Assignment of Pharmacology

Topic: Corticosteroids
Submitted to: Miss Saima Hanif
Submitted by: Mubeen-Ul-Hassan
Roll # 208-P-365
Page # 1
Drug Catagory Drug Name Introduction Machanism of
action
Effects of drug Pharmacokinetics Clinical uses Adverse effect Withdrawl
A
D
R
E
N
O
C
O
R
T
I
C
O
S
T
E
R
O
I
D
S
Examples of
Drugs
Beclomethasone
Betamethasone
Cortisone
Dexamethasone
Hydrocortisone
Prednisone
Prednisolone
Triamcinolone
Fludrocortisone
Methyl
prednisolone
Desoxycorticost-
erone
Adrenal gland
consists of cortex
and medulla.
Medulla secretes
epinephrine &
cortex secretes
two major classes
of steroid
hormones
adrenocorticoster-
iod & adrenal
adrogens.
Adrenocorticoster-
iod consist of
glucocorticosteroid
& mineralocortic-
oids
Binds to specific
intracellular
cytomplasmic
receptors in target
tissues.
Receptor hormone
complex
translocates into
nucleus.
Attaches to gene
promoter elements.
Act as
transcription factor
to turn gene on or
off.
Absorption & fate
Corti costeriods are
metabolized by liver
microsomal
oxidizing enzymes.
Metabolites are
conjugated to
glucoronic acid or
sulfate, and product
are excreted by the
kidney.
Dose:
In determining the
dose of
adrenalcortico
steroids, many
factors need to be
consider as duration
of action type of
preparation and time
of day when steroid
is administrated.
1) Replacement
therapy for
primary
adrenocortical
insufficiency
(Addison's
disease)
This disease is
caused by adernal
cortex dysfunction
eg: Hydrocortis-
one is identical to
natural cortisol
and given to
correct defficiency
2) Replacement
therapy
secondary or
teriary
adrenocortical
insufficiency
Caused by a defect
either in CRH
production by the
hypothalamus or
Osteoporosis
Inhibit bone
formation
Decrease sex
hormone
synthesis
Cushing like
snydrome
Puffy face
Increased body
Hair growth
Acne
Insomnia
Increased epitite
Hyperglycemia
lead to diabated
mellitus
Hypokalemia
Abrupt
removal of
corticosteroids
cause an acute
adrenal
insufficiency
syndrome that
can be lethal.
Psychologic
dependence on
the drug.
Withdrawl
might cause an
exacerbation of
disease.
Page # 2
Drug Catagory Drug
Name
Introduction Machanism
of action
Effects of
drug
Pharmacokinetics Clinical uses Adverse
effect
Withdrawl
A
D
R
E
N
O
C
O
R
T
I
C
O
S
T
E
R
O
I
D
S
in corticotropin production by the pituitary. eg: Hydrocortisone is
used for these defficiencies.
3) Diagnosis of cushing's syndrome
Caused by a hypersecretion of glucocorticosteroids that result
either from excessive from realease of corticotropin by anterior
pituitary or an adrenal tumor eg: Dexamethasone supression test
used to diagnose cushing's syndrome.
4) Replacement therapy for congenital adrenal hyperplasia
Group of diseases resulting from an enzyme defect in the synthesis
of adrenal steroid harmone. eg: Corticosteroids are given to
normalize the harmone level.
5) Relief of inflamanary symptoms
Glucocorticoids reduce the manifestations of inflammation.
6) Treatment of allergies:
Glucocorticoids are beneficial in the treatment of allergies. eg:
asthma, allergic rhinits.
7) Acceleration of lung maturation
Fetal cortesol is a regulator of lung maturation. eg: beclomethasone
is given I/M to mother 48 hrs prior to birth and 2nd dose 24 hrs
before delivery.
Page # 3
Drug Catagory Drug Name Introduction Machanism of
action
Effects of drug Pharmacokinetics Clinical uses Adverse effect Withdrawl
G
L
U
C
O
C
O
R
T
I
C
O
I
D
S
AND THEIR
A
G
O
N
I
S
T
Cortisol is the
principle human
glucocorticioid. It
has important
effect on
intermediary
metabolism,
catabolism,
immune responses
and inflammation.
Binds to specific
intracellular
cytomplasmic
receptors in
target tissues.
Receptor hormone
complex
translocates into
nucleus.
Attaches to gene
promoter
elements.
Act as
transcription
factor to turn
gene on or off.
1) Promote
normal
intermediary
metabolism
Favor gluc-
oneogenesis
through
increasing
aminoacid
uptake by
liver and
kidney.
Stimulate
catabolism
and lipolysis.
Increasing in
activity of
hormone
sensitivity
lipase.
2) Increase
resistance to
stress
By raising
plasma
glucose level
to combat
stress.
Absorption and
fate:
Synthetic
glucocorticoid
preperation some of
which are given
orally & readily
absorbed in GIT.
Selected are
administered I/V,
I/M, intrarticutarlly,
topically or as
aerosole for
inhalation.
