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VETM 443 Pharmacology > Endocrine Pharmacology > Flashcards

Endocrine Pharmacology Flashcards

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1
Q

Explain the HPA axis and the hormones involved

A

Hypothalamus: Produces releasing hormones
- GnRH
- GHRH
- CRH
- TRP
- PIH/ dopamine (prolactin inhibiting hormone
- GHIH (growth hormone inhibiting hormone)

Pituitary: Produces stimulating hormones
Anterior: ACTH/TSH/FSH/LH/MSH/Prl/GH
Posterior: Oxytocin/ADH

Target Gland: releases hormones that have a negative feedback role on the hypothalamus and anterior pituitary
- Oxytocin will have a positive feedback loop with the hypothalamus
- T3/4
- glucocorticoids
- estrogen

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2
Q

Describe the 2 types of hormones produced by the HPA axis and how their type impacts their function.

A

water soluble
- bind cell membrane receptors = second messenger cascade results in impact on molecular activity
- peptide or monoamine hormones (catecholamines/eicosanoids like prostaglandin/prostacyclin/thromboxane/leukotriene/epoxyeicosatrienoic acid)

lipid soluble:
- can enter cell and act on intracellular receptors = change gene transcription
- steroids/thyroid hormones

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3
Q

List 4 factors that affect the action of hormones

A

age
reproductive status
sex
environmental factors

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4
Q

How are hormones secreted? What is required for secretion

A

non-constitutive
- impacted by seasonality/diurnal/pulsatile

require receptor binding/signal transduction/response - impact feedback control

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5
Q

What are 4 uses/goals for endocrine therapeutics

A

replacement therapy (ex. hypothyroid)

regulation (ex. hypothyroid + methimazole)

reproduction

supraphysiologic response (ex. rBST causing excess lactation in cows - illegal in CA)

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6
Q

What are 5 uses/goals of reproductive therapeutics

A

induce/synch estrus

suppress estrus

maintain pregnancy

induce parturition/abortion

expel uterine fluid/metritis/endometritis and fetal membranes

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7
Q

List 5 reasons why we manipulate the estrus of cows

A

estrus is difficult to detect

large farm sizes

improves production for dairy cows - they have more subtle signs of estrus

fixes poor conception rates

synchronizes calving

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8
Q

How long is the estrus cycle of a cow

A

21d

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9
Q

Describe the estrus cycle of a cow and the hormone fluctuations that occur

A

Estrus: high estrogen and low progesterone

Metestrus (post ovulation): decreasing estrogen and increasing progesterone

Diestrus:
1st follicular wave: estrogen increases but ovulation is suppressed by progesterone from the existing CL
2nd follicular wave: estrogen increases and stimulates the LH surge which triggers ovulation
- this occurs after luteolysis (CL degrade)

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10
Q

What structure is primarily responsible for making estrogen?

A

the follicle - follicular granulosa cells

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11
Q

What structure is primarily responsible for making progesterone?

A

corpus luteum

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12
Q

What structure is primarily responsible for making prostaglandin F2a?

A

the endometrium

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13
Q

What are 3 functions of prostaglandin F2a

A

relax the cervix

luteal regression

uterine muscle contraction

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14
Q

What are 4 uses for PGF2a

A

estrus synchronization - shorten cycle

abortion in cows between d5-130

treat endometritis/pyometra/retained fetal membranes

induce parturition

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15
Q

What are the adverse effects associated with prostaglandin F2a

A

small animals are very sensitive to the adverse effects

diarrhea
vomit
abdominal pain/colic
hyperthermia if overdosed

use gloves when administering because it can induce bronchospasm in people with asthma and miscarriages

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16
Q

Give 2 types of PGF2a drugs commonly used

A

dinoprost: natural prostaglandin

chlorpostanol: synthetic prostaglandin

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17
Q

What are dinoprost PGF2a labelled for? Provide 2 examples of these drugs

A

beef
dairy
swine
horse

ex. lutalyse/enzaprost T

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18
Q

What are chlorpostanol PGF2a labelled for? Provide 2 examples of these drugs

A

beef
dairy
swine

ex. estrumate/ bioestrovet/ alfaglandin C / planate/ cloprostenol veyx

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19
Q

Compare dinoprost and chlorpostanol

A

dinoprost: in cows it has a short t1/2 - 30m

chlorpostanol: in cows it has a longer half life = 3h

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20
Q

What is the function of GnRH use in estrus manipulation

A

it can trigger the LH surge/ovulation

induce ovulation in cows
treat cystic ovaries in cows and camelids
induce estrus in small animals

