ENDOCRINE PHARMACOLOGY • Growth - promoting effects mediated by IGF-1

aka somatomedin C
1. HYPOTHALAMIC AND PITUITARY
HORMONES GROWTH HORMONE DRUGS

• ANTERIOR PITUITARY HORMONES

a. Growth Hormone (GH)

b. Follicle Stimulating Hormone (FSH) and

Luteinizing Hormone (LH)

c. Prolactin

d. Adrenocorticotropin (ACTH)

e. Thyroid Stimulating Hormone (TSH)

• POSTERIOR PITUITARY HORMONES

a. Oxytocin

b. Vasopressin

ANTERIOR PITUITARY HORMONES

• All are under the control of a HYPOTHALAMIC

B. Gonadotropins (FSH & LH)
HORMONE
• An anterior pituitary hormone

• Gonadotropins are produced by

GONADOTROPH cells

• Serve complementary functions in the

reproductive process

• FSH & LH are used for OVARIAN

steroidogenesis

• FSH is mainly for FOLLICLE development in

women, spermatogenesis in men

• LH stimulates ANDROGEN production

GONADOTROPINS

A. Growth Hormone (GH)

• An anterior pituitary hormone

• Required for attainment of normal adult size

 POSTERIOR PITUITARY HORMONES

• Oxytocin

• Anti-Diuretic Hormone/Vasopressin (ADH)

• Are synthesized in neuronal cell bodies in the

hypothalamus and transported via their axons
to the posterior pituitary, where they are stored
and then released into the circulation. Each has
limited but important clinical uses.

OXYTOCIN

• Oxytocin is a peptide hormone secreted by

the posterior pituitary.

• Oxytocin stimulates muscular contractions in

the uterus and myoepithelial contractions in the
breast.

• Responsible for “MILK-LET-DOWN”

C. Prolactin

• An anterior pituitary drug

• Principle hormone responsible for LACTATION

PROLACTIN DRUGS

ANTI-DIURETIC HORMONE (ADH) /

VASOPRESSIN

• Vasopressin is a peptide hormone released by

the posterior pituitary in response to rising
plasma tonicity or falling blood pressure.

• It possesses antidiuretic and vasopressor

properties.

• A deficiency of this hormone results in

diabetes insipidus.
• Diabetes insipidus is a syndrome of polyuria, KEY FEATURES OF HYPERTHYROIDISM AND
polydipsia, and hypernatremia. Excessive HYPOTHYROIDISM
urination due to kidney’s inability resorb water
properly from urine.

HYPOTHYROIDISM

• Is a syndrome resulting from deficiency of

thyroid hormones and is manifested largely by a
reversible slowing down of all body functions

• Hypothyroidism can occur with or without

thyroid enlargement (goiter).

• The laboratory diagnosis of hypothyroidism in

the adult is easily made by the combination of
low free thyroxine and elevated serum TSH
levels

• MYXEDEMA COMA – a result of untreated

hypothyroidism; medical emergency
2. Thyroid and Antithyroid Drugs
HYPERTHYROIDISM

• AKA Thyrotoxicosis

• Is a result of high levels of thyroid hormone

• Most common form is called GRAVE’S DISEASE 3. ADRENAL CORTICOSTEROID DRUGS

or diffuse toxic goiter
• Major groups are MINELAROCORTICOIDS and
• Laboratory diagnosis is high T3, T4, FT3, FT4, GLUCOCORTICOIDS
and low serum TSH
• Mineralocorticoids – regulates sodium and
DRUGS FOR HYPERTHYROIDISM potassium reabsorption in the collecting tubules
of kidney

• Glucocorticoids – important effects on

metabolism, catabolism, immune responses,
and inflammation
GLUCOCORTICOID RELATED DRUGS
CUSHING’S SYNDROME
• Syndrome caused by any condition that
produces elevated glucocorticoid levels
MINERALOCORTICOID RELATED DRUGS
4. ANTIDIABETIC DRUGS
• DIABETES MELLITUS - chronic disorder of
carbohydrate, fat, and protein metabolism due
to a relative or absolute deficiency in insulin
secretory response
• TYPE 1 DIABETES - usually has its onset during
childhood and results from autoimmune
destruction of pancreatic b cells; NO C-PEPTIDE
• TYPE 2 DIABETES - progressive disorder
characterized by increasing insulin resistance
- frequently associated with obesity and
is much more common than type 1
diabetes
- usually has its onset in adulthood; HAS
C-PEPTIDE
INSULIN

