would you rather use a bacteriostatic or bactericidal drug in a severely dz'ed pt?
bacteriostatic drugs only inhibit growth and then depend on the immune system to clean them up-- but if they are super dz'd and their immune system is compromised, you should pic cidal instead of static
In clinical pharm you need to be able to put the pieces together-- what are the factors you should consider? (list)
what is an example of an insecticide that FSIS might check the food for
2 examples of IMMEDIATE EFFECTS of residues in food (Which we want to avoid, hence FSIS)
anaphylactic reactions, allergies
2 examples of DELAYED EFFECTS of residues in food (which we want to avoid, hence FSIS)
(1) Drug resistance (hence put programmes in place) (2) impact on immune response
drug resistance is a possible delayed effect of residues in food. Two things greatly impacted by drug resistance are...
(1) Therapy failures (2) economics
What you need to know when you treat food producing animals (list of things to think about)
Contaminated feed, Illegal use of VMP (vet med. products- or others), Drug residues and withdrawal times, MRL (maximum residue limit- which ties in with withdrawal times), AMDUCA (Animal Medicinal Drug Use Clarification Act)
what is AMDUCA?
Animal Medicinal Drug Use Clarification Act- PURPOSE: The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) made ELDU an FDA-regulated veterinary medical activity, allowing veterinarians to prescribe extra-label uses of approved animal and human drugs when the health of an animal is threatened, or when suffering or death may result from failure to treat animals. Prior to the passage of the AMDUCA, ELDU of animal drugs was illegal. AMDUCA amended the Federal Food, Drug, and Cosmetic Act to legalize ELDU under a valid VCPR as well as certain other conditions describing requirements for use, record requirements, and label requirements according to FDA regulations.
what is "withdrawal time" (definition)
the interval between the time of the last administration of a registered compound and the time when the animal products can safely be consumed. (meaning: Concentrations of the drug are below the maximal residue limit (MRL) )
explain the MRL and what it ties in with
Maximum Residue Limit: the maximum concentration of a residue, resulting from the registered use of an agricultural or veterinary chemical, that is recommend to be legally permitted or recognised as acceptable for use in animals. This relates to the withdrawal time, as you have to wait X amount of time for drug levels to reach MRL before it is safe to consume (hence the withdrawal time)
Know this graph, explain all the lines
sloped lines down are the conc of the drug in the meat which reduces over time. two diff diagonal lines bc the high dose vs the low dose. There are two different MRL examples in this graph, which are either grey or red, with their corresponding withdrawal times. The first (left most) WDT, which is WDT1, is when you give the low dose, and WDT2 is the higher dose. The RED MRL is if you are more strict, because you are dropping down the MRL from higher to lower, meaning you need less in the meat before it is acceptable-- notice that this also lengthens the low and high dose WDTs (in red)
explain No Observed Adverse Effect Level (NOAEL)
result of toxicological testing (90 days rodent assay). Most sensitive endpoint in the most sensitive laboratory animal species\
explain the UF/SF (uncertainty factor)...what is the cutoff for this value?
Extrapolation from laboratory animal to human (10) * variability within the human population (10). A UF >100 is always a cause for concern
Deriving a MRL (maximum residue limit)--> you will need to figure out an Acceptable daily intake for the animal. Explain this equation:
take the No Observed Adverse Effect Level and multiply it by the bodyweight. Then, take this and divide it by the UF/SF which is in this case, Extrapolation from laboratory animal to human (10) * (times) variability within the human population (10)
explain ELDU (extra label drug use)
Using drugs in a way that doesnt match the label. This can be Drugs approved for use in the species, but to be used in a different dose/concentration, administration route, Drugs used for other indications, or drugs used in other species
If you are going to do ELDU on an animal, what will that do to withdrawal time?
he still loves this dumb flowchart
based on the graph, you can determine withdrawl time by..
the intersection of the MRL (max residue limit) with the slope of drug conc over time (two diff slopes depends on if high or low dose)
Drugs prohibited for extra label use in food animals--> Sulphonamide drugs in dairy cattle EXCEPT
sulfadimethoxine, sulfabromomethazine and sulfaethoxypyridazine (these can be used)
when can and cannot you use Phenylbutazone in cattle?
you CANT give to female diary cattle 20 months of age or older. (which means if they are male, beef, or female dairy but UNDER 20 mo, you can give)
WHO are Cephalosporins prohibited in, under which circumstances?
prohibited in... cattle, swine, chickens or turkeys WHEN used for disease prevention purposes ( tx is fine), At unapproved doses, frequencies, durations, or routes of administration (so no ELDU but can do LDU) and cant give If the drug is not approved for that species and production class
what is the one cephalosporin which CAN be used ELDU/for dz prevention in cattle/swine/chicken/turkey?
what two kind of drugs are Prohibited for extra label use in chickens, turkeys and ducks?
adamantanes and neuraminidase inhibitors (basically antivirals)
Compounds with a potential risk in humans--> what will Tilmicosin do?
cardiotoxic on accidental injection
Compounds with a potential risk in humans--> why do we not like Carbapenems and glycopeptides?
play a role in selecting resistant bacteria in animals which can be passed to immune compromised humans
Compounds with a potential risk in humans--> why do we not like Chloramphenicol?
aplastic anaemia in humans
Compounds with a potential risk in humans--> why do we not like Prostaglandines?
can abort pregnant women
(from other/older ppt) what are the 5 abx not allowed in food animals?
