Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

Chapter 48: Drugs Affecting Corticosteroid Levels:

I.

Definitions Related to Corticosteroids:

a. Corticosteroids are used in replacement therapy to maintain adequate levels of
hormones in patients with inadequate adrenal function and diminished natural
corticosteroid production
i. Also used as: anti-inflammatory: reducing swelling and irritation; antiallergenic:
minimizing and or preventing bodys response to allergens; and
immunosuppressive: decreasing the bodys harmful response to diseases that
affect the immune system
ii. Have to taper off of medication; cannot abruptly stop
**Where are the Adrenal Glands located: top of the kidneys**
II.
Physiology:
a. Adrenal Glands:
i. Two adrenal glands: one above each kidney: each consisting of medulla and
cortex
ii. Medulla and cortex crucial to metabolism, stress response, fluid and electrolyte
balance
iii. Adrenal medulla synthesis and secretes catecholoamines (epinephrine and
norepinephrine)
iv. Adrenal cortex: synthesis and secretion of the glucocorticoid and
mineralocorticoid supply

Adrenal
Glands
Adrenal Glands

Adrenal
Adrenal
Medulla

catecholoamine
s: epinephrine
and
and
norepinephrine

Adrenal
Cortex
Adrenal Cortex

glucocorticoids

mineralcorticoi
ds

b. Adrenal Corticosteroids:
i. Effect on almost every organ in the body
ii. Primary actions: metabolism, carbohydrates, protein, fats, electrolytes, and water
iii. Also role in cardiovascular function and immune effects
iv. Zona Reticularis region of adrenal cortex important in production and secretion of
other steroid hormones
1. Adrenal androgens
2. Progesterone
3. Estrogens
c. Glucocorticoids: (acquired name from their role in glucose metabolism)
i. Role in glucose metabolism:
1. Increase blood glucose concentrations and glucose secretion by the
liver
2. Increase hepatic sensitivity to the gluconeogenic actions of glucagon
and catecholamines
3. Decrease glucose uptake and utilization by peripheral tissue
4. Increasing proteolysis

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

5. Decreasing protein synthesis in muscles

ii. Metabolic Effects
1. Gluconeogenesis
2. Mobilization of amino acids from protein in striated muscle
3. Protein catabolism
4. Fat synthesis and lipolysis
5. Hepatic enzymatic activities that convert amino acids to glucose
iii. Exert potent and diverse actions on glucose, protein, and bone metabolism and
possess anti-inflammatory, antiallergenic, and immunosuppressant actions
iv. Metabolic effects of the glucocorticoids result in the following:
1. An increase in circulating amino acid levels
2. An overall depletion of muscle protein
3. A negative nitrogen balance
4. A mobilization of fatty acids, converting cell metabolism from using
glucose for energy to using fatty acids for energy
5. An antagonistic effect on antidiuretic hormones to maintain water balance
6. A lowering of the threshold for electrical excitation in the brain
7. A reduction in the amount of new bone synthesis
v. Hypothalamic cortocotrophin-releasing factor (CRF) stimulates the release of
pituitary adrenocorticotropic hormone (ACTH)
vi. This hypothalamic-pituitary-adrenal (HPA) axis regulates and stimulates cortisol
synthesis release by the adrenal cortex
vii. Three factors important in regulating ACTH secretion:
1. Circulating Cortisol Levels
2. Stress Levels
3. Circadian (diurnal) Rhythm
viii. Symptoms related to glucocorticoid deficiency:
1. Hypoglycemia
2. Anorexia
3. Nausea and vomiting
4. Flatulence
5. Diarrhea
6. Hyper-pigmentation of the skin
7. Anxiety
8. Depression and loss of mental activity
d. Mineralocorticoids:
i. Most prevalent naturally occurring aldosterone
1. Production occurring the outer layer of the cells of adrenal cortex
2. Regulation of potassium, sodium, and water balance
3. Aldosterone: role in promoting the reabsorption of sodium into the blood
in exchange for potassium secreted into the renal tubules for urinary
excretion
4. Angiotensin II: impact on synthesis and secretion of aldosterone
5. Mechanisms controlling aldosterone levels:
a. Renal renin releasea reduction in renal blood flow increases
aldosterone levels by the renin-angiotensin-aldosterone system
b. Pituitary adrenocorticotropic hormone (ACTH)
c. When sodium level low/ K level high/ aldosterone will increase
6. Symptoms related to mineralocorticoid deficiency:
a. Fluid and electrolyte imbalance
b. Orthostatic hypotension
c. Hyponatremia
d. Hyperkalemia
e. General malaise
f. Muscle weakness

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

g. Muscle pain
h. Cardiac arrhythmias

III.

e. Sex steroids:
i. Amount of sex steroids and some weak anabolic androgens produced in adrenal
cortex insignificant compared to hormone secretions by gonads
ii. A substantial endocrine imbalance possible with certain conditions
Pathophysiology:

a. Adrenal Insufficiency:
i. Primary (Addison Disease): due to destruction of adrenal cortex by infection or
hemorrhage
1. Resulting in hyposecretion of all adrenocortical hormones
2. Characteristics of Addison Disease
3. Major Complications: sudden life threatening exacerbation called
addisonian crisis(extremes of hypotension, hyponatremia, dehydration,
hyperkalemia, and hyperthermia)
4. Characteristics related to glucocorticoid deficiency: hypoglycemia,
anorexia, nausea, vomiting, flatulence, diarrhea, hyperpigmentation,
anxiety, depression, loss of mental acuity
5. Characteristics related to mineralocorticoid deficiency: fluid/electrolyte
imbalance, orthostatic hypotension, hyponatremia, hyperkalemia, general
malaise, muscle weakness, muscle pain, cardiac arrhythmias
ii. Secondary adrenal insufficiency: due to insufficient secretion of ACTH by anterior
pituitary; little or no alteration in aldosterone secretiontherefore there is
glucocorticoid insufficiency with no effect on mineralocorticoid
1. Most common cause: long term tx of nonendocrine disorders with
pharmacologic doses of glucocorticoid drugs
b. Cushing Syndrome: rare disorder resulting from increased adrenocortical secretion
of cortisol, resulting in chronic elevation in glucocorticoid and adrenal androgen
hormones
i. Mineralcorticoid levels usually not affected
ii. Causes: ACTH-dependent adrenocortical hyperplasia; tumor; ACTH secreting
tumor; long-term administration of large doses of glucocorticoids
iii. Characteristics: moon face, glaucoma, hirsutism and masculinization,
cervicodorsal fat (buffalo hump), extremity thinning/atrophy, abdominal straie,
protuberant abdomen, truncal obesity, swelling, brittle bones

c. Salt-Losing Adrenogenital Syndrome;

i. Congenital condition: inherited enzymatic interference with normal biosynthesis
of glucocorticoids and mineralcorticoids
ii. Low levels of corticosteroids stimulate production of large amounts of
corticotropin (ACTH)
iii. Adrenal glands respond to increased ACTH by increasing production of adrenal
androgens leading to abnormally high testosterone levels resulting in
masculinization

d. Hyperaldosteronism:

i. Production of excessive aldosterone by some tumors of adrenal cortex impacting

hormone action in the distal renal tubule
1. Hypertension secondary to sodium and water retention
2. Hypokalaemia: induced muscle weakness
ii. Surgical removal of tumor necessary

IV.

