disc are compared to agreed breakpoints
Kirby-Bauer disc diffusion
in Kirby-Bauer disc diffusion tests, what shows that the infection is susceptible
zone of inhibition (ZI) exceeds the breakpoint
in Kirby-Bauer disc diffusion tests, what shows that the infection is resistant
zone of inhibition (ZI) is less than the breakpoint
these methods determine the lowest concentration of antimicrobial that inhibits bacterial growth
MIC methods
if MIC is (lower or higher?) than the breakpoint the infection is considered susceptible
lower
if MIC is (lower or higher?) than the breakpoint the infection is considered resistant
higher
the capital letters (‘S’ or ‘R’ or ‘I’) on a bacterial AST refer to this
the exact MIC
how to determine which antimicrobial is most effective from an AST
compare breakpoint:MIC ratio (want >1)
this breakpoint:MIC ratio means that the tissue concentration is only just sufficient enough to treat the infection and there is a risk of treatment failure
1
this breakpoint:MIC ratio means that the efficacy is less likely to be affected by factors that alter tissue concentration
> 1
these can be effective in surface and superficial infections & some focal deep infections
topical microbials and antibiotics
name some effective antimicrobials
- chlorohexidine
- manuka honey
- hypochlorous acid
- polihexanide
- bleach
these antimicrobials have well established breakpoints, efficacy and saftey;
appropriate for empirical treatment
first line antimicrobials
these antimicrobials have a concern for AMR;
they should only be used when there is culture evidence and/or PK/PD factors suggesting that first line drugs would not be appropriate
second line antimicrobials
these antibiotics are critically important andd AMR is of great concern;
they may not be licensed for use in animals;
breakpoint, efficacy and sfety data may be limited;
must only be used where no first or second line antibiotics are effective and topical antimicrobial therapy is not feasible or effective
third line antibiotics
what line are these antibiotics?
Penicillins
Ampicillin & amoxicillin
1st & 2nd gen. cephalosporins
Clindamycin & lincomycin
Tetracyclines
Trimethoprim-sulphonamides
Spiramycin
Metronidazole
first line antimicrobials
what line are these antimicrobials?
3rd gen. cephalosporins
Fluoroquinolones
Florfenicol (in cattle)
2nd line antimicobials
what line are these antimicrobials?
Aminoglycosides
Anti-Pseudomonas penicillins
Azithromycin & clarithromycin
3rd & 4th gen. cephalosporins
Chloramphenicol & florfenicol (in horses and small animals)
Rifampicin
Nitrofurantoin
3rd line antimicrobials
name the common antimicrobial combination
high tissue perfusion;
effective against gram- anaerobes, anaerobes, staphylococci and most gram+ aerobes (except streptococci)
Fluoroquinolone & Metronidazole
name the common antimicrobial combination
low tissue penetration;
effective against gram- aerobes, most anaerobes and gram+ aerobes
Aminoglycoside & Amoxicillin-clavulanate
name the common antimicrobial combination
mixed tissue penetration;
effective against gram- aerobes, most anaerobes & gram+ aerobes
Aminoglycoside & Lincosamides
name the common antimicrobial combination
Mixed tissue penetration;
effective against gram- aerobes, most anaerobes and gram+aerobes;
high potential for AMR
Fluroquionolone & Amoxicillin-clavulanate
name the 4 principles of prophylactic treatment
- select antimicrobial appropriate to the infection risk
- start treatment before procedure for adequate plasma and tissue levels
- repeat treatment to maintain tissue levels
- pot-op treatment continued only if necessary
this is the treatment of the whole group including infected and non-infected animals;
may be considered to prevent the spread of disease
metaphylaxis
what is the mode of action for penicillins
disrupt bacterial cell wall causing lysis (penicillin-binding proteins - PBP)
what bacteria are penicillins most active against
gram-pos bacteria
name 3 categories of penicillins
- narrow spectrum penicillins
- aminopenicillins
- anti-staphylococcal pennicillins
amoxicillin is often combined with this beta-lactamase inhibitor
clavulanic acid
some bacterial PBPs act as beta-lactamases to cleave the beta-lactam ring and inactivate this class of antibiotics
penicillins
name 3 types of beta-lactamase inhibitors
- clavulanic acid
- sulbactam
- tazobactam
name the antibiotic class
inhibit beta-lactamases and enhance activity for penicillins susceptible to these enzymes
beta-lactamase inhibitors
how are cephalosporins classed?
(antibiotic)
generations (1G, 2G, 3G, 4G)
what is the mode of action for cephalosporin antibiotics?
similar to penicillins (disrupt the bacterial cell wall causing lysis)
what bacteria type are Cephalosporins NOT active against
enterococci (limited against anaerobes)
what is the mode of action for lincosamides and macrolides?
(antibiotics)
bind to 50S ribosome subunit to prevent protein synthesis
name 2 types of lincosamides
(antibiotics)
- clindamycin
- lincomycin
what type of bacteria are lincosamides and macrolides most effective against?
gram-positive bacteria
what type of bacteria are lincosamides and macrolides NOT effective against?
gram-negative bacteria
name 3 things resistance to lincosamides and macrolides is associated with
- modified ribosome binding site (erm genes)
- efflux pumps
- bacteria drug modification
what is the mode of action for Trimethoprim-sulphonamide ?
(antibiotics)
block folic acid synthesis (required for purine and pyrimidine synthesis)
name an adverse effect of trimethoprim-sulphonamide
very bitter - salivation and foaming (cats)
what type of bacteria are trimethoprim-sulphonamides most effective against (moderate activity)
gram-positive bacteria
what is the mode of action for fluorquinolones?
