LESSON 2: GLUCOCORTICOIDS & IMMUNOSUPPRESSANTS AGENTS

Question 1

are steroidal agent produced and released by the adrenal cortex

Answer 1

glucocorticoids

Question 2

2 glucocorticoids predominantly affect carbohydrate metabolism; this 2 are also important naturally occuring glucocoticoids

Answer 2

1. Cortisol
2. corticosterone

Question 3

Aldosterone, predominantly affect electrolyte and water metabolism

Answer 3

Mineralocorticoids

Question 4

Predominates in human beings, pigs, and dogs

Answer 4

cortisol

Question 5

Predominates in rabbit, mouse, and rat

Answer 5

corticosterones

Question 6

to the non-esterified steroid component and determines its glucocorticoid, an anti-inflammatory potency, and extents its duration of action

Answer 6

glucocorticoid base

Question 7

The ability of glucocorticoid formulation to suppress the hypothalamus-pituitary-adrenal axis (HPAA) is determined by:

Answer 7

● The dose
● Potency of the base, and
● Duration of the action of the formulation.

Question 7

one of the major adverse effects of the glucocorticoids therapy

Answer 7

secondary hypoadrenocorticism

Question 8

Therapeutic success with fewer side effects is possible with?

Answer 8

alternate-day therapy

Question 9

hypothalamus secretes _________, which is brought to the anterior pituitary through the
hypothalamus-pituitary portal system

Answer 9

corticotropin –releasing hormone (CRH)

Question 10

The ____ which are generally active during daytime (diurnal), have high blood
glucocorticoid concentration during the day, and low at night

Answer 10

DOG

Question 11

_____ which are active at night (nocturnal), show the reverse pattern

Answer 11

cat

Question 12

action, which may lead to increase glucose production from amino acid by way of gluconeogenesis, and to reduce the rate of incorporation of amino acid into proteins

Answer 12

hyperglycemic action

Question 13

Glucocorticoids in large amounts (hyperadrenocorticism or Cushing’s disease)
inevitably lead to :

Answer 13

1. polyuria- excretion of excessive volume of urine
2. polydipsia- excessive thirst

Question 14

Overdose of glucocorticoids may be leads to:

Answer 14

1. hypernatremia- retention of high sodium concen. in blood
2. hypokalemia- low cacium concen. in blood

Question 15

Glucocorticoids in use of physiological replacement therapy:

Answer 15

This is used in the treatment of:
1. hypoadrenocorticism (Addison’s disease)
2. In iatrogenic HPA axis suppression, and
3. Adrenalectromized patients.

Question 16

example of drugs with slow onset and intermediate duration are used for acute disease processes used for once-a-day therapy

Answer 16

● Triamcinolone acetonde
● Dexamethasone in propylene glycol

Question 17

drugs with short duration are used for
acute and chronic condition and for
alternate –day therapy.

Answer 17

Prednisolone
Prednisone
Methylprednisolone

Question 18

mimics diurnal cortisol production in most
animals; causes sodium retention
(not significant in dogs and cats)

Answer 18

Prednisolone

Question 19

Those with slow onset and long
duration are for skin and joints.

Answer 19

● Triamcinolone acetonide
● Methylprednisolone acetate

Question 20

Those with very rapid onset and short
duration are used in emergency
situation such as hemorrhagic-shock
and anaphylaxis. These are fast-acting
(within1 min) with short plasma
half-life (1-2 h), but are rather
expensive

Answer 20

● Hydrocortisone sodium succinate
● Hydrocortisone sodium
phosphate
● Prednisolone sodium succinate

Question 21

glucocorticoids used in anti-inflammatory and anti – allergic therapy;

Answer 21

This is commonly employed in:
a. Symptomatic therapy of pruritic dermatoses
b. Allergic pulmonary disease, and
c. Allergic gastroenteritis

Question 22

Immunosuppressive therapy (“immunosuppressive Agents “)
This use is designed for:

Answer 22

a. Immune mediated thrombocytopenia
b. Autoimmune hemolytic anemia
c. Systemic lupus erythematosus, and some forms of neoplasm

Question 23

Prednisolone (for induction )

Answer 23

2.2-6.6 mg/kg divided bid until effects

Question 24

Dexamethasone (for maintenance)

Answer 24

2-2.2 mg/kg every 2 days

Question 25

Prednisolone (for maintenance)

Answer 25

0.33-1.1 mg/kg

Question 26

This is employed in the condition such as chronic arthritis, hip dysplasia, etc. dosing may be intermittent or on alternate-day basis. Do not withdraw erratically, this may lead to pseudorheumatism

Answer 26

Chronic palliative therapy

Question 27

Proper weaning from long-term glucocorticoids therapy should be tedious and drawn out. Animals do not complain of minor aches and pains or of changes in mood. However, the following signs might suggest that further prolongation of the weaning process is necessary;

Answer 27

⮚ Dullness ⮚ Mental depression ⮚ Increase fatigability ⮚ Incoordination ⮚ Unthriftiness and weight loss ⮚ Diarrhea ⮚ Behavioural changes

Question 28

This compound has been found to suppress adrenal cortical activity in the dog, but it is less successful in other species. Rats and monkeys are unaffected. in goats caused atrophy of the cortex and transitory cytopathologic effects of adrenal cortical cells of calves

Answer 28

o,p’DDD

Question 29

Is (3, 3- bis p-aminophenyl butane). It inhibits 17 - ketosteroid production in human and dog

