Describe how adverse effects and toxicity came about?
Many year ago, drug therapies used many ineffictive drugs, compounds, and placebos
"good ones" did not produce serious side effects
some were highly toxic (used to use- didnt have therpay value)
most were of little therapeutic value
with more stringent development and control of drugs came greter efficacy (became difficult to market ineffective drugs)
potency also increased (how strong/good it is)
with potency also came increased risk of serious adverse effects in some cases
Define Adverse Drug Reactions
Any noxious change in a patient's condition which a physician/vetrinarian believes to be caused by a drug
MAY:
require treatment of sypmtoms
recquire cessation of treatment with suspected drug because may be having a reaction
suggest that future treatment with this drug carries an unusual risk in this patient
(have to adjust dose and still treat or stop treatment of will die)
What are the 3 types of Drug Reactions and Toxicities ***
Intrinsic drug reactions
Idiosyncratic Drug Reactions
Allergic Responses (inclduing anaphylaxis)
What arre Intrinsic drug reactions?
related to how the drug is used and how it normally works
Dose related
predictable
reproducible
underlying mechanism: usually an exaggeration of desired effct
its an exaggeration of what drug normally does
ie stop blood clotting--> adverse bleed to death because inability to clot
ie Chemotherapy drugs kill rapidly dividing and growing cells- skin and hair- but could also kill gamets, gut lining etc
What are Idiosyncratic drug reactions?
usually not does related
(occurs in a few) not predictable: who when
occurs in small proportion of exposed animals or people
mechanism not always known ("idio")
example is human reactions to choramphenicol (aplastic anema rate is 1:30 000) so banned for use in food animals (will develop this and because it is sug a serious reaction it is banned)
tollerance may depen on time of year
What are alleric drug reactions?
not dose-related
unrelated to pharmacolical effects people think it all reactions are allergic- not true!
may be minimized or decreased by prior administrtation of antihistamines (anitinlfammatory), coticosteroids (immune suppressors), epinephrine
related to immune system forming a response to substance given
not related to drug: body reacts against invadors- memory cells if exposed second time get bigger faster response)
What do the nature of drug reactions depend on?
organ specificity and Ag-Ab reaction
Includes:
-immediate reaction (anaphylactic)
-immune complex reactions (antibodies stick onto drug and acumulate largely and create spots)
-"Drug Fevers"
cytokines released
i clicker If somebody over doses on cold medication and sleeps what kind of reaction is this?
Intrinsic reaction
define "Broad spectrum antimicrobrial"?
an antimicrobial effective against a large number of bacterial genera;
generally describes antibiotics effective against gram positive and gram negative bacteria indicative of which will kill
broadspectrum - kills many types
define "Narrow Spectrum Antimicrobial"
antimicrobial effective against a limited number of bacterial genera often applied to an antimicrobial active against either Gram + or gram - bacteries
specific type of bacteria
know what, where, type and ID
Differentiate between Broad and Narrow Spectrum Antimicrobial
Narrow: antimicrobial effective against a limited number of bacterial genera
Broad
an antimicrobial effective against a large number of bacterial genera;generally describes antibiotics effective against gram positive and gram negative bacteri
How do Penicillins, cephalospotins, carbapenems, and vancomycin Antibiotics work?
How do others work?
kill bacteria by damagind or inhibiting the synthesis of bacterial cell walls because bacteria cant grow if have damaged wallsOther antibitoics act through effects on:
bacterial DNA or RNA- prevention of replication
proteins
bacterial metabolism affects ability if cell inside
What is Antibiotic Resistance?
A property of bacteria that confers:
the capacity to inactivate or exclude antibiotics
or
a mechansims that blocks the inhibitory or killing effects of antibiotics
Why is antibiotics resistance a concern?