• synthesized as prohormone proinsulin

• cleavage of proinsulin and cross linking result

in formation of insulin and a residual C-peptide

• C-peptide is used to differentiate type 1 and

type 2 DM

MOA - binds to a tyrosine kinase receptor

INSULIN SENSITIZERS

INSULIN SECRETAGOGUES (NON-INSULIN

AGENTS)

• stimulate the release of endogenous insulin

by promoting closure of potassium channels in
the pancreatic B-cell membrane

• depolarizes the cell and triggers insulin

release

• not effective in patients who lack functional

pancreatic B cells
OTHER NON-INSULIN DRUGS

1. PROGESTINS

WOMEN’S HEALTH

1. ESTROGEN

• major ovarian estrogen in women is estradiol

• synthetic estrogens with high bioavailability
(ethinyl estradiol, mestranol) are used as
hormonal contraceptives
HORMONAL CONTRACEPTIVES • prevent pregnancy if administered within 72 h
after unprotected intercourse
• contain either a combination of an estrogen
and a progestin or a progestin alone • progestin (L-Norgestrel) alone, estrogen
alone, combination of estrogen and progestin
• available in a variety of preparations
• progestin-only preparation causes fewer side
- oral pills
effects than the estrogen-containing
- ong-acting injections (good for 3
preparations
months)
2. CONTRACEPTIVES
• implants (good for 3 years)

- transdermal patches
- vaginal rings
- intrauterine devices (IUDs)

MOA OF COMBINATION HORMONAL

CONTRACEPTIVES

• inhibition of ovulation (the primary action)

• effects on the cervical mucus glands, uterine

tubes, and

• endometrium that decrease the likelihood of

fertilization and implantation
SELECTIVE ESTROGEN RECEPTOR
TYPES OF ORAL CONTRACEPTIVE MODULATORS (SERMS)
MONOPHASIC

• combination estrogen-progestin tablets that

has a constant dosage throughout the
menstrual cycle

BIPHASIC or TRIPHASIC

• combination preparations in which the

progestin or estrogen dosage, or both, changes
during the month

• more closely mimics hormonal changes in

menstrual cycle

PROGESTIN-ONLY PREPARATIONS

• recommended for breeastfeeding moms since

they do not affect lactation

Postcoital Contraceptives/ Emergency

Contraception
 MISCELLANEOUS ESTROGEN ANTAGONISTS INFERTILITY DRUGS (GONADTROPIN)

3. INFERTILITY DRUGS

If a couple has not been able to conceive within

a reasonable period, doctor’s evaluation will be
needed

Couples will be tested with regards to their

fertility

INFERTILITY DRUGS (SERM)

INFERTILITY DRUGS (INSULIN

SENSITIZER/BIGUANIDE)

GIVEN WHEN INSULIN RESISTANCE IS A KNOWN

OR SUSPECTED CAUSE OF INFERTILITY -
USUALLY IN WOMEN WITH PCOS
 INFERTILITY DRUGS SURGERIES TO RESTORE FERTILITY

WORKS SAME AS CLOMIPHENE. USUALLY USED  LAPARASCOPIC OF HYSTEROSCOPIC

FOR WOMEN YOUNGER THAN 39 WHO HAVE SURGERY – to correct problems with
PCOS uterine anatomy, removing endometrial
polyps, or removing pelvic or uterine
adhesions
 TUBAL SURGERIES – can be done if your
fallopian tubes are blocked or filled
with fluid

REPRODUCTIVE ASSISTANCE

 INTRAUTERINE INSEMINATION –
millions of healthy sperm will be placed
inside the uterus around the time of
ovulation
 ASSISTED REPRODUCTIVE TECHNOLOGY
(IVF) – involves retrieving mature eggs,
fertilizing them with sperm in a dish in a
lab, then transferring it to the uterus
after

RISKS OF FERTILITY DRUGS

 Pregnancy with multiples

 Ovarian Hyperstimulation Syndrome
INFERTILITY DRUGS
 Long-term risk of ovarian tumors
USED WHEN OVULATION PROBLEMS ARE
4. DRUGS AFFECTING UTERINE FUNCTION
CAUSED BY EXCESS PRODUCTION OF
PROLACTIN (HYPERPROLACTINEMIA)

PROSTGLANDIN E1 ANALOG
(MISOPROSTOL)

