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Pharmacological applications
Of drugs ‘mimic or block’

•Replacement
therapy
•Antagonists for
diseases of excess
•Diagnostic tool
 GROWTH HORMONE
(SOMATOTROPIN)
Mediation of Its effects:
IGF-1, IGF-2
Pituitaries of human cadavers.
Contaminated with prions -cause Creutzfeldt-
Jakob disease
GH has a half-life of 20-25 minutes
Somatropin Somatrem
rhGH----36 hours. 4-6/week
Uses:
1. GH Def----- 2. Idiopathic short stature????? 3. Catabolic
states 4. Anti aging 5. Banned drug-sports 6. Cattle-Milk
production
ADE-
↑ICT
MECASERMIN-
rhIGF-1 & rhIGFBP-3
 GROWTH HORMONE
ANTAGONISTS
Somatostatin USES
Octreotide-analog Acromegaly
Bromocriptine-DA ago Gigantism
Pegvisomant-GH Hormone secreting
Rec.Anta tumors-Carcinoid
ADE
? MOA
Gallstones
Bradycardia
 Answer:

•Octreotide, 50-
200 mcg
given s.c 8th
Q. hourly

•Octreotide acetate injectable

long-acting suspension
-slow-release microsphere formulation
[After effect is established by short
acting]
Q.

Answer:
•Somatrem
•Somatropin
GONADOTROPIN-RELEASING HORMONE & ITS
ANALOGS
Gonadorelin PD;
-acetate salt of
synthetic human Pulsatile i.v:
GnRH.
Synthetic analogs
Stim.-FSH &
 Goserelin, Lh
Histrelin, Continuous
Leuprolide,
Nafarelin Biphasic
Triptorelin. respones
7-10 days-
Route; I.v, i.m, s.c.
Nasal Stimulation
 GnRH-Uses
Stimulation-Not common
Inhibition
use
Controlled ovarian
Female infertility
Hyperstimulation
To ↓ LH surge Male infertility
Diagnosis of LH
responsiveness

Endometriosis
Uterine fibroids
Prostate cancer
Central precocious
puberty
GnRH Rec. Antagonists
Ganirelix and cetrorelix
Competitive antagonists of
GnRH receptors
Used to Prevent the LH surge
during controlled ovarian
hyperstimulation
Advantages and disadvantages
over GnRH agonists????????
 Answer:

•Endometriosis

•Assisted
reproduction

•Central
precocious
puberty
Q:
Diabetes mellitus
Types
1, 2, 3, 4
Insulin
Oral anti-diabetic drugs
 Endocrine secretions of pancreas

Alpha Glucagon,
proglucagon
Insulin, C-peptide,
Beta proinsulin, amylin

Somatostatin
Delta

F(PP) Pancreatic
polypeptide (PP)
Control of insulin release from the pancreatic B cell
by Glucose [Chemical][Hormonal, Neural are other
stimuli]

Oral>i.v

First phase- Within 2 minutes

Delayed phase
Insulin Degradation

Endogenous Liver[60%]
Kidney[40%]

s.c Liver?? Kidney??

[40 %] [60%]
 Glut 1 All tissues
Glut 2 Pancreas
Glut 3 Brain, kidney
Muscle, adipose
Glut 4 [Insulin-
mediated uptake
Glut 5 of glucose]
Gut, kidney

TRANSLOCATION

Phosphorylation of
tyrosine residues
on the β subunits
and tyrosine kinase
activity
directed at cytoplasmic
The Insulin Receptor proteins
 Gluconeogenes
Absorption is
IN LIVER
Glycogenolysis
In
Insulin [-] su
lin

No
[-]
actio
n
Processes add glucose Blood
[Hyperglycemia]
l in
Processes utilize In su
[+
glucose su In
[Hypoglycemia] l in ]
[+ Insuli
] n [+
] Peripheral
utilization
Lipogenesis
Protein Synth. In Muscles
 Sources and insulin
preperations
Species A Chain B Chain
8th AA 10th AA 30th AA
Human THR ILEU THR
Pork THR ILEU ALA
Conventional prep.
Beef ALA VAL ALA •Impurities
•Antigenic
1. Highly purified pork •Less expensive
Insulins •Replaced by
• Monocomponent insulins 2.Highly purified pork
Insulins
1. Human insulins
4.Human insulins
• Recombninant DNA
5.Insulin analogs
Technology[E.Coli, porcine, Yeast]

3. Insulin analogs
Changing or replacing AA sequences
3. Lispro
4. Aspart
5. Glulisine
6. Glargine 5. Detemir
 Principal Types and Duration of Action of Insulin
Preparations