(antibiotics)
inhibit topoisomoerase II (DNA gyrase) in gram-neg bacteria
(disrupts DNA cleavage, reunion and super-coiling)
what 3 things is resistance to fluoroquinolones associated with
(antibiotics)
- decreased cell permeability
- efflux pumps
- altered topoisomerases
what is the mode of action for aminoglycosides
(antibiotics)
block protein synthesis at 30S ribosome subunit
what type of bacteria are aminoglycosides most effective against
gram-neg bacteria
list the 6 aminoglycosides in order of most to least efficacy
(antibiotics)
amikacin > tobramycin > gentamycin > neomycin = kanamycin > streptomycin
aktgnks
what 2 things is resistance to aminoglycosides associated with
(antibiotics)
- modification of ribosome binding site
- efflux pumps
this is an antibiotic closely related to aminoglycosides;
lack most of the systemic toxicity assoc. with aminoglycosides BUT chromosomal resistance can occur rapidly
aminocyclitols
what is the mode of action for tetracyclines
(antibiotics)
block protein synthesis through 30S ribosome subunit
name 5 types of tetracyclines
(antibiotics)
- tetracycline
- chlortetracycline
- oxytetracycline
- doxycycline
- minocycline
name 3 things resistance to tetracyclines is associated with
(antibiotics)
- multiple genes for efflux
- ribosome binding
- drug modification
what is the mode of action for chloramphenicols
(antibiotics)
disrupt protein synthesis through 30S and 50S subunits
what type of bacteria are chloramphenicols most effective against
anaerobes
what is resistance to chloramphenicols associated with
drug inactivating enzymes
what is the major adverse effect of chloramphenicols
(antibiotics)
fatal aplastic anemia in humans
what is the mode of action for metronidazole
(antibiotics)
disrupts DNA strands and inhibits repair enzyme (DNAase-1)
what conditions are required for metronidazole to be effective?
what is the only type of bacteria metronidazole is effective against
anaerobic
what is an adverse effect of metronidazole
(antibiotics)
bitter - inappetance and hypersalivation (cats)
what is the mode of action for rifampicin
(antibiotics)
inhibits RNA polymerase and DNA transcription
what type of bacteria is rifampicin NOT effective against
(antibiotics)
gram-negative
what is an adverse effect of rifampicin
(antibiotics)
red-orange discoloration of bodily fluids
what is the mode of action for nitrofurans
(antibiotics)
disrupts mRNA translation (from intracellular bacterial metabolism)
what type of bacteria is nitrofurantoin NOT effective against
(antibiotics)
anaerobes
what type of infection is nitrofurantoin (nitrofurans) restricted to and why
UTIs bc of rapid renal excretion
what are 3 adverse effects of nitrofurans
(antibiotics)
- erythema
- pruritic
- oedema
(also toxicity and carcinogenic potential)
name 5 antibiotics that are limited to topical use only due to toxicity and PD/PK factors
- polymixin B
- bacitacin
- silver sulphadiazine
- fusidic acid
- mupirocin
name the topical antibiotic
cationic agent: disrupts bacterial cell membrane phospholipids;
more effective against gram-neg bacteria;
resistance (decr. permeability) is uncommon;
inactivated by pus and debris
Polymixin B
name the topical antibiotic
acts on gram-pos bacteria by inhibitng cell wall peptoglycan synthesis
bacitracin
name the topical antibiotic
inhibits ribosomal activity and protein synthesis;
mainly active against gram-pos bacteria (staph, strep, corynebacteria);
NOT active against enterococci;
resistance associated with decreased ribosomal binding
fusidic acid
name the topical antibiotic
blocks nucleic acid synthesis;
active against gram-pos bacteria
novobiocin
name the topical antibiotic
inhibits RNA synthesis;
active against gram-pos bacteria (incl MRSP and MRSA) - narrow spectrum ;
resistance associated with mutations in target enzyme
mupirocin
what is the initial treatment choice for most fungal infections?
Azoles (imidazoles and triazoles)
what is the mode of action for azoles
(antifungal)
inhibit ergosterol synthesis disrupting fungal cell wall metabolism
are azoles fungistatic or fungicidal?
fungistatic
which azole’s absorption is not affected by food
(antifungal)
Fluconazole
whih azole’s absorption is decreased with food
(antifungal)
voriconazole
list the 4 main azoles in order from most well-tolerated to least well-tolerated in terms of adverse effects
(antifungal)
fluconazole > itraconazole = voriconazole > ketoconazole
FIVK
what is the most common adverse effect of azoles
(antifungal)
GIT upset
what is the mode of action for Allylamines (terbinafine)
(antifungal)
blocks ergosterol synthesis through inhibition of aqualene epoxidase
are allylamines (terbinafine) fungistatic or fungicidal?
fungicidal
what type of fungi are allylamines (terbinafine) effective against
dermatophytes
is absorption of allylamines (terbinafine) affected by food?
(antifungal)
no
how are allylamines (terbinafine) excreted
(antifungal)
hepatic metabolism
name 2 common polyenes
(antifungal)
nyastatin and natamycin
what is the mode of action for polyenes
(antifungal)
disrupt fungal cell membranes by occupying ergosterol binding sites
are polyenes fungistatic or fungicidal
fungicidal
what type of fungi are polyenes used for
superficial fungal infections only (Malassezia and Candida)
what is the mode of action for griseofulvin
(antifungal)
inhibits mitosis, nucleic acid synthesis and cell wall metabolism
is griseofulvin fungistatic or fungicidal?
fungistatic
what type of fungi is griseofulvin mainly used for
dermatophytosis in horses
name the antifungal
fungicidal;
poorly absorbed by GI tract so must be given parenterally;
dose-related nephrotoxicity
Amphotericin B
name the antifungal
traditional antifungal treatment;
mode of action unclear;
used systemically and topically;
can cause GIT upsets, sialadenitis, and goitre
sodium or potassium iodide
name the antifungal
blocks RNA synthesis;
synergy with amphotericin B for Cryptococcus and Candida;
NOT effective for dermatophytes;
renal excretion;
can cause GIT upsets, bone marrow suppression, hypersensitivity reactions, and neurological problems (cats)
flucytosine
what is the mode of action for Acyclovir, Famiciclovir, Ixouridine, and Remdesivir?
(antiviral)
nucleoside analogues that inhibit DNA/RNA synthesis
what is Acyclovir most commonly used alongside to increase anti-viral effect
(antiviral)
recombinent feline IFN-omega OR human IFN-alpha
what s Famiciclovir used systemically for?
(antiviral)
FHV-1 infections
what is ixouridine used to treat?
(antiviral)
topically in FHV-1
what is Remdesivir used to treat and how long must it be given?
(antiviral)
FIP (give SQ or IV for over 12 weeks)
what is the mode of action of amantidine?
