Adrenocorticosteroids
Adrenal
gland
zona fasciculata 25%
Secretes glucocorticoids
cortex
Adrenal Gland
Adrenocorticosteroids
Mineralocorticoids,
have salt retaining
capacity
aldosterone
Cortisol
desoxycorticosterone
(Hydrocortisone)
Structure-activity
relationships
dehydroepiandrosterone
21
hydrocortisone
aldosterone
20
17
dehydroepiandrosterone
Adrenocrtical steroids
include:
Glucocorticoids( cortisol,
hydrocortisone) with
electrolyte balance(homeostasis) by
altering K+ & Mg+2 secretion & Na+
tubular reabsorption.
5
dehydroepiandroeterone(DHEA)sul
phate
&
estradiol
infleunce
reproductive system as well as affecting
primary
&
secondary
sex
characteristics
androgens or estrogen(by
conversion)
Adrenal androgens are the main
precursors of
Adrenocorticosteroid
s
Physiological
secretion
(Hypothalamus-pituitar
_
othalamus
_+ CRH
_
Hyp
Anterior pituitary
+ ACTH
pla
Adrenal cortex
Cortisol(hydrocortisone)
secretion
CRH: corticotropin
adrenocorticotrophic
hormone
Actions of
mineralocorticoids &
syndrom
e
Excess aldosterone(called Cronns
syndrome,
or primary
hyperaldosteronism) causes
disturbances in Na+ and K+
balance.
Secondary hyperaldosteronism is
due to
Pharmacokin
etics:
Cortisol regulates many body functions
including:
and immunity.
Synthesis & secretion are regulated by CNS
which is
(CBG)
CBG is increased in pregnancy, with
estrogen
administration and in
hyperthyroidism &
decreased by hypothyriodism,
genetic
defects
& protein deficiency
states
12
dihydroxyketone
etc)
13
Pharmacodyna
mics
A :Mechanism of action of
corticosteroids:
Mechanism of action of
glucocorticoids
15
B.PhysiologicalEffects 19/11/2015
They influence the function of most
body cells.
presence of glucocorticoids to
occur, eg the response of vascular and
C. Metabolic Effects
Glucocorticoids have important dose related
effects
D.
Large concentrations of
glucocorticoids or
in Cushings syndrome.
Anti-inflammatory
&
.
D
immunosuprressive
effects:
Reduce manifestation of
inflammation
by:
Decrease concentration and
function of
leuckocytes
Decreased function and
concentration of
inflammatory cytokines,
chemokines and other
inflammatory mediators
They also inhibit functions of
tissue
macrophages and other
antigen20
Antiinflammatory effects of
glucocorticoids
Glucocorticoids increase
the synthesis of
lipocortin-1, that has
inhibitory effect on
phospholipas A2 and
therefore inhibit the
production of lipid
mediators as well as
inhbit genes coding for
COX-2.
22
Immunosuppressive action of
glucocorticoids
23
F. Other actions of
glucocorticoids
Large amounts cause insomnia,
euphoria then
depressio
n
Increased intracranial pressure in
large doses
ACTH,GH,TSH, and
LH
Large doses may cause peptic ulcer
due to
function,increased vaspressin
secretion and diminished ability
to excrete water load
They are important in development of
fetal lungs.
Pharmacological
effects
H. Hematic effects:
)Stimulation of
Pharmacological effects
J.Gastrointestinal effects:
Increased gastric acid, increased pepsin
leading to peptic ulceration.
K. Central nervous exciting
effects: Euphoria, excitation,
insomnia; Anoia induced
occasionally;
Representative Glucocorticoids:
Natural:
hydrocortisone cortisone
Synthetic:
prednisone
prednisolone
methylprednisolone
triamcinolone
dexamethasone
betamethasone fluocilonone
beclometasone
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Clinical use:
1. Replacement therapy(Adrenocortical insufficiency)
Addisons disease, anterior hypopituitarism , postsubtotal bilateral adrenalectomy .
2. Antiinflammatory effect Acute serious infectionsas
adjuvants in:
Bacterial infection: fulminant dysentery, bacterial
meningitis, toxic pneumonia, heavy typhoid, acute miliary
tuberculosis, scarlatina, septicemia
Viral infection: heavy infectious hepatitis, epidemic
parotitis, measles, encephalitis
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Clinical use:
4. Autoimmunity diseases & allergic diseases
3) Allergic diseases
urticaria, pollenosis, serum sickness, angioneurotic
edema, allergic rhinitis, asthma, etc.