Steroid Hormone Agonists:

a. Glucocorticoids:
i. The primary endogenous glucocorticoids produced by the adrenal gland are
cortisol (hydrocortisone) and cortisone

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

ii. They have no role in any systemic anti-inflammatory therapeutic regimen

because of their high mineralcorticoid activity relative to their anti-inflammatory
activity
iii. All natural and synthetic glucocorticoids act by binding to a specific cytoplasmic
glucocorticoid receptor
iv. Used mainly as anti-inflammatory agents, immunosuppressive agents,
replacement therapy for individuals with adrenal insufficiency, and adjunctive
treatment in selected malignant disorders
v. A common adverse effect of synthetic glucocorticoids administered in high doses
for anti-inflammatory and immunosuppressant effects (combined or separately) is
suppression of the HPA Axis and may lead to secondary adrenal insufficiency
vi. Abrupt discontinuation of a glucocorticoid following prolonged administration may
result in acute adrenal insufficiency; to prevent this the drug must be tapered
vii. Prototype Drug: prednisone (Deltasone, Prednicot) four times more
potent than naturally occurring cortisol resulting in longer acting and a more
potent anti-inflammatory response
1. Most often used for treatment of inflammatory conditions and autoimmune
diseases
viii. Drugs Closely Related to Prednisone:
1. Hydrocortisone: Solu-Cortef (rectal preparations are absorbed as much
as 50%)
a. Structurally identical to cortisol
b. Treatment of choice: adrenal insufficiency replacement therapy
c. Rectal preparations used for ulcerative colitis
2. Methylprednisone: Medrol (potent anti-inflammatory and
immunosuppressive effects)
3. Dexamethasone: Decadron
a. No mineralocorticoid activity with maximum anti-inflammatory
activity
b. Used in short term situations requiring the max anti-inflammatory
(cerebral edema and septic shock), or replacement therapy, or
antiemetic
c. Used to diagnose Cushing Diease
4. Betamethasone: Celestone
a. Produces anti-inflammatory and immunosuppressive effects
b. Uses similar to those of dexamethasone and methylprednisolone
c. Also used to prevent respiratory distress syndrome in premature
infants
5. Inhaled glucocorticoids:
a. Metabolized in lungtherefore reducing systematic effects
b. Can develop dysphonia & oropharyngeal Candida albicans
infection)
6. Topical glucocorticoids:
a. Non-specific anti-inflammatory activity leading to decrease in
edema, erythema, and pruritus
7. Intra-articular injection (injected glucocorticoids)
a. Produce local effects for symptomatic relief of joint pain and
increased joint mobility
b. Allow treated area sufficient time to heal 24-48 hours
b. Mineralocorticoids
i. Aldosterone, the naturally occurring mineralocorticoid, is expensive and requires
parenteral administration
ii. Therefore, fludrocortisone is prototype
iii. This adrenal corticosteroid has both high mineralocorticoid and glucocorticoid
activity

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
1. Its glucocorticoid potency is 15 times greater than that of
hydrocortisone
iv. However, when used as replacement therapy in adrenocortical deficiency, its
therapeutic effect is mineralocorticoid activity
v. Prototype Drug: fludrocortisone (Florinef Acetate)

V.

Steroid Hormone Antagonists:

a. Steroid hormone antagonists act to inhibit or suppress the adrenal cortex, thus
controlling the symptoms of Cushing syndrome (adrenocortical hormone excess)
i. Prototype Drug: aminoglutethimide (Cytadren)

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
Chapter 49: Drugs Affecting Blood Glucose Levels
I.

II.

Diabetes Mellitus:
a. Although an estimated 23.6 million people are diagnosed with diabetes, 5.7 million are
unaware they have the disease
b. Approximately 5% to 10% of Americans diagnosed with diabetes have type 1, whereas
90%-95% have type 2
c. People with diabetes are at increased risk for cardiovascular disease, kidney failure,
blindness, nervous system disease, extremity amputations, dental disease, and
complications of pregnancy
d. In 2007, the total annual economic cost of diabetes was estimated to be $174 billion
e. Exogenous insulins are used to replicate deficient intrinsic insulins prototype drug is
regular insulin
f. Other types of insulin: oral antidiabetic drugstwo groups: sulfonylureas and
nonsulfonylureas
i. Prototype of sulfonylureas (antiglycemics) is glyburide
ii. Prototype of nonsulfonylureas (antihyperglycemics) is metformin
Physiology:
a. Glucose is made available to the body from food that is ingested and from the
production of glucose by the liver
b. Unable to store or synthesize glucose, the brain depends on a steady supply of glucose
from the circulation and extracts its energy on a nearly continuous basis
c. Three body systems are involved in the regulation and use of glucosethe liver,
pancreas, and skeletal muscle tissue
d. The liver synthesizes its own glucose supply (a process called gluconeogenesis) in
addition to storing the releasing glucose
e. The pancreas is both an exocrine and an endocrine gland
i. Endocrine function is to synthesize and secrete peptide hormones (insulin,
glucagon, and somatostatin) by the islets of Langerhans
f. These three hormones regulate and maintain homeostasis of blood glucoseislets of
Langerhans contain the following types of cells:
i. Beta Cells: secrete hypoglycemic hormone insulin
ii. Alpha Cells: secrete hyperglycemic hormone glucagon
iii. Delta Cells: release somatostatin, hormone that inhibits both glucagon and
insulin secretion
iv. F Cells: synthesize and secrete pancreatic polypeptides used in digestion
g. Insulin regulates carbohydrate metabolism and blood glucose levels
i. Functions of Insulin: regulates carbohydrate metabolism but also plays important
role in metabolizing fats and proteins
1. Lowers blood glucose levels by stimulating peripheral glucose uptake
2. Specific Receptor sites allow the glucose to enter the cells
3. Insulin resistance: inappropriately elevated hepatic glucose output and
impaired glucose uptake by the muscle tissue
4. In the liver, insulin: promotes the uptake and storage of glucose in the
form of glycogen, promotes the conversion of excess glucose into fat, and
suppresses hepatic gluconeogenesis and glycogenolysis
5. All tissues in body need insulin for glucose to enter cells: except brain,
nerves, intestine, liver, retina, erythrocytes, and renal tubules
ii. Insulin synthesis and release:
1. Plasma glucose level single most important factor in controlling rate of
insulin synthesis and release
2. Other factors that influence release: blood levels of sugars, levels of free
fatty acids, growth hormone, thyroid-stimulating hormone, glucagon,
sympathetic and parasympathetic stimulation, adrenocorticotropic
hormone, and cortisol
iii. Any of the following can affect blood glucose levels:

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

III.

