Pharmacology Exam 4 2

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GnRH: stimulates release of FSH, LH

released intermittently & controlled by neural pulse in hypothalamus
somatotropin (growth hormone): growth of all organs except brain & eye

(+): GHRH (somatocrinin), (-) GHRIH (somatostatin)
acromegaly: growth hormone hypersecretion
prolactin: stimulates lactation during postpartum period

(-): dopamine
lutenizing hormone (LH): male: stimulates androgen synthesis
female: stimulates development of ovarian follicles, induces ovulation, produces estrogens & progesterone
follicle stimulating hormone (FSH): male: sperm maturation
female: stimulates development of ovarian follicles, induces ovulation, produces estrogens & progesterone
adrenocorticotropic hormone (ACTH): stimulates release of glucocorticoids, mineralocorticoids from adrenal cortex
thyroid stimulating hormone (TSH): stimulates iodic ion uptake by thyroid gland (critical step in biosynthesis of thyroxine)
oxytocin: increases frequency & force of uterine contraction, stimulates milk ejection
vasopressin (ADH): regulation of body fluid osmolality (thru renal conservation of water), vasoconstriction

released d/t: increased plasma osmolality, hypovolemia/hypotension
diabetes insipidus: excretion of large volumes of dilute urine, polydipsia

nephrogenic: d/t insufficient renal response to ADH

central: d/t inadequate secretion of ADH from posterior pituitary
thyroxine: growth & development
maintainence of BMR
CV effects
increased glucose absorption from gut
decrease lipids by enhancing lipolytic response to fat cells
insulin: from beta cells of pancreatic islets

secreted in response to increased blood glucose

aids in entry of glucose into muscle, adipose, other tissues
stimulates storage of glucose in liver as glycogen
fat sparing effect d/t synthesis of FA's in liver, inhibition of fat breakdown in adipose tissue
decreases protein catabolism

(-): somatostatin
diabetes mellitus: insulin dependent: no insulin secretion d/t destruction of beta cells
tx: insulin replacement therapy

non-insulin dependent: insulin resistance b/c target tissue fails to respond properly to insulin
tx: eliminate obesity, change diet, hypoglycemic agents
glucagon: from alpha cells of pancreatic islets

increases blood glucose by:
stimulating glycogenolysis
activating hepatic gluconeogenesis

released in response to hypoglycemia, increased plasma amino acids, exercise

(-): somatostatin
somatostatin: from delta cells of pancreatic islets

inhibits insulin, glucagon, growth hormone
glucocorticoids: prototype: cortisol

increases & maintains normal blood glucose concentration
anti-inflammatory & immunosuppressive
combat stress d/t trauma, fright, infection, or dz

site: ZF, ZR of adrenal cortex
mineralocorticoids: prototype: aldosterone

regulate Na & K concentrations in extracellular fluid
aldosterone: causes increased reabsorption of Na, H2O & increased secretion of K in distal tubule of kidney

site: ZG of adrenal cortex
hyperadrenocorticism: excessive production of cortisol d/t:
primary adrenal tumor (ACTH independent)
excess secretion of ACTH d/t pituitary tumor (ACTH dependent)
hypoadrenocorticism: deficiency in cortisol & aldosterone d/t infection or autoimmune destruction of adrenal cortex
principles of glucocorticoid therapy: alternate day therapy
gradual withdrawal from chronic use
do NOT use w/ NSAIDs, diabetics, pregnant animals
PGF-2alpha: luteolytic agent produced by uterus

mediates decrease in circulating progesterone via luteolysis (CL regression)
used to induce abortion, decrease estrous cycle length & thereby hasten onset of estrus, stimulate uterine contraction in parturition, tx uterine infections
gonadorelin: synthetic GnRH: stimulates release of FSH, LH
clinical uses of gonadorelin: induction of ovulation
tx of cystic ovaries in cattle (tx of choice)
termination of estrus in ferrets
diagnostic use: pituitary function test
chorionic gonadotropin (HCP): has LH-like activity