it is licensed for estrus synch and cystic ovary tx in dairy cows

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21
Q

What are the adverse effects associated with GnRH

A

safe
few effects

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22
Q

What are some examples of GnRH drugs

A

cystorelin
factrel
fertiline
ovu-gel
maprelin XP-10

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23
Q

What are 4 effects of estrogen

A

induce estrus behaviour

contribute to LH surge

increase mammary development

endometrial proliferation (anabolic steroid)

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24
Q

What are 2 types of estrogen

A

estradiol cypionate (ECP): natural estrogen

diethysilbestrol (DES): synthetic

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25
What is estradiol cypionate used for? What species is it used in?
Cows: - speed up uterine involution - correct anestrus - treat metritis and retained placentas Dog: not recommended anymore - urinary incontinence/palliative/prevent ovum implantation
26
What is diethylsilbestrol used for? What species is it used in?
urinary incontinence treatment in dogs
27
What are the adverse effects associated with diethysilbestrol
bone marrow suppression increase mammary tumor risk human carcinogen
28
What are the adverse effects of estrogen in SA
bone marrow suppression endometrial hyperplasia and uterine cancer pyometra
29
What are the adverse effects of estrogen in LA
prolonged estrus cyst development reduced lactation
30
What is the role of progesterone secretion on the HPA axis
negative feedback on the hypothalamus/anterior pituitary = reduce LH and FSH secretion
31
What is the function of progesterone
prevent ovulation and maintain endometrium/preganancy
32
What are 3 examples of progesterone drugs that are commonly used
CIDR MGA Altrenogest
33
Provide 3 examples of synch protocols for dairy cows. What is their function/purpose
Ovsynch Cosynch SelectSynch estrus synchronization for times artificial insemination it will can also treat follicular and luteal cysts
34
Explain the OvSynch protocol
Day -12 (12d before): Presynch: give 2 prostaglandin injections 14 days apart 0: give GnRH when the cow is in diestrus to start a new wave of follicles 7: give prostaglandin to induce luteolysis and allow for a new wave of follicles to develop (reduce progesterone) 9: Give GnRH to induce the LH surge and stimulate ovulation 10: AI (won't show estrus but can still breed)
35
Explain the CoSynch Protocol
Day -12 (12d before): Presynch: give 2 prostaglandin injections 14 days apart 0: give GnRH when the cow is in diestrus to start a new wave of follicles 7: give prostaglandin to induce luteolysis and allow for a new wave of follicles to develop (reduce progesterone) 9.5: Give GnRH and AI This will reduce the number of times ou need to handle the cows but is less efficacious vs OvSynch
36
Explain the SelectSynch protocol
Day -12 (12d before): Presynch: give 2 prostaglandin injections 14 days apart 0: give GnRH when the cow is in diestrus to start a new wave of follicles 7: give prostaglandin to induce luteolysis and allow for a new wave of follicles to develop (reduce progesterone) Allow the cow to ovulate and observe estrus - which should be between day 6-13 more labour
37
How do beef estrus synch protocols compare to dairy
Same basic principles but less handling
38
What is a CIDR?
controlled internal drug release release progesterone over 7d inserted into the vagina
39
Explain how to use a CIDR
Day 0: insert the CIDR 6: prostaglandin injection 7: remove the CIDR 8-10: heat detection/AI
40
What is the function of a CIDR
it can start an anestrus cow cycling again by giving and removing progesterone it simulates a CL The prostaglandin injection will induce luteolysis of the old follicles
41
What is CIDR1380? What is it used for?
1380 is the amount (mg) of progesterone in the device it is labelled for dairy and beef in Canada
42
What is the withdrawal time and adverse effects of CIDR1380
milk: no withdrawal meat - 1 d adverse: vaginal irritation wear gloves because it can be absorbed across the skin
43
What is CIDR330 for?
sheep
44
What is melengestrol acetate? What is it used for?
oral progesterone used to suppress estrus in feedlot heifers
45
How do you use melengestrol acetate?
0.5mg/head/d for 14d synch estrus + cause poor quality egg and reduced conception rates you can combine it with prostaglandin 17-19d after the last MGA feed
46
What is the goal of estrus manipulation in horses?
