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First Year Veterinary School > EndoPharm 2 > Flashcards

EndoPharm 2 Flashcards

1
Q

Mineralcorticoids function to?

A

Mineralocorticoids regulate electrolyte and water balance

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2
Q

List three examples of mineralcorticoids.

A

➢ Aldosterone
➢ Deoxycorticosterone
➢ Fludrocortisone (aldosterone analog)

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3
Q

How do mineralcorticoids act on the kidneys?

A

▪ Increases Na+ reabsorption into the blood
▪ Promotes excretion of K+ and H+ into the urine

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4
Q

How do mineralcorticoids act on the brain?

A

Stimulates production of ADH (vasopressin)

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5
Q

How do mineralcorticoids act on the heart?

A

Renin-angiotensin-aldosterone system
Blood pressure
( ^ ^ ^ Na++ –> Hypertension)

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6
Q

Describe the cellular mechanism of action of mineralcorticoids.

A

When aldosteorne binds to receptor and transfers into cyotplasm and then the nucleus, MR (mineral cortico receptor responsiv element ) undergoes conformational changes and dissociates with ? proteins and dimerization. Goes down signaling pathway. Regulates transcription of many genes.

MR recpetorsw find in kidney, colon, heart, brain.

MR has affinity for different mineralcoritcoid (see blue box in image)

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7
Q

Aldosterone deficiency results in?

A

We need agonists in order to boost aldosterone levels.
Both things in green happening at the same time.

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8
Q

Name the Aldosterone agonists used to treat aldosterone deficiency.

A

❖ Aldosterone
❖ Deoxycorticosterone
❖ Fludrocortisone (aldosterone analog); side effects = rare

Not available as a drug due to its short duration of action when administered orally.

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9
Q

What are the functions of Aldosterone agonists

A

▪ Increase Na+ reabsorption into the blood
▪ Promote excretion of K+ and H+ into the urine
▪ Regulate blood pressure

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10
Q

Aldosterone agonists are used to treat which medical conditions?

A

Used to treat hypoadrenocortism (addison’s disease) in dogs and cats.

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11
Q

Excess aldosterone results in?

A
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12
Q

Name the aldosterone antagonists and describe what medical conditions they treat?

A
  1. Spironolactone
  2. Caneronone
  3. Epierenone

Treats hypertension and CHF and other conditions where the body remains with excess fluid (edematous states).

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13
Q

Spironolactone functions as?

A

❖ Spironolactone is a competitive aldosterone antagonist:
▪ Decreases Na+ reabsorption and K+ excretion
▪ Has effects on renin-angiotensin-aldosterone system

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14
Q

Canrenone functions as?

A

Canrenone is a diuretic metabolite of spironolactone

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15
Q

Eplerenone functions as?

A

Eplerenone antagonizes the MR (does not bind to PR or AR)

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16
Q

Remember: corticosteroids exhibit effects of both mineral and gluco. In some conditions, the effects of both types is beneficial. Do not need to know numbers.

Flu has both gluco and mineral <– she said to remember this specifically

A
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17
Q

Thryoid gland secretes two hormones: triiodo (T3) and thyroxine (T4). T3 and T4 control many body functions including heart rate, temp, metabolism, and many other physiological functions.
PG produces thyroid stimulating hormone. Stimulates thyroid gland to produce T3 and T4.
4 thyroid glands in dogs and cats
Parathyroid gland produces its own hormones.

A
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18
Q

What compound is an essential component of T3 and T4? Explain why.

A

▪ Iodine (I-) is an essential component of T3 and T4
▪ The correct functioning of thyroid gland depends
on a good supply of iodine from the diet
▪ Deficiency of iodine leads to decrease production of T3 & T4

T4 = inactive form of hormone
T3 = active form of hormone

Diodinase enzymes plays active role in changing inactive T4 into biologically active T3.

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19
Q

What is the difference between T3 and T4?

A
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20
Q

Explain the binding activities of T3 and T4.

A

T3 and T4 do not circulate freely. usually found to these three proteins. TBG is secreted in liver and plasma.
Unbound bind to receptors only.

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21
Q

How does protein-binding TH differ among animal species?

A

Humans = 99% of T4 and 99% of T3 are bound. by plasma proteins.
Dogs = less is bound.
Humans have 4x TBG than dogs.
Cats, birds, etc do not have detectable levels.

See image.

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22
Q

What does T3 function as?

A

T3 affects almost every physiological process in the body, including growth
and development, metabolism, body temperature, and heart rate

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23
Q

What are the genomic effects? of T3?

A

Not acting about molecular pathway on left.
Genomic actions: transcription of different genes, mRNA, as well as metabolic rate and neuro development.

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24
Q

What are the non-genomic effects? of T3?

A

TR metabolites may be coupled to Na++ channels,
Na+, K+- ATPase to affect electrolytes balance

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25
Q

Hypothyroidism is a result of?

