20 Hypothalamic pituitary pharmacology Flashcards
What is the receptor for Growth hormone? What are the 3 main effects of growth hormones?
Tyrosine kinase GH receptor (requires dimerization to activate the following actions)
Effects
- Lipolysis at adipocytes
- Induce IGF-1 from liver
- Anabolic effect on skeletal muscle and on cartilage at epiphyses of long bone (longitudinal growth)
V1, V3 receptors and oxytocin also belongs to the G__ pathway and activates the subsequent messengers _____________.
Gq pathway: PLC > IP3 > Ca2+ pathway
How is oxytocin administered during parturition?
Slow IV infusion.
- regular coordinated contractions
- dose related to increase of amplitude and frequency of contraction
- large dose: increased frequency with incomplete relaxation
- very large dose: sustained contractions interfering blood flow
Give the 2 main recombinant GH preparations for GH deficiency.
How are they administered?
- Somatropin: identical sequence as GH
- Somatrem (extra methionine)
Daily subcutaneous administration in the evening
What is the possible drug interactions of recombinant GH preparations for GH deficiency?
Cytochrome P450 enzyme induction may cause increased metabolism of corticosteroids, sex steroids and anticonvulsant
Recombinant GH preparations is for treating short stature due to Turner’s syndrome and GH deficiency. It is also used in treating GH deficiency in adults and AIDS-related wasting problems. What is the main use for synthetic human GHRH preparations?
Give the 2 common examples of these preparation.
Use to diagnosis of pituitary GH secretory capacity (check whether is it due to the defect)
For those that is not due to defects of anterior pituitary
- GHRH
- Sermorelin: specific agonist of GHRH receptors
Other than recombinant GH preparations and synthetic human GHRH preparations, synthetic human IGF-1 is also used in treating GH deficiency in a long term for children with growth failure. Give the name of the drug and way of administration.
Mecasermin - agonist of IGF-1 receptor
subcutaneous, twice daily
What is octreotide?
What is it used for?
How is it administered?
It is a somatostatin analogue. It can be used to treat GH excess.
It is administered subcutaneously.
(It is 40X more potent than SST in suppressing GH release but only 2X in reducing insulin release)
Which of the following is false about octreotide?
A. It is a somatostatin analogue
B. Its action is to affect the synthesis of GH so as to reduce the levels of GH
C. It can reduce symptoms of gastroenteropancreatic endocrine tumours
D. It can control bleeding esophageal varices
B
Synthesis of GH is not affected, but the timing and amplitude of GH release!
C: potent inhibitory effect on the release of peptides of gastroenteropancreatic endocrine system
D: inhibition of vasodilatory hormones, indirectly causes splanchnic vasoconstriction and decreases portal blood flow
Give an example of GH-receptor antagonist.
Pegvisomant
(derived from modified hGH)
- as binding to receptor requires dimerization, it binds to receptor at one side and prevent GH binding
- no effect in reducing tumour size
What class of drug do bromocriptine, cabergoline,pergolide and quinagolide belongs to? which of the above is "different" from the other two?
Dopamine D2 receptor agonists.
Quinagolide is a non-ergot while the others are ergot derivatives
Which of the following about bromocriptine is correct?
A. It is a dopamine D2 antagonist
B. Side effects include nausea, dizziness, postural hypotension and fatigue
C. It is used to treat hyperprolactinemia
D. It works by activating the Gi protein to reduce AC
E. it can be combined with cabergoline for intravaginal route
All except A
should be dopamine D2 agonist
C: dopamine is a prolactin inhibiting factor
Give 2 drugs that can be used in diabetes insipidus.
- Vasopressin
2. Desmopressin (V2 selective agonists)
Which of the following is false about desmopressin?
A. It is a V2 selective agonist
B. It can be used to treat mild hemophilia and von Willebrand’s disease
C. It can be used in patients for minor surgery e.g. tooth extraction
D. It is administered orally
E. It does not work in patients with severe clotting factor deficiency
D.
It is administered subcutaneously / intranasal
***It is for treating DI mainly
Name the 2 drugs used in bleeding esophageal varices.
- Vasopressin
2. Terlipressin (V1 selective analogue)
What is the drug class of Terlipressin? What is its relationship with vasopressin?
V1 selective analogue.
It is converted to lysine vasopressin after IV jection
What are the 2 main effects of vasopressin and terlipressin to control bleeding esophageal varices?
- directly constricts mesenteric arterioles and reduce portal flow
- Reduce portal pressure and control varcieal bleeding episodes
- it may increase mortality rate due to vasoconstriction of other organs
- concomitant nitroglycerin alleviates some vasoconstriction (between than vasopressin alone)
It is the drug class of Syntocinon? What are its major effects?
oxytocin
- increases uterine contraction ,reduces fetal blood supply, increase fetal heart rate
Which of the following is true about oxytocin?
A. It is used to control postpartum bleeding
B. Management of incomplete, missed or inevitable abortion (high dose)
C. Augmentation of dys functional labour
D. induction of labour by slow IV
E. Water retention is not one of the side effects
All except E
E: side effects occur at high doses
- Occur at high doses
- Transient but serious hypotension with tachycardia
- Water retention (weak ADH action) : water intoxication
- Sustained uterine contraction and interference of placental blood flow (umbilical vessel constriction)
- Damage to fetus or mother
Ergot alkaloids like Ergometrine is also used in labour. What are there main effects?
What is the precaution of using it?
- Postent uterotonic effects (a1 adrenoceptors and 5-HT receptors)
- Moderate vasoconstriction
- Control postpartum bleeding
- Promote uterine involution when delayed
- should not be given prior to delivery
- it can be given in oral, IV, IM routes
What drug class do Dinoprostone, Carboprost, and Misoprostol + gemeprost belong to?
They are prostaglandins (E and F)
Dinoprostone: PGE2
Misoprostol + gemeprost: PGE1 analogue
What are the major effects of prostaglandins in labour?
- Cervical ripening: increase the compliance of cervix
- Uterine contraction
- Induction of labour (dinoprostone)
- Treat postpartum hemorrhage (caboprost)
- First trimester abortion (gemeprost/ misoprostol)
- Second trimester abortion: dinoprostone (vaginal gel)
