Pharmacology

Question 1

oral absorption of drugs during pregnancy is affected by progesterone. Progesterone (increases/decreases) GI motility and (increases/decreases) GI blood flow and may increase, decrease, or not affect the rate and extent of absorption of drugs.

Answer 1

decreases GI motility
increases GI blood flow

Question 2

Giving drugs extravascularly during pregnancy may increase blood volume, cardiac output, and blood flow to some organs (muscle, SQ space, lungs, skin), what would be the effect of this?

Answer 2

increased absorption – EV parenteral, inhaled, and topical/transdermal admin

Question 3

Giving drugs during pregnancy causes increased plasma volume and increased cardiac output / altered blood flow to organs, what effect does this have?

Answer 3

increased volume of distribution – this can affect plasma concentration and redistribute blood to different organs

Question 4

T/F: Giving drugs during pregnancy causes decreased albumin concentration (dilution) and increased acute phase proteins (increases PPB of drugs), however, the significance of this is relatively unknown and likely minimal

Answer 4

True

Question 5

Giving drugs during pregnancy causes increased metabolism which (increases/decreases) hepatic blood flow and (increases/decreases) protein binding.

Answer 5

increased hepatic blood flow
decreases PPB

Question 6

elimination of drugs given during pregnancy is impacted in the sense that ….

Answer 6

increased plasma/blood volume and cardiac output –> increases renal blood flow and GFR
this could increase renal elimination of hydrophilic drugs

Question 7

T/F: Gentamicin volume of distribution and clearance was shown to be relatively the same in mares (preg, lactating, and nonpreg), however in sheep Vd doubled and clearance increased by 150%.

Answer 7

True

Question 8

Administering Excede / CCFA in pregnant mares will (increase/decrease) maximum concentration absorbed compared to administration to non-pregnant mare? why?

Answer 8

increase – because increased bloof flow to extravascular sites increases absoprtion of drug

Question 9

Which drug has LOWER absorption in pregnant and post-partum mares when compared to non-pregnant mares due to the effects of progesterone decreasing GI motility?

Answer 9

firocoxib (cox-2 selective NSAID)

Question 10

True/False: there is currently a decent amount of literature regarding dose adjustments that need to be made for pregnant mares, so there is no need to use lowest effective dose

Answer 10

FALSE – always exercise caution and use lowest effective dose

Question 11

Name the 3 characteristics of the placenta that alter drug crossing from mother to fetus

Answer 11

1. multiple layers of placenta
2. different blood flow patterns
3. tight junctions

Question 12

Which species have the placenta with the most barriers? Least?

Answer 12

most – horses, pigs, ruminants
least – dogs, cat, humans, rodents

Question 13

What are 3 physiologic functions of the placenta that can affect drug transfer?

Answer 13

1. endocrine activity – producing hormones that maintain pregnancy, induce parturition, and promote mammary development
2. metabolizing activity – might metabolize drug before it gets to fetus
3. transporter activity – may increase drug transport or increase drug efflux (P-glycoprotein, etc.)

Question 14

Name drug characteristics that maximize drug transfer across placenta

Answer 14

1. smaller MW
2. higher lipid solubility
3. unionized
4. lower PPB / unbound drugs
5. higher concentration gradient

Question 15

Which antibiotics are lipophilic and cross placenta well?

Answer 15

macrolides, fluoroquinolone

Question 16

the pH of the fetal blood is more acidic that maternal blood. what is the significance of this?

Answer 16

weak bases diffuse across the palcenta, but then become trapped and can accumulate in fetus
ex. aminoglycosides

Question 17

T/F: the placenta is an incomplete barrier and all drugs will cross to some degree, however gases (anesthesia) have no barriers and will affect the fetus

Answer 17

true

Question 18

define terratogen

Answer 18

agent or factor that causes malformation of embryo

Question 19

what 4 ways do drugs cause teratogenesis?

Answer 19

1. alter gene expression in fetus
2. alter apoptosis, cell migration, and cell proliferation
3. alter synthesis and function of proteins and nucleic acids
4. alter supply of energy source

Question 20

what 2 things does susceptibility to teratogenesis depend on?

