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Pharmacology II > 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
1. Hypothyroidism is a result of? 2. What species are commonly affected? 3. Which species are least affected?
1. Hypothyroidism is caused as a result of insufficient production of thyroxine by the thyroid gland. 2. It is seen in dogs and horses. 3. It is very rarely seen in cats.
26
1. Hyperthyroidism is a result of? What does it cause? 2. This condition is commonly seen in which species? Of what age group? 3. In other species, what is this condition commonly caused by? 4. What forms of medication are recommended to treat the species affected in #2?
1. Hyperthyroidism: when the thyroid gland produces more thyroxine (T4) resulting in increased metabolic rate. 2. It is usually seen in older cats. 3. In other species it is likely caused by adenocarcinoma. 4. Anti-thyroid agents are only recommended for cats.
27
What is Levothyroxine? What endogenous hormone does it mimic?
1. Levothyroxine is a thyroid hormone used to treat animals that don't make enough thyroid hormone. 2. Levothyroxine is the name of the synthetic form of the thyroid hormone T4.
28
What is Levothyronine?
Levothyronine is the synthetic version of T3.
29
Thyroid agents, such as T3 and T4, are used for what?
Uses: replacement therapy: T4 is preferred to T3 because T4 can maintain higher TH activity in brain than T3
30
Levothyroxine: Initial dose is 20 μg/kg/day, orally
31
Levothyronine: Initial dose is 5 μg/kg/day, 2-3 times per day, orally
32
know this
33
PTH regulates?
Ca2+ homeostasis
34
When Calcium decreases, what happens to PTH?
Increase in PTH
35
When Calcium increases, what happens to PTH?
Decrease in PTH
36
Calcium functions to?
* Bone growth and remodeling * Secretion (exocytosis) * Stabilization of membrane potential * Enzyme co-factor (factor IV) * Intracellular second messenger
37
1. What controls Calcium in the blood? 2. What makes this factor more effective? 3. What opposes this factor?
➢ PTH: ➢ Vitamin D: makes PTH more effective ➢ Calcitonin (CT): opposes the effects of PTH
38
Know this
Vitamin D is critical for absorption of Calcium from the intestines.
39
1. Define hypoparathyroidism. 2. What does this condition lead to? What is this characterized by? 3. This condition is seen in which species?
1. Hypoparathyroidism (insufficient PTH secretion).2 2. Leads to hypocalcemia which is characterized by neuromuscular excitability and restlessness, bradycardia, and convulsions. 3. It is seen in dogs and cats, rare in horses
40
1. Define hyperparathyroidism 2. What does this lead to? What is this characterized by? 3. What species are affected by this condition?
1. Hyperparathyroidism (overproduction of PTH). 2. Leads to hypercalcemia characterized by renal, skeletal, GI, and neurological ramifications. 3. 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
Calcium gluconate MOA?
Regulating important cellular functions associated with Ca++-mediated events
42
Calcium gluconate Uses? Injected via?
In animals with symptomatic hypocalcemia (dietary supplemental therapy or injections)
43
Calcium gluconate Adverse Effects?
Hypercalcemia in animals with cardiac or renal diseases. Rapid IV injection can cause cardiac arrhythmias and arrest
44
Dihydrotachysterol (DHT): vitamin D2 analog MOA?
Mobilizing Ca++ from the bone, increasing intestinal absorption, reducing Ca++ loss in urine. Controlling phosphorus levels
45
Dihydrotachysterol (DHT): vitamin D2 analog Uses?
In small animals to treat hypocalcemia secondary to hypoparathyroidism or severe renal disease
46
Dihydrotachysterol (DHT): vitamin D2 analog Adverse Effects?
Hypercalcemia, nephrocalcinosis, and hyperphosphatemia
47
Calcitriol: vitamin D3 metabolite MOA?
Increasing plasma Ca++ and controlling phosphorus levels
48
Calcitriol: vitamin D3 metabolite Uses?
In small animals to treat hypocalcemia secondary to hypoparathyroidism or severe renal disease
49
Calcitriol: vitamin D3 metabolite Adverse Effects?
Hypercalcemia, nephrocalcinosis, and hyperphosphatemia but the duration of these effects is shorter than that of DHT
50
Within the Islets of Langerhans, alpha cells produce?
51
Within the Islets of Langerhans, beta cells produce?