IV.

1. Stress or illness
2. Secretion of insulin-antagonistic hormones that affect glucose metabolism
3. Rates of hepatic synthesis of glucose or conversion of glycogen to yield
glucose
4. Presence and levels of insulin antibodies
5. Use of glucose by peripheral cells or tissues
6. Number of cellular insulin receptors
iv. In response to postprandial levels: insulin is released into bloodstream by the
beta cells
v. When serum glucose decreases, the alpha cells release glucagon into the
bloodstream, stimulating release of glycogen from hepatic storage sites
vi. Hepatic glycogen stores are depleted 6 hours after a meal
vii. Muscles begin to release amino acids that are converted to glucose; free fatty
acids broken down from adipose tissue converted in to glucose by the muscle and
liver cells
h. Glucagon:
i. Declining blood glucose levels stimulate the release from pancreatic islet alpha
cells
ii. Sympathetic nerve impulses, exercise, infection, and trauma also stimulate
release
iii. In the liver, it stimulates glycogenolysis and gluconeogenesis resulting in a
release of glucose into the blood
Pathophysiology:
a. Diabetes mellitus is a serious chronic disease that affects people of all ages and ethnic
groups
b. Type 1 diabetes is an autoimmune disorder characterized by the destruction of the
insulin-secreting beta cells, in the pancreas, leading to absolute insulin deficiency
i. Hyperglycemiacirculating blood glucose is not acceptable to cells, so body
mistakenly interprets this to mean that there is not enough glucose and thus
initiates two other processes to gain energy Breaking down lipids and proteins
c. Type 2 diabetes is the result of insulin resistance by tissues and usually a decrease in
insulin production
i. Abnormalities of carbohydrate, fat, and protein metabolism
ii. No appreciable loss of pancreatic beta cells or cellular activity from the islets
occurs in type 2 diabetes
iii. Pancreas tries to overcome resistance by producing insulin; because peripheral
tissue is resistant to insulin, it does not enter the cells but stays in the
bloodstream
iv. Metabolic syndrome is a precursor to type 2 diabetes
d. Gestational diabetes mellitus (GDM) occurs when a womans pancreatic function is not
sufficient to overcome the insulin resistance created by the anti-insulin hormones
secreted by the placenta
e. Criteria for Diabetes Mellitus Diagnosis:
i. Plasma glucose=126mg/dL after fasting for 8 hours or
ii. Plasma glucose=200mg/dL during and oral glucose tolerance test (OGTT) or
iii. An A1C level of 6.5% or higher or
iv. Symptoms of diabetes and hyperglycemia or hyperglycemic crisis (plasma
glucose greater than 200mg/dL anytime throughout the day)

Insulins:
a. Synthetic insulin (exogenous) acts in the same manner as endogenously produced
insulin
i. Sources of exogenous insulin, historically included pork and beef pancreas, but
not only recombinant DNA technology or genetic engineering is used to create
human-like insulin

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

ii. Modifying the amino acid sequence of the human insulin molecule has resulted in
new, rapid-acting insulin analogues, such as aspart, lispro, or gluisine (produce by
rDNA technology)
iii. Human sourced insulin is considered the standard therapy
iv. The potency of insulin is expressed in the United States Pharmacopeia (USP) or
international units
b. Drugs Closely Related to Regular Insulin: Rapid Acting Insulins
i. Rapid acting insulin: that are analogues of rapid-acting regular insulin are now
available: aspart (NovaLog), lispro (Humalog), and glulisine (Apidra)
1. Administer within 15 minutes of start of the meal
2. Can be used in insulin pumps
c. Drugs Different from Regular Insulin: Long-Acting Insulin
i. NPH: (intermediate) protamine is added to insulin to create NPH
1. Humulin N
2. Onset: 1-1.5 hours
3. Peak: 4-12 hours
4. Duration: up to 24 hours
5. Considered intermediate acting
6. Cloudy (suspension must be rolled gently)
7. Given SC (NEVER IV)
8. Observe for hypoglycemia in mid to late afternoon
ii. Detemir: long acting insulin
1. Administered once or twice daily only SC not IV or pump
2. Cannot be mixed with any other insulins
3. Less weight gain and lower risk for nocturnal hypoglycemia than NPH
iii. Glargine:
1. Administered once daily at bedtime
2. Duration: 24 hours (no peak)
iv. Exubera:
1. Onset: 10-20 minutes
2. Inhaled insulin

V.

Noninsulin Antidiabetic Medications

a. Until the mid-1990s, the sulfonylurea drugs were the only class of oral antidiabetic
agents available to manage type 2 diabetes
b. Currently five chemical classes of oral antidiabetic agents are available

c. Sulfonylureas
i. First and second generation drugs (same class but developed at different times
and have some different characteristic)
ii. Glyburide is the prototype and is a second generation drug
iii. Prototype Drug: glyburide (DiaBeta)

d. Nonsulfonylureas:
i. The nonsulfonylurea antidiabetics compromise three different classes grouped by
their chemical structure:
1. Biguanides
2. Thiazolidinediones
3. Alpha-glucosidase inhibitors
ii. These drugs are considered by their mode of action:
1. Improving insulin action
2. Delaying the digestion of carbohydrates
iii. Prototype Drug: metformin (Fortamet, Glucophage)

VI.

Glucose-Elevating Agents
a. Glucagon is a hyperglycemic polypeptide hormone produced by the alpha cells of the
pancreatic islets of Langerhans
b. Its physiologic effect is generally the opposite of that of insulin

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
c. Glucagon is the bodys first line of defense against hypoglycemia
d. The main stimulus to glucagon secretion to decrease in intracellular glucose
concentrations that usually occurs as a result of a drop in serum blood sugar
i. Prototype Drug: Glucogon (GlucaGen)
1. Used in unconscious patients to reverse insulin overdose
a. Drugs Different:
i. Diazoxide:
1. Hyperglycemic effects
2. Inhibits insulin release from the pancreas

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
Chapter 50: Drugs Affecting Pituitary, Thyroid, Parathyroid, and
Hypothalamic Function:
I.

II.