Answer 20

1. genotype (differences among species)
2. developmental stage – most susceptible in 1st trimester or period of organogenesis

Question 21

What stage are dogs, cats, and horses most susceptible to teratogenesis?

Answer 21

dog - 14-20 days
cat - 14-26 days
horse - less than 60 days

Question 22

What occurs when drugs are administered and exerting teratogenic effects during pregnancy?

Answer 22

very early on - dies and gets reabsorbed
1st trimester – death or obvious birth defects
2nd trimester+ – long term effects

Question 23

True/False: teratogenic effects on fetus are dose-dependent and not linear. AKA under a certain concentration, there may be no effects, but once you reach a certain concentration, no worse effects can be found.

Answer 23

true

Question 24

true/false: maternal susceptibility equals fetal susceptibility

Answer 24

FALSE – it is possible to give a dose of drug that is harmless to the mother and it be toxic to the fetus and vice versa

Question 25

which drug is used to treat ringworm but is known to cause congenital anomalies in dogs, horses, but mostly cats?

Answer 25

griseofulvin

Question 26

In which species does trimethoprim-sulfa, pyrimethamine, folic acid, and vitamin E combo cause congenital abnormalities?

Answer 26

horses

Question 27

exogenous testosterone and estrogen causes congenital anomalies in which 2 species?

Answer 27

cats and dogs

Question 28

What antibiotic has potential to cause congenital anomalies in dogs and cats that include decreases long bone growth and dental discoloration.

Answer 28

tetracyclines

Question 29

trilostane and mitotane have been shown to cause congenital anomalies in _____

Answer 29

dogs

Question 30

oxfendazole, albendazole, and fenbantel cause congenital anomalies in ______

Answer 30

sheep

Question 31

which 3 antibiotics are known to be safe for use during pregnancy?

Answer 31

1. beta lactam antibiotics** 2. macrolides 3. lincosamides (exc. horses)

Question 32

which endocrine drugs are safe to use during pregnancy?

Answer 32

insulin levothyroxine

Question 33

True/False: opioids are safe to use during pregnancy

Answer 33

true

Question 34

which 2 heartworm preventatives are safe for pregnancy use?

Answer 34

heartgard and revolution

Question 35

which flea and tick prevention is safe for pregnancy?

Answer 35

frontline

Question 36

what is the advantage to systemic administration of antibiotics for uterine infection?

Answer 36

few barriers to penetrate into uterine wall

Question 37

What are the disadvantages of systemic admin of antibiotics for uterine infection?

Answer 37

cost -- expensive toxicity frequency of admin -- more

Question 38

true/false: endometrial concentration of a drug is equal to the placental concentration

Answer 38

false

Question 39

Doxycycline in horses has been shown to reach higher concentrations in the endometrium or serum?

Answer 39

endometrium

Question 40

What antibiotic is water-soluble, reaches high concentrations in uterus, and no drug in serum making it a good option to treat uterine infections in patients with kidney infections?

Answer 40

amikacin

Question 41

what are the 2 advantages of intrauterine admin of antibiotics?

Answer 41

1. high conc of drug at the site of infection 2. limited systemic absorption of drug

Question 42

true/false: intrauterine administration is NOT appropriate for pregnant animals d/t inducing abortion

Answer 42

true

Question 43

What local factors affect intrauterine administration of antibiotics?

Answer 43

1. low oxygen tension 2. presence of degradative enzymes 3. presence of mucopurulent discharge or organic debris 4. adverse effects on local leukocyte function

Question 44

T/F: there is decreased absorptive capability of the uterus immediately post-partum so intrauterine drug administration is not the best choice

Answer 44

true

Question 45

what are indications for intrauterine administration of antibiotics?

Answer 45

mild cases of endometritis pre- and post-breeding -- (if she has history of previous metritis or preg loss, degree of IU fluid at breeding, and routine for natural cover)

Question 46

What are the approved products for intrauterine administration?