52
Within the Islets of Langerhans, gamma cells produce?
Somatostatin
53
Insulin functions to?
▪ 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
How does insulin decrease blood glucose concentrations? ▪ Increasing ________ synthesis ▪ Increasing the uptake of ________ ______ and _________ synthesis ▪ Decreasing hepatic ___________ ▪ Decreasing ____________ ▪ Increasing glucose transport into _______ cells and ________ via activation and translocation of _____.
▪ 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
What is the difference between Type I and Type II Diabetes?
Type I = genetic Type II = elderly diabetes; beta cells are usually normal but insulin receptors are not functioning.
56
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 cytoplasm to membrane. Glut 4 protein channels become embedded into membrane allowing glucose to be transported into cells. In cases of insulin resistance, GLUT 4 levels are reduced which is why glucose can't enter the cells. GLUT 1 = glucose transporters constitutively expressed in low levels in endothelial levels and is important for stress.
57
1. Define hyperglycemia (aka?). 2. What is the most common cause? 3. What species, and which age group, are most commonly affected? 4. When is this condition usually diagnosed?
1. hypoinsulinemia 2. Diabetes mellitus is the most common cause. 3. It is seen most often in dogs and casts > 7 years old. Can affect also pigs, horses, and apes 4. Usually diagnosed at the late stage, when beta-cells have mostly been destroyed by severe hyperglycemia
58
Define hypoglycemia (aka?). What is the potetnail cause?
Hypoglycemia (hyperinsulinemia) may be caused by insulin overdose
59
What causes Diabetes Mellitus?
▪ Deficiency of insulin secretion from pancreas ▪ Decreased glucose uptake into cells ▪ Increase hepatic glucose production
60
What are the symptoms of Diabetes Mellitus?
▪ High blood glucose (hyperglycemia) ▪ Glucose in urine (glycosuria) ▪ Excessive excretion of urine (polyuria) ▪ Excessive thirst (polydipsia) ▪ Excessive hunger (polyphagia) ▪ Fatigue
61
Define Type I Diabetes Mellitus
▪ Irreversible loss of insulin secretion from pancreas ▪ Insulin dependence ▪ Usually permanent
62
Define Type II Diabetes Mellitus
▪ Impaired insulin secretion from pancreas ▪ Insulin resistance ▪ Diabetic remission is possible
63
Diabetes mellitus in dogs: 1. Which sex is commonly affected? 2. What ate group is commonly affected? 3. Is Type I or Type II more common in dogs? 4. What causes Diabetes mellitus to develop in dogs?
1. Females 2. Middle aged 3. Type I 4. Causes: Pancreatitis, Immune attack, Breed, Lifestyle factors
64
Explain diabetes mellitus in cats 1. Which sex is commonly affected? 2. What ate group is commonly affected? 3.Is Type I or Type II more common in cats? 4. What causes Diabetes mellitus to develop in catsw?
1. Males 2. Older age (geriatric disease) 3. > 80% Type II 4. Causes Pancreatitis, Pancreatic amyloidosis, Insulin resistance, andHigh blood glucose damages cells
65
How do you diagnose and treat DM in dogs and cats?
See below
66
Insulin is a protein consisting of how many amino acids?
51 amino acids (human is shown)
67
Insulin consists of how many peptide chains?
Insulin consists of two peptide chains (A: 21 aa) and (B: 30 aa) joined by disulfide linkages
68
What does the structure of insulin dictate?
The structure of insulin dictates its folding, shape, trafficking, and receptor binding
69
True or False: The amino acid sequence of insulin varies among species
True Recombinant space specific insulin is best ? Dogs have only 1 AA difference, cats have three. Different ?
70
Do we need to know?
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
72
What are the adverse effects of insulin treatment?
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
What are the adverse effects of insulin treatment?
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
Metformin is what type of drug?
oral antihyperglycemic but not hypoglycemic (does not stimulate insulin secretion) drug
75
Metformin MOA
▪ Decreasing glucose absorption from the GI tract ▪ Decreasing glucose output from the liver ▪ Increasing insulin receptor sensitivity
76
Metformin Uses
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
Metformin Adverse Effects
Vomiting, appetite loss, weight loss, and lethargy Not safe for use in cats with kidney insufficiency Drug-drug interaction Lactic acidosis (rare)

Pharmacology II (27 decks)

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