Endo, Repro, Teratogens pharm

Question 1

Insulin and its effects

Answer 1

Preproinsulin (synthesized in RER) > cleavage
of “presignal” > proinsulin (stored in secretory
granules) > cleavage of proinsulin > exocytosis
of insulin and C-peptide equally. Insulin and
C-peptide are increased in insulinoma and sulfonylurea
use, whereas exogenous insulin lacks C-peptide.

Glucose is the major regulator of insulin release. INcreased insulin response with oral vs IV glucose because of incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are released after meals and increase β cell sensitivity to glucose. Release decreased by α2, increased by β2 (2 = regulates insulin)
RELEASE:
Glucose enters β cells > increasing ATP generated from glucose metabolism closes K+ channels (target
of sulfonylureas) and depolarizes β cell membrane . Voltage-gated Ca2+ channels open
>leading to Ca2+ influx and stimulation of insulin exocytosis

Binds insulin receptors (tyrosine kinase
activity ), inducing glucose uptake (carrier mediated
transport) into insulin-dependent
tissue and gene transcription.
Anabolic effects of insulin:
􀂃 increase glucose transport in skeletal muscle and
adipose tissue
􀂃 increase glycogen synthesis and storage, inhibit lysis
􀂃 increase triglyceride synthesis
􀂃 increase Na+ retention (kidneys)
􀂃 increase protein synthesis (muscles)
􀂃 increase cellular uptake of K+ and amino acids
􀂃 decrease glucagon release
􀂃 decrease lipolysis in adipose tissue
Unlike glucose, insulin does not cross placenta.
Brain utilizes glucose for metabolism normally
and ketone bodies during starvation. RBCs
utilize glucose because they lack mitochondria
for aerobic metabolism.

Question 2

Nateglinide

Repaglinide

Answer 2

Meglitinides

Used as monotherapy in
type 2 DM or combined with
metformin.

Stimulate postprandial
insulin release by binding
to K+ channels on β cell
membranes (site differs from
sulfonylureas). 

Hypoglycemia (increase risk with renal failure), weight gain (same as sulfonylureas - increase TG storage).
-no sulfa group so no allergy

INcrease C PEPTIDE

Question 3

Metformin - biguanides

Answer 3

Oral. First-line therapy in type
2 DM, causes modest weight
loss.
Can be used in patients
WITH NO islet function.
[MECH]
-Inhibit hepatic gluconeogenesis (inhibits GDPC, increase AMPK - think ENZYMES) 
and the action of glucagon.
decrease gluconeogenesis,
increase peripheral
glucose uptake (􀁱 insulin
sensitivity).
GI upset; most serious adverse effect is lactic acidosis (thus contraindicated in renal
insufficiency).
-lactate can't be used for gluconeogensis, also metformin is excreted all renaly with no metabolism. 

*increase glycolysis which makes no sense because insulin reduces lysis while glucagon induces lysis.

Question 4

Pioglitazone

Answer 4

A glitazone/thiazolidinediones

Used as monotherapy in
type 2 DM or combined with
above agents. 
Safe to use in
--renal impairment.

INcreases insulin sensitivity in peripheral tissue. Binds to
PPAR-γ intracellular nuclear transcription
regulator which is found in muscle, liver, and fat
1. increase glucose utilization
2. decrease glucose production
3. Increases expression of Glut4
4. Produces adiponectin - increasing insulin sensitivity and fatty acid oxidation
-since effects are via gene expression takes days to weeks to lower glucose

Weight gain - differentiation of adipocytes, lowering blood TGs, uptake into cells, increased fat mass
Edema - water retention in the collecting ducts
HF - exacerbation via increased volume
Increase risk of fractures - thought to be because of inhibition of osteoblasts

Genes activated by PPAR-γ regulate fatty acid storage and glucose metabolism. Activation of PPAR-γ INcrease insulin sensitivity and levels of adiponectin.

Question 5

Acarbose,

Miglitol

Answer 5

"wigglers" no carbs sugar free 
Inhibit intestinal brush-border
α-glucosidases which dissociates polysaccharides into monomers that can be absorbed. .
Delayed carbohydrate
hydrolysis and glucose
absorption > decreasedpostprandial
hyperglycemia.
SEVERE GI disturbances - really gassy, diarrhea

Question 6

Exenatide,

liraglutide

Answer 6

GLP-1 analogs
Exenatide,
liraglutide (sc injection)

Type 2 DM. increases glucose-dependent insulin
release, ironically decreases glucagon release,
decreases gastric emptying (slows glucose reabsorption), decreases satiety.
-its glucose dependent so hypoglycemia is NOT a concern.
-HAS C PEPTIDE

Nausea, vomiting, **pancreatitis;
modest weight loss.