10

Physiology
a. Pituitary Gland Function
i. Anterior lobe of the pituitary gland: it controls the function of glucocorticoid
hormone levels (ACTH), body growth and metabolism (GH), function of the thyroid
gland (TSH), gonadal function (FSH and LH), milk production and breast growth
(prolactin)
ii. Posterior lobe of the pituitary gland: it stores and secretes two effector
hormones (hormones that produce an effect when stimulated): oxytocin and
vasopressin (also known as antidiuretic hormone [ADH])
b. Thyroid gland function:
i. It controls cellular metabolism and promotes normal growth and development
ii. 100-200mcg of iodide is adequate for thyroid gland to make normal hormones
iii. controls celllar metabolism and promotes normal growth and development:
regulate heat/energy productin, blood volume, cardiac output, oxygen
consumption, and metabolism of fats, carbs, and proteins
iv. produces calcitonin
c. Parathyroid gland function
i. PTH affects three target organs: bone, kidneys, and GI tract
ii. The major controlling factor for PTH secretion is serum calcium
Pathophysiology
a. Anterior pituitary gland dysfunction: it includes growth hormone deficiency and excess
i. Deficiency:
1. In childrenidiopathic (most commoninadequate GHRH) or congenital
(decreased growth rate within first years of life)
2. AdultsGH deficiency as children or develop it in adulthood secondary to
a pituitary tumor or its treatment
ii. Excess:
1. Gigantism: uncommon condition in childrencaused by excessive
secretion of GH by somatrope adenomas (7ft or taller)
2. Acromegalyin adults: after puberty and the closure of the epiphyseal
plate closesvery uncommon
a. Enlarged heart, hypertension, accelerated atherosclerosis,
peripheral neuropathies, and muscle weakness
b. Posterior pituitary gland dysfunction: major disorders are diabetes insipidus (DI) and
syndrome of inappropriate antidiuretic hormone (SIADH)
i. DIcaused by either a deficiency in or decreased response to ADH
ii. SIADHexcessive ADH secretion secondary to failure of the negative feedback
system responsible for its release and inhibition
c. Thyroid Gland Dysfunction: hyperfunctioning or hypofunctioning gland, malfunctions
that may be caused by either a congenital defect of by a problem that occurs later in life
i. Dramatic changes in patterns of growth and development, functions of the
cardiovascular, respiratory, GI, neuromusclular, skeletal, and reproductive
systems can result
ii. Increase in the size of the thyroidgoiter
iii. Congenital Hypothyroidism: occurs from abnormal synthesis of of hormone,
deficient TSH, or absence of thyroid gland (Hashimotos)
iv. Drop of blood taken from heel to measure newborns thyroid hormone levels
v. Hyperthyroidism (thyrotoxicosis)Graves Disease is the most common cause
d. Parathyroid Gland Dysfunction: PTH is a major regulator of serum calcium and
phosphate
i. A decrease in serum calcium concentration is the dominant regulator of PTH, with
a response of just a few seconds

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

11

ii. A decrease in phosphate causes an indirect effect on PTH by combining with

calcium and decreasing serum calcium concentrations

III.

Growth Hormones:
a. GH deficiency, leading to short stature, was initially treated with GH injections extracted
from the pituitary glands of cadavers
b. Presently, synthetic human GH (rhGH), produced from recombinant DNA, is available
c. rhGH is very expensive
d. Prototype Drug: somatropin
e. **Patients taking somatropin should have which lab values monitored on a routine basis
due to adverse effects of drug therapyTSH and Glucose Level
f. Drugs Different from Somatrophin:
i. GH antagonists decrease GH secretion
ii. Almost all are conditions caused by pituitary tumor and require surgery or
radiation
iii. Octreotide Acetate (sandostatin)
1. Potent inhibitor of GH secretion
2. Long acting antagonistic analogues
3. Treatment for acromegaly

IV.

Posterior Pituitary Hormone Regulators:

a. The posterior pituitary stores two hormones that are produced in the hypothalamus
i. Vasopressin
ii. Oxytocin
b. Desmopressin and vasopressin are synthetic analogues of the naturally occurring
posterior pituitary hormone
c. Prototype Drug: desmopressin
d. **Desmopressin is used to treatcentral DI, primary nocturnal enuresis, hemophilia A**

V.

VI.

Thyroid Drugs
a. Thyroid hormones influence essentially every organ system in the body
b. Thyroid disorders involve an alteration in the quantity of thyroid hormone secretion,
enlargement of the thyroid gland (goiter), or both and are classified as either
hyperthyroidism or hypothyroidism
c. Hypothyroidism may be mistaken for the normal aging process
d. The only treatment for hypothyroidism is lifelong replacement of thyroid hormones that
are adequate to meet the individuals metabolic needs
e. Prototype Drug: levothyroxine ( T 4 ; Levothroid, Synthroid)

Antithyroid Compounds:
a. Hyperthyroidism is treated with thyroid-hormone antagonist drugs, surgery, or
radioactive iodine
b. The purpose of treatment is to reduce the amount of functional thyroid tissue
c. Prototype Drug: methimazole (MMI)

VII.

Parathyroid Drugs
a. Antihypercalcemia, Calcium-Regulator Drugs

i. Antihypercalcemic drugs do not directly affect the parathyroid gland or PTH but
rather inhibit bone reabsorption of calcium
ii. These agents are frequently used in the treatment of Paget diseasebone
inflammation that results in thickening, softening, and bowing of the affect bones
iii. Individuals with symptomatic disease experience bone pain and deformity,
fractures, spinal cord compression, or cranial and spinal cord entrapment
iv. Prototype Drug: calcitonin, salmon

b. Antihypocalcemic Drugs:
i. Vitamin D compounds regulate absorption of calcium and phosphate
ii. Vitamin D is considered a hormone although it is not a natural human hormone
iii. Vitamin D metabolites:

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

iv.
v.
vi.
vii.