start cycling earlier - all racehorses have a 'birthday' of Jan 1 so if you are born earlier = advantage
47
What are 3 methods of inducing estrus in horses?
increase light exposure progesterone sulpiride (dopamine antagonist)
48
What is the function of progesterone administration in horses? What drugs are commonly used
Use - shorten transition from anestrus to estrus - suppress estrus in performance mares - maintain preganancy Altrenogest aka regumate
49
How is altrenogest used in horses?
PO for 10-16d they will ovulate around 10 days after treatment stops
50
How long is an equine estrus cycle
21d
51
Why is inducing ovulation important in horses
an ovulated egg will only be viable for 12h - while sperm will live much longer - mating should be done 1-2d pre-ovulation
52
When do you induce ovulation in horses
when the dominant follicle is seen on u/s
53
What are 2 drugs that are commonly used to induce ovulation in horses
human chorionic gonadotropin: large glycoprotein deslorelin: synthetic GnRH analogue
54
When should HCG be used in horses
to induce ovulation when the follicle is >35mm they will ovulate within 2 days repeated use will reduce the efficacy
55
What is deslorelin
a super-agonist not licensed in CA
56
What 3 scenarios are repro drugs used in SA
cats: induce ovulation to stop estrous with GnRH and HCG dogs/cats: deslorelin used as a contraceptive - chronic GnRH causes (-) feedback and reduced FSH/LH prostaglandin can be used to induce abortion - lots of adverse effects
57
When are repro drugs used to help maintain equine pregnancies
when they are high risk - colic/placentitis/history of pregnancy loss must balance with the potential risk of fetal abnormalities
58
What is used to help maintain pregnancy in horses? Why?
progesterone - altrinogest some mares dont make enough progesterone early (pre day 120) - supplement until day 120 - when the placenta takes over if they have a placentitis they may need supplementation the whole pregnancy
59
Explain how a normal equine pregnancy is maintained
DAY 17: implantation - primary CL producing progesterone 40: endometrial cups form - produce equine chorionic gonadotropin (like FSH/LH) - cause ovulation of follicles that happened earlier in pregnancy and induce lutenization of l=follicles - induce the development of accessory CLs for increase progesterone - beginning of placentation 120: placental progesterone is enough to maintain pregnancy
60
What are 4 reasons why you would induce a cows parturition
to increase the time before the next breeding to reduce the calf size and dystocia risk to reduce excess udder edema to take advantage of the available foliage for lactation
61
What are 2 ways to induce parturition in a cow
glucocorticoids - dexamethasone prostaglandin - PGF2a best effect = a combo of both
62
What is the reasoning behind using glucocorticoids and prostaglandin to induce parturition in cows
glucocorticoids (cortisol) are released by the fetus to stimulate birth - it would induce PGF2a and estradiol 2 release PGF2a = causes luteolysis and relaxin release (resulting in the stretching of the pelvic ligament) estradiol 2: causes myometrial contraction - the increased pressure and cervical stimulation cause oxytocin release
63
How is parturition induced in horses
oxytocin: they will deliver within 90m - if you use a low dose the mare won't deliver unless she is ready using glucocorticoids and prostaglandin are not that effective
64
Why do retained fetal membranes occur? What factors increases your risk for this?
collagenase fails to degrade between cotyledons and caruncles Higher risk if... - parturition was induced - dystocia/fetotomy/ or c-section was performed - immunosuppressed or nutritional deficiency - twins
65
What are 7 ways to treat retained fetal membranes in a cow
- do nothing if the cow seems healthy - systemic abx if there are clinical signs (do not use if early/healthy) - intrauterine abx - PGF2a - oxytocin can be used close to calving - collagenase (expensive) - Ca supplement to treat underlying hypoCa
66
What are 5 ways to treat retained fetal membranes in a horse
oxytocin (low dose) Ca PGF2a NSAID systemic abx
67
How does retained fetal membranes in a cow compare to a horse
in a horse it is an emergency - acute metritis/endotoxemia/laminitis/death in a cow it may not be a problem
68
What is used to increase milk let down or uterine contractions
oxytocin - it increases the contraction of the mammary myoepithelium
69
How is oxytocin administered