Question 7

-agliptins-
Linagliptin,
Saxagliptin,
Sitagliptin

Answer 7

.DPP-4 inhibitors
Type 2 DM. Inhibit DPP-4 enzyme that deactivates GLP-1, thereby
increasing glucose-dependent insulin
release, decrease glucagon release,
decrease gastric emptying, increase satiety.

Mild urinary or ***respiratory
infections; *weight neutral.

Question 8

Pramlintide

Answer 8

.Amylin agonist (sc injection)

• **Type 1 DM, type 2 DM. delays gastric emptying, decreases glucagon.
• **amyloid peptide that is usually secreted with insulin and can be used for postprandial glucose spike)

Hypoglycemia (in setting of
mistimed prandial insulin),
nausea.

Question 9

Canagliflozin,
Dapagliflozin,
Empagliflozin
-agliflozins

Answer 9

.Type 2 DM. Block reabsorption of glucose
in PCT.

Glucosuria leads to: 
UTIs, 
vaginal yeast infections, hyperkalemia,
dehydration (orthostatic
hypotension), 
weight loss.

Question 10

The GLUTS

Answer 10

Insulin-dependent glucose transporters:
􀂃 GLUT4: adipose tissue, striated muscle
(exercise can also increase GLUT4
expression)

Insulin-independent transporters:
􀂃 GLUT1: RBCs, brain, cornea, placenta
􀂃 GLUT2 (bidirectional): β islet cells, liver,
kidney, small intestine
􀂃 GLUT3: brain, placenta
􀂃 GLUT5 (fructose): spermatocytes, GI tract

BRICK L (insulin-independent glucose uptake):
Brain, RBCs, Intestine, Cornea, Kidney, Liver.

Question 11

Glulisine, Aspart, Lispro

gals and lads

Answer 11

Rapid acting 
Type 1 DM, type 2 DM,
GDM (postprandial glucose
control).
Binds insulin receptor (tyrosine kinase activity).

-Liver: increased glucose stored as
glycogen.
-Muscle: increased glycogen, protein synthesis; increased K+ uptake.
-Fat: increased TG storage.

[ADVERSE]
Hypoglycemia, lipodystrophy,
rare hypersensitivity reactions.

-do not polymerize into hexamers, their onset is 15 min, they can mimic nrmal insulin spike which makes them useful for postprandial

Question 12

Regular Insulin

NPH

Answer 12

Insulin, short acting
Regular: Type 1 DM, type 2 DM, GDM, DKA (IV), hyperkalemia (+ glucose),
stress hyperglycemia.
-regular insulin is the only one that can be administer IV and so you see its blood implications (hyperkalemia + DKA)
-for IV dilutions it dissociates immediately for fast onset

[Insulin, intermediate acting
NPH]
Type 1 DM, type 2 DM,
GDM.

For both the concerns are expected, hypoglycemia

Question 13

Detemir, Glargine

Answer 13

Type 1 DM, type 2 DM, GDM
(basal glucose control).
These are long acting with glargine lasting the longest with 24 hrs. Most people with diabetes need a mix of short acting for post meals and long acting.

Question 14

Chlorpropamide,

Tolbutamide

Answer 14

First gen sulfonyl urea
Stimulate release of
endogenous insulin in
type 2 DM. Require some
islet function, so useless in
type 1 DM.

BINDS AND CLOSES K+ channel in β cell
membrane > cell depolarizes
> insulin release via > Ca2+
influx.
Risk of hypoglycemia in renal failure, weight gain.

First generation: disulfiram-like effects. Especially alcohol ingestion with chlorpropamide

These are barely used

-INCREASED C PEPTIDE

Question 15

glimepiride,
glipizide,
glyburide

Answer 15

2nd gen sulfonyl urea
Stimulate release of
endogenous insulin in
type 2 DM. Require some
islet function, so useless in
type 1 DM.

