Endocrine Drugs

Front 1

8 Steps in Thyroid Hormone Synthesis

Back 1

1. Iodide Uptake

2. Oxidation

3. Iodination (Organification)

4. Coupling (Conjugation)

5. Formation of T4 and T3 from iodothyronine

6. Secretion of hormones (proteolysis of thyroglobulin)

7. I2 recycling within the thyroid cell via deiodination of MIT and DIT

8. Conversion of T4 to T3 in peripheral tissues

Hint 1

U

O

I

C

F

S

I R

C

Front 2

Iodine in the circulation:

95% __________

Thyroxine = _____%

Triiodothyronine = ____%

5% __________

Back 2

Iodine in the circulation:

95% ORGANIC IODIDE

Thyroxine = 90-95 %

Triiodothyronine = 5 %

5% IODIDE

Front 3

Volume of distribution T4 ___ T3

(>) or (<)

Back 3

T4 (10L) < T3 (40L)

Front 4

Daily Production T4 ___ T3(>) or (<)

Back 4

T4 (75 ug) > T3 (25ug)

Front 5

Metabolic Clearance T4 ___ T3(>) or (<)

Back 5

T4 (1.1L) < T3 (24L)

Front 6

Biologic Half-Life T4 ___ T3(>) or (<)

Back 6

T4 (7days) > T3 (1day)

Front 7

Amount Bound T4 ___ T3(>) or (<)

Back 7

T4 (99.96%) > T3 (99.6%)

Front 8

Amount Free T4 ___ T3(>) or (<)

Back 8

T4 (0.04%) < T3 (0.4%)

Front 9

Biologic Potency T4 ___ T3(>) or (<)

Back 9

T4 (1) < T3 (4)

Front 10

Oral Absorption T4 ___ T3(>) or (<)

Back 10

T4 (80%) < T3 (95%)

Front 11

Major Route of Elimination of thyroid hormones

1. ___

2. ___

Back 11

1. Metabolism = deiodination to either T3 or Reverse T3

2. Liver = Main site of non-deiodinative degradation of thyroid hormones

Hint 11

1. Deiodination

2. Non-Deiodinative Degradation

Front 12

Thyroid Hormone Carriers

1. T_______

2. T______

3. A_____

4. A____

Back 12

Thyroid Hormone Carriers

1. Thyroxine Binding globulin
2. Transthyretin
3. Albumin
4. Apolipoproteins

Front 13

Thyroxine Binding to TBG

Increase or Decrease?

Liver Disease

Back 13

Increases Binding

Front 14

Thyroxine Binding to TBG

Increase or Decrease?

HIV Infection

Back 14

Increases Binding

Front 15

Thyroxine Binding to TBG

Increase or Decrease?

Pregnancy

Back 15

Increases Binding

Front 16

Thyroxine Binding to TBG

Increase or Decrease?

Acute or Chronic Illness

Back 16

Decreases Binding

Front 17

Thyroxine Binding to TBG

Increase or Decrease?

Nephrotic Syndrome

Back 17

Decreases Binding

Front 18

Thyroxine Binding to TBG

Increase or Decrease?

Chronic Renal Failure

Back 18

Decreases Binding

Front 19

Thyroxine Binding to TBG

Increase or Decrease?

Malnutrition

Back 19

Decreases Binding

Front 20

Thyroxine Binding to TBG

Increase or Decrease?

Severe Systemic Illness

Back 20

Decreases Binding

Front 21

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

PITUITARY

Back 21

RESPONSIVE

Front 22

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

LIVER

Back 22

RESPONSIVE

Front 23

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

KIDNEY

Back 23

RESPONSIVE

Front 24

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

HEART

Back 24

RESPONSIVE

Front 25

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

SKELETAL MUSCLE

Back 25

RESPONSIVE

Front 26

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

LUNG

Back 26

RESPONSIVE

Front 27

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

INTESTINES

Back 27

RESPONSIVE

Front 28

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

BRAIN

Back 28

INTERMEDIATE

Front 29

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

SPLEEN

Back 29

NON-RESPONSIVE

Front 30

Thyroid Hormone Tissue Responsiveness

(Responsive, Intermediate or Non-Responsive?)