A

Hypothyroidism is caused as a result of insufficient production of thyroxine by the thyroid gland. It is seen in dogs and horses (it is very rarely seen in cats)

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26
Q

Hyperthyroidism is a result of?

A

Hyperthyroidism: when the thyroid gland produces more thyroxine (T4) resulting
in increased metabolic rate. It is usually seen in older cats. In other species it is likely caused by adenocarcinoma.
Thus, anti-thyroid agents are only recommended for cats.

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27
Q

Which thyroid agent is T4?

A

Levothyroxine

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28
Q

Which thyroid agent is T3?

A

Levothyronine

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29
Q

Thyroid agents, such as T3 and T4, are used for what?

A

Uses: replacement therapy: T4 is preferred to T3 because T4 can maintain higher TH activity in brain than T3

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30
Q

Levothyroxine: Initial dose is 20 μg/kg/day, orally

A
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31
Q

Levothyronine: Initial dose is 5 μg/kg/day, 2-3 times per day, orally

A
32
Q

know this

A
33
Q

PTH regulates?

A

Ca2+ homeostasis

34
Q

When Calcium decreases, what happens to PTH?

A

Increase in PTH

35
Q

When Calcium increases, what happens to PTH?

A

Decrease in PTH

36
Q

Calcium functions to?

A
  • Bone growth and remodeling
  • Secretion (exocytosis)
  • Stabilization of membrane potential
  • Enzyme co-factor (factor IV)
  • Intracellular second messenger
37
Q

What controls Calcium in the blood?

A

➢ PTH:
➢ Vitamin D: makes PTH more
effective
➢ Calcitonin (CT): opposes the
effects of PTH

38
Q

Know this

A

Vitamin D is critical for absorption of Calcium from the intestines.

39
Q

Define hypoparathyroidism

A

Hypoparathyroidism (insufficient PTH secretion) leads to hypocalcemia which is characterized by neuromuscular excitability and restlessness, bradycardia,
and convulsions. It is seen in dogs and cats, rare in horses

40
Q

Define hyperparathyroidism

A

Hyperparathyroidism (overproduction of PTH) leads to hypercalcemia
characterized by renal, skeletal, GI, and neurological ramifications.
It is seen in dogs, and less commonly, in cats. Nutritional secondary
hyperparathyroidism is seen in horses grazing exclusively on grasses
containing high levels of oxalate

41
Q

Calcium gluconate
MOA?

A

Regulating important cellular
functions associated with
Ca++-mediated events

42
Q

Calcium gluconate
Uses?

A

In animals with symptomatic
hypocalcemia (dietary supplemental therapy or injections)

43
Q

Calcium gluconate
Adverse Effects?

A

Hypercalcemia in animals with
cardiac or renal diseases
Rapid IV injection can cause
cardiac arrhythmias and arrest

44
Q

Dihydrotachysterol (DHT): vitamin D2 analog
MOA?

A

Mobilizing Ca++ from the
bone, increasing intestinal
absorption, reducing Ca++
loss in urine
Controlling phosphorus
levels

45
Q

Dihydrotachysterol (DHT): vitamin D2 analog
Uses?

A

In small animals to treat
hypocalcemia secondary
to hypoparathyroidism or
severe renal disease

46
Q

Dihydrotachysterol (DHT): vitamin D2 analog
Adverse Effects?

A

Hypercalcemia, nephrocalcinosis,
and hyperphosphatemia

47
Q

Calcitriol: vitamin D3 metabolite
MOA?

A

Increasing plasma Ca++
and controlling
phosphorus levels

48
Q

Calcitriol: vitamin D3
metabolite
Uses?

A

In small animals to treat
hypocalcemia secondary
to hypoparathyroidism or
severe renal disease

49
Q

Calcitriol: vitamin D3
metabolite
Adverse Effects?

A

Hypercalcemia, nephrocalcinosis,
and hyperphosphatemia but
the duration of these effects is
Shorter than that of DHT

50
Q

Within the Islets of Langerhans, alpha cells produce?

A
51
Q

Within the Islets of Langerhans, beta cells produce?

A
52
Q

Within the Islets of Langerhans, gamma cells produce?

A

Somatostatin

53
Q

Insulin functions to?

A

▪ Regulates the normal cellular lipid and carbohydrate metabolism
▪ Helps to regulate the lipid, protein, and glucose absorption by all the cells of the body

54
Q

How does insulin decrease blood glucose concentrations?

A

▪ Increasing glycogen synthesis
▪ Increasing the uptake of amino acids and protein synthesis
▪ Decreasing hepatic glycogenolysis
▪ Decreasing gluconeogenesis
▪ Increasing glucose transport into muscle cells and
adipocytes via activation and translocation of GLUT4

55
Q

What is the difference between Type I and Type II Diabetes?

