2nd Year Batch
PHARMACOLOGY
Lecture- 03 Endocrine System
By- Dr. Siraj Ahmad
Topics to be Covered
1 Growth Hormone Basics
2 GHRH and GHIH analogue
3 Uses and Side Effects of GH
4 GH antagonists
5 Osteoprosis Pharmacotherapy
Growth Hormone
HYPOTHALAMUS AND PITUITARY
Auntie somatotrophs
somatostali
Em Pathway
paustat
Bone
pg F1 Muscle
cartilage
Glucose
Gt Muscle
ORGANSG Bone
Adipocyte
HYPOTHALAMUS AND PITUITARY
0 Somatotroplus
GHIHSomatostatin
GHRH Glucose YPOGLYCEMiAMY
BONE Growth ossification
Ñ IGF 1
Growth
Cartilage
chondrocyticdifferentiation
G Ydegrowth length Bone
of
Act organs
HYPOTHALAMUS AND PITUITARY
0 Somatotroplus
GHIHSomatostatin
GHRH Glucose
YPOGYCEMiAYy
m
fi
BONE ciasticactivity Borman
IGF 1 1,8 angigt
differentiation
Cartilage chondrocyte
Length bone of
G Mu I
YueMsGrowth chondroblastic proliferation
so
Act organs HighAAin
Blood
Et
Eff 1
HYPOTHALAMUS AND PITUITARY
0 Somatotroplus
GHIHSomatostatin
GHRH Glucose MYPOGYCEMiAYy
mteo'clasticactivity
BONE
1 19at
1
Bowman
IGF 1
Cartilage chondrocyte
differentiation
Length bone
72
of
G I
MudeMsGrowth chondroblastic proliferation
so
Act organs ToMsGrowth Mass
Muscle AA Enlingintoms cell
Gluconeogenesis
Glycerol
[Link] iprotusis
Fattyauidtpautgose
HYPOTHALAMUS AND PITUITARY
hfl
Somatitti GHRH Bonetti
of
TRH ti
gain IGFs
[Link]
GA II ymfg
a [Link]
Act orga
mEttigrowth
Gonad THYROID
ii a
fi ff
Adipocytelipolysis511 ngoen
• GHRH → act at Anti pituitary → release GH (from somatotrophs)
of pituitary
• GH release stimulated by:
o High amino acid in blood
o Hypoglycemia
o Low fatty acid in blood
o Exercise
Sleep GH
• GH acts at certain target organ:
Januskinase
o Liver: interact with TK → activate JAK → activate STAT →
STAT binds to specific DNA sequence → translate mRNA
→ Protein formed (IGF-1) → released in circulation
o Bone
o Adipose tissue: lipolysis → Inc gluconeogenesis
EFFECT OF IGF-1
• IGF1 promote protein synthesis → act on muscle (inc AA
uptake in ms.) → Inc muscle size
• IGF1 at bone: inc O’blast and O’clast activity →
endochondral ossification → inc bone mass
• Inc collagen type 1 production
• IGF1 increases the cartilages size and proliferation of
chondroblast at diaphyseal plate → inc length
• At Glucose: Hypoglycemia
2024
1 GHRH Analogue
SOMARELIN t t Dwarfism
TESAMORELIN
to diagnose cause of Dwarfism
inj GHRHanalogue
inGH
GHlevel Noeffect NO
Ab TauseinTotHPaxis
Cause II axism
GH Resistance
Recomb GH
SOMATROPIN
child
Use small for age o
muscle man loss
Hiv induced
afw Glucose Hyperglycemia
sfe
3 Recomb IGF 1
MECASERMIN
GH is resistant
used if
small fur age child
Ht Dwarfism stunting
Sfe afwGlucose Hypoglycemia
GH Excess
GIGANTISM L ACROMEGALY
start Puberty
Onset child Manifest 15 20 yr
Hands finger size Thick stubby
more thanaverage fingers
Ht N
Protruding Jaw
Jaw protruding
Ht
secretion
Somatostatin Analogue GHIH
USE Prett in Ht Acromegaly Gigantism
OCTREOTIDE carcinoid synd
D
PASIREOTIDE Glucagonoma
LANREOTIDE sp gealvaricealbleed
Insulin
alsoavailable as DepotPrep Insulinoma
Deep Yan
other uses DOC DIAZOXIDE
I long the preff in
Acromegaly
In Secretary diarrhea
maintenancetherapy
Sfe of somatostatin Analogue
MC Mv B12deficiency Egan
Intrinsicfactor B12 absorption
soluble
Bile secretion Deficiency of fat [Link]
a
Cholelithiasis risk
GH
PEGVISOMANT
Acromegaly Gigantism
Use Resistantcasesof
Sf Nfv
visualfielddefect TumpChiasma
Pituitaryadenoma
Hemianopia
Bitemporal
R L
DA t
DA
t
GH Sle Mc Nv
Pleuro palm fibrosis
BROMOCRIPTINE
Pericardialfibrosis
CABERGOLINE Mcused
Ien she long Gangrene
PERGOLIDE DOA v60HRS Erythrometalgia
Red Tender Painfulswollen it
PRL
Use hyper Imgay
palkinsondisease
SIDE EFFECT OF GH
• Anti insulin → Hyperglycemia
o MECASERMIN- recomb IGF1 → Hypoglycemia
o MECASERMIN used if impaired GH receptor
• Inc risk of T2DM in child
• Intracranial HTN
• Scoliosis
MedianN
• Carpal tunnel syndrome Entrapment of
• Arthralgia, myalgia
OSTEOPOROSIS
OSTEOPOROSIS
WHO CRITERIA FOR OSTEOPOROSIS
DEXA Scan
Dual Energy
Category T-score
Ray
Normal -1.0 and above Absorptioneling
Low bone mass Between -1.0 to -2.5
(osteopenia)