Type Duration] Onset Peak Appearance

Rapid acting
I.Lispro 3-5 Clear
I.Aspart 3-5 Clear
I.Glulisine 2-4 Clear
Short acting
Regular[Soluble 6-8 Clear
]
Intermediate acting
I.Zinc[Lente] 20-24 Cloudy
Isophane.I [NPH] 20-24 Cloudy
Long acting
Protamine zinc I. 24-36 Cloudy
[Ultra lente]
I.Glargine 24 Clear
Complications of insulin
therapy
Lipodystroph
Hypoglycemia Immunopathology
y
Diagnosi Atrop •Insulin
s hy allergy
Hypertrop
Treatme hy •Insulin
nt resistance
Q

Answer:
•Regular human insulin
•NPH Human insulin
•70/30 Human insulin
Q

Answer:
•Non-antigenic, less allergenic
•Less lipodystrophy,
•Preferred in insulin resistance
 Why?
•Infection
•DKA
•Chronic tt with
conventional
What to do?
Q •Treat the cause
•Use newer
Answer: preparations

When insulin requirement is > 200 i.u

 Q

Answer:
•Regular insulin
•Intravenous
•Bolus [0.1-0.2u/kg] →Infusion [0.1u/kg/hr.]
 Q
Why shoud serum potassium be
monitored with Insulin therapy
in diabetic ketoacidosis?
Answer:
+
•Though K is lost in urine in DKA
+
serum K is normal [Intracellular
exchange]
•Insulin→ DKA subsides →
+
K is driven intracellular →Hypokalemia
•So, after 4 hrs →10-20mEq/hr KCL to
i.v.fluid
 ORAL ANTIDIABETIC
Insulin [
Biguanide
HYPOGLYCAEMIC ] AGENTS
Thiazolidinedion
secretagog s es
ues Metformin
1. •Rosiglitazone
Sulfonylureas •Pioglitazone
I Gen
•Tolbutamide, •a-
•Chlorpropamide
•Tolazamide glucosidase
II Gen inhibitors.
•Glibenclamide •Acarbose
•Glipizide
•Gliclazide •Miglitol
•Glimepiride
2.
Meglinitides
•Repaglinide

3. D-
phenylalanine
derivative
 Sulfonylureas :Mechanism of Action
ACUTE ADMINISTRATION:
INSULIN RELEASE FROM
PANCREATIC Beta CELLS↑

CHRONIC ADMINISTRATION:
1. Down regulation of sulf.receptors on pancreas

Insulinaemia decreased
But antidiabetic action maintained?????????

Increase in the insulin receptors in target tissues

2.Reduction of serum
glucagon concentrations….
[Minor action]
Biguanides Gluconeogenesis
:Metformin
Glycogenolysis
t ion M
et
or p
Ab
s [-] fo
[-]

n
rm

mi
in

r
tfo
Me

Processes add glucose Blood

[Hyperglycemia]
in
o rm
Processes utilize
glucose e t f [+
M ]
[Hypoglycemia]
Blood sugar
reduced
Peripheral
utilization
Lipogenesis
Protein Synth.
 Pio
Glitazon THIAZOLIDINEDIONES (Tzds)
es
Bind to Reduce
nuclear blood
PPAR-γ glucose
Rec. by
• Increasing Glu
tpt into muscles
and adipose
tissues
• Inhibiting
hepatic
gluconeogenesis
• Promoting
lipogenesis

Peroxisome Proliferator-
Activated Receptor-gamma
(PPAR-γ),
 ALPHA-GLUCOSIDASE
INHIBITORS

Oligosaccharides Monosaccharide Not

and [Glucose Absorbe
Disaccharides Fructose ]
d

Uses:
Acarbos
Add on drugs in Type 2
e
Miglitol
ADE:
Flatulence, diarrhea,
and abdominal pain
Q:

Answ •Fewer adverse effects

er and drug interactions
•More potent
•Longer acting
 Q:

Answer:
Anorexic-Clinical relevance????
Does not promote weight gain
Reduces plasma triglycerides .
nsulin sensitizer-Obesity + Insulin resistance
Q:

Answer:
•Reduces postprandial
glycemic elevations
•Fewer episodes of
hypoglycemia
Q:

Answer:
•Increase in weight-edema
•Expansion of plasma volume
•Reduction in renal sodium excretion
•↑ Vascular permeability
 Q:

Answer:
Unacceptable levels of hyperglycemia
n who respond initially to a sulfonylurea
hange in drug metabolism,
rogression of β-cell failure,
hange in dietary compliance,
Misdiagnosis of a patient with slow-onset type 1 DM.
Q:

Answer:
•Levothyroxine of 10 to 15 µg/kg
•Life long
 Grave’s disease
↓
Hyperthyroidism
↓
Thyrotoxicosis
↑
Q: Thyrotoxicosis
Without
Hyperthyroidism
↑
Answer:
Thyroiditis
•Carbimazole
•Radioactive iodine