- Promotes uterine contraction

Common side effects
include cramping,
Is used as an abortifacient
miscarriage, and teratogenic
effect
PROSTAGLANDIN E2 ANALOG
(DINOPROSTONE)
- Low concentrations contract, higher
concentrations relax uterine and cervical
smooth muscle, soften cervix at term before
induction with oxytocin
- Used for Induction of labor (Cervical ripening),
Abortifacient
- Side effects include cramping and fetal trauma
- Approved abortifacient in the 2nd trimester
- Although effective in inducing labor, it
produces more SE than other oxytocics
PROSTAGLANDIN F2A ANALOG
(CARBOPROST)
- Activates FP receptor
- Control of postpartum hemorrhage, for
refractory postpartum bleeding, abortifacient
OXYTOCIN - Activates oxytocin receptors -
Stimulates uterine contraction and labor - Use
for labor induction, labor augmentation, control
of postpartum hemorrhage
- Contraindicated in patients with cardiac
defects, arrythmia, glaucoma, and
thyrotoxicosis
B2-ADRENOMIMETICS (MAGNESIUM SULFATE)
- Decreases uterine contraction
- Acts as a CALCIUM ANTAGONIST
- Also possess hypotensive effects
MEN’S HEALTH
1. ANDROGENS
TESTOSTERONE
- synthesized from progesterone and
dehydroepiandrosterone (DHEA)
- increased by estrogen, thyroid hormone and
cirrhosis
- decreased by androgen, growth hormone and
obesity
- converted in several organs (e.g. prostate) to
dihydrotestosterone (DHT), which is the active
hormone in those tissues

ERGOT ALKALOID (ERGONOVINE and

METHYLERGONOVINE)

- Uteroselective serotonin receptor antagonist

- Used for post-partum bleeding

- Should never be given before the delivery of

placenta

B2-ADRENOMIMETICS (FENOTEROL)

- Causes uterine relaxation

- Stops premature labor

- Does not cause any negative effects to the

fetus

ANTI-ANDROGENS
 DRUGS THAT CAN CAUSE ERECTILE
DYSFUNCTION

DRUGS THAT CAN CAUSE PRIAPISM

2. DRUGS FOR ERECTILE DYSFUNCTION

ALPHA 2-BLOCKER (YOHIMBINE)

• Obsolete

• Blocks a2 receptors

• Was used for male erectile dysfunction

3. DRUGS FOR BENIGN PROSTATIC
• Can greatly elevate BP
HYPERPLASIA

 ALPHA 1- BLOCKER (PRAZOSIN)

PROSTAGLANDIN E-1 ANALOG (ALPROSTADIL)
 Blocks a1 receptors
- Activates EP receptors, causes vascular  Tamsulosin: most selective for prostatic
smooth muscle relaxation and vasodilation smooth muscle

- Used for erectile dysfunction 3. DRUGS FOR BENIGN PROSTATIC

HYPERPLASIA
- Given as injection into the cavernosa
 ANDROGEN SYNTHESIS INHIBITOR
PHOSPHODIESTERASE 5 INHIBITOR
(FINASTERIDE)
(SILDENAFIL)
 Inhibits 5areductase enzyme that
- Inhibits PDE5 which degrades cGMP to converts testosterone to
inactive GMP → vasodilation dihydrotestosterone
 Controversial use in prevention of
- Do not take with Nitrates (ISDN, ISMN, NTG)
prostate cancer
because it may lead to fatal hypotension
 Giving 5-alpha reductase aids in the
- Used for erectile dysfunction management of smooth muscle
hypertrophy in the prostate.
 Anti-Inflammatory, Anti-Allergy, and
Immunologic Drugs

ACTIVE IMMUNIZATION

the host to induce formation of antibodies and

cell-mediated immunity

immunization—in most cases because higher

antibody levels are sustained for longer periods
of time, requiring less frequent immunization,
and in some cases because of the development
of concurrent cell-mediated immunity

generally inactive at the time of a specific

exposure

PASSIVE IMMUNIZATION

- consists of transfer of immunity to a host using

preformed immunologic products

- Passive immunization is useful for

- (1) individuals unable to form antibodies (eg,

congenital agammaglobulinemia);

- (2) prevention of disease when time does not

permit active immunization (eg, postexposure)

- (3) for treatment of certain diseases normally

prevented by immunization (eg, tetanus); and

- (4) for treatment of conditions for which

active immunization is unavailable or
impractical (eg, snakebite)

CHILDHOOD IMMUNIZATION
RECOMMENDED SCHEDULE
PASSIVE IMMUNIZATION

CANCER CHEMOTHERAPY

- Classifications of drugs: Based on Cell cycle

- CELL CYCLE NONSPECIFIC DRUGS (CCNS)