Public health and epidemiologic concern
economic concern (cost and danger):
-exisitng drugs no longer useful
-new ones must be developed
What are the two types of Antibiotic resistances?********
Intrinsic or natural resistance: intrinsic property confers resistance- ie penecillins only work on organisms with cell walls
Acquired Resistance organism obtains means to survive exposure get mist worries about because if use improperly they can become resistant!
Ellaborate on Intrinsic Resistance
normal characherisitics render them immune to the antibiotic's mechanism of effect (whether or not antibiotic is misused)
Eg * outer membrane gram - bacteria makes them relatively impermeable to hydrophobic compounds such as macrolide antibiotics
What are the two types of acquired resistance?
Transmissible Resistance
1. Echange conjugative plasmids (circular units of DNA)
2. Transfer resistance genes packaged in bacterial viruses
3. Acquire segments of DNA released from dead bacterial cells
Virus may pick up a gene and transfer to bacteria or bacteria suck up DNA from a dead bacteria and incorperate teh resistance). Remember antibiotics were derived from live species
i clciker True of False
Bacteria may be inheritently be resistant to an antibiotic due to the normal characteristic cell wall type or it may acqyure it by mutation or by transmission from other bacteria
true
What are the different ways that bacteria share DNA?
plasmid transfer of a resistant gene
transfer of free DNA from a dead bacteriume
Transfer by viral delivery
Give some examples of acquired resistance characteristics
changes to bacterial membrane to prevent antibiotics from entering the cell
use enzymes to break down antibiotics
use "efflux pumps" to removie the antibiotic entirely or reduce its concentration below effective levels
if more than one mechanism is acquired, resistance of a bacterium to more than one type of antibiotic is possible
worry because if give too early or not enough then select for that population. can have multiple forms of resistance
What is mutational resistance
chromosomal mutations can occur spontaneously and then be transmitted to progeny bacteria during replication (become transmitted)
relatively rare
eg some resistance to fluoroquinolone antibiotics
***How can Bacterial Resistance be minimized?
only use if necessary
broad-spectrum agent should not be used if a narrow spectrum agent will do (because then kill normal bacteria which get resistant genes that can spill into enviro)
follow appropriate dose rates
use full dose of both agens if used in combination (ie dont drop one or both)
antibiotics used topically should be those less prone to development of resistance (so its not exposed to entire body)
use bacteriocidal agents for prophylaxis (so kill entirely and dont just prevent division)
avoid new antibiotic generations when ol ones will do
i clicker
True or false
Antibiotics develop resistance to bacteria by changing once they are administered
FALSE bacteria develop resistance to the antibiotics (antibiotics dont change)
i clicker T or F
Animals given too many antibiotics can dvelop resistance so that the antibiotics no longer work for them
FALSE bacteria develop resistance NOT animals
In the USA how many animals in each species are fed antimicrobrial drugs at some time from poultry, swine, dairy calves and feedlots cattle?
poultry 80%
swine 75%
dairy calves 75%
feedlot cattle %60
What are the issues with banning antibiotics?
Euro did this and saw
death rate increase
decrease production
welfare issues
higher ccost of production (because lose animals to death, more sick, take longer to grow)
What are the benefits of antimicrobrial drugs in animal feeds?
increased feed efficiency (2-5%)
increased rate of gain (3-5%)
disease preventin ie liver abscesses in feedlot cattle
economics: eliminating antimicrobials estimated would icnrease cost of retail beef between 2.7 and 10.4 %
enviro benefits: proponents say more efficiency means less feed, manure, funoff, real estate use
better welfare to prevent sickness or treat them
AHI (animal health insitute)
AHI is a trade association representing countries that manufacture drugs for the pet and farm industries: antimicrobial use has gone up
-overall use for non therapeutic uses has risen, driven by poultry whose nontherap use has increased since the 80s, swines nontherap use has declined but growing reliance on tetracycline
Of what concern are antibiotic resistant organisms?
public health and epidemiologic concern
economic concern: existing drugs no longer useful, new ones must be developed