Osteoporosis -2.5 and below
CLINICAL FEATURES
• No specific symptoms
• Called “silent disease” – progress without symptoms
• With disease progression-
o Back pain
o Loss of height
o Skeletal deformity (kyphoscoliosis)
o Fragility fractures
Osteoporosis Types
82
Hormone Regulators of Bone Mineral Homeostasis
is Vit D it PTH Act
[Link] .Act
via Intracellular
PO absorptionfrom
CYTOPLASMIC
intestine
cat [Link]
Boneresorption
scat Sr POG Isr Pou
dosing
dose intermittent
osteoblast RecombPTH Low
Depotsition
in Bone By
01haction
FBI
A CALCITONIN
O'CL and stimulate O'BL [Link]
srP04
Renal excretion of catd
POT
PT Gland
f
cat cat cat Hypercat
[Link] IN Activated on
BLRamIFm
um 0 m
Oice
Dental feftkfla
[Link] Bisphosphonates
BPN
CL DRONATE
PTHanalogue
SERM
DRUGS FOR OSTEOPOROSIS
1. Antiresorptive drugs 5. MAB
o Bisphosphonates Rank
o HRT/ SERMs
DIC
o Calcitonin DENOSUMAB
2. Bone anabolic drugs
o Teriparatide ABALOPARATIDE rPTH
6. Sclerostin Inhibitor
o Sodium fluoride
3. Dual action bone agents
o Strontium ranelate 7. Diuretics: Thiazides
4. Adjuvant therapy catRead
Loss cat
o Calcium supplements of
o Vit.D3 HYDROCHLORTHIAZIDE
CHLORTHALIDONE
Bisphosphonates
1st Gen: BPNs 2nd Gen: BPNs 3rd Gen: BPNs
Prototype
• ETIDRONATE • PAMIDRONATE • RISEDRONATE 1000x potent
• TILUDRONATE • ALENDRONATE • OXIDRONATE
• CLODRONATE • IBANDRONATE • NERIDRONATE
• ZOLEDRONATE
O'clastic apoptosis O'clast
MOA Mostpotent BPN
5000 potent
Bisphosphonate
• Inhibit osteoclast
o DOC for osteoporosis
o DOC for hypercalcemia of malignancy
o Paget’s disease, dec risk of vertebral and
nonvertebral fractures
o Drug induced osteoporosis: Alendronate
PK
absorbed Absorption interfered
I Meal
Orally
Given empty stomach
Distribution to bone othertissues
DO NOT BBB
long the weekly dosing preff
GERD mins
Risk of Maintain
upright posture 30 40 after
To 10 Adv dry water
Take drug orally ifullglassof
• Potency compared with Etidronate (least potent)
• Most potent: zoledronate: 5000 x
o Zoledronate a/w nephrotoxicity
• Risedronate 1000 x potent
• Alendronate, risedronate, ibandronate, and zoledronic
acid are approved for the prevention and treatment of
postmenopausal osteoporosis
Side Effect
Nfv irritation
Olt gastric esophageal
GERD risk
Nethrotoxicity
Hypocat
Osteomandibular necrosis
Jaw necrosis
Max I Zolendionate
Ho PUD pts HloEpilepsy
CI Renal failurepts
motility disorder
Esophageal
SERM
TO'BI activity O'd activity
RALOXIFENE
use Eft 1 Postmenopausal O'porosis
DVT
Sfe Risk of
Hot flushes
Risk Endometrial CA
TAMOXIFEN of
CALCITONIN
Bone resorption by to'll brush border
SALCATONIN
Of
Synthetic SalmanCalcitonin
100 20010 dose
Route SC nasal spray
O porosis
menopausal 5yr
for post
His reaction
Sfe Nfv
Nasal irritation Facialflushing
Tingling digits
in
Vitamin D Adjuvant therapy
• ↑ Intestinal Ca & phosphate absorption → promote bone
mineralization
• Suppresses Parathyroids & ↓bone resorption
• Vit D + Calcium → improve Ca balance in osteoporotic
females & elderly males
Active Calcitriol
2022
overdose v [Link] DEXAMETHASONE
of R
HYPERVITAMINOSIS cat absfromGIT
rPTH Analogue
TERIPARAIDE Bone anabolic activity
Low dose Intermittent dosing
ABALOPARATIDE
99 Oblasticactivity
BMD Bone Mineral Dority
Route SC 20
mg 1 vertebral Non vertebral risk
Abd Thigh
she
P
Headache
leg cramps
Risk BoneTumor osteosarcoma
New agents for osteoporosis
OOCLAST
STRONTIUM RANELATE: Dual action
O BLAST
Sfe DVT Thromboembolism
clin Not used
O'BL O'cL activation
DENOSUMAB: Rank L
she Mu
Routs AVN ofJaw
Turnover
GCT SuperBone
Use O porosis
PTH CA Delayeta
healing
Hypercat a w Infection risk
DENOSUMAB
• Potential Adverse Effects
o Atypical fragility fractures
o AVN of Jaw
É o Increased risk of infections (cellulitis, endocarditis)
o Suppression of bone turnover (delayed fracture healing)
ROMOSOZUMAB
Sclerostin Bone formation
MAB against
Bone breakdown
Sclerostin
lug 01131
Resting
Sclerostic
Produced by Osteocyte
ooo
STOP Boneformation
Summary
O'poon
I BPN
SERM Post menopausal
RATH BRIPARATIDE
Calcitonin Post menopausal Syr
Vit D cat
DENOSUMAB
MAB
YROMOSOZUMAB
Thank
You