Answer 29

Amphenome B

Question 30

is very lipophilic and hydrophobic and must be solubilized before administration. It specifically inhibits T cells early in their immune response to antigenic and regulatory stimuli without affecting suppressor T cells

Answer 30

Cylosporin A

Question 31

Cylosporin binds with its cytoplasmic receptor protein

Answer 31

cyclophilin

Question 32

The resulting cylosporin – cylosphilin complex then binds with

Answer 32

calcineurin (a phosphatase)

Question 33

Unwanted effects of cylosporin is include:

Answer 33

⮚ Nephrotoxicity ⮚ Hepatotoxicity, and ⮚ Hypertension

Question 34

Less severe side effects are:

Answer 34

⮚ Anorexia ⮚ Hirsutism (in human) tremor ⮚ Paraesthesia, gum hypertrophy, and ⮚ Gastrointestinal disturbance.

Question 35

It is macrolide antibiotic with a very similar mechanism of action to cylosporin. The main difference is that its cytoplasmic receptor is not cyclophilin but protein called FK binding protein (FKBP)

Answer 35

Tacrolimus (a.k.a FK506)

Question 36

another macrolides, also binds with FKBP. However, the rampamycin-FKBP complex does not bind with calcinuerin nor does it effects IL-2 transcription. It interferes with signal transduction pathway blocking the cell cycle of activated T cells in G1 phase by inhibiting a novel kinase called mTOR

Answer 36

Rapamycin

Question 37

It is an alkylating agent with particular action on lymphocytes. As a immunosuppressant it effects the clonal proliferative phase of the immune response and reduce both antibody-mediated and cell-mediated immune reactions.

Answer 37

Cyclophosphamide

Question 37

It is another alkylating cytotoxic agent similar to cyclophosphamide

Answer 37

Chlorambucil

Question 38

It is used particularly for tissue rejection in transplant surgery. It is metabolized to mercaptopurine, a purine analogue that inhibits DNA synthesis. Both cell-mediated & antibody-mediated immune reactions, and are depressed by this drug since it inhibits clonal proliferation in the induction phase of the immune response by a cytotoxic reaction on dividing cells.

Answer 38

Azathioprine

Question 39

A semi-synthetic derivative of a fungal antibiotic, it is converted to mycophenolic acid, which restrains the proliferation of both B and tT lymphocytes and reduces the production of cytotoxic. T cells by inhibiting inosine monophosphate dehydrogenase. This pathway is essential for de novo purine synthesis B and T lymphocytes are particularly dependent on this enzyme

Answer 39

Mycophenolate mofetil

Question 40

in ring A, the double bond at _____ and keto group at ______ are essential for activity. Reduction of the double bond and the keto group result in loss of activity

Answer 40

c4 & c3

Question 41

enhances the glucocorticoid activity and decreases mineralocorticoid activity

Answer 41

double bond c1

Question 42

this 2 are present in ring b

Answer 42

1. a-fluorination at c9 2. a- methylation at c6

Question 43

this increases glucocorticoids & mineralacortiocids activity

Answer 43

a-fluorination at c9

Question 44

this enhances glucocorticoids effects

Answer 44

a-methylation at c6

Question 45

a glucocorticoid commonly use in clinical therapy, differs from cortisol only in having a keto- rather than B-hydroxyll group at c11

Answer 45

Cortisone

Question 46

Cortisone is inactive, but can be transformed to _______ in the liver.

Answer 46

cortisol

Question 47

It is not useful when administered topically or injected in ???

Answer 47

joint

Question 48

in ring d The OH group at C21 must be free for ??

Answer 48

biologcal activity

Question 49

______ markedly decreases mineralocorticoid effect

Answer 49

α - or β – methylation at C16

Question 50

________ also markedly decrease mineralocorticoids effect

Answer 50

α – hydroxylation at C16

Question 51

LONG ACTING DRUGS "

Answer 51

Paramethasone Betamethasone Dexamethasone

Question 52

this 2 glucocorticoid ester is rapid onset of action; for IV and IM route

Answer 52

1. Phosphates 2. Hemmisuccinate

Question 53

a glucocorticoid ester is poorly water soluble; used as depot

Answer 53

Acetonide

Question 54

this glucocorticoid ester is very long duration of action (weeks to mo

Answer 54

Pivalate

Question 55

this glucocorticod ester is slow absorption; available as depot; action last days duration

Answer 55

Acetate, diacetate, tebutate

Question 56

secretion of _______ by the anterior pituitary is episodic rather than continuous.

Answer 56

corticotropin

Question 57

In the normal animal, the blood glucocorticoid concentration varies with the ??

Answer 57

circadian rhythm

Question 58

Pharmacological Effects of Glucocorticoids

Answer 58

The pharmacological effects of glucocorticoids are produced by rather than high doses. When a clinician administers a glucocorticoid to a patient, effect other than those originally desired may also occur

Question 59

glucocorticoids cause ________ and _______ an effect secondary to cell redistribution and/or lysis, and lead to increase de-margination of neutrophils

Answer 59

lymphocytopenia & eosinopenia

Question 60

DNA-binding domain. The steroid-receptor complexes move into the nucleus and bind to steroid-response elements in the DNA. The effects is either to ??

Answer 60

1. repress- prevent transcription or 2. induce- initiate expression

Question 61

Effectively blocks cortisol production but not corticosterone production in young pig

Answer 61

Metyrapone