90% of absorbed
glucocorticoids
are bound to
plasma proteins.
Prednisone
(Prodrug) only
glucocorticoids
which has no
effect on fetus in
pregnancy.
Osteoporosis
Inhibit bone
formation
Decrease sex
hormone
synthesis
Cushing like
snydrome
Puffy face
Increased body
Hair growth
Acne
Insomnia
Increased epitite
Hyperglycemia
lead to diabated
mellitus
Hypokalemia
Abrupt
removal of
corticosteroids
cause an acute
adrenal
insufficiency
syndrome that
can be lethal.
Psychologic
dependence on
the drug.
Withdrawl
might cause an
exacerbation of
disease.
Page # 4
Drug
Catagory
Drug
Name
Introdu-
ction
Machanism
of action
Effects of drug Pharm-
acokinetics
Clinical
uses
Adverse
effect
Withdrawl
G
L
U
C
O
C
O
R
T
I
C
O
I
D
S
AND
THEIR
A
G
O
N
I
S
T
3) After blood cell level in plasma
Glucocorticoid cause a decrease in eosinophils, monocytes, basophils
and lymphocytes by redistributing them from the circulation to lymphoid
tissue.
4) Have anti inflammatory action
Glucocorticoid has the ability to reduce the inflammatory response & to
supress immunity.
5) Effect other component of the endocrine system
Feedback i nhi bi ti on of cort i cot ropin product ion by el evat ed
glucocorticoid causes inhibition further glucocorticoid synthesis and
production of thyroid stimulating hormone and increase production of
growth hormone.
6) Can have effect on other systems
High doses of glucocorticosteroid stimulate gestric acid and pepsin
production & exacerbate ulcers.
Mental status influence on CNS.
Chronic glucocorticoid therapy can cause severe bone loss.
Myopathy leads to weakness.
Page # 5
Drug Catagory Drug Name Introduction Machanism of action Effects of
drug
Pharma-
cokinetics
Clinical uses Adverse effect Withdrawl
A
N
T
A
G
O
N
I
S
T
S
OF
Glucocorticoid
Metyrapone
Aminogluteth-
imide
Interfares with corticosteroids
synthesis by blocking the final
step in glucocorticoid synthesis
leading to increase in 11-deoxy
cortisol as well as adrenal
adrogens and the potent
mineralocoticoid 11-deoxy
coticosterone.
Inhibit the conversion of
cholesterol to pregnenolone and
reduce the synthesis of all
hormonly active steroids.
Used for the tests of
adrenal function.
Used for the treatment
of pregnant woman
with cushing's
syndrome.
Used in the treatment of
breast cancer to reduce
androgen and estrogen
production.
Used in conjunction
with dexamethasone.
Useful in treatment of
malignancies of adrenal
cortex to reduce the
secretions of steroids.
Salt and water
retention
Hirsutism
Transient
dizziness
GIT disturbance
Salt and water
retention
Hirsutism
Transient
dizziness
GIT disturbance
Page # 6
Drug Catagory Drug Name Introduction Machanism of action Effects of drug Pharmacokinetics Clinical uses Adverse effect Withdrawl
A
N
T
A
G
O
N
I
S
T
S
OF
Glucocorticoid
Ketoconazole
Trilostane
Mifepristone
Antifungal
agent
Antifungal
agent
Antifungal
agent
Inhibit all gonadal and
adrenal steroid hormone,
cortisol and gonadal
hormone synthesis.
Reversibly inhibits 3
Beta hydroxyste- roid
dehydrogena- se and
thus effects aldosterone,
cortisol and gonadal
hormone synthesis.
Form complex with
Glucocort- icoid
receptor.
Faulty transloca- tion
into the nucleus
accompanied rapid
dissociation of the drug
from receptor.
Used in the
treatment of
cushing's
syndrome
Use is limited to
the treatment of
inoperable patients
with ectopic
ACTH syndrome.
GIT disturbance
Page # 7
Drug Catagory Drug
Name
Introduction Machanism of action Effects of drug Pharmacokinetics Clinical uses Adverse effect Withdrawl
MINERALOCO-
RTICOIDS
A
N
T
A
G
O
N
I
S
T
of
mineralocorticoids
1) Spirono-
lacton
2)
Eplerenone
Regul ates sodium
a n d p o t a s s i u m
r e a b s or pt i on i n
collecting tubules of
kidney.
Aldosterone is the
p r i n c i p l e
mineralocorticoids
in human body.
Ant i hyper t ensi ve
drug
Ant i hyper t ensi ve
drug
Same mechansim as
glucocorticoid
Inhibit sodium
reabsorption in kidney
Antagonize
aldosterone and
testosterone synthesis.
Specifically binds to the
mineralocorticiods
receptor.
Effective
against hyper-
aldosteronism.
Useful in the
treatment of
hirsutism in
women.
Hyperkalemia
Gynecomastia
Menstrual
irregularities
Skin rashes
Gynecomastia
associated with
the use of
spironolactone
Page # 8