Endocrine Med Chem Osteoporosis Agents Flashcards
Selective Estrogen Receptor Modulators (SERMs) such as Raloxifene has ___ activity at the ___.
A. Antagonistic, Bone
B. Agonistic, Bone
C. Agonistic, Breast
D. Agonistic, Uterus
B. Agonistic, Bone
In the SERM Raloxifene Hydrochloride (Evista) the boxed group is known as a ____.
A. Indole
B. Thiol
C. Thiophene
D. Benziol
C. Thiophene
If you include the benzne ring structure on the left it is known as a Benzothiophene.
Also know that the benzothiophene ring mimics the estrogen A ring
All of the following statemtns regarding SERMs are true EXCEPT:
A. Decent oral absorption
B. Undergoes extensive phase II metabolism
C. Substrate for P-glycoprotein
D. Increases risk of VTE
E. Has high bioavailability
E. Has high bioavailability
The SERM medications have decent oral absorption but terrible bioavailability due to being a substrate for PgP and undergoing extensive Phase II metabolism.
The picture provided shows the metabolism of the SERM medication Raloxifene. What type of metabolism is occuring here?
A. Hydroxylation
B. Reduction
C. Sulfation
D. Glucuronidation
D. Glucuronidation
The red structures that are added are glucose groups so glucuronidation is occuring in this molecule. Also remember that SERMs undergo extensive phase II metabolism and glucuronidation is a phase II reaction.
Also know that ANY exposed OH group can be glucuronidated
The boxed structure in the SERM medication Bazedoxifene is known as a(n)___.
A. Indole
B. Nitrothiophene
C. Pyrazine
D. Nitrobenzene
A. Indole
Bisphosphonate medications resemble the natural substance ____ in the body.
A. Phosphokinase
B. Phosphofuroate
C. Pyrophosphate
D. Furophosphate
C. Pyrophosphate
The following picture shows the similarity of bisphosphonate medications to pyrophosphate.
When comparing the structure of natural Pyrophosphate with the structure of bisphosphonate what is the purpose of substituting the Oxygen atom with the Carbon atom?
A. The carbon atom will allow the medication to be hydrolyzed more easily to an active form
B. The carbon atom will prevent the medication from being hydrolyzed to an inactive form
C. The carbon atom will allow the medication to be more succeptible to oxidation
D. None of the above
B. The carbon atom will prevent the medication from being hydrolyzed to an inactive form
Bisphosphonates have selective binding to the ____ portion of the bone.
A. Hyaluronate
B. Hydroxyapatite
C. Hydroxyperitol
D. Hydroxyperitite
B. Hydroxyapatite
What is the name of the boxed groups found in Pyrophosphate and Bisphosphonate structures?
A. Pyrophosphate
B. Phosphate
C. Phostrioxyl
D. Phosphonate
D. Phosphonate
Bis-Two
Phosphonate=Phosphonate groups
Bisphosphonate=Two Phosphonate groups
T/F
Non-Nitrogen containing Bisphosphonates will inhibit the mevalonate pathway and Nitrogen-containing Bisphosphonates will inhibit ATP-depending enzymes
F
Which of the following statements is true regarding Bisphosphonates? (Select All)
A. Bisphosphonate moiety (two phosphonate groups) is essential for activity
B. Phosphonate groups can be stubstituted for other negatively charged groups but will have slightly less activity
C. R1 group is always an OH group
D. R2 groups that contain an Amino-substituted group are generally less potent than non-amino R2 groups
E. R2 groups containing an Amino-substituted group are generally more potent than Non-amino containing groups
A, C, E
Of the Bisphosphonates shown here which is the LEAST potent?
A. Alendronate
B. Zoledronic Acid
C. Ibandronate Sodium
D. Risedronate
A. Alendronate
It contains an R2 amino group like the others however the others have alkyl groups attached to them, making them more potent than alendronate.
When comparing the structures of Alendronate and Zoledronic Acid, the additional alkyl groups of the amine (nitrogen) group on zoledronic acid ____ potency of the medication.
A. Increases
B. Decreases
A. Increases
Alkylation (addition of alkyl or methyl groups) of the amino groups in bisphosphonates will increase potency of the medication in comparison to bisphosphonates without alkyl substituted amino groups.
Which of the following is NOT a counseling point of Bisphosphonates?
A. Take in the morning before breakfast (empty stomach) with full glass of water
B. Remain upright for at least 30 min after taking
C. Preferrably take with calcium or other metal ion-containing substances in order to increase absorption
D. Can cause esophagitis
E. Can cause Osteonecrosis
C. Preferrably take with calcium or other metal ion-containing substances in order to increase absorption
Bisphosphonates have negatively charged phosphonate groups that will chelate and bind to positively charged metal ions such as calcium and iron and thus should not be given with the medication.
What is the benefit of taking Calcitonin Salmon over normal Human Calcitonin?
A. Less toxicity is associated with Calcitonin Salmon
B. Calcitonin Salmon utilizes a different mechanism in the body that is more efficacious than human calcitonin
C. Uses different amino acid sequences that give it greater affinity to calcitonin receptors and increased half-life
D. All of the above
C. Uses different amino acid sequences that give it greater affinity to calcitonin receptors and increased half-life