12

1. Control intestinal absorption of dietary calcium

2. Tubular reabsorption of calcium by the kidney
3. Mobilization of calcium from the skeleton, in conjunction with PTH
Vitamin D is also involved in magnesium metabolism
Vitamin D works together with PTH and calcitonin to regulate calcium
homeostasis
Vitamin D stimulates calcium absorption from the intestine and restores the
serum calcium to normal level
Prototype Drug: calcitriol (1,25dihydroxyvitamin D3, Rocaltrol
[capsules, solution], Calcijex [parenteral])

Chapter 15: Drugs Relieving Anxiety and Promoting Sleep:

**What system in the brain is responsible for emotion?limbic system
I.
Emotions and Neurotransmitters
a. The limbic system in the brain is known to be primarily responsible for emotions
b. The amygdala receives incoming sensory signals and then communicates with the frontal
lobes of the brain
c. The amygdala can signal the brain that a threat is present and set off a fear response or
anxiety
d. Another part of the brain, the hippocampus is responsible for processing threatening or
traumatic stimuli
e. The brain sends its messages to the body by way of the nervous system
f. Neuroplasticity: structures of the brain undergo frequent refinement in response to the
internal and external environment
g. GABA: gamma aminobutyric acid is a neurotransmitter that either inhibits or excites
receptors
II.
Sleep:
a. Sleep is a time of bodily rest, although the brain remains active
b. There are two phases:
i. Rapid Eye movements (REM)
ii. Non-rapid eye movement (NREM)
1. Stage 1light sleep; muscles relax; brain waves are irregular and rapid
2. Stage 2brain waves are larger than in stage 1, with bursts of electrical
activity
3. Stages 3 and 4deep sleep, with even larger, slower brain waves called
delta waves
c. A number of physiologic changes occur during sleep
d. The amount of sleep needed by a person varies throughout the life span, with infants
requiring the most sleep and adults requiring the least
III.
Anxiety:
a. A feeling of unease that something bad or undesirable may happen
b. Some anxiety is normal; it is a protective mechanism
c. Anxiety becomes pathologic when it is severe and chronic and interferes with a persons
ability to function in normal life
d. Anxiety disorders can become progressively worse if they are untreated
e. Anxiety commonly occurs in combination with other mental or physical illness ting
f. Types of anxiety disorders:
i. Panic disorder: sudden feelings of terror that come on suddenly or repeatedly
without warning
ii. Phobic Disorders: persistent, unrealistic fears of situations or objects that do not
realistically pose a significant threat or danger
1. Social Phobia (Social anxiety disorder)
2. Specific Phobia: intense, irrational fear of a particular thing or situation
that poses little or no actual danger

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

IV.

V.

13

3. Obsessive Compulsive Disorder (OCD)recurrent, unwelcome thoughts

with rituals attempting to control the anxiety resulting from these thoughts
4. Post Traumatic Stress DisorderPTSD
5. Generalized Anxiety Disorder(GAD) chronic anxiety lasting longer than 6
months and can cause the person to have exaggerated worry and tension
every day

Sleep Disorders:
a. Between 50-70 million Americans have a sleep disorder
b. These disorders are many and may include the following problems:
i. Narcolepsy: sudden irresistible sleep attacks of unknown origin lasting from
seconds to minutes, two to six times a day
ii. Sleep apnea: a group of disorders characterized by cessation of breathing during
sleep
iii. Sleepwalking: getting up and walking about while still asleep
c. These disorders are many and may include the following problems:
i. Night terrors: occur only in children, with period of fright, crying, moaning, or
screaming after a brief time asleep
ii. Excessive daytime sedation
iii. Insomnia: difficulty falling asleep or staying asleep, waking up too early in the
morning without being able to return to sleep, waking up frequently during the
night with difficulty returning to sleep, not sleeping long enough, feeling that
sleep was not restful, sleeping poorly

Drugs to Relieve Anxiety:

a. Selective Serotonin Reuptake Inhibitors:
i. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant
drugs, some of which are now considered first-line therapy for anxiety disorders
ii. Low serotonin levels are known to be present in severe stress and in many mood
and anxiety-related disorders
iii. SSRIs indirectly increase the amount of the neurotransmitter serotonin available
in the synapses
iv. SSRIs are generally well tolerated with few adverse effects
v. Must be taken for a few weeks for their full anti-anxiety effect to take place
vi. Prototype drug is sertraline

b. Tricylcic Antidepressants:
i.
ii.
iii.
iv.

TCAs are another class of antidepressants

TCAs are as effective as the SSRIs in treating most anxiety disorders
TCAs work by affecting the regulation of serotonin or norepinephrine in the brain
TCAs have a higher adverse effect profile than SSRIs, which limits their use as
antidepressantsdizziness, drowsiness, dry mouth, weight gain
v. Prototype drug: nortriptyline

c. Monoamine Oxidase Inhibitors

i. MAOIs are the oldest class of antidepressants
ii. Used to treat anxiety disorders are phenelzine, tranylchpromine, and
isocarboxazid
iii. These drugs are occasionally prescribed for panic disorder and social phobia
iv. Monoamine oxidase is the enzyme that degrades serotonin in the synapse
v. By inhibiting the enzyme, higher levels of serotonin can remain in the synapse
and be active
vi. The MAOIs are associated with significant risk for serious drug-food interactions
vii. Prototype drug is phenelzine

d. Beta-Blockers:
i. Adrenergic drugs most frequently used for a wide variety of cardiac conditions
ii. Among other actions, they slow heart rate

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

14

iii. This helps the patient with some types of anxiety who may be uncomfortable and
highly aware of the tachycardia and palpitations
iv. Prototype drug: propranolol

e. Benzodiazepines:
i. Used for a number of therapeutic effects
ii. As a class, they appear to potentiate the effects of GABA
iii. The result is more CNS depression than would normally be found
iv. Benzodiazepines bind to specific receptor sites to produce their effects
v. As a drug class, they have high margin of safety
vi. Prototype Drug: Lorazepam
**Benzodiazepines are used to treatanxiety, seizures, and alcohol withdrawal**
**Benzodiazepines has a short duration of action**

VI.

Nonbenzodiazepines:
a. Buspirone
i. Azaspirodecanedione that is not chemically or pharmacologically related to
benzodiasepines
ii. It is used to treat the symptoms of anxiety although exactly how it works is
unknown
iii. Optimum relief of anxiety usually occurs after 3-4 weeks of treatment
iv. Buspirone is intended for short-term therapy; patients who have been treated
with buspirone for up to 1 year have not required a dosage increase to maintain
therapeutic effect and withdrawal symptoms did not occur when the drug was
stopped

b. Hydroxyzine:
i. Hydroxyzine is a miscellaneous antianxiety drug
ii. It exerts CNS depressant activity in subcortical areas
iii. It rapidly produces a feeling of calm and relieves anxiety without impairing
mental alertness
iv. It may be coadministered with a narcotic to control pain while minimizing the
nausea that may be an adverse effect from the narcotic

c. Meprobamate:

i. Used for short-term management of anxiety symptoms

ii. Has selective effects at multiple sites within the CNS, including the thalamus and
the limbic system
iii. It may also inhibit multineuronal spinal reflexes
iv. It has mild tranquilizing properties and some anticonvulsant and muscle-relaxant
properties
v. Meprobamate can produce several CNS adverse effects
vi. Pregnancy category C drug

VII.