(antiviral)
block M2 protein ion channels to prevent endocytosis
what type of viruses is amantidine active against
(antiviral)
enveloped RNA viruses
what is teh mode of action for L-lysine
(antiviral)
peptide, competitive inhibitor of arginine
what is L-lysine used for in cats
(antiviral)
FHV-1
name the interferon
active against many DNA and RNA viruses by direct inhibition of viral replication and stimulating anti-viral immunity;
used for FIV and FeLV in cats;
used for papilloma virus infections in dogs;
topical administration alongside acyclovir for FHV-1 keratitis
(antiviral)
recombinent human IFN-alpha
name the interferon
used in cats and dogs for acute and chronic viral conditions (FeLV, FIP, FCV and canine parvovirus infection)
(antiviral)
recombinent feline IFN-omega
name 2 mycobacterial derived immunomodulators
(antiviral)
- Bacille Calmett-Guerin (BCG)
- Regressin-V
name the 4 nucleoside analogue DNA/RNA synthesis inhitors used in animals
(antiviral)
- acyclovir
- famciclovir
- idoxuridine
- remdesivir
AFIR
name a peptide antiviral drug used in animals
L-lysine
what does VMR stand for?
veterinary medicines regulations
what does VMD stand for?
veterinary medicines directorate
this is the executive agency of DEFRA;
they operate the licensing system for animal medicines with aim to safe guard public health, animal health and the environment
veterinary medicines directorate (VMD)
this is a national surveillance scheme run by the VMD which aims to record and monitor reports of suspected adverse reactions to veterinary medicines in both animals and humans
SARSS (suspected adverse reaction surveillance scheme)
this is designed to provide information on the work of the VMD, plans and results, as well as general developments on the controls on veterinary medicines; publish quarterly reports
MAVIS (Marketing Authorizations Veterinary Information Service)
this governing body offers advice to the VMD on behalf of the Secretary of State, in respect of new and renewal marketing authorizations (MA), provisional MAs, variations to MAs and Animal Test Certificates (ATCs)
VPC (veterinary products committee)
who should adverse drug reactions be reported to
veterinary medicines directorate (VMD)
(under SARSS)
what 3 things make it ideal to use licensed veterinary products
- safety
- quality
- efficacy
name the 6 steps involved in drug development
- pre-discovery
- discovery
- pre-clinical testing
- clinical trials
- licensing
- marketing
name the 4 legally classified categories of veterinary medicines
- prescription only medicine - vet (POM-V)
- POM-vet, pharmacist, SQP (POM-VPS)
- non-food animal - vet, pharmacist, SPQ (NFA-VPS)
- authorized vet medicine-general sales list (AVM-GSL)
name the legally classified category of veterinary medicine
Can be prescribed by a VS after clinical assessment of the animal or herd;
in this category if contains a new active ingredient, has safety issues, a narrow safety margin, due to government policy or because specialised veterinary knowledge required for its use
Prescription Only Medicine – Veterinarian (POM‐V)
name the legally classified category of veterinary medicine
Can be prescribed by VS or SQP, No clinical assessment is required but the prescriber must be sure owner is competent to administer the product;
in this category if: it is used to reduce or prevent endemic disease in herds or flocks or individual animals, there is some risk for user, consumer, animal or environment, but users made aware by verbal or written advice
Prescription Only Medicine – Veterinarian, Pharmacist, SQP (POM‐VPS)
name the legally classified category of veterinary medicine
Similar to POM‐VPS but must be for non‐food animals
Non‐Food Animal – Veterinarian, Pharmacist, SQP (NFA–VPS)
name the legally classified category of veterinary medicine
No restrictions on its supply;
wide safety margin and specialist advice is not required
Authorised Veterinary Medicine – General Sales List (AVM‐GSL)
this is an assessment of relevant clinical information, which may include an examination of the animal
“clinical assessment”
which step of ‘the cascade’ ?
Veterinary medicine with a Marketing Authorisation valid in GB or UK wide for indicated species and
condition
step 1
which step of ‘the cascade’ ?
Veterinary medicine with a Marketing Authorisation valid in NI for indicated species and condition
step 2
which step of ‘the cascade’ ?
veterinary medicine with a Marketing Authorization valid in GB, NI or UK wide for a different species or condition
step 3
which step of ‘the cascade’ ?
human medicine with a Marketing Authorization valid in GB, NI or UK wide OR an authorized vet med from outside the UK
step 4
which step of ‘the cascade’ ?
extemporaneous preparation prepared by a vet, pharmacist or person holding an appropriate Manufacturer’s Authorization, located in the UK
step 5
if the withdrawal period is not specified on a veterinary medicine, what should it be set at for eggs and milk
no less than 7 days
if the withdrawal period is not specified on a veterinary medicine, what should it be set at for meat
not less than 28 days
if the withdrawal period is not specified on a veterinary medicine, what should it be set at for meat from fish
not less than 500 degree days
this is a means of defining the product, its dose and other relevant instructions
prescription
what must a written prescription contain?
(10)
- Name, address and phone number of prescriber
- Credentials of the prescriber
- Name and address of the person receiving the prescription
- A description of animal
- Drug, dose and instructions (incl. withdrawal period)
- Note if prescribing under the cascade
- Date
- Written in indelible format
- Signed
- “For animals under my care”
what does the abbreviation od mean in prescriptions
once daily (omni die)
what does the abbreviation sid mean in prescriptions
once daily (semel in die)
what does the abbreviation bd mean in prescriptions
twice daily (bis die)
what does the abbreviation tid mean in prescriptions
three times daily (ter in die)
what does the abbreviation qid mean in prescriptions
four times daily (quarter in die)
what does the abbreviation pc mean in prescriptions
after food (post cibum)
what does the abbreviation ac mean in prescriptions
before food (ante cibum)
what does the abbreviation prn mean in prescriptions
when required (pro re nata)
are controlled drugs regulated under the VMR (veterinary medicines regulation)?
no
name the schedule of controlled drugs
Vets have no authority to possess or prescribe these except with special license from Home Office
(ex: cannabis and LSD)
schedule 1
name the schedule of controlled drugs
Special requirements for requisition, prescribing, record keeping, storage and disposal;
Requisition in writing to the supplier signed by the VS;
Stored in a home office approved, locked receptacle;
Destroyed in presence of a person authorised by the Secretary of State
(Ex: morphine, ketamine, fentanyl, secobarbital)
schedule 2
name the schedule of controlled drugs
Subject to the same prescription and requisition requirements as schedule 2, BUT do not need to keep a record in a register;
Most should be kept in a locked receptacle;
(ex: pentobarbital, phenobarbital, buprenorphine and midazolam)
schedule 3
name the schedule of controlled drugs
Exempt from most of the restrictions of controlled drugs;
(ex: benzodiazepines and anabolic substances)
schedule 4
name the schedule of controlled drugs
Certain preparations containing codeine, cocaine and morphine in less than specified amounts;
Exempt from most of the requirements except that invoices need to be kept for two years
schedule 5
what 3 things must you record on obtaining a schedule 2 drug
- date
- name and address of supplier
- amount obtained
what 4 things must you record on supplying a schedule 2 drug
- date
- name and address of person supplied
- vet’s name
- amount supplied
how long are controlled drug prescriptions valid for?