TESTES

Back 30

NON-RESPONSIVE

Front 31

THYROID HORMONE INDICATIONS

1. H___

2. S___ G____

3.T___ C___

Back 31

1. Hypothyroidism = replacement of thyroid hormones

2. Simple Goiter = Suppression and replacement if with concomitant hypothyroidism

3. Thyroid Cancer = suppression and replacement after thyroidectomy and radioactive iodine ablation

Front 32

Synthetic Thyroid Preparations

1.__ T4

2.__ T3

3.__ T3 AND T4

Back 32

Levothyroxine = T4

Liothyronine = T3

Liotrix = T3 and T4

Hint 32

T4

T3

T3 and T4

Front 33

Organ/s where Levothyroxine is absorbed?

Back 33

Stomach and Small Intestine (80%)

Front 34

Condition where Levothyroxine is best absorbed?

Back 34

Empty Stomach

Serum T4 peaks at 2-4 hours after ingestion, Plasma half life 7days

Front 35

Levothyroxine is the preparation of choice for replacement therapy because it is:

1. S

2. U

3. L___A

4. C

5. L

Back 35

1. Stable

2. Uniform Content

3. Lack Allergic foreign protein

4. Can easily be monitored

5. Long Half Life

Front 36

L-Thyroxine is the most expensice among the three with the shortest half life?

True or False

Back 36

FALSE

L- Thyroxine is the cheapest among the three with the longest half life

Front 37

Shelf Life of these hormones is 4 years stored in Dark bottles

True or False

Back 37

FALSE

Shelf Life of these hormones is 2 years stored in Dark bottles

Front 38

Liothyronine oral absorption is almost ____%, peaks in ___ to __ hours, plasma half life 0.75 days or 18 hours

Back 38

Liothyronine oral absorption is almost 100%, peaks in 2 to 4 hours, plasma half life 0.75 days or 18 hours

Front 39

Liothyronine is used for treatment of _________ for rapid reversal of symptoms

Back 39

MYXEDEMA COMA

Front 40

Liothyronine is used in preparation for R_____ I____ A____ because of it's ____ half life

Back 40

Liothyronine is used in preparation for Radioactive Iodine Ablation because of it's short half life

Front 41

Adverse Effect of Liotrix?

Back 41

CARDIOTOXIC

Front 42

What are the Natural Hormone Extracts?

1. __

2. __

Back 42

Dessicated THyroid

Thyroglobulin

Front 43

Natural Hormone Extracts are no longer recommended nor justified for the Tx of Hypothyroidism because:

1. U

2. V

3. P

4. C

5. S

Back 43

1. UNSTABLE

2. VARIABLE HORMONE CONCENTRATIONS

3. PROTEIN ANTIGENICETY

4. CANNOT BE EASILY MONITORED

5. SIGNIFICANT AMOUNTS OF T3 (= greater toxicity)

Front 44

Clinical Indications for Anti-Thyroid and Thyroid Inhibitor Drugs

1. C

2. T

3. R

Back 44

1. Control Hyperthyroidism

2. Thyroid Cancer with the use of radioactive iodine

3. Render patients euthyroid prior to thyroidectomy

Front 45

Thioamides

1.

2.

3.

Back 45

1. Propylthiouracil = PTU

2. Methimazole

3. Carbimazole = Converted to Methimazole after absorption

Front 46

MOA of Thioamides?

1. O

2. C

Back 46

Prevent Hormone Synthesis by:

1. Block Iodide Organification through inhibition of thyroid peroxidase catalyzed reactions

2. Block Coupling or Conjugation of iodothyronines also by inhibition of TPO enzyme

Front 47

Relative Potency

PTU __ Methimazole

(>) or (<)

Back 47

Relative Potency

PTU (1) < Methimazole(10)

Front 48

Absorption Rate

PTU __ Methimazole

(>) or (<)

Back 48

Absorption Rate

PTU (RAPID) > Methimazole (Variable)

Front 49

Volume of Distribution

PTU __ Methimazole

(>) or (<)

Back 49

Volume of Distribution

PTU (20L) < Methimazole (40L)

Front 50

Bioavailability

PTU __ Methimazole

(>) or (<)

Back 50

Bioavailability

PTU (50-80% due to incomplete absorption or hepatic 1st pass effect) < Methimazole

Front 51

Protein Binding

PTU __ Methimazole

(>) or (<)

Back 51

Protein Binding

PTU (75%) > Methimazole(Nil)

Front 52

Plasma Half Life

PTU __ Methimazole

(>) or (<)

Back 52

Plasma Half Life

PTU (1.5 hrs) < Methimazole (4-6hrs)

Front 53

Dose (ease of dosing)

PTU _ Methimazole

(>) or (<)

Back 53

Dose (ease of dosing)

PTU (100mg / 6hrs) < Methimazole (30-40mg / once a day)