BINDS AND CLOSES K+ channel in β cell
membrane > cell depolarizes
> insulin release via > Ca2+
influx.
Risk of hypoglycemia in renal failure, weight gain
Only hypoglycemia is the concern 

-INCREASED C PEPTIDE

Question 16

Rosiglitazone

Answer 16

A glitazone/thiazolidinediones

Used as monotherapy in
type 2 DM or combined with
above agents. 
Safe to use in
--renal impairment.

INcreases insulin sensitivity in peripheral tissue. Binds to
PPAR-γ intracellular nuclear transcription
regulator which is found in muscle, liver, and fat
1. increase glucose utilization
2. decrease glucose production
3. Increases expression of Glut4
4. Produces adiponectin - increasing insulin sensitivity and fatty acid oxidation
-since effects are via gene expression takes days to weeks to lower glucose

Weight gain - differentiation of adipocytes, lowering blood TGs, uptake into cells, increased fat mass
Edema - water retention in the collecting ducts
HF - exacerbation via increased volume
Increase risk of fractures - thought to be because of inhibition of osteoblasts

Genes activated by PPAR-γ regulate fatty acid storage and glucose metabolism. Activation of PPAR-γ INcrease insulin sensitivity and levels of adiponectin.

Question 17

Somatropin used for?

Answer 17

Recombinant GH
These conditions include genetic disorders like Prader-Willi, Turner, and Noonan
Syndromes, as well as Idiopathic Short Stature

Children generally tolerate GH treatment well.
• Adverse events are rare and include pseudotumor cerebri (intracranial
pressure), progression of scoliosis, edema, and hyperglycemia (due to induction
of peripheral insulin resistance)

Toxicities in Adults:
• Adults tend to have more adverse effects from GH therapy.
• Peripheral edema, myalgias, and arthralgias (especially in the hands and wrists)
occur commonly, but remit with dosage reduction.
• Carpal tunnel syndrome can also occur.`

Question 18

Mecasermin

Answer 18

severe IGF-1 deficiency that
is not responsive to exogenous GH.
• A recombinant form of human IGF-1 termed Mecasermin (Increlex®) has been approved for treatment of severe IGF-1 deficiency
• The most important adverse effect with mecasermin is hypoglycemia, which is
thought to be related to potentiation of the actions of insulin (activates insulin
receptor).
• As a result, the prescribing instructions require consumption of a carbohydratecontaining
meal or snack 20 minutes before or after drug administration.`

Question 19

Octreotide (Generic) & Lanreotide

Answer 19

Long acting somatostatin analog
Uses: Acromegaly,
carcinoid syndrome (secreting serotonins), gastrinoma,
glucagonoma,
insulinoma
esophageal varices - reduces portal pressure by reducing portal flow.

Nausea, cramps, steatorrhea. increase risk of cholelithiasis due to CCK inhibition.

Question 20

Pegvisomant

Answer 20

Pegvisomant is a GH receptor antagonist used to treat acromegaly.
• It is a pegylated derivative of a mutant GH that targets the GH receptor, but does
not result in signal transduction.

Can lead to increased GH levels

Question 21

Urofollitropin, Follitropin a and Follitropin b

Answer 21

Urofollitropin (a.k.a., uFSH) is a purified preparation of human FSH extracted
from the urine of postmenopausal women.

Follitropin a and Follitropin b are recombinant forms of FSH (rFSH) with
shorter half-lives than urofollitropin. They are also much more expensive.

The gonadotropins are used in states of infertility to stimulate spermatogenesis in men and to induce ovulation in women.
• They are generally reserved for anovulatory women who fail to respond to other
less complicated and less expensive forms of treatment (e.g., clomiphene).

Most commonly used for controlled
ovarian hyperstimulation (COH) in
assisted reproductive procedures,
such as in vitro fertilization (IVF).

two most serious
complications are:
1. Ovarian Hyperstimulation Syndrome (OHSS) – 0.5 to 4% of patients
(It is characterized by ovarian enlargement,
ascites, hydrothorax, and hypovolemia,
sometimes resulting in shock.)
2. Multiple Pregnancies – 15 to 20% of patients