There is a Extralabel drug use algorithm which you can find on FDA website, and slide 17. Before you start using flow chart, what must be already present/done?
You have made a careful diagnosis in the presence of a valid veterinarian/client/patient relationship.
basic questions the flow chart for how to ELDU asks are listed here, for reading over for familiarity
If they are being used for food, is there a different drug that IS approved for them? If not, Is there a drug approved for food producing animals which could be used extralabelly? if not, If compounding of approved drugs will prevent animal pain and suffering, refer to CPG 608.400 for compounding guidance. If yes, check if there Is there adequate scientific information available to determine a withdrawal period. If not, Drugs must not be used, OR animal must not enter the food chain. If yes, Proceed with ELDU, establish withdrawal period and ensure food safety. Maintain adequate records and label properly
if it is not being used for food, can you use human meds in the animal?
In non-food animals you may use a human drug extralabelly even when an animal drug exists. Economic reasons are valid. Maintain required records and label properly
HACCP (hazard analysis and critical control points) compatible production practice-- what are the 5 things you should be doing for this
(1) Keep medication record for at least 12 months following marketing of any medicated livestock (2) Maintain medication and production records (3) Properly store, label and account for all drugs and medicated feed (4) Valid Veterinarian Client Patient Relationship (5) Administering medications - residue testing when appropriate
what is Antimicrobial stewardship?
Antimicrobial stewardship refers to the coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose, duration of therapy and route of administration. BASICALLY, Treat the right animal with the right drug at the right dose for the right amount of time, communicating the right withdrawal time
Antimicrobial stewardship seeks to accomplish what 4 things?
(1) Achieve optimal clinical outcomes, related to antimicrobial use (2) Minimise toxicity and other adverse events (3) Reduce the costs of health care for infections, and (4) Limit the selection for antimicrobial resistant strains
what is "Guidance 152" of the FDA?
Evaluating the safety of new antimicrobial drugs for veterinary medicine, with regard to their microbiological effects on bacteria of human health concern: Quantitative Risk Assessment.... Example: cefquinome (4th generation cephalosporin) in food animals (2007): “the probability of the emergence of cefquinomeresistance food-borne bacteria is low” (so basically, if there is a new drug, before we can approve it for ELDU, we need to test it's affects on humans before it is approved for ELDU.) \
How will this impact you? (1) in an example of Loss of ELDU discretion for cephalosporins, what would the FDA be concerned about?
“FDA is concerned that certain extra label uses of cephalosporins in food-producing major species are likely to lead to the emergence and dissemination of resistant strains of food-borne bacterial pathogens. If these strains infect humans, it is likely that cephalosporins will no longer be effective for treating diseases in those people”
How will this impact you? (2) Changes in feed and water medications--> what are two guidances (labeled with numbers) which pertain to changes in feed/water meds
(1) Guidance 209: The judicious use of medically important antimicrobial drugs in food producing animals (2) Guidance 2013: New Animal drugs and new animal drug combination products administered in or on medicated feed or drinking water of food producing animals. Recommendations for drug sponsors to voluntarily aligning product use conditions with GFI #209 ( In GFI #209 the FDA/CVM has determined that the use of medically important antibiotics for growth promotion os injudicious and will be phased out based on the mechanisms described in GFI #213)
what is considered one of the most critical public health issues of the 21st century
Antimicrobial resistance (AMR)
Antimicrobial resistance (AMR) causes additional health care expenditures of ___ annually
$4-7 billion annually
The perceived veterinary contribution to AMR will influence what kinda things?
current and future drug approvals and label indications
This is the No Observed Adverse Effect Level, a level you determine as a result of toxicological testing (90 days rodent assay). Most sensitive endpoint in the most sensitive laboratory animal species
What is a withdrawal time and how does disease influence these times
Withdrawal time is the point at which the concentration of whatever drug/residue in the meat/animal product becomes low enough to reach the MRL (maximum residue limit) which means it has been long enough for there to be harmless levels left. Now disease can can often extend the withdrawal time because the body is weakened and not as efficient at removing substances, or the disease might require a higher dose of the abx which also inc the withdrawl time
What is ELDU and what are the requirements for ELDU?
ELDU= extra label drug use. ELDU is when there are Drugs approved for use in the species, but to be used in a different dose/concentration, administration route OR Drugs used for other indications OR Drugs used in different species. The requirements for use must be You have made a careful diagnosis in the presence of a valid veterinarian/client/patient relationship, and if it is a food animal, Establish extended withdrawal period, ensure food safety. Maintain required records and label properly. If there is not a you must have adequate scientific information available to determine a withdrawal period. If you cannot do this the animal cannot enter the food chain
Which drugs are prohibited from use in food producing animals?
which drugs can not be used in an extra label manner?