28 days
how long should incoming and outgoing transaction records of POM-V and POM-VPS drugs be kept for
5 years
name the scheme
Some veterinary products can be marketed without a marketing authorisation and therefore are not required to prove safety, quality or efficacy (but must be manufactured to certain standards)
exemption scheme for small pet animals
products including these 3 agents are not included in the exemption scheme for small pet animals
- antibiotics
- narcotics
- psychotropics
how long is a prescription for medicated feedstuffs valid for
3 months
name 5 categories of feed additives
- technological additives
- sensory additives
- nutritional additives
- zootechnical additives
- coccidostats and histomonostats
these can be defined as a substance used to maintain animals in good health or favorably affect their performance
feed additives
name 2 things the person supplied sheep dip must have one of
- Certificate of Competence in the Safe Use of Sheep Dips
- NPTC Level 2 Award in the Safe Use of Sheep Dip (QCF)
name the 2 things that must be given to the purchaser if the sheep dip is an organophosphorous compound
- two pairs of heavy duty gauntlet style gloves
- A4 laminated safety notice
name 4 features the permanent building for storing medicines must have
- secure
- clean
- vermin proof
- refridgerated space with temp monitoring
these are monoamines derived from the amino acid tyrosine;
they are water soluble and 50% bound to plasma proteins in circulation;
include adrenaline, noradrenaline and dopamine
catecholamine transmitters
these are drugs with similar actions to the postganlionic fibers of the SNS;
they resemble adrenaline in their actions and are also referred to as adrenergics
sympathomimetics
these are drugs that oppose the actions of the postganglionic fibers of the SNS;
they are also referred to as antiadrenergics or sympathetic (adrenergic) antagonists
sympatholytic
these are drugs that stimulate postsynaptic muscarinic receptors;
their actions resemble acetylcholine and they are also referred to as cholinergics or parasympathetic agonists
parasympathomimetics
these are drugs that oppose the actions of the PNS at the muscarinic receptors by blocking the actions of acetylcholine;
also referred to as anticholinergics, parasympathetic antagonists or occasionally vagolytics
parasympatholytics
adrenergic or cholinergic?
all presynaptic efferent autonomic fibers and the somatic motor fibers
cholinergic
what do most postsynaptic sympathetic fibers release
noradrenaline
what is the effect of the sympathetic nervous system on the heart?
increased activity (beta1)
(rate, strength, conduction)
what is the effect of the sympathetic nervous system on blood vessels
vasoconstriction (alpha1 and alpha2)
what is the effect of the sympathetic nervous system on the iris
dilation of pupil (mydriasis) (alpha1)
what is the effect of the sympathetic nervous system on the bronchi?
relaxation (beta2)
what is the effect of the sympathetic nervous system on the GIT
decreased activity (alpha1&2, beta1&2)
what is the effect of the sympathetic nervous system on the adrenal medulla
secretion (adrenaline)
name the 5 key features of neurotransmitter function that provide potential targets for pharmacologic therapy
- synthesis
- storage
- release
- binding to receptor
- termination of action of the transmitter and receptor effects
what is the synthesis step of adrenergic neurotransmission?
- Tyrosine converted to Dopa by tyrosine hydroxylase
- Dopa converted to dopamine
what is the storage step of adrenergic neurotransmission?
- dopamine transported into synaptic vessel by VMAT
- dopamine converted to NE in the vesicle
what is the release step of adrenergic neurotransmission?
- action potential opens calcium channels
- fusion of vesicles with surface membrane using SNARE receptors and VAMP proteins
- release of NE
what can block the release of noradrealine in adrenergic neurotransmission
botulinum toxin
(cleaves SNARE proteins in neurons)
what can be used to block the reuptake of noradrenaline by the norepinephrne transporter (NET)
tricyclic antidepressants
name the adrenergic receptor
contracts smooth muscles:
1. vasoconstriction
2. pyloric sphincter contraction (stomach)
3. urinary sphincter contraction
4. pupillary dilation (mydriasis)
5. positive ionotropic effect (myocardium)
(Gq)
Alpha1 receptors
name the adrenergic receptor
Presynaptic nerve terminals:
1. inhibits norepinephrine release
2. inhibits ACh release
3. inhibits insulin release
(Gi)
Alpha2 receptors
name the adrenergic receptor
Heart and Kidneys:
1. incr. heart rate
2. incr. cardiac contractility and stroke
3. incr. renin release
(Gs)
Beta1 receptors
name the adrenergic receptor
Relaxes Smooth Muscles, liver, pancreas, eye:
1. bronchodilation
2. decr. gastric contraction
3. decr. intestinal peristalsis
4. urinary retention
5. liver: glycogen to glucose
6. vasodilation
(Gs)
Beta2
name the adrenergic receptor
Adipose Tissue:
1. sdipose tissue lipolysis
2. decr. urination
(Gs)
Beta3 receptors
what is the effect of the parasympathetic nervous system on the heart
decr. activity
(M2 > M3)
what is the effect of the parasympathetic nervous system on the blood vessels
vasodilation
(M2)
what is the effect of the parasympathetic nervous system on the iris
contraction of pupil (myosis)
(M2, M3)
what is the effect of the parasympathetic nervous system on the bronchi
constriction
(M2 = M3)
what is the effect of the parasympathetic nervous system on the GIT
incr. activity
(M2=M3)
what is the effect of the parasympathetic nervous system on the adrenal medulla
no effect
what is the synthesis step of cholinergic neurotransmission
- choline transported into presynaptic nerve terminal
- ACh synthesized from choline and acetyl CoA by choline acetyltransferase (ChAT)
what is the storage step of cholinergic neurotransmission
- ACh transported into large, clear vesicles by VAT along with neuropeptides and ATP
what is the release step of cholinergic neurotransmission
- voltage sensitive Ca2+ channels open
- influx of Ca2+
- fusion of vesicles with surface membrane (involves SNAPs and VAMPs)
- expulsion of ACh and co-transmitters into synaptic cleft
what can the release of ACh from the nerve terminal be blocked by
botulinum toxin
how many muscarinic receptors are there
5 (M1-M5)
what do muscarinic receptors M1, M4, and M5 act on
CNS
what does muscarinic receptor 2 act on
heart (reduces HR)
what does muscarinic receptor 3 act on
smooth muscle (contract)
which cholinergic receptor?