Question 22

Lutropin a

Answer 22

a recombinant form of LH (rLH) available in the US.
• It is approved only for use in combination with follitropin a for stimulation of
follicular development in infertile women with profound LH deficiency.
The gonadotropins are used in states of infertility to stimulate spermatogenesis in
men and to induce ovulation in women.
• They are generally reserved for anovulatory women who fail to respond to other
less complicated and less expensive forms of treatment (e.g., clomiphene)
Most commonly used for controlled
ovarian hyperstimulation (COH) in
assisted reproductive procedures,
such as in vitro fertilization (IVF).
.
two most serious
complications are:
1. Ovarian Hyperstimulation Syndrome (OHSS) – 0.5 to 4% of patients
(It is characterized by ovarian enlargement,
ascites, hydrothorax, and hypovolemia,
sometimes resulting in shock.)
2. Multiple Pregnancies – 15 to 20% of patients

Question 23

Leuprolide

others (Goserelin, Histrelin, Leuprolide, Nafarelin, and Triptorelin)

Answer 23

Leuprolide
MECHANISM GnRH analog with agonist properties
when used in pulsatile fashion; antagonist
properties when used in continuous fashion
(downregulates GnRH receptor in pituitary
> decreased FSH/LH).
Leuprolide can be used in lieu of GnRH.

CLINICAL USE
Uterine fibroids, endometriosis, precocious
puberty, prostate cancer, infertility.

Adverse effects:
women - causes the typical symptoms of
menopause, which include hot flashes, sweats, and headaches.
Depression, diminished libido, generalized pain, vaginal dryness, and breast
atrophy may also occur.
• Reduced bone density and osteoporosis may occur with prolonged use, so bone
density should be monitored before repeated treatment courses.

In Men
• Adverse effects of continuous treatment include hot flashes, edema,
gynecomastia, decreased libido, decreased hematocrit, reduced bone density,
and asthenia.

Endometriosis
• A syndrome of cyclical abdominal pain in premenopausal women caused by the
presence of estrogen-sensitive endometrium-like tissue outside the uterus.
• The pain of endometriosis is often reduced by abolishing exposure to the cyclical changes in estrogen and progesterone that occur during the menstrual cycle.
• Continuous treatment with a GnRH agonist
greatly reduces estrogen and progesterone
levels and prevents cyclical changes.

Uterine Leiomyomata (Uterine Fibroids)
• Uterine fibroids are benign, estrogen-sensitive, fibrous growths in the uterus that
can cause menorrhagia, with associated anemia and pelvic pain.
• Treatment for 3 to 6 months with a GnRH agonist reduces fibroid size and, when combined with supplemental iron, improves anemia

Anti-androgen therapy is the 1st-line pharmacological therapy for prostate cancer.
• Combined therapy with a continuous GnRH agonist and an androgen receptor
antagonist (such as flutamide or bicalutamide) is effective in reducing serum
testosterone levels and effects

CPP is the onset of secondary sex characteristics before 7 to 8 years of age in
girls or 9 years of age in boys.
• Continuous administration of a GnRH agonist is indicated for treatment of GnRH dependent

1. A child whose final height would be otherwise significantly compromised (as evidenced by a significantly advanced bone age).
2. A child in whom the development of pubertal secondary sexual
   characteristics or menses causes significant emotional distress.
   • Treatment most commonly entails a monthly IM depot injection of leuprolide or a
   once-yearly implant of histrelin.
   • Treatment is generally continued to age 11 in females and to age 12 in males.

Question 24

Ganirelix, Cetrorelix, and Degarelix

Answer 24

Ganirelix, Cetrorelix, and Degarelix
inhibit the secretion of FSH and LH in a
dose-dependent and more complete manner than do GnRH agonists.

controlled ovarian
hyperstimulation procedures, with a lower risk of OHSS than with GnRH agonists.

approved for the treatment of symptomatic advanced prostate
cancer.
• Like continuous treatment with GnRH agonists, degarelix leads to the signs and
symptoms of androgen deprivation (e.g., hot flashes and edema).

