Transcript pharmacy technician chapter twenty nine

CHAPTER TWENTY NINE
1
The Endocrine System
 A “communication”
system for the body
 Major components of
the endocrine system
are:
 Hypothalamus
 Pituitary gland
2
The Endocrine System (cont.)
 Secondary components of the endocrine system
are:
 Thyroid
 Parathyroid
 Pancreas
 Adrenal glands
 Gonads
 The pituitary gland controls the secondary
components of the endocrine system
 During pregnancy, the placenta also acts as an
endocrine gland
3
The Hypothalamus and Pituitary
Gland
 Hypothalamus
 Part of the brainstem
 Controls the activity of the pituitary gland
 Pituitary gland
 About the size of a large pea
 Called the “master gland” because it controls many other
glands
 Composed of anterior and posterior lobes
 Each lobe contains a number of hormones
 Hormones—chemical substances that regulate
certain bodily functions
4
Hormones
 Transfer information and instructions from one set
of cells to another
 Each hormone affects only the cells that are
genetically programmed to receive and respond to
its message
 Hormones are divided into two groups according
to their structure:
 Steroids—slow acting, long lasting, and usually end in
the suffix “-rone” (examples: testosterone, progesterone)
 Peptides and amines—made of proteins, fast acting, and
short lived (examples: insulin, ADH)
5
Female Sex Hormones
 Estrogen—responsible for:
 Development of secondary sex characteristics
 Formation of osteoblasts
 Inhibition of osteoclasts
 Bone loss
 Progesterone—prepares lining of uterus for
implantation of fertilized egg
 Replacement female hormones may be derived
from animal, plant, or lab-modified sources
6
Male Sex Hormones
 Also called androgens or masculinizing hormones
 Primary male sex hormone is testosterone:
 Produced in the testes
 Stimulates the development of male sex organs
 Maintains secondary sex characteristics
 Progesterone—maintains healthy prostate
 Replacement male hormones are typically anabolic
steroids
7
Glandular Disease States
 Some cancers (breast, uterus, prostate gland) are
dependent on sex hormones
 Use of opposite sex hormones appears to antagonize or
inhibit tumor growth
 Endocrine therapy is palliative only
8
Diabetes Mellitus
 A disorder of carbohydrate metabolism
 Type I DM
 Genetic factors involved
 Environmental factors (i.e. Coxsackie virus)
 Involves destruction of pancreas by the immune system
 Begins as children and young adults
 Patients are described as insulinopenic (i.e pancreas
secretes almost no insulin)
 Patients are described as thin
 Blood abnormalities includes high blood glucose, high
triglycerides level (VLDL), high blood levels of ketone
 Physical signs are extreme thirst, nocturia, hypertension
and possible kidney disease.
9
 Type II Diabetes Mellitus
 Genetic factors involved
 Environmental factors involved
 Involves the resistance of the body to the hormone,
Insulin.
 Also described as Insulin resistance syndrome
 Signs and symptoms include those of Type I DM
 Metabolic Syndrome or Syndrome X






Independent risk factor for cardiovascular disease
Seen in men and women
Biochemically marked by high blood glucose, cholesterol,
trigycerides
BMI>25
Hypertension of greater than 130 mmHg systolic
Waistline of more than 40 in in men; 35 in in women
10
Therapy of Diabetes
 Insulin
 Regular insulin or short acting insulin


Humulin R or Novolin R
Humalog or Novolog
 Intermediate acting insulin
 Humulin N or Novolin N
 Mixture of intermediate acting /regular insulin
 Humulin 70/30 or Novolin 70/30
 Novolog 70/30
 Long acting insulin
 Lantus ® (insulin glargine)
 In general, insulin is the first line of therapy in type I
DM
 In type II DM, oral drugs are tried first, ultimately
insulin is required in this class of people as well
11
 In general the dose of insulin in type I DM is about 0.5
units/kg of body weight which half of this dose given
as long acting insulin and the other half is given as
bolus dose with meals
 Type II DM patients are initiated on long acting or
intermediate acting Insulin at bedtime. The dose is
titrated according to fasting blood glucose and is
determined by the patient’s endocrinologist
12
Oral Drugs for Diabetes Mellitus
 Type I DM patients can not be treated with most of
these drugs
 Used in Type II DM
 Sulfonyureas
 Increases insulin secretion from the pancreas
 Should be given with food



Glipizide (Glucotrol®)
Glyburide (Diabeta®)
Tolbutamide (Orinase®)
 Biguanides
 Inhibits hepatic gluconeogenesis during fasting

Metformin (Glucophage®)
13
 Meglitinides
 Similar to sulfonylureas
 Taken before a meal


Repaglinide (Prandin®)
Nateglinide (Starlix®)
 Thiazolidinediones
 Also known as the glitazones
 Increases insulin sensitivity in adipose tissue and muscles