blocked by curare;
linked to ion channels;
response is fast and brief;
located at neuromuscular junctions and autonomic ganglia;
mediate excitation in target cells;
post-synaptic
nicotinic
which cholinergic receptor?
blocked by atropine;
linked to G-couple proteins;
found in smooth muscle;
mediate excitation and inhibition in target cells;
both pre- and postsynaptic
muscarinic
name 3 possible mechanisms of drugs acting on the autonomic nervous system
- act on neurotransmitter receptor
- interfere with NT biosynthesis
- interfere with degradation of NT
what do direct acting agonists or antagonists act on
(adrenergic drugs)
one or more postsynaptic adrenergic receptors (alpha1&2, beta1&2)
name the type of adrenergic drug
increase release of NE or inhibit reuptake or block metabolising enzyme
indirect acting agonists
name 2 ways a drug acting on the ANS can interfere with degradation of neurotransmitter
- inhibit degradation enzyme
- inhibit neurotransmitter reuptake
name 2 ways a drug acting on the ANS can interfere with neurotransmitter biosynthesis
- inhibit precursor uptake
- inhibit enzyme for biosynthesis
what are the ACh receptors
nicotinic and muscarinic
what are teh 3 main types of nicotinic receptors
- muscle (NMJ)
- ganglionic (ANS)
- CNS (brain)
name the 4 main classes of drugs affecting PNS
- Muscarinic agonists (parasympathomimetics)
- muscarinic antagonists (anticholinergics)
- nicotinic agonists
- nicotinic antagonists (ganglion blockers)
name 4 choline ester drugs (direct muscarinic agonists)
(parasympathomimetics)
- ACh
- Methacholine
- Bethanecol
- Carbachol
what receptor do choline esters have a direct action on?
muscarinic receptors
name the choline ester drug (muscarinic agonist - parasympathomimetic)
mainly muscarinic;
used inhaled for bronchial reactivity diagnosis
methacholine
name the choline ester drug (muscarinic agonist - parasympathomimetic)
long acting;
highly specific for muscarinic receptors;
minimal cardiac negative chronotropic and ionotropic effects;
used to induce urination
bethanechol
name the choline ester drug (muscarinic agonist - parasympathomimetic)
long acting;
significant nicotinic action;
used to induce gastric motility and urination and tpically to induce miosis
carbachol
name 3 types of alkaloid drugs (direct muscarinic agonists)
(parasympathomimetics)
- pilocarpine
- muscarine
- arecoline
name the alkaloid drug (muscarinic agonist - parasympathomimetic)
dominant muscarinic activity;
tertiary amine alkaloid, so increased lipid solubility;
added topically to the eye to induce miosis;
used for treatment of glaucoma;
contraindicated in uveitis and anterior lens luxation
pilocarpine
these are indirectly acting parasympathomimetics;
they inhibit AChE to incr. ACh activity;
have a cholinergic effect initially but prolonged depolarization may have desensitization
anticholinesterases
name 3 factors that contribute to the effects/toxicity of anticholinesterases
(indirect parasympathomimetics)
- reversible or irreversible
- affinity for receptor
- how readily they can access receptor (volatility and lipid solubility)
name the 6 cholinergic effects of anticholinesterases that may lead to toxicity if in excess
(indirect parasympathomimetics)
- Salivation
- Lacrimation
- Urination
- Defecation
- Gastrointestinal distress
- Emesis
(SLUDGE)
what are the 3 main uses of anticholinesterases?