5. Shocks
1) Septic shock: early, short, large dose.
2) Anaphylactic shock: the support drugs
3) Cardiogenic shock
4) Hypovolemic shock: transfusion first
Clinical use
6. Hematic diseases
acute lymphoblastic leukemia, aplastic anemia,
granulocytopenia, thrombocytopenia, allergic
purpura syndrome
7. Local use on skin
contact dermatitis, eczema, anus tickle, psoriasis,
neurodermatitis
Hydrocortisone, prednisolone & fluocilonone p
Adverse Effects:
1. Complications during chronic uses
1) Cushings syndromes
body obesity, rounded face, increased fat around
the neck, thinning arms & legs, acne, hirsutism,
edema, hypokalemia, hypertension, diabetes.
2) Inducement or aggravation of infections
3) Complications of digestive system
inducement or aggravation of peptic
ulcer
Adverse effects of
corticosteroids
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2.Adverse Reactions
1. Complications during chronic uses
4) Complications of cardiovascular system
hypertension, atherosclerosis.
5) Osteoporosis, sweeny and wound healing delay
6) Other complications
anoia, teratogenesis
2. Withdraw
1) Iatrogenic adrenal insufficiency
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Contraindications:
Patients with:
peptic ulcer, heart disease, heavy hypertension
with heart failure,infectious disease such as varicella,
tuberculosis, and psychoses, epilepsy, osteoporosis,
diabetes, or glaucoma
Carefully used or forbidden!
In summary, decision & caution both needed for
the use of glucocorticoids; evaluate advantages &
disadvantages of using glucocorticoids before use .
Pharmacokinetics
1. Absorption:
Oral or injectable
administration is easily
absorbed.
2. Transport: >90 % ofhydrocortisone is
reversibly bound to protein if its total
concentration in plasma < 25g %; 2
plasma proteins: cortisosteroid-binding
globulin (CBG) & albumin.
3. Distribution: The concentration in liver is
high.
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4.
Metabolism: Activity
losing for all &
activation for some are
performed in liver
=O in C11 replaced by OH in
liver are
cortisonehydrocortisone;
prednisone
prednisolon
e.
5.
kidney
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Excretion:
inflammations, rheumatoid
arthritis,
lymphoma, lymphoblastic
leukemia.
Started with prednisone 10
20 mg, tds; gradually decreased to
the maintenance dose
after obtained the initial
effect.
42
Serious infections:
hydrocortisone i.v.d. 200300 mg, 1
g/d.
Shocks: hydrocortisone v.d. 1
g, 4-6 g/d.
43
Antagonists of Adrenocortical
Agents:
antagonists:
(1) Aminoglutethemide blocks the
conversion
of cholesterol to pregnenolone thus
reduces
production of
steroids
or hydrocortisone to reduce or
eliminate estrogen production in
breast carcinoma
(2) ketoconazole is an antifungal
that inhibits
synthesis of adrenal and gonadal
steroids
It is used to treat Cushings
syndrome
anterior pituitary
function
Can be given to pregnants with Cushings
syndrome
(4)
Trilostane: is a 3-17
hydroxysteroid
dehydrogenase inhibitor .It interferes with
adrenal&
gonadal hormones
synthesis
(5)
Abiratero
ne:
It blocks 17 hydroxylase and 17,20
lyase and
cancer
(6)
Mifepristo
ne:
Is an antagonist at steroid
receptor
It has strong antiprogestin and
antiglucocorticoid
receptor
activity
Is used in treatment of Cushings
syndrome
(7) Mitotane: has cytotoxic effect
on adrenal
Mineralocorticoids
Antagonists
Agents that inhibit aldosterone
synthesis
include
:
Agents that interfere with aldosterone
action
discontinue
d
Used in treatment of primary
aldosteronism.
Eplerinone is a selective
receptor
Is used in
hypertension.
Drospirenone is a
progestin that
antagonizes the effects of
aldosterone
Objectives for
Adrenocorticosteroids
Diseases and clinical manifestations to
consider:
insufficiency: (Addisons
disease)
-weakness, fatigue,weight loss, inability
to maintain
hyperplasia)
-adrenocortical hypertrophy(due to
hyperstimulation
by ACTH),virilization(due to excessive
androgen
production)
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Cushings
syndrome:
-hypertension,polyuria,muscle
weakness and
Aldosterone antagonists:
spironolactone.
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Thank
you
fo
r
listeni
ng
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