Pioglitazone (Actos®)
Rosiglitazone (Avandia®)
 Basically good drugs but since 2010, both drugs have been
implicated in serious adverse medical events
 After November 2011, Avandia and all avandia products are
restricted in distribution to the FDA REMS program
 www.fda.gov/Drugs/DrugSafety/ucm255005
14
Novel New Drugs
 dipeptidyl peptidase- 4 inhibitors
 Blocks an enzyme in the kidney called dipeptidyl
peptidase- 4
 Blockade of this enzyme allows a hormone called
glucagon like peptide I or GLP1 to last longer
 GLP1 helps augment insulin release in response to a
sugar rich meal
 Onglyza ®(saxagliptin)
 Januvia ® (sitagliptin)
 Incretin Mimetics (GLP like)
 Exenatide (Byetta®)
 Liraglutide (Victoza®)


Injectable hormones
GLP-1 agonists
15
CHAPTER THIRTY ONE
16
The Nervous System
 Divided into central nervous system (CNS) and
peripheral nervous system (PNS)
 Central nervous system
 Includes brain and spinal cord
 Controls all nervous system functions
 Control may be direct or indirect
 Peripheral nervous system
 Includes all other nerves and sensory organs
 Controlled by central nervous system
 Divided into somatic and autonomic nervous systems
17
Functions of the Nervous System
 Sensory (afferent)
 Sends impulses from other parts of body toward the
CNS
 Senses external changes or conditions in the
environment, such as cold or heat
 Senses internal changes in the body, such as decrease in
potassium or calcium
 Integrative
 Processes perceived information about the sensory
changes
 Interprets or explains changes in external/internal
environments
18
Functions of the Nervous System
(cont.)
 Motor (efferent)
 Sends impulses away from the CNS to other parts of the
body
 Allows and controls body movement
 Causes glands to secrete hormones or other chemicals
into the bloodstream
19
Sympathetic Nervous System
 Governed by the neurotransmitter norepinephrine
 Prepares body for energetic tasks, stressful situations,
and the “fight or flight” response
 Stimulates heart, lungs, and blood vessels
 Decreases activity of gastrointestinal and
genitourinary functions
20
Parasympathetic Nervous System





Governed by the neurotransmitter acetylcholine
Activates body for sleep in nonstressful periods
Effects the “rest and relaxation” response
Decreases activity of heart, lungs, and blood vessels
Increases activity of gastrointestinal and genitourinary
functions
21
Neuron
 Smallest unit of the
nervous system
 Brain is composed of
approximately 100
billion neurons
 Highly differentiated
from other cells
22
Neuron (cont.)
 Has specialized projections called dendrites and axons
that communicate with the rest of the body:
 Dendrites bring information to the cell body from the
central nervous system
 Axons take information away from the cell body to the
central nervous system
23
Nervous System Communication
 Neurons communicate with each other through an
electrochemical process
 Can be compared to a computer sending electrical
signals over its wires
 Brain sends electrical signals through neurons
instead of wires
 Neurons produce electrochemical hormones called
neurotransmitters
 Neurotransmitters are stored in the ends of the
nerve cells
24
Neurotransmitters
 Released at the end of the neuron
 Synapse is the space between two different
neurons
 Neurons transfer information by crossing
synapses
 Neurotransmitters travel across the synapse to
reach a receiving neuron
 Attach to special structures called receptors
 Communicate with and control glands, organs,
and muscles
25
Blood-Brain Barrier (BBB)
 Semipermeable membrane that allows some substances to





enter brain, prevents others from entering
Protects brain from substances in the blood that could injure
the brain and protects the brain from hormones and
neurotransmitters in the rest of the body
Maintains a constant environment, or homeostasis, for the
brain
Water-soluble or low-lipid/low-fat-soluble molecules do not
penetrate and highly-lipid/fat-soluble molecules, such as
barbiturates, rapidly cross
Large molecules do not easily pass through
Highly electrically charged molecules are slowed down
26
Anxiety
 Uncomfortable emotional state characterized by
apprehension, worry, and fear
 Associated with the following risk factors:
 Genetics
 Brain chemistry
 Life events
 Personality
• Treated with benzodiazepines, antidepressants
•
•
•
Xanax ® Alprazolam
Restoril® Temazepam
Valium ® Diazepam
27
Depression
 Symptoms include feelings of despair, lack of energy,
inability to concentrate
 Related to decreases in concentration of the
neurotransmitters
 Treated with drugs that:
 Block the reuptake of neurotransmitters
 TCA (tricyclic antidepressents)
 Nortripyline (Pamelor®), Amitripyline (Elavil®)
 Dangerous in overdose
 Doses over 1 gram can be fatal
 SSRI
 Fluoxetine (Prozac®)
 Paroxetine (Paxil®)
 SNRI
 Duloxetine (Cymbalta®)
 Safer in overdose than TCA’s
28
 Interfere with the breakdown of the monoamines within
the synaptic cleft
 MAOI