IV it has a short half life so it may need to be re-dosed should correct any hypoCa before giving
70
What are the adverse effects associated with oxytocin administration
overdoses can cause tetanic uterine contractions and water intoxication (has a an antidiuretic effect)
71
What are the cells that make up the thyroid? What are their general function
colloid: contain thyroglobulin and precursor thyroid hormone thyroid follicular cells: synthesize thyroid hormone
72
Explain how thyroid hormone is made
The thyroid follicular cells uptake iodine via Na/I pumps I is secreted into the colloid > it binds thyroglobulin - for either diiodotyrosine or monoiodotyrosine Thyroid peroxidase couples MIT and DIT to for with T3 (DIT+MIT) or T4 (DIT+DIT) T3/4 is endocytosed from the colloid into follicular cells T3/4 is released into circulation for thyroid follicular cells - more T4 is released vs T3
73
How is thyroid hormone transported through the body? What does it act on?
protein bound in circulation - only the free hormone can interact with target so there is lots of storage hormone in the blood If there is enough dietary iodine then T4 os preferentially made - it is converted to the more biologically active T3 at the tissue target it is lipid soluble so it acts on intracellular receptors
74
What should you measure to evaluate the productivity of the thyroid?
total and free T4 is all made from the thyroid = can indicate function T3 can be up or down regulated depending on tissues/other factors and is not reflective of thyroid function
75
What are 6 functions of thyroid hormones
increase metabolic rate growth and development increase sensitivity to catecholamines increase protein synthesis/glycolysis/glyconeogenesis positive inotrope increase immunity
76
How is HPA regulation of thyroid hormone useful diagnostically?
T3/4 has a negative feedback on the hypothalamus (TRH) and the anterior pituitary (TSH) if primary thyroid dysfunction hypothyroid = high TSH hyperthyroid = low TSH
77
What is the common signalment and cause of hyperthyroidism
mid/old cats mainly due to benign thyroid hyperplasia
78
What are the clinical signs associated with hyperthyroidism
weight loss with a good appetite PU/PD hyperactivity vomit diarrhea
79
How is hyperthyroidism treated
methimazole
80
What is the mechanism of action of methimazole
It disrupts thyroid peroxidase mediated iodination of tyrosine on thyroglobin = no DIT/MIT formed it acts as an alternative substrate for thyroid peroxidase it concentrates in the thyroid resulting in reduced T3/4 production = normal T3 and low T4
81
What are the adverse effects of methimazole
vomit lethargy pruritis hepatomegaly it can cross the placenta
82
How should methimazole be administered and monitored
start slowly at a low dose and adjust accordingly PO or transdermal - varied bioavail since there is lot of protein-bound thyroid hormone that acts as a storage = weeks before an effect is seen - check total T4/CBC q2-3 weeks for 3 months - check total T4 at 3-6 month intervals
83
How is methimazole metabolized
liver
84
What are other non-methimazole options in treating hyperthyroidism
carbimazole (prodrug of methimazole) radioactive I sugery
85
What are the clinical signs of hypothyroidism
weight gain lethargy hair loss neuropathy myxedema
86
What are the 2 most common causes of primary hypothyroidism
lymphocytic thyroiditis idiopathic atrophy
87
How do you diagnose hypothyroidism
PE/clinical signs total and free T4 TSH levels (high) there can be lots of overlap between normal T4 levels and hypothyroid ranges so you need the clinical signs and TSH levels to confirm
88
What is used to treat hypothyroidism
levothyroxine - a lipophilic synthetic T4
89
What is the pharmacokinetics associated with levothyroxine
it has a high first pass effect - not all formulations have the same bioavailability - more will be absorbed on an empty stomach it is excreted in bile
90
How to administer levothyroxine
SID or BID PO give at a consistent time after a meal - there will be more absorption on an empty stomach but it is easier to adjust dose if it is consistently given with or without food
91
What are the adverse effects of levothyroxine
iatrogenic hyperthyroidism overdoses can cause osteoporosis in humans
92
How is levothyroxine monitored
1-2 months after treatment started - measure peak total T4 (3-4 h after last dose ) = should be in the upper half of the reference range recheck 2-4 weeks after a dose change

VETM 443 Pharmacology (23 decks)

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