(indirect parasympathomimetics)
- diagnosis of myasthenia gravis
- in anaesthesia to reverse neuromuscular blockade
- in connection with eye and GIT
name the anticholinesterase (indirect parasympathomimetic)
very short acting quaternary ammonium compound;
reversal of non-depolarizing muscle relaxants;
diagnosis of myasthenia gravis
Edrophonium chloride ‘tensilon’
name the anticholinesterase (indirect parasympathomimetic)
moderate duration of action;
reversal of non-depolarizing muscle relaxants;
treatment of myasthenia gravis (orally: TID, dose reduced as required)
Neostigmine
name the anticholinesterase (indirect parasympathomimetic)
moderat duration;
more lipid soluble;
treatment of myasthenia gravis (orally: BID)
Pyridostigmine
name the anticholinergic drug (muscarinic antagonist)
lipid soluble (crosses BBB);
used to increase HR and with anticholinesterases to prevent side effects from muscarinic stimulation;
not recommended in horses and rabbits are resistant;
atropine
name the anticholinergic drug (muscarinic antagonist)
naturally ocurring agent;
crosses BBB - sedation;
used for drying secretions;
has antemetic properties;
contained in antispasmodic Buscopan with dipyrone metamizole
scopolamine (aka hyoscine)
name the anticholinergic drug (muscarinic antagonist)
synthetic agent;
does not cross placenta or BBB;
less tachycardia;
slower onset and longer duration;
used to prevent and treat bradycadia (anaesthesia, vagal stimulation);
less CNS effects
Glycopirrolate
name the anticholinergic drug (muscarinic antagonist)
bronchodilation in horses (R.A.O.);
inhalation - poor absorption therefore minimal side effects
Ipratopium bromide
name the anticholinergic drug (muscarinic antagonist)
mydriatic and cycloplegic;
long duration of action
cyclopentolate
name the anticholinergic drug (muscarinic antagonist)
used as a mydriatic (NOT cycloplegic);
drug of choice for intra-occular exam;
rapid acting, shorter duration of several hours
tropicamide
name 3 naturally occuring catecholamines
(sympathomimetics)
- adrenaline
- noradrenaline
- dopamine
name the sympathomimetic drug
non-selective: acts at both alpha- and beta-adrenoceptors;
effects: incr. HR, incr. force of contraction, vasocontriction;
used for cardiac arrest and anaphylaxis;
can induce tachycardias and arrhythmias
adrenaline
name the sympathomimetic drug
alpha effects > beta1 effects > beta2 effects;
primarily a vasopressor via alpha stimulation;
used to treat hypotension
noradrenaline
name the sympathomimetic drug
acts at dopamine receptors alpha- and beta-adrenoceptors;
dose dependent effect;
mixed effects in practice;
used to treat hypotension
dopamine
what is the effect of dopamine at low doses
dopa effects:
1. vasodilation
2. incr. renal perfusion and filtration
what is the effect of dopamine at medium doses
beta effects:
positive inotropy and chronotropy
what is the effect of dopamine at high doses
alpha effects:
vasoconstriction
name the sympathomimetic drug category
induces vasoconstriction and can increase the force of myocardial contraction;
includes phenylephrine and methoxamine
alpha1 agonists
name the sympathomimetic drug
alpha1 agonist;
used in ocular preparations to induce mydriasis;
used in anaesthesia to increase arterial pressure;
used following anaesthesia in horses as nasal spray to cause vasoconstriction and reduce nasal congestion
phenylephrine
name the sympathomimetic drug category
extensively used in vet med for their sedative nd analgesic properties;
CV effects: incr. SVR leading to reflex bradycardia;
includes: dexmedetomidine, medetomidine, xylazine, detomidine, romifidine
alpha2 agonists
name the sympathomimetic drug
Beta1:
in equine anaesthesia to maintain mean arterial pressure;
used in SA for inotropic support in acute cardiac crisis;
short half life and rapid metabolism;
beta1 > beta2 > alpha1
Dobutamine
name the sympathomimetic drug
beta2 agonist;
used in treatment of R.A.O. in horses;
can induce vasodilation;
growth promoting effect: hypertrophy of muscle fibers, protein deposition and lipolysis in adipose cells
Clenbuterol
what are the 2 main effects of beta2 agonists?
(sympathomimetics)
bronchodilation and uterine relaxation
name the sympathomimetic drug
beta2 agonist;
used in equine anaesthesia to treat hypoxemia due to V/Q mismatch;
can produce tachycardia
Salbutamol
name the sympathomimetic drug
beta2 agonists;
used as a bronchodilator;
more cardiac side effects;
can be used to treat hyperkalemia
Terbutaline
name the sympathomimetic drug
beta2 agonists;
used in the treatment of navicular disease;
induces vasodilation;
used as a tocolytic drug (decr. uterine contraction and delay parturition)
isoxuprine
name the sympathomimetic drug
mixed effects on alpha and beta;
direct and indirect actions;
prone to tachyphylaxis;
used as a bolus to treat hypotension under GA
ephedrine
name the sympathomimetic drug
alpha1-agonist properties (direct) and triggers noradrenaline release (indirect);
used for treatment of urinary incontinence in dogs;
has been used as a nasal decongestant
Phenylpropanolamine
name the adrenoceptor antagonist drug
alpha1 antagonist:
highly selective;
produces vasodilation;
used in treatment of certain urinary tract conditions
Prazosin
name the adrenoceptor antagonist drug
non-selective alpha antagonist:
irreversible, long-acting alpha-antagonist;
predominant alpha1-adrenoceptor blocking effect;
uses: pheochromocytoma stabilization, laminitis
Phenoxybenzamine
name the adrenoceptor antagonist drug
non-selective alpha antagonists:
competitive, short acting;
predominant, alpha1-adrenoceptor blocking effect;
used to treat hypertensive crises;
can cause insulin secretion, leading to hypoglycemia
Phentolamine
name the 4 cardinal signs of inflammation
- redness
- heat
- swelling
- pain (loss of function)
name 4 benefits of inflammation
- incr. blood flow to injured tissue
- oedema formation (dilution effect)
- attraction of leukocytes and macrophages
- antibody production at site of infection
name the 4 main uses of anti-inflammatory drugs (control of adverse effects of inflammatory response)
- analgesia (acute and chronic)
- anti-pyretic
- anti-endotoxic effect
- anti-thrombotic effect
name the inflammatory mediator
released from mast cells, basophils, eosinophils;
causes vasodilation, incr. vascular permeability
histamine
name the inflammatory mediator
originates from plasma, formed from kininogen by factor XII;
causes vasodilation, pain mediator
bradykinin
name the inflammatory mediator
produced by many cell types;
causes gastroprotection, renoprotection, inflammation, reduction of pain threshold
prostaglandins (PGF2alpha, PGD2, PGE2)
name the inflammatory mediator
produced by platelets;
causes platelet aggregation, vasoconstriction
thromboxanes (TXA2)
name the inflammatory mediator
produced by platelets, mast cells;
cause incr. vascular permeability
Leukotrienes (LTB4)
name the inflammatory mediator
produced by WBC, mast cells;
causes platelet aggregation, adherence of leukocytes to endothelium, lysosomal enzyme release
platelet aggregating factor
name the inflammatory mediator
produced by plasma proteins;
cuase chemotaxis, opsonization
complement
name the inflammatory mediator
produced by macrophages and mast cells;
cause initiation of inflammation and chemotaxis, pain mediator
cytokines
name the inflammatory mediator
produced by mast cells and platelets;
cause vasoconstriction
5-HT
name the 2 broad groups of NSAIDs
- enolic acids
- carboxylic acids
what is the mechanism of action for NSAIDs?
inhibit cyclo-oxygenase (COX) enzyme 1 and/or 2
which COX?
contitutive, constant production;
produce PGs involved in normal physiological processes
COX1
which COX?
inducible, produced by inflammatory cells;
produce PGs invlved in inflammation
COX2
name 2 NSAIDs which lead to an increased bleeding time
aspirin and ketoprofen
name 2 NSAIDs which do NOT lead to increased bleeding time
meloxicam and carprofen
where are NSAIDs absorbed well
stomach
is metabolism and excretion of NSAIDs in young animals faster or slower?
slower
what order of kinetics do most NSAIDs display?