Nonbenzodiapines to Promote Sleep:

a. Eszopiclone
i. Lunesta: nonbenzodiazepine hypnotic
ii. The drug induces sleep quickly, prevents waking during the night
iii. Believed to achieve its therapeutic effect from interaction with GABAreceptor/benzodiazepine-receptor complexes
iv. It is the only drug for insomnia that is approved for long-term use (up to 6
months)
v. Rapid onset: within 1 hour and is metabolized in the liver and excreted in the
urine
vi. The most common adverse effects after 6 weeks of use were headache,
prolonged drowsiness, and an unpleasant taste

b. Zaleplon:
i. Sonata is a sedative for short-term use (up to 28 days)

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

15

ii. Although a nonbenzodiazepine and not chemically related to the

benzodiazepines, it does interact with GABA-benzadiazepines (BZ) complex
iii. The most common adverse effects are drowsiness, dizziness, light-headedness,
and difficulty with coordination
iv. Pregnancy category C drug
v. May lead to dependency and rebound insomnia is possible

c. Zolpidem:
i. Ambien: used for short term treatment of insomniagenerally not for more than
7-10days
ii. It induces sleep rapidly and should be taken immediately before going to bed
iii. Although it is not chemically related to the benzodiazepines
iv. Generally preserves all of the sleep stages and has only minor effects on REM
sleep
v. The most common adverse effecs from zolpidem are headache, prolonged
drowsiness, and dizziness

d. Ramelteon
i. Melatonin receptor agonists stimulate the same receptor sites as endogenous
melatonin
ii. Ramelteon is used in the treatment of insomnia when the patient has difficulty
falling asleep
iii. Ramelteon has high affinity at two specific melatonin receptors
iv. Common adverse effects of ramelteon include headache, daytime sleepiness,
dizziness, tiredness, nausea, worsening insomnia, and colds

VIII.

Drugs that Promote Sleep from Other Classes:

a. Trazodone:
i. Trazodone (Desyrel) is an atypical antidepressant
ii. This drug causes significant sedation as an adverse effect
iii. Trazodone is most commonly used to promote sleep

b. Chloral Hydrate:
i. Chloral hydrate is a non-barbiturate hypnotic used to induce sleep and to cause
preoperative sedation
ii. It can be used as an adjunct to opiates and analgesics in pain control
iii. In therapeutic doses, chloral hydrate has little effect on respirations, blood
pressure, or relflexes
iv. It does produce numerous adverse effects in CNS

IX.

Barbituates:
a. Such as phenobarbital, secobarbital, and pentobarbital were used to treat insomnia
before the availability of benzodiazepines.
b. Although they are effective short-term treatment of insomnia, they are also highly habit
forming
c. Patients can develop tolerance and physical and psychological dependence on the drugs

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
Chapter 18: Drugs Treating Seizure Disorders:
I.

II.

III.

IV.

V.
VI.

16

Epilepsy: a brain disorder

a. Seizures are loss of consciousness with generalized muscle twitching or mild alterations
in consciousness with repetitive blinking
b. Patients with patterns of seizures who are diagnosed with epilepsy are treated with
antiepileptic drugs
c. The three main ways that antiepileptic drugs work are
i. Decreasing the rate at which sodium flows into the cell
ii. Inhibiting calcium flow rate into the cell through specific channels
iii. Increasing the effect of the neuroinhibitor gama aminobutyric acid (GABA)
Physiology:
a. Action potentials within neurons are initiated by an influx of sodium into the cell
b. Influx of calcium through specialized voltage-dependent channels also plays a role in
creating an action potential
c. When the cell fires, there is a release of neurotransmitters into the synaptic cleft
d. The neurotransmitter glutamate produces excitation
e. GABA normally acts as a counterbalance to glutamate, preventing hyperexcitation
Pathophysiology:
a. When a group of neurons exhibits coordinated, high-frequency discharge, it is termed a
focus
b. The causes of a focus include head trauma, tumor growth, hypoxia, and inherited birth
defects
c. When the activity from a focus spreads to other areas of the brain, causing other neurons
to join in the hyperactivity, seizures result
d. Seizures may result from either high levels of glutamate or low levels of GABA
e. Partial seizures occur when focus activity is limited to an area of the brain
i. Simple: twitching a particular muscle group
ii. Complex: involve some involuntary muscle twitching or movement also, but the
patient seems confused or exhibits odd behavior (loss of consciousness)
f. When the focus activity is within both hemispheres, generalized seizure symptoms
occur
i. Tonic-clonic: entire cerebral cortex is altered by hyperexcited neurons
ii. Absence seizure: very brief loss of consciousness, lasting several seconds but less
than 1 minute
iii. Atonic seizure: a sudden loss of muscle tonehead drop or drop attack
iv. Myoclonic seizure: sudden rapid muscle contractions
v. Status epilepticus: one seizure follows another without recovery of consciousness
between events or return baseline clinical state, or lasts longer than 5 minutes
Antiepileptic Drugs that Decrease Sodium Influx
a. Control seizures by decreasing sodium influx into the cells
b. Sodium influx causes an action potential
c. Phenytoin is a representative of a class of drugs called hyandoins
d. Prototype Drug: phenytoin (Dilantin)
e. **What condition places the patient at greater risk for toxicity to phenytoinMalnutrition
(affects protein albumin that will be available for binding)**
Antiepileptic Drugs that Decrease Calcium Influx
a. Prototype Drug: ethosuximide (Zarontin)
b. **Ethosuximide is used to treat absence seizures**
Drugs used in Seizures related to pre-eclampsia and eclampsia:
a. Magnesium sulfatecompletely different from othersalso used to control preterm labor
i. Depresses CNSblocks neuromuscular transmission of acetycholine and
decreasing amount neurotransmitter liberated at the end plate by motor nerve
impulses

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

17

Chapter 20: Drugs Affecting Muscle Spasm and Spasticity:

I.

II.

III.

Chapter summary:
a. Spasmolytics:
i. Treats spasticity: involuntary muscle contraction that is not coordinated with other
muscles and is associated with upper motor neuron syndromes
ii. Centrally acting or peripherally acting
b. Skeletal muscle relaxants:
i. Used in combination with physical therapy and anti-inflammatory agents to treat
muscle sapsms
Physiology:
a. The human body contains approximately 600 skeletal muscles
b. Skeletal muscles movement is voluntary
c. Striated muscle is composed of two contractile proteins
d. Muscle contraction is triggered by a sudden inflow of calcium ions (Ca2+)
e. In the resting state, the protein tropomyosin winds around actin and covers the myosinbinding sites
f. Muscle contraction stops when Ca2+ is removed from the immediate environment of the
myofilaments
Pathophysiology:
a. Muscle Spasm
i. Muscle spasm is a sudden, violent involuntary contraction of a muscle or group
of muscles resulting from an imbalance of excitatory and inhibitory input from
descending motor pathways
ii. Spasms are related to a localized skeletal muscle injury or an imbalance in
electrolytes
iii. Tonic spasm is characterized by an unusually prolonged and strong muscular
contraction, with relaxation occurring slowly
iv. Clonic: contractions of the affected muscles occur repeatedly, forcibly, and in
quick succession, with equally sudden and frequent relaxations
b. Spasticity
i. Spasticity is a condition in which certain muscles are continuously
ii. Motor disorder of involuntary velocity-dependent increased muscle tone that is
associated with neurologic conditions or trauma to CNS
iii. This contraction causes stiffness or tightness of the muscles
iv. Spasticity may be associated with spinal cord injury

IV.

