Pharmacology 1 Flashcards
What does AVP do to the distal convoluted tubules and collecting ducts?
Increases cAMP
What is the result of increased cAMP in the distal convoluted tubules and collecting ducts?
Enhances permeability to water and resorption
What does water resorption do to urine volume and osmolality?
It reduces urine volume and increases osmolality
True or False: AVP and it’s effects of water resorption should restore DI patients to normal
TRUE
Only if it is CENTRAL DI. Nephrogenic DI does not respond to Desmopressin (AVP)
What are 3 other things that AVP can do?
- Increase vasoconstriction
- ACTH and cortisol release
- Smooth muscle contraction (some in the gut too)
Will the receptors respond to desmopressin in nephrogenic DM?
NO…the receptors are mutated
What 3 effects of neurogenic diabetes insipidus will desmopressin help?
- Polyuria
- Polydypsia
- Dehydration
Because of the V1 effect desmopressin has, what is an AE of it?
Smooth muscle contractions (vasoconstrictions)
True or False: Desmopressin is a synthetic analog of AVP with a shorter duration of action
FALSE… longer duration of action
What type of administration is preferred for desmopressin?
Intranasal- Longer action and fewer AE
What are 2 uses for desmopressin other than diabetes insipidus?
- Nocturnal enuresis
- Bleeding with hemophilia A
- After pituitary surgery
What are 2 GH analogues?
- Somatotropin (GH)
2. Somatrem (GH with an extra methionine)
What are the 2 predominant causes of GH deficiency?
- Diseases of hypothalamus-hypophyseal regions
2. Crainopharyngiomas (mostly due to lack of releaseing factors)
In infants, what 2 things can GH deficiency result in?
Hypoglycemia and seizures
What 2 things can lead to a diagnosis of GH deficiency?
- Growth under 4cm per year
2. Absence of GH response to 2 secretagogues
What is one complication that can arise from GH treatments that requires monitoring?
Hypothyroidism
Also cardiac hypertrophy
What are 2 synthetic agonists of somatostatin receptors?
Octreotide and lanreotide
What are octreotide and lanreotide used for?
Reduce GH production in Acromegalics
What is a GH antagonist?
Pegvisomant
What is pegvisomant used for?
Acromegaly
How does GH normally work?
It binds to 2 dimers fo the GH receptor and both have to be brought in close proximity for the receptor to be activated
What does Pegvisomant due to the GH receptor?
It binds to one well, but has reduced affinity for the second site, thus allowing dimerization of the receptor, but blocking the conformational change required for signal transduction
What is DA?
A PRL-inhibiting factor (PIF)
What is a DA2 agonist that is used to lower PRL levels?
Bromocriptine (an ergot alkaloid)
What is the most common of pituitary cancers?
PRL-secreting adenomas
What is used as the initial treatment in PRL-secreting ademonas to reduce tumor size and PRL levels?
Bromocriptine
What is eventually required for PRL-secreting adenomas??
Surgery with or without radiation
What is seen in the ovaries of patient with Turners?
Absent or rudimentary ovaries
What is used to help with Turner’s Syndrome?
GH must be combined with gonadal steroids to achieve maximal height effect
What receptors are specific to the convulted tubule of the kidney?
V2
What drug has less V1 activity so it doesn’t increase vascular contraction or release of ACTH like vasopressin?
Desmopressin
True or False: Desmopressin has longer action than vasopressin for polyuria, polydypsia and dehydration with DI
TRUE
What 2 places are vasopressin receptors found?
Renal tubules and vascular smooth muscle
What receptors are on renal tubules?
V2
At the V2 receptors, what does AVP do?
Reduces urine volume and increases urine osmolarity (ANTI-DIURETIC HORMONE)
V2 receptors on Renal Tubules work through Gs receptor —> cAMP —> PKA. This will have a cellular and genomic effect that eventually leads to an increase in Aquaporins in the tubules –> Increased H20 Uptake)
At the V1 receptors, what does AVP do?
Increase vasoconstriction (AVP on V1 receptors work through the Gq system, so it would raise levels of PLC, PKC, IP3/DAG and Ca++ ultimately leading to smooth muscle contraction.)
V2 receptors on Renal Tubules work through Gs receptor —> cAMP –> PKA. This will have a cellular and genomic effect that eventually leads to an increase in Aquaporins in the tubules –> Increased H20 Uptake)
GH acts on membrane receptors via what pathway?
JAK-STAT
After a few hours, what are the effects of GH?
- Increase lipolysis
2. Decreased glucose uptake
What is released by GH from most tissues?
Somatomedins (insulin-like GF)
Mainly synthesized in the liver in response to GH.
What do somatomedins do?
Increase uptake of sulfate into cartilage and mediate bone growth
(also act in numerous tissues including cardiomyocytes)
Before the epiphyseal plates close, GH increases uptake of what 2 things into osteoblasts?
Thymidine (DNA)
Uridine (RNA
What is a complex of IGFs and the IGF-binding protein what is given in conditions where GH receptor isn’t function or Abs against GH?
Mecasermin
What is bromocriptine?
A synthetic dopamine agonist (ergot alkaloid)
What is bromocriptine used for?
A variety of hyperprolactinemia syndromes
- Infertility
- Acromegaly
- PRL-secreting pituitary tumors ***
What receptors does bromocriptine stimulate?
DA2 receptors (associated with psychosis)
What if an initial treatment for PRL-secreting adenomas (ammenorrhea-galactorhea) which reduces PRL effectively?
Bromocriptine
What is a more radical treatment for PRL-secreting Adenmoas?
Surgery or irradiation
True or False: Bromocriptime can be used alone or in combination with surgery or irradiation for acromegaly?
TRUE
45,X?
Turners Syndrome
True or False: Girls with Turners Syndrome have nomral growth hormone (GH) levels, they have reduced responsibeness to GH that often responds to supraphysiologic concentrations of the hormones?
TRUE
Where is vasopressin produced?
PVN, SON, Suprachiasmatic nucleus
along with Neurophysin II
Where is vasopressin released from?
Neruophypophysis, median eminance, lateral septal nucleus
What stimulates Vasopressin release ?
Hyperosmotic blood
What causes polyuria and polydipsia secondary to an inability to concentrate urine and retain free water?
Diabetes insipidus
Neurogenic DI versus Nephrogenic DI?
Neurogenic: Low AVP secretion
Nephrogenic: Renal insensitivity
What 3 things can be used for SIADH?
- Perfused hypertonic saline plus furosemide
- Conivaptan (AVP antagonist) - For hyponatremia
- Tolvaptan- Oral
How does GH act?
Indirect anabolic effects through somatomedins
What is a condition where GH levels are too high for a long time?
Acromegaly
What can acromegaly cause?
Frequent CV problems including CAD, ventricular arrhythmias, and CHF (cardiac hypertrophy?)
What are 3 things prolactin is involved in?
- Maternal and sexual behaviors
- Induced mitogenesis in lymphocytes
- Necessary for milk production in lactating mammals
What inhibits PRL release?
Dopamine (major catecholamine in brain of tuberoinfundibular origin)
So what is DA?
PRL-inhibitng factor
Bromocriptine stimulates GH in normal people, but does what in acromegalics?
Suppresses GH