Question 25

Bromocriptine and Cabergoline

Answer 25

Hyperprolactinemia is a condition of elevated serum prolactin most commonly
caused by the presence of prolactin-secreting adenomas.
• It produces a syndrome of amenorrhea and galactorrhea in women, and loss of
libido and infertility in men.
• Bromocriptine and Cabergoline are ergot derivatives with a high affinity for dopamine D2
receptors.
• These DA agonists shrink pituitary prolactin-secreting tumors, lower circulating
prolactin levels, and restore ovulation in approximately 70% of women with
microadenomas and 30% of women with macroadenomas. Can also be used for Parkinsons
Dopamine agonists can cause nausea, headache, light-headedness, orthostatic
hypotension, and fatigue

Question 26

Pitocin

Answer 26

(Pitocin®) is used to induce labor for conditions requiring
early vaginal delivery, such as uncontrolled maternal diabetes, worsening
preeclampsia, or intrauterine infection.
it is also useful for controlling uterine
hemorrhage due to uterine atony

Adverse efffects
The toxicity that does occur is due either to excessive stimulation of uterine
contractions or to inadvertent activation of vasopressin (ADH) receptors.

Question 27

Conivaptan and Tolvaptan

Answer 27

Both “vaptans” have a high affinity for V2
receptors, with tolvaptan being 30-times
more selective for V2
than V1
receptors.
• Useful in the treatment of syndrome of inappropriate ADH secretion (SIADH).

Question 28

Tamoxifen, raloxifene

Answer 28

Selective estrogen receptor modulators (SERMS)
– Approved for the treatment of Breast cancer that is ER+

Selective estrogen receptor modulators (SERMs)—receptor antagonists in breast and agonists in
bone. Block the binding of estrogen to ER ⊕ cells.

CLINICAL USE Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent
osteoporosis.
ADVERSE EFFECTS Tamoxifen—partial agonist in endometrium, which increase the risk of endometrial cancer; “hot flashes.”
Raloxifene—no in endometrial carcinoma (so you can relax!), because it is an estrogen receptor
antagonist in endometrial tissue.
Both increase risk of thromboembolic events (eg, DVT, PE).

chemoprevention of breast cancer in high-risk women

partial agonist at the endometrium, antagonist at the breast

Question 29

Toremifene

Answer 29

Selective estrogen receptor modulators (SERMS)

– Approved for the treatment of Breast cancer that is ER+

Question 30

Anastrozole

Answer 30

Aromatase inhibitor
Inhibit peripheral conversion of androgens to estrogen.
CLINICAL USE ER ⊕ breast cancer in postmenopausal women.
– Inhibit aromatase, the enzyme responsible for the
synthesis of estrogens from androgenic substrates
(the synthesis of estrone from the preferred substrate
androstenedione and estradiol from testosterone).

Cholesterol > pregnelenone > androstenedione > estrone
or testosterone > estradiol

Question 31

Fulvestrant

Answer 31

Pure ER receptor antagonist

– Tamoxifen-resistant breast cancer

Question 32

Fetal effects of 
ACE Inhibitors
Aminoglycosides
Carbamezapine
DES
Folate antagonists
Lithium
Methimazole

Answer 32

ACE Inhibitors: Renal damage
Aminoglycosides: Absence digits, ear&facial
anomalies

Carbamezapine: NTD, craniofacial defects, IUGR,
fingernail hypoplasia, developmental delay

DES: Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies

Folate antagonists: NTD
Lithium: Ebstein anomaly
Methimazole: Aplasia cutis congenita

Question 33

Teratogen

Iodine, maternal diabetes, vitamin A
cocaine, alcohol, isotretinoin

Answer 33

Iodine (lack or excess) Congenital goiter or
hypothyroidism (cretinism)

Maternal diabetes: Caudal regression syndrome,
congenital heart defects, neural
tube defects

Vitamin A (excess) isotretinoin: Spontaneous abortions, cleft palate, cardiac abnormalities

Cocaine: intrauterine growth retardation, and placental abruption
Alcohol: most common cause of mental retardation, also leads to facial abnormalities and microcephaly

Question 34

Phenytoin, Tetracycline, Thalidomide, Valproate, Warfarin, SSRI, angiotensin II,
thiazide

Answer 34

Phenytoin: Fetal hydantoin syndrome, microcephaly, dysmorphic craniofacial features, hypoplastic nails, cardiac defects, IUGR

Tetracyclines Discolored teeth

Thalidomide Limb defects

Valproate: NTD (inhibits folic acid absorption)

Warfarin Bone deformities, nasal and
midface hypoplasia, (hydrocephalus in late exposure)

SSRI Paroxetine (VSD and ASD)

All: neonatal behavioral syndrome
with exposure late pregnancy

Thiazide diuretics Thrombocytopenia, electrolyte
abnormalities