- act on tumor stem cells when they are

traversing the cell cycle and when they
are in the resting phase

- CELL CYCLE SPECIFIC DRUGS (CCS)

- act selectively on tumor stem cells when they

are traversing the cell cycle, and not when they
are in the G0 phase
CANCER TREATMENT MODALITIES ALKYLATING AGENTS

- PRIMARY INDUCTION CHEMOTHERAPY

- drug therapy is administered as the

primary treatment

- NEOADJUVANT CHEMOTHERAPY

- use of chemotherapy in patients with

localized cancer before performing local
therapy (surgery)

- goal is to render the local therapy ANTIMETABOLITES

more effective

- ADJUVANT CHEMOTHERAPY

- chemotherapy done after local

treatment procedures such as surgery
or radiation

- reduce the risk of local and systemic

recurrence and to improve disease-free
and overall survival

CHEMOTHERAPY TOXICITIES

NATURAL PRODUCT ANTICANCER DRUGS

 ANTITUMOR ANTIBIOTICS HORMONAL ANTICANCER DRUGS

MISCELLANEOUS ANTICANCER DRUGS

HITAMINERGIC AGENTS

HISTAMINE

- formed from the amino acid histidine,

metabolized by the enzymes monoamine
oxidase and diamine oxidase

- important pathophysiologic roles

- seasonal rhinitis (hay fever), urticaria,

and angioedema

- control of acid secretion in the

stomach
Triple Response of Lewis (wheal, flush and NON-STEROIDAL ANTI-INFLAMMATORY
flare)
DRUGS

General Classification of NSAIDs

- SALICYLATES

- Aspirin
intradermal injection
- NONSELECTIVE NSAIDs
wheal - Ibuprofen, Indomethacin, Ketorolac,
Piroxicam
H1 RECEPTOR ANTAGONISTS
- COX-2 SELECTIVE

- Celecoxib, Etoricoxib, Parecoxib

y
are more susceptible to antimuscarinic effects
sess antimuscarinic, adrenaline-
antagonising, serotonin antagonising, and local
anaesthetic effects.
COMMON NSAID TOXICITIES
- CNS: headaches, tinnitus, dizziness
- CVS: hypertension, edema, heart failure

-channel blocking activity - GIT: abdominal pain, dysplasia, nausea,

vomiting, ulcers, bleeding

sedative effects of CNS depressants including - HEMATOLOGIC: thrombocytopenia,

alcohol, barbiturates, hypnotics, opioid neutropenia, aplastic anemia
analgesics, anxiolytic sedatives, and - HEPATIC: abnormal liver function tests, liver
antipsychotics failure

- PULMONARY: asthma
eyes)
- RASHES: all types, pruritus

- RENAL: renal insufficiency, renal failure,

HISTAMINERGIC DRUGS/ANTIHISTAMINES hyperkalemia, proteinuria

ASPIRIN: DOSAGE RANGES

- low range (<300 mg/d)

- effective in reducing platelet aggregation

- follows first-order elimination kinetics

- intermediate doses (300–2400 mg/d)

- antipyretic and analgesic effects

- high doses (2400–4000 mg/d)

- anti-inflammatory effects NSAIDS

- follows zero-order elimination kinetics

PARACETAMOL OVERDOSE

- Mechanism of Paracetamol Overdose

- oxidation to a cytotoxic intermediate called N-

acetyl-p benzoquinoneimine (NAPQI) by phase
I cytochrome P450 enzymes (CYP2E1)

- occurs if substrates for phase II conjugation

reactions (acetate and glucuronide) are lacking

- centrilobular region (zone III) is preferentially

involved because it is the area of greatest
concentration of CYP2E1

- antidote is N-acetylcysteine (NAC), a sulfhydryl

donor

- DOSAGE

- toxic dose: 150mg/kg (21 Paracetamol

500 mg tabs) o lethal dose: 15g (30
Paracetamol 500 mg tabs)