Centrally Acting Muscle Relaxants:

V.

Centrally Acting Spasmolytics

a. They act in the central nervous system (CNS)

b. Prototype Drug: cyclobenzaprine (Flexeril)
c. **Cyclobenzaprine is chemically similar to which of the following drugs?
a. The centrally acting spasmolytics work in the CNS to reduce excessive reflex activity and
to allow muscle relaxation
b. Used to alleviate musculoskeletal pain and spasms and reduce spasticity in a variety of
neurologic disorders
c. Prototype Drug: baclofen (Lioresal)
d. **Baclofen therapy is effective at treating muscle spasms due to cerebral vascular
accidentfalse

VI.

Peripherally Acting Spasmolytics

a. Peripherally acting spasmolytics relax muscles through direct action on the skeletal
muscle fibers
b. They do not interfere with neuromuscular communication
c. They have NO CNS effects
d. Prototype Drug: dantrolene (Dantrium)
e. **Dantrolene is used to treat which of the following conditions?--

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

18

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

19

Chapter 13: Drugs Affecting Adrenergic Function:

**The sympathetic nervous system produces what type of response?fight or flight
I.
Chapter Summary:
a. The nervous system is divided into two main branches, the central nervous system
(CNS) and the peripheral nervous system (PNS)
b. The efferent division has neurons that carry signals away from the brain and spinal cord
to the periphery
i. Divided into the autonomic and somatic nervous system (works on skeletal
muscle and voluntary movement)
c. Afferent divisions carry impulses from the periphery to the CNS
d. The autonomic nervous system (ANS) is in turn subdivided into the sympathetic
nervous system (SNS)adrenergicand the parasympathetic nervous system (PSNS)
cholinergic
i. Involuntary system responsible for control of smooth muscle, cardiac muscle, and
exocrine glands
ii. Sympathetic nervous system is responsible for the fight or flight response
1. Increase our heart rate, dilate our pupils, mobilize our energy, and redirect
our blood flow from non-essential organs to skeletal muscles
II.
Function of the Autonomic Nervous System:
a. The ANS has been identified as an involuntary system responsible for control of smooth
muscle
b. The actual connection between neurons and effector organs and tissues relies on
neurotransmitters and synaptic transmission
c. Neurotransmitters in the ANS include acetylcholine (Ach), norepinephrine (NE), and
epinephrine (Epi)
d. Synaptic transmission initially involves the synthesis of neurotransmitters in the nerve
terminal
e. In the SNS, preganglionic transmission is mediated by ACh, whereas prostganglionic
transmission is mediated by NE
III.
Neurotransmitters:
a. Acetylcholine: preganglionic neurotransmitter in the SNS and both preganglionic and
postganglionic in the PSNS
b. Norepinephrine: postganglionic neurotransmitter in the SNS and thus responsible for
stimulation of various organs under control of SNS
c. Epinephrine: adrenalinstored in adrenal medullaresponds to action potential however
it is a hormone
d. Dopamine: precursor to NEcapable of stimulating all adrenergic receptors
IV.
Adrenergic Receptors:
a. In the SNS, there are several types of adrenergic receptors, including alpha-adrenergic
and beta-adrenergic receptors
b. Another type of receptor, the dopaminergic receptor, is related to adrenergic receptors in
that dopamine is the precursor to NE
c. Alpha and beta receptors are located throughout the body
d. Alpha-1 and beta-1 receptors respond to Epi, dopamine, and NE
e. Beta-2 receptors respond only to blank
f. Beta-2 and alpha-2 respond to NE and Epi
V.
Pathophysiology:
a. The therapeutic uses of sympathetic drugs are related to providing extra-adrenergic
stimulation or blockade of normal ANS functioning
b. One of the most frequent indications for adrenergic agonist drugs is shock
c. Shock is the result of inadequate tissue perfusion, leaving the cells without the oxygen
and nutrients they need to function normally and survive
d. Drugs create therapeutic effect on the postganglionic side
VI.
Adrenergic Agonists:

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

20

a. Drugs that mimic the action of the SNS

b. They exert their effects by direct or indirect stimulation of adrenergic receptors
i. Indirectincreasing transmission of NE, inhibiting NE reuptake, and inhibiting
MAOI or COMT
c. These drugs are generally divided into two groupscatecholamines and
noncatecholamines
i. Catecholamines: must be given IV infusion, do not cross blood brain barrier, short
duration of actionnoncatecholamines are completely opposite
d. Adrenergic agonists are also classified according to their selectivity
e. Nonselective adrenergic agonists stimulate both alpha and beta receptors
f. Prototype Drug nonselective adrenergic agonist: Epinephrine
g. **Which of the following receptors is stimulated by epinephrine? Alpha 1, alpha 2, beta

1, beta 2
VII.
VIII.

IX.

X.

XI.

Alpha-1 Adrenergic Agonists

a. The alpha-1 adrenergic agonist are drugs that stimulate the alpha-1 receptor directly
b. Prototype drug: Phenylephrine (Allerest)
Alpha-2 and Beta-Adrenergic Agonists:
a. Alpha-2 adrenergic agonists:
i. Stimulation of alpha-2 receptors in the CNS decreases sympathetic outflow by
inhibiting the release of norepinephrine
ii. Prototype Drug: Clonidine (Catapres)
1. Narrow range of specific clinical indications and has fallen out of practice
2. Pharmacotherapeutics: treatment of hypertensiondecreased HR, BP,
vasoconstriction, and renal vascular resistance
3. Renal blood flow and glomerular filtration rate remain unchanged
4. Off-Label: symptoms of alcohol, methadone, or opiate withdrawal during
detoxification; reduction of allergen-induced inflammatory reactions in
patients with extrinsic asthma; smoking cessation, and ulcerative colitis
5. Can also be administered via epidural line to control pain
6. Orally, parenterally, or most frequently transdermally
7. Adverse effects: dry mouth, drowsiness, dizziness, sedation, and
constipationand rebound hypertension and erythema is common
8. Black market exists due to narcotic withdrawal properties
b. Beta-adrenergic agonists:
i. Also mimic the action of the SNS and classified as either catecholamines or
noncatecholamines
ii. Also labeled according to their selectivity
iii. Prototype Drug: Dopamine (Intropin)
iv. What route is dopamine administered by?
Dopaminergic Agonists
a. There are 5 types of dopamine receptors; only dopamine-1 (DA1) and dopamine-2 (DA2)
receptors mediate responses in the adrenergic nervous system
b. Stimulation of DA1 and DA2 receptors results in peripheral vasodilation
c. Stimulating both receptors may have either complementary or opposing effects
d. Prototype Drug: Fenoldopam (Corlopam)
Alpha-Adrenergic Antagonists:
a. Alpha-adrenergic antagonists blank the stimulation of the alpha receptors
b. Alpha-1a receptors mediate human prostatic smooth muscle contraction
c. Alpha-1b and alpha-1d receptors are involved in vascular smooth muscle contraction
d. Prototype Drug: Prazosin (Minipress)
Beta-Adrenergic Antagonists: BETA-BLOCKERS
a. Grouped according to their specificity of action at the beta-1 and beta-2 receptors
b. Stimulation of beta-1 only (tachycardia, increased lipolysis, inotropy)
c. Stimulation of both beta-1 and beta-2 receptors (vasodilation, decreased peripheral
resistance, bronchodilaiton)