(incr. concentration, faster clearance)
first order kinetics
name 5 adverse side effects of NSAIDs (related mainly to inhibition of COX1)
- GI ulceration
- nephrotoxicity
- hepatotoxicity
- coagulation effects
- wound healing
what species is paracetamol contraindicated in?
they have reduced levels of glutathione, so a much lower toxic dose
cats
name the NSAID
alternatice mechanism of action (COX1, COX2, myeloperoxidase inhibitor);
good anitpyretic and analgesic, poor anti-inflammatory;
metabolism: glucoronidation, conjugaton, N-hydroxylation;
glutathione binds toxic metabolites which would otherwise cause hepatic necrosis
paracetamol
name the NSAID
COX2 selective;
licensed in dogs, cats, horses, cattle, pigs, guinea pigs;
uses: acute and chronic musculoskeletal disorders, postoperative surgical pain, perioperative use;
do NOT use in prgnant or lactating animals OR animals < 6 weeks of age OR cats < 2kg
meloxicam
name the NSAID
COX2 selective;
licensed in dogs, cats, cattle, horses;
uses: postoperative soft tissue/orthopedic pain, OA, perioperative use;
animals < 6 weeks have additional risk
carprofen
name the NSAID
COX2 selective;
dogs and cats;
uses: peri and postoperative use, ST and orthopedic pain, OA;
safety NOT established in pregnancy/lactation, cats <4mo, dogs <2mo, or animals <2.5kg
Robenacoxib
name the NSAID
COX2 selective;
dogs, horses;
uses: postoperative analgesia, OA;
cotraindications: pregnancy and lactation
firocoxib
name the NSAID
COX2 selective;
dogs;
long term analgesia for OA in dogs;
contraindications: <12mo, < 5 kg
Mavacoxib
name the NSAID
COX2 selective;
dogs;
uses: peri and postoperative pain due to orthopedic and soft tissue surgery, OA;
contraindications: <10 weeks, pregnancy and lactation
Cimicoxib
name the equine NSAID
anti-inflammatory > analgesic;
COX1 and COX2;
concentrates in inflammatory exudate;
toxicity: PLE;
not for use in food-producing horses
Phenylbutazone aka “Bute”
name the equine NSAID
prodrug, metabolized to phenylbutazone in liver;
more palatable, reduced GI ulceration;
expensive
Suxibuzone “Danilon”
name the equine NSAID
analgesic dose and “anto-endotoxic” dose;
injectable, use in colic/ST or orthopedic pain
Flunixin
name the equine NSAID
oral paste licensed for ST or orthopedic pain, preoperative use;
COX2 > COX1 ;
licensed in pregnancy;
has food withdrawal
Vedaprofen
name the farm animal NSAID
name 3 farm animal NSAIDs
- flunixin
- meloxicam
- ketoprofen
name the novel drug
non-COX inhibiting, specific prostaglandin receptor antagonist;
specifically targets EP4 receptor therefore minimal side effects;
long-term pain control for OA;
expensive
Grapiprant
name 3 NSAIDs licensed for perioperative use
- meloxicam
- carprofen
- robenacoxib
what are endogenous corticosteroids produced by
adrenal cortex
what are the 2 categories of endogenous corticosteroids
- mineralocorticoids
- glucocorticoids
what a re endogenous corticosteroids synthesized from
cholesterol
where are corticosteroids metabolized
liver
what is the active form of cortisone
cortisol
what is the active form of prednisone
prednisolone
what 4 types of effects do corticosteroids have
- metabolic effects
- systemic effects
- anti-inflammatory effects
- immune suppressive effects
what type of effect do low doeses of corticosteroids have
physiological
what type of effect do medium doeses of corticosteroids have
anti-inflammatory
what type of effect do high doeses of corticosteroids have
immune suppressive
name 5 systemic effects of corticosteroids
- elevated liver enzymes (dogs)
- alteration of CNS function
- PU/PD
- incr. appetite
- muscle wastage
what do corticosteroids inhibit for effective anti-inflammatory action
inhibit PLA2 (entire AA pathway)
name 7 adverse effects of corticosteroids
- gastric ulceration
- PU/PD
- hyperglycemia
- muscle atrophy
- osteoporotic effect
- Cushing’s disease
- suppression of HPA axis
name 3 short acting (<24h) glucocorticoids
- predisolone
- Prednisone
- Methylprednisolone
name 3 long acting (>24h) glucocorticoids
- dexamethasone
- betamethasone
- triamcinolone
name the corticosteroid
parenteral formulation;
water soluble salts, ideal for IV administration
Dexamethasone
name the corticosteroid
parenteral formulation;
insoluble esters, long acting, IM administration
- methylprednisolone acetate
- dexamethasone phenylproprionate / isonicotinate
name 5 clinical uses of corticosteroids
- anti-inflammatory
- immune-mediated disease
- neoplasia
- treatment for hypoadrenocorticism
5n. septic shock
name 3 clinical uses of corticosteroids in farm animals
- termination of pregnancy / induce parturition
- acute trauma, neuropathies
- chronic resp. disease
what are the two most commonly used classes of anthelmintic drugs in small animal practice
- Benzimidazoles
- Macrocylic lactones
what do all Benzimidazole drugs licensed for dogs and cats contain (or its prodrug)
(anthelmintics)
fenbedazole (febental)
name the small animal anthelmintic class
given orally, poorly absorbed from GIT (enhanced with food);
inhibit nematode tubulin polymerization and prevent microtubule formation affecting cellular transpot and energy metabolism;
metabolized in liver and mostly excreted in feces (small amount in urine and milk);
broad spectrum of action agaist nematodes in GIT and resp. tract (both adult and immature);
will treat Giardia;
limited action against cestodes
Benzimidazoles
what are the two classes of Macrocyclic lactones
(anthelmintics)
- Avermectins
- Milbemycins
name the small animal anthelmintic class
topical or oral admin;
accumulate in fat so long duration of action;
act on glutamate-gated chloride channels in nerve cells (paralysis);
narrower safety margin in cats;
largely excreted in feces and urine (small amount in milk);
topical products removed by bathing or swimming (harmful to aquatic life);
effective against wide range of nematodes in larval, immature and adult stages;
no activity against cestodes;
some can be used against Diofilaria
Macocytic lactones
name the small animal anthelmintic