Answer 46

chlorhexidine gentamicin ticarcillin sodium amikacin ELDU -- penicillin, oxytet, and diluted iodine

Question 47

T/F: systemic absorption of an intrauterine drug is increased if disease is worse.

Answer 47

true

Question 48

IU admin of WATER-SOLUBLE oxytet in cattle has a withdrawal time for meat and milk of...

Answer 48

meat -- 28-35d milk -- 72-192 hr Depends on dose

Question 49

What should you do prior to administering intrauterine antibiotics in order to optimize their efficacy?

Answer 49

uterine lavage -- antibiotics do not work if you stick them into pus.

Question 50

What factors should a drug have to be given systemically and effectively transported into milk?

Answer 50

low MW lipid soluble / lipophilic unionized low PPB high concentration gradient

Question 51

what are 2 important factors you must consider when administering systemic antibiotics with goal that they will reach the milk?

Answer 51

1. effects on nursing animals 2. residue (food animal) --- withdrawal

Question 52

Mastitis causes vascular permeability changes. What effect does this have on systemic drug administration?

Answer 52

may increase distribution of drugs into the udder

Question 53

If a cow becomes septic and her milk production decreases, what effect does this have on drug clearance?

Answer 53

decreases drug clearance

Question 54

_____________ administration of antibiotics is common in cattle, small ruminants, and horses for the treatment and prevention of mastitis.

Answer 54

intramammary

Question 55

what are the advantages to intramammary administration?

Answer 55

1. high conc of drug at site of infection 2. minimal systemic absorption 3. multiple approved products available

Question 56

what are the disadvantages to intramammary administration?

Answer 56

1. milk residues 2. kicked during admin (horses)

Question 57

What drugs are approved for intramammary administration in cattle?

Answer 57

betalactams (-illin), macrolides (-mycin), aminoglycodides (-mycin),

Question 58

what intramammary formulation should you use for dry cows? lactating cows?

Answer 58

dry -- oil-based lactating -- water based

Question 59

T/F: you should administer drug within the teat that you want to treat so that the drug does not spread to the other teats.

Answer 59

false -- drugs administered in intramammary way will spread throughout all teats and this will result in residues from all teats.

Question 60

What antibiotics should not be given to dairy animals d/t staying in the milk long-term?

Answer 60

macrolides and avermectins

Question 61

drugs used to treat ___________ can affect ability to maintain pregnancy, gestation length, lactation, and sperm quality.

Answer 61

endocrine diseases

Question 62

What drugs are used to treat hyperadrenocorticism in pregnant horses?

Answer 62

pergolide cyproheptadine trilostane

Question 63

what drugs are used to treat hyperadrenocorticism in pregnant dogs that will have adverse effects on the fetus?

Answer 63

mitotane, trilostane, ketoconazole, selegiline

Question 64

what is the recommendation when using pergolide during pregnancy?

Answer 64

stop treatment 2 weeks prior to foaling and restart 4 weeks after foaling

Question 65

what effect does pergolide have on sperm?

Answer 65

decreased sperm count, but it returns to normal in most horses after discontinuing the drug

Question 66

NSAIDs block prostaglandin release and therefore they have what effect on pregnancy?

Answer 66

prolongation of parturition

Question 67

NSAIDs are considered teratogens and may cause _________. Therefore you should use short duration and lowest dose possible.

Answer 67

renal agenesis

Question 68

B-2 agonists (ex. clenbuterol) cause uterine muscle relaxation. what effect does this have on pregnancy?

Answer 68

prolongs parturition

Question 69

Ca channel blockers (ex. amlodipine) block L-type Ca channels and have what effect on pregnancy?

Answer 69

prolongs parturition

Question 70

Corticosteroids, trilostane, and misoprostol can have what effect on pregnancy?

Answer 70

early induction of parturition

Question 71

Oxytocin and Dopamine type 2 receptor antagonists (metoclopramide, domperidone, acepromazine) have what effect on lactation?

Answer 71

stimulate it

Question 72

Dopamine agonists (pergolide, bromocriptine) and prolactin antagonist (cabergoline) have what effect on lactation?

Answer 72

inhibit it