produced by cells of placenta & extracted from urine of pregnant women
clinical uses of chorionic gonadotropin: infertility therapy
tx of cystic ovaries
tx of impotence in stallions
cryptorchidism
cosyntropin: truncated ACTH agonist
clinical uses of cosyntropin: ACTH stimulation test: drug administered & cortisol measured just before & 30-60 minutes later
clinical uses of oxytocin: induction of labor
to assist in parturition (uterine inertia)
tx uterine prolapse
stimulate milk letdown in dogs
side effects of oxytocin: OD or repeated dosing: painful contractions or uterine rupture & fetal death
clinical uses of vasopressin: tx of central diabetes insipidus
tx esophageal closure in ruminants
side effects of vasopression: bronchoconstriction
water intoxication
desmopressin acetate: selective vasopressin V2 receptor agonist (V2: collecting ducts of kidney)
clinical uses & side effects of desmopressin acetate: tx central diabetes insipidus
dx of diabetes insipidus
modified water deprivation test
tx of von Willebrand's dz (to induce hemostasis)

side effects: water intoxication
levothyroxine: =T4
drug of choice for tx of hypothyroidism in all species
side effects/special considerations with levothyroxine: dogs need higher dose than other species d/t higher metabolic rate & poor oral absorption
OD --> hyperthyroidism
care should be taken in patient's w/ Addison's, DM, CV dz
increases activity of epi & norepi, decreases efficacy of insulin & digoxin, significant interaction w/ ketamine may occur
liothyronine: =T3
faster acting than Levo, but shorter half life & higher cost
may lack physiologically diverse tissue specific distribution
used rarely (critically ill patients)
methimazole: drug of choice for tx of hyperthyroidism
long acting, orally available
blocks iodination of tyrosine residues of thyroglobulin & condensation of DIT & MIT
onset of effects: 5+ days, 2-3 wks to normalize T4
side effects of methimazole: bitter taste, anorexia, vomiting, transient lethargy

rare toxicity: thrombocytopenia, amnesia

OD does NOT cause hypothyroidism
propranolol (used in hyperthyroidism): beta blocker
used as adjunct to control tachycardia & other cardiac abnormalities assoc. w/ severe hyperthyroidism

normal dosage should be decreased in hyperthyroid cats

side effects: bronchoconstriction, hypoglycemia, hypotension, bradycardia
shorting acting insulin products: rapid onset (30 min), short duration (5-8 hrs)

can be given IV in emergencies

ex. regular (crystalline) insulin
intermediate acting insulin products: last 18-24 hrs

lente: insulin of choice for dogs w/ uncomplicated DM

NPH: often used in dogs in combo w/ regular or lente insulin
long acting insulin products: onset: 4-6 hrs

prolonged, flat peak of action (20-36 hrs)

provide low basal conc. thru out day

ex. PZI, ultralente
glipizide: adjunct in management of non-insulin dependent DM

response variable, can be used w/ insulin
mechanisms of action of glipizide: blocks K channels in pancreatic B cell mems --> depolarization induced insulin release from functioning B cells

decreases glucagon level

increases binding of insulin to its receptors
side effects of glipizide: hypoglycemia, hepatotoxicity, contraindicated w/ diabetic ketoacidosis
glyburide: adjunct in management of non-insulin dependent DM

longer duration of action than glipizide (24 hrs vs. 10-16 hrs)

not widely used
mitotane (Lysodren): most commonly used drug to tx Cushing's

DDT insecticide analog

selectively destroys adrenal ZF & ZR
side effects of mitotane (Lysodren): high doses chemically ablate adrenal cortex --> adrenal insufficiency
highly toxic
GI upset
CNS depression
liver damage
ketoconazole: used to tx Cushing's

cytochrome p450scc & 17alpha-hydroxylase inhibitor --> blocks synthesis of ALL cholesterol derived steroids
side effects of ketoconazole: vomiting, anorexia, teratogenic
pergolide: used to tx Cushing's in horses

dopamine (D2) receptor agonist --> inhibits release of ACTH
bromocriptine: used to tx Cushing's in horses

ergot derived dopamine receptor agonist --> inhibits release of ACTH

therapy only palliative
tolerance often develops
L-Deprenyl (Anipryl): used to tx uncomplicated Cushing's