Front 54

Dose Response (Speed)

PTU _ Methimazole

(>) or (<)

Back 54

Dose Response (Speed)

PTU (Rapid = brings down activated thyroid levels faster due to inhibition of T4 -> T3 conversion) > Methimazole (Slower)

Front 55

Pregnancy (Both Category D)

PTU _ Methimazole

(>) or (<)

Back 55

Pregnancy (Both Category D)

PTU (preferred as its strong protein binding prevents ready crossing of placenta) > Methimazole

Front 56

Levels in Breastmilk

PTU _ Methimazole

Back 56

Levels in Breastmilk

PTU = Methimazole

Front 57

Adverse Reactions (Thioamides)

Most common:

___

Back 57

Mild Urticarial Papular Rash

Front 58

Adverse Reactions (Thioamides)

Less frequent:

___

Back 58

Joint pain, stiffness, paresthesias, nausea, headache, skin pigmentation, hair loss

Front 59

Adverse Reactions (Thioamides)

Rare:

____

PTU common: H___ and A___

Back 59

Drug fever, Nephritis

PTU common: Hepatitis, ANCA (+) vasculitis (50% of cases)

Front 60

Adverse Reactions (Thioamides)

Most Serious Reaction:

___

Back 60

AGRANULOCYTOSIS (with fever and sore throat)

Front 61

Iodides MOA?

1. O___ and H___

2. D

Back 61

1. Inhibits Organification and Hormone Release through possible inhibition of thyroglobulin proteolysis. Effects seen in 2-7 days

2. Decreases the size and vascularity of the hyperplastic gland in prep for Sx

Front 62

Iodide Indications

1. T__

2. P__

3. P__

Back 62

1. Thyroid storm to immediately block release of thyroid hormones from the gland

2. Pre-op for thyroid Sx

3. Protection of thyroid gland against fallout Nuke Accident

Front 63

Iodide Toxicity?

A

R

C

B

A

P

M

S

Back 63

Acneiform Rash,

Rhinorrhea,

Conjunctivitis,

Bleeding Tendencies,

Anaphylactoid Rxns,

Polyarteritis nodosa,

Mucosal Ulcers, and

Swollen Salivary Glands

Front 64

Radioactive Iodine MOA

Back 64

Destruction of the Thyroid Gland

(After oral admin, it's rapidly absorbed, concentrated by the thyroid and incorporated into storage follicles. Destruction of thyroid parenchyma occurred within 6-12 wks)

Front 65

Radioactive Iodine Advantages

1. S

2. N

3. A

4. R

5. H

6. P

Back 65

1. Safe

2. No tissue other than thyroid is exposed to sufficient ionizing radiation

3. Absence of Pain

4. Relatively Cheaper

5. Hospitalization not required (except: Thyroid CA, Big Toxic Goiter req higher doses)

6. Patients can indulge in customary activities during procedure

Front 66

Radioactive Iodine Disadvantages

1. H

2. L

3. P

4. C

Back 66

1. High incidence of delayed hypothyroidism

2. Longer period of time req before hyperthyroidism is controlled

3. Pregnancy is restricted for 6 mos after procedure

4. Crosses placenta to destroy fetal thyroid

Front 67

Radioactive Iodide Indications

1. A

2. D

3. P_F_

4. P_A_

5. P_R_

6. A

Back 67

1. All px above 21 yrs not pregnant or breast feeding

2. Debilitated, Cardiac or Elderly Px with Hyperthyroid poor Sx risk

3. Px Failing to respond to drug therapy

4. Px with ADR with anti thyroid drugs

5. Px with Recurrence after Thyroid Sx

6. Ablating thyroid remnant post-op in Thyroid CA

Front 68

Adjunct Drugs

1. B

2. L

3. P

Back 68

1. Beta Blockers (Propanolol)

2. Lithium

3. Prednisone

Front 69

Beta Blocker (propanolol) MOA for thyroid

B

B

P

A

Back 69

Block peripheral effects of thyroid hormone

Block peripheral conv of T4 -> T3

Pre-op for Thyroid Sx

Adjuct Tx for thyroid Storm

Front 70

Lithium MOA for thyroid

B

L

Back 70

Blocks Conv of T4 -> T3

Last Resort alternative to iodides and thioamides when CI

Front 71

Prednisone MOA for thyroid

B

A

M

Back 71

Blocks conv of T4-> T3

Anti-Inflamm for thyroiditis cases

MAY be useful in Thyroid Storm, Myxedema Coma and Opthalmopathy in Grave's Dx