available as a spot on preparation for cats only in combination with ectoparasiticides and praziquantel;
slow absorption;
will treat GI nematodes, hookworm and capillaria;
effective against D. immitis larvae but not adults
Eprinomectin (Avermectin)
(Macrocyclic lactone)
name the small animal anthelmintic
available for both cats and dogs;
applied topically, bathing will not affect efficacy after 2h drying time;
will treat roundworms, hookworms and prevent D. immitis;
some reports of salivation or vomiting in cats after licking site & of alopecia at site
Selamectin (Avermectin)
(Macrocyclic lactone)
name the small animal anthelmintic
administered orally and largely excreted unchanged in feces;
any that is absorbed will be excreted in bile;
absorbed quickly but eliminated rapidly;
treats GI roundworms, hookworm and whipworm;
can be used as lungworm treatment or prevention
Milbemycin
(Macrocyclic lactone)
what is the available drug for small animals in the Tetrahydropyrimidines class of anthelmintics
Pyrantel
name the small animal anthelmintic
act on nicotinic acetylcholine receptors to initially cause muscle contraction and then paralysis;
giving with food will delay absorption;
max concentration achieved is more important than duration of exposure for effectiveness;
effective against adult and larval stages of GI nematodes;
can be used in puppies and kittens and during pregnancy
Pyrantel
(Tetrahydropyrimidines)
name the small animal anthelmintic
acts at neuromuscular junction to stimulate presynaptic secretin receptors which causes paralysis of the parasite;
available as a spot on preparation for cats;
effective against GI nematodes, hookworm and A. abstrusus;
absorbed slowly over 2-3 days and thought to be stored in fat;
eliminated slowly in bile and feces
Emodepside
(Cyclodepsipeptides)
name the small animal anthelmintic
effective against roundworm (adult only);
blocks neuromuscular transmission via GABA-gated chloride channels and causes paralysis of parasite;
rapidly absorbed and metabolized;
wide safety margin, can be used in puppies, kittens and pregnant animals but NOT in animals with liver or renal disease;
should not be used with Pyrantel (agonists)
Piperazine
name the small animal anthelmintic
diphenylether;
may act by uncoupling oxidative phosphorylation and depleting energy;
given orally to dogs only;
causes neurological signs in cats;
broad spectrum of acticity against GI nematodes and some tapeworms;
irritant and can cause vomiting so give whole tablets to dogs
Nitroscante
name 4 clinical uses of GnRH
- induction of follicular growth
- induction of ovulation
- improvement of conception rates (cattle)
- Tx of follicular cysts (dairy cattle)
when would you give GnRH in cattle to improve conception rates
11-12 days post-service
name the 2 categories of gonadotropins
- pituitary (FSH, LH)
- chorionic (CGs)
which has a longer half life, FSH/LH or CGs, and why?
CGs because more heavily sialylated (more sialic acid residues)
name 5 clinical uses of gonadotropins
- Induction of ovulation
- Induction of follicular growth during anestrus
- Detection of cryptorchidism (horses)
- Induction of spermatogenesis or enhance libido
- Induction of superovulation (cattle)
what gonadotropin is used to induce ovulation
hCG
whih gonadotropins are used to induce follicular growth during anestrus
eCG / rFSH
what gonadotropin stimulation test is used for detection of cryptorchidism in horses
hCG
which gonadotropins are used to induce spermatogenesis or enhance libido
eCG / rFSH
when to start rFSH injections for induction of superovulation in cattle
mid estrus cycle (day 9-14)
name 6 indications for use of oxytocin
- dystocia due to uterine inertia
- promote uterine involution
- expulsion of retained fetal membranes (horses)
- uterine prolapse
- facilitate clearance of uterine discharge (mares)
- milk let down
name 3 cases where oxytocin is contra-indicated and could lead to uterine rupture if used
- abnormal fetal position
- insufficient cervical dilation
- previous uterine surgery
name the two blood proteins that bind reproductive steroids
- sex hormone binding globulin (SHBG)
- corticosteroid binding globulin (CBG)
what 2 reproductive steroids are bound by sex hormone binding globulin (SHBG)
- testosterone
- estradiol
what 2 reproductive steroids are bound by Corticosteroid binding globulin (CBG)
- cortisol
- progesterone
what 2 ways do binding proteins regulate reproductive steroid activity
- regulating steroid metabolism
- regulating steroid access to target cells
name 2 clinical uses of Progestagens
- synchroniztion of estrus (cattle)
- induction of estrus in anestrus animals
name 3 adverse effects of progestagens in small animals
- uterine disorders (endometrial hyperplasia, pyometra)
- adrenal corticol suppression
- mammary tumors, pseudopregnancy, exacerbate diabetes
what is the main clinical use of PGF2⍺
induction of luteolysis
name 3 indications of PGF2⍺ as a luteolytic agent in mares
- persistent CL
- termination of pregnancy
- synchronization of estrus
name 6 indications of PGF2⍺ as a luteolytic agent in cattle
- luteal cysts
- persistent CL
- endometritis
- pyometra
- termination of pregnancy
- synchronization of estrus
in order to terminate pregnancy, PGF2⍺ must be given before this day of pregnancy in cattle
day 150
in order to terminate pregnancy, PGF2⍺ must be given before this day of pregnancy in sheep
day 50
in order to terminate pregnancy, PGF2⍺ must be given before this day of pregnancy in horses
day 35
what must be present in order for PGF2⍺ to work
responsive CL
how far apart should 2 injections of PGF2⍺ be given in order to synchronize estrus in cattle
11 days
name 5 adverse effects of PGF2⍺
- transient sweating
- mild colic
- incr. HR
- incr. resp. rate
- muscle weakness
name the hormone
induces Lh/FSH release from the pituitary;
stimulates follicular maturation/ovulation
GnRH
name the hormone
FSH/LH agonist which stimulates maturation of follicles
eCG / PMSG
these provide exogenous progesterone source to prevent ovulation (“a CL on a stick”)
progesterone implants
name the hormone
induces luteolysis
PGF2⍺