A

Type I = genetic
Type II = elderly diabetes; beta cells are usually normal but insulin receptors are not functioning.

56
Q
A

after eat meal, glucose levels are increased in blood. insulin activated with a goal of decreasing glucose. insulin binds to IR on membrane (not nuclear bound). Alpha phosphorlation of receptor, stimulates trnaslocation of glut 4 (another receptor) from ? to membrane. Glut 4 protein channel;s become embedded into membrane allowing glucose to be transported into cells.
In cases of insulin resistance, GLUT 4 levels are reduced.

GLUT 1 = glucose transporters consti? expressed ? and is important for stress.

57
Q

Define hyperglycemia (aka?).

A

hypoinsulinemia
▪ Diabetes mellitus is the most common cause.
▪ It is seen most often in dogs and casts > 7 years old. Can affect also pigs, horses, and apes
▪ Usually diagnosed at the late stage, when beta-cells have mostly been destroyed by severe hyperglycemia

58
Q

Define hypoglycemia (aka?).

A

Hypoglycemia (hyperinsulinemia) may be caused by insulin overdose

59
Q

What causes Diabetes Mellitus?

A

▪ Deficiency of insulin secretion from pancreas
▪ Decreased glucose uptake into cells
▪ Increase hepatic glucose production

60
Q

What are the symptoms of Diabetes Mellitus?

A

▪ High blood glucose (hyperglycemia)
▪ Glucose in urine (glycosuria)
▪ Excessive excretion of urine (polyuria)
▪ Excessive thirst (polydipsia)
▪ Excessive hunger (polyphagia)
▪ Fatigue

61
Q

Define Type I Diabetes Mellitus

A

▪ Irreversible loss of insulin secretion
from pancreas
▪ Insulin dependence
▪ Usually permanent

62
Q

Define Type II Diabetes Mellitus

A

▪ Impaired insulin secretion
from pancreas
▪ Insulin resistance
▪ Diabetic remission is possible

63
Q

Explain diabetes mellitus in dogs

A

❑ Females
❑ Middle aged
❑ Type I
❑ Causes:
▪ Pancreatitis
▪ Immune attack
▪ Breed
▪ Lifestyle factors

64
Q

Explain diabetes mellitus in cats

A

❑ Males
❑ Older age (geriatric disease)
❑ > 80% Type II

Causes
▪ Pancreatitis
▪ Pancreatic amyloidosis
▪ Insulin resistance
▪ High blood glucose damages cells

65
Q

How do you diagnose and treat DM in cats?

A
66
Q

Insulin is a protein consisting of how many amino acids?

A

51 amino acids (human is shown)

67
Q

Insulin consists of how many peptide chains?

A

Insulin consists of two peptide chains (A: 21 aa) and (B: 30 aa) joined by disulfide linkages

68
Q

What does the structure of insulin dictate?

A

The structure of insulin dictates its folding, shape, trafficking, and receptor binding

69
Q

True or False: The amino acid sequence of insulin varies among species

A

True

Recombinant space specific insulin is best ? Dogs have only 1 AA difference, cats have three. Different ?

70
Q

Do we need to know?

A

Commercial is mostly of human origin.
We need to know
Vetsulin we need to know especially
porcine insulin can be used in dogs and cats

71
Q
A
72
Q

What are the adverse effects of insulin treatment?

A

Adverse effects:
❖ Hypoglycemia……. Insulin shock
▪ CNS disturbances, including convulsions and coma
❖ Insulin resistance
▪ Insulin antibodies may attenuate response to treatment (seen more in cats than in dogs)
▪ Excessive secretion of hyperglycemic hormones including stress hormones
▪ At the receptor level

73
Q

What are the adverse effects of insulin treatment?

A

Adverse effects:
❖ Hypoglycemia……. Insulin shock
▪ CNS disturbances, including convulsions and coma
❖ Insulin resistance
▪ Insulin antibodies may attenuate response to treatment (seen more in cats than in dogs)
▪ Excessive secretion of hyperglycemic hormones including stress hormones
▪ At the receptor level

74
Q

Metformin is what type of drug?

A

oral antihyperglycemic but not hypoglycemic (does not stimulate insulin secretion) drug

75
Q

Metformin
MOA

A

▪ Decreasing glucose absorption from the GI tract
▪ Decreasing glucose output from the liver
▪ Increasing insulin receptor sensitivity

76
Q

Metformin
Uses

A

PO, with food
To treat non-insulin dependent DM in cats (usually with other medications)
In dogs with obesity problems or resistance to insulin

77
Q

Metformin
Adverse Effects

A

Vomiting, appetite loss, weight loss, and lethargy
Not safe for use in cats with kidney insufficiency
Drug-drug interaction
Lactic acidosis (rare)

First Year Veterinary School (43 decks)

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