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
d. Prototype Drug: Metoprolol (Lopressor, Toprol XL)

21

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18
Chapter 14: Drugs Affecting Cholinergic Function:
I.

II.

III.

IV.

V.

Chapter Summary:
a. Autonomic Nervous System: divided into sympathetic and pararsympathetic nervous
systemswoprk in combination or opposition to maintain homeostasis within the body
i. Because a receptor is stimulated by Achit is referred to as cholinergic receptor
b. Drugs categorized into:
i. Cholinergic agonists: stimulate cholinergic receptors
ii. Cholinergic antagonists: block cholinergic receptor and prevent Ach from
attaching to the receptor
Function of the Autonomic Nervous System
a. The autonomic nervous system (ANS) is an involuntary system responsible for the control
of smooth muscle, cardiac muscle, and exocrine glands
b. The sympathetic (SNS) and parasympathetic (PSNS) nervous systems work either as
complementary or oppositional systems to maintain involuntary functions of the body
c. Parasympathetic system: rest and digest system
i. Increased salivation
ii. Increased GI tone and motility
iii. Increased gastric secretions
iv. SLUDD: salivation, lacrimation, urination, digestion, defecation
Cholinergic Neurotransmitters:
a. Cholinergic drugs act on the parasympathetic nervous system
b. Acetycholine (Ach) is the presynaptic and postsynaptic neurotransmitter in the
parasympathetic nervous system
c. Ach is released in response to an action potential, diffuses across the synaptic cleft, and
binds to cholinergic receptors on the target organs or tissues
d. After dissociation, Ach is degraded into two inactive products, acetate, and choline by
acetylcholinesterase
Cholinergic Receptors: three typesnicotinic-N, nicotinic-M, and muscarinic
a. Nicotine receptors
i. Activation of Nicotine N receptors in the adrenal medulla results in the release
of epinephrine
ii. Stimulation of nicotinic M receptors results in skeletal muscle contraction
b. Muscarinic Receptors
i. Stimulation of the receptors results in the pharmacologic response of the
vasodilation, resulting in decreasing blood pressure
Pathophysiology:
a. The therapeutic uses of parasympathetic drugs are related to providing extra
cholinergic stimulation or blockade normal ANS functioning
b. Disorders of the bronchi, cardiovascular system, GI or GU tract, skeletal
muscle, eyes, and various glands may respond to cholinergic stimulation

Cholinergic Agonists
VI.

VII.

22

Direct-Acting Muscarinic Agonists:

a. Drugs that bind to the muscarinic receptors located in various tissues and organs
throughout the body
b. Their activation elicits a response that resembles the action of the parasympathetic
nervous system
c. Prototype Drug: Pilocarpine (Akarpine)
d. What is the antidote for Pilocarpine overdosageatropine
Direct-Acting Nicotinic Agonists:
a. The direct acting-nicotinic are also called ganglionic stimulating agents
b. These drugs stimulate nicotininc receptors directly
c. The two significant classes of nicotinic stimulants are
i. Ganglionic stimulants
ii. The neurotransmitter nicotinic stimulants

Pharmacology Test 3: Chapters 48, 49, 50, 13, 14, 20, 15, and 18

VIII.

IX.

23

d. Prototype Drug: Nicotine

e. Monotherapy use of nicotine replacement is the preferred treatment for smoking
cessationFalse
i. Rationale: nicotine is considered an adjunct of smoking cessation
Indirect-Acting Cholinergic Agonists:
a. After the neurotransmitter crosses the synaptic gap and binds to a receptor, the
neurotransmitter is cleared from the synaptic gap
b. Acetycholine is cleared from the synaptic gap by acetycholinesterase
c. Any drug that inhibits cholinesterase will be functional equivalent of a cholinergic
receptor
d. Reversible cholinesterase inhibitor
e. Prototype Drug: neostigmine (Prostigmin)
f. Neostigmine is absorbed well when given orallyFalse
i. Rationale: 2-4 hours orally and 10-30 minutes parenterally

Cholinergic Antagonists:
a. The cholinergic antagonists are drugs that antagonize, or block, muscarinic or nicotinic
receptors directly
b. The clinical importance is in decreasing blood pressure
c. Include: antinicotinic ganglionic blockers, antinicotinic neuromuscular blockers, and
antimuscinaric/anticholinergic Drugs
d. Prototype Drug: atropineanticholinergic drugs specifically targeting muscarinic
cholinergic receptors
e. Atropine causes which of the following adverse effects
i. Urinary retention
ii. Dry mouth
iii. Mydriasis
iv. All of the above
f. Summary of Cholinergic Antagonists: TABLE 14.7
i. Atropine
ii. Benztropineextrapyramidal symptoms, akathisia, dystonic rxn, haloperidol,
parkinsonian, drooling, myoclonus, priapism
iii. Darifenacinoveractive bladder
iv. Dicyclomine--IBS
v. Flavoxate hydrochlorideoveractive bladder
vi. Glycopyrrolateinhibit salivation and excessive respiratory tract secretions
vii. Hyosyamineabd cramps, colic, dysentery, IBS, parkinsons, PUD, spastic colon,
pancreatitis, rhinitis
viii. Ipratropiumasthma, chronic bronchitis, COPD, rhinorrhea
ix. Oxybutyninoveractive bladder
x. Propanthelineduodenal ulcer, GI spasmolytic, hyperhidrosis, sialorrhea, urinary
incontinence
xi. Scopolaminemotion sickness, preanesthesia, antidelirium, obstetric amnesia,
glaucoma, opthlamology, uveitis