- TREATMENT

- antidote is N-acetylcysteine

- supportive management

- gastric decontamination with

activated charcoal
GLUCOCORTICOIDS FOR NON-ENDOCRINE
DISORDERS
- A large number of glucocorticoid preparations
are available for oral, parenteral, inhalational,
or topical administration for the treatment of a
wide range of inflammatory, allergic,
autoimmune, and other disorders
- Topical administration is widely used in the
treatment of allergic or inflammatory
conditions affecting the skin, mucous
membranes, or eyes
- topical ocular glucocorticoids are used to treat
acute uveitis (inflammation of the iris, ciliary
body, or choroid).
- Glucocorticoids are given by inhalation to treat
allergic rhinitis, aspiration pneumonia, asthma,
and other respiratory conditions
MEDIUM POTENCY, INTERMEDIATE-ACTING
GLUCOCORTICOIDS
- Prednisone, prednisolone,
methylprednisolone, and triamcinolone are the
glucocorticoids used most often for systemic
treatment
- intermediate-acting glucocorticoids have a
duration of action of 12 to 36 hours and are
often used to treat cancer, inflammation,
allergy, and autoimmune disorders.
HIGH POTENCY, LONG-ACTING
GLUCOCORTICOIDS
- Betamethasone is available for systemic use,
and it is also used in the topical treatment of a
number of skin disorders, including psoriasis,
seborrheic or atopic dermatitis, and
neurodermatitis
- Budesonide is a long-acting glucocorticoid
administered by inhalation. Budesonide is also
approved for the treatment of ulcerative colitis
- glucocorticoids are frequently used to
suppress inflammation and immune dysfunction
associated with diseases affecting almost every
organ in the body
- Glucocorticoids counteract inflammation
evoked by physical trauma, extreme
temperatures, noxious chemicals, radiation
damage, and microbial pathogens.
- They also suppress inflammation caused by
allergic and autoimmune reactions and other
disease states
- Examples of diseases treated with
corticosteroids include
- systemic lupus erythematosus
- autoimmune thrombocytopenia purpura
- polyarteritis nodosa
- multiple sclerosis
- ulcerative colitis
- polymyositis.
- beclomethasone and mometasone, are
available for nasal insufflation or oral inhalation
to treat allergic rhinitis or asthma
- Ciclesonide is a newer agent also indicated for
hay fever or allergic rhinitis
- For corneal inflammation and keratitis, many
glucocorticoids are available in eyedrops,
including a new combination of loteprednol and
the antibiotic tobramycin
- There are also combinations for the treatment
of superficial bacterial infections of the external
auditory canal (swimmer’s ear) containing
hydrocortisone and neomycin
- Because of their lymphotoxic effects,
glucocorticoids are used in the treatment of
lymphocytic leukemias and lymphomas
- Betamethasone is used to prevent respiratory - For acute disorders, glucocorticoids are often
distress syndrome in premature infants more effective when they are initially given in
large doses that are gradually tapered over
- Corticosteroids are often used to treat a wide
several days until treatment is discontinued.
range of dermatologic conditions, including
atopic (contact) and seborrheic dermatitis, - For severe autoimmune and inflammatory
pruritus (itching) from various causes, psoriasis, disorders (e.g., systemic lupus erythematous
sunburn, and a number of other conditions and polymyositis with dermatomyositis), large
doses of prednisone must be given daily for
- Low-potency drugs are preferred for treating
several months until a remission is achieved,
areas with thinner skin (e.g., the face, eyes) and
and then the dose is slowly tapered and
intertriginous areas where skin is folded or
continued for 1 to 2 years or longer
overlapped
- In some conditions, it may be possible to
- Low- to medium-potency steroids can be used
convert the patient to alternate day therapy
on the ears, trunk, arms, legs, and scalp.
- This dosage schedule appears to reduce the
- Medium to very-high-potency drugs may be
severity of adverse effects and produces less
needed to treat disorders in areas of thicker
suppression of the hypothalamic-pituitary-
skin (e.g., the palms and soles)
adrenal axis by allowing more time for recovery
- Low-potency topical steroids include between doses.
hydrocortisone, which is available without
- Glucocorticoids are administered parenterally
prescription for treating minor allergic reactions
to treat acute adrenal crises, acute allergic
(e.g., insect bites).
reactions, and similar emergencies.
- Other low-potency topical steroids include
- In some cases, the drugs are given
desonide and dexamethasone.
intravenously.
- Medium-potency topical steroids include
- In other cases, they are given intramuscularly,
triamcinolone and fluticasone.
either as a rapidly absorbed solution or as a
- Desoximetasone and fluocinonide are high- slowly absorbed drug suspension (depot
potency steroids, whereas betamethasone preparation).
dipropionate and clobetasol are very-high-
potency steroids

- Glucocorticoids are used to treat

hypercalcemia, and they are the drugs of choice
for managing sarcoidosis (a systemic
granulomatous disorder).

- Glucocorticoids are also used as

immunosuppressant drugs to prevent organ
graft rejection

SYSTEMIC ADMINISTRATION AND

PHARMACOKINETICS