irreversible monoamine oxidase B inhibitor --> blocks degradation of dopamine & other catecholamines --> inhibits release of ACTH
trilostane: used to tx Cushing's (not available commercially)

inhibits enzyme that converts pregnenolone to progesterone --> inhibits all prenenolone derived steroids
deoxycorticosterone (Percorten): used in tx of Addison's

naturally occurring mineralocorticoid

short & long acting forms (given IM)
side effects of deoxycorticosterone (Percorten): hypokalemia, hypernatremia, muscle weakness, hypertension
fludrocortisone: used in tx of Addison's

orally active, synthetic, long-acting mineralocorticoid
altrenogest (Regumate): synthetic orally active progretin

used to control estrous cycle in mare & pig

use of PGF 2alpha immediately after therapy will induce estrous

contraindicated in pregnant mare --> fetal abnormalities
synchro-mate B (SMB): progesterone-estrogen combo (not available in US)

used for estrous synchronization in cattle & goats

ear implant + injection

estrogen --> luteolysis via PG release
progestin --> inhibits LH secretion --> inhibits CL function
stanazolol (Winstrol-V): anabolic steroid

potentially useful as adjunct to management of catabolic dz states

recommended to stimulate erythropoiesis, increase appetite, promote wt. gain, increase strength & vitality
side effects of stanazolol (Winstrol-V): hepatotoxicity, wt. gain, sodium & water retention, CARCINOGENIC

contraindicated w/ benign prostatic hyperplasia
finasteride: used to tx BPH

irreversible 5alpha-reductase inhibitor: blocks conversion of testosterone to dihydro-testosterone --> prostatic involution

adverse effects: impotence
hydrocortisone: =cortisol, Solu-Cortef

short acting natural glucocorticoid
methylprednisolone (Medrol): prednisolone derivative
betamethasone: highly potent, long acting injectable glucocorticoid

clinical uses:
pruritis
ophthalmic conditions
skin conditions
prednisolone: most widely used glucocorticoid in small animals

clinical uses:
adrenal insufficiency
shock
inflammatory conditions of skin & joints
supportive care during periods of stress

prednisone: prodrug metabolized in liver to prednisolone
dexamethasone: most widely used glucocorticoid in large animals

long acting

clinical uses:
dermatoses
inflammatory conditions involving joints
management of hydrocephalus in toy breeds
adjunct to cranial & spinal trauma
tx of shock
triamcinolone (Vetalog): potent synthetic glucocorticoid

clinical uses:
arthritis
allergic & dermatologic conditions
soft tissue injuries (horses)
uses of glucocorticoids: inflammation/allergies
to suppress immune system
shock
cancer chemo
inflammatory ophthalmic conditions
inflammatory skin conditions
thyroid hormone synthesis: 1. uptake of iodiide from diet
2. oxidation & iodination (thyroglobulin --> mono- or di-iodotyrosine)
3. condensation (DIT + DIT = T4, DIT + MIT = T3)
4. proteolysis: hormone released
5. deiodination: much of circulating T3 formed by deiodination of T4 in peripheral tissues
types & clinical signs of hypothyroidism: congenital: dwarfish, dullness, retention of puppy coat, neuro abnormalities (rare)

acquired: bilaterally symmetric alopecia, myxedema, obesity, lethargy, bradycardia, weakness (common)
causes & clinical signs hyperthyroidism: d/t malignant tumor of thryoid gland (inc. T3 & T4) or pituitary thyrotropes (inc. TSH)

palpable thyroid nodule, wt. loss, PU/PD, hyperactivity, tachycardia, derm lesions, hypertension
clinical uses of anabolic steroids: aplastic anemia (dogs, cats)
myeloproliferative dz
lymphoma assoc. w/ non-regen. anemia
to inc. athletic performance in horses
membrane receptors: H20 soluble hormones, peptides, polypeps (activation of 2nd messengers)
intracellular receptors: lipid soluble hormones, steroids, thyroid hormones (regulation of gene expression)

cortisol
aldosterone
estrogen
progesterone
testosterone
thyroxine

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