Used in the 50 and 60’s
Very dangerous in overdose
Many drug interactions especially with hypoglycemic drugs
and antihypertensive drugs
Drug food interactions with foods with high tyramine content
like cheeses, wine, chocolates, etc
Phenelzine (Nardil®)
Tranylcypromine (Parnate®)
 Used now only a last ditch effort to treat SSRI resistant
depression
29
Bipolar Disorder
 Characterized by severe emotional highs (mania) and
lows (depression)
 Episodes, referred to as mood swings, can last hours,
days, months, or years
 Treatment may include:
 Lithium—reduces hyperexcitability of the nerves
 Antidepressant drugs
30
Psychosis
 State in which a person is out of touch with reality
 One cause may be an increase in dopamine
 Treated with antipsychotic drugs that attach to the
dopamine D2 receptor
31
Mental Disorders
 The following mental disorders may be treated
psychotherapeutically:
 Psychosis
 Depression
 Anxiety
 Obsessive-compulsive disorder
 Panic disorder
• Although there is no cure for mental illness, drugs will
help the patient to have a better experience in daily living
and function more effectively
32
Mental Disorders (cont.)
 The National Institutes of Mental Health classifies the
following four types of psychotherapeutic agents:
 Antianxiety
 Antidepressant
 Antimanic
 Antipsychotic
33
Parkinson’s Disease
 Degenerating neurons in the basal ganglia of the brain
characterizes this disease
 These neurons are dopaminergic and secrete
dopamine as a neurotransmitter
 These neurons coordinate with neurons in the motor
cortex to help initiate movement
 Signs and symptoms
 Resting tremor: shaking limbs and hands at rest which goes
away with movement (first sign noticed by family or patient)
 Gait imbalances: patient has problems initiating movement
and may show signs of bradykinesia and muscle rigidity often
called dystonia
 Weak and achy muscle in the face progresses to slurring
speech
 Autonomic disregulation (low blood pressure)
34
Treatment of PD
 Dopaminergic drugs
 Used to “replace” dopamine in the brain
 Taken orally
 Sinemet® Carbidopa/Levodopa



Levodopa is converted to dopamine in the brain
Dramatically improves symptoms
Often effective for several years before drug resistance sets in
 Dopaminergic type drugs

Ergot alkaloid drugs that act at dopamine receptor
 Bromocriptine (Parlodel)
 Cabergoline (Dostinex®)
 Ropinirole (Requip®)
35
The Immune System
 Consists of two types
 Humoral Immunity
 Cell mediated Immunity
 Humoral Immunity
 Involves blood proteins
 Is recruited when physical barriers like the skin are breached
 Complement proteins are proteins in the blood that recognize
bacterial cells and other microorganisms.

They basically open holes in those cells and allow osmosis of water to
lyze and kill them
 Antibodies
 These are proteins that are secreted by an activated B lymphocyte
called a plasma cell.
 Antibodies are highly specific for the bacteria, fungi, protozoa that
they target
36
 Cell Mediated Immunity
 Immune reactions that are carried out by cells




Macrophages are cells that engulf and “swallow” invader cell,
bacteria and particles
Neutrophils are cells that destroy invaders by engulfing these
invaders and destroying them by reactive chemical contain oxygen
radicals. Sometimes this process causes the rapture of the cell and
causes inflammation
B lymphocytes are cells that make antibodies to an given antigen (a
marker on an invader)
T lymphocytes are cells that orchestrate and guide the immune
response
 CD4 or helper T cells help B cells make antibodies and are very
important in the immune response. They are the targets for the
HIV virus
 CD8 cells are cells that recognize viral infected cells are carry out
an attack on these cells. They kill these cells to spare the host
organism.
 NK Cells are cells that are similar to CD8 cells. These cells are
important in cancer.
37
Pathogens
 Bacteria are unicellular organisms that are know to be
the simplest form of life. They grow and divide and
require nutrition. Most bacteria are harmless but
some are virulent pathogens to humans.
 Broadly speaking bacteria are divided into gram positive
and gram negative depending a their cell wall chemistry
 Bacteria are aerobic and some are anaerobic
 Some are defined as fastidious and non fastidious
(which means that some require a special growth
medium) Brucella requires blood agar
 Some are intracellular parasites (they live inside the cell)

Examples are chlamydia and Brucella and Rickettsia
38
Serious Bacterial Infections
 Bacterial Meningitis
 Caused by Neisseria Meningitidis, Streptococcus,
Streptococcus species
 Mortality is high even with treatment
 Bubonic Plague
 Caused by Yersinia pestis, a gram negative intracellular
bacterium
 Caused the black death in Europe during the 14th century that
killed millions
 Today easily treated with fluoroquinolones
 Tuleremia
 Caused by Francisella Turensis (gram negative)
 Infects macrophages
 Carried to every organ in the body
 10-20% mortality
 Fluoroquinolones, aminoglycosides, and tetracycline can be
used
39
 Flesh Eating Disease
 Called Necrotizing Fasciitis
 Commonly caused by a strain of bacteria called Group A
Streptococcus or Streptococcus pyogenes
 Other bacterial species can cause as well
 Since the late 1990’s MRSA is the second leading cause
 Infection begins in the skin (subcutaneous tissue)
 Spread is very fast to the connective tissue called the
fascia, which is the coating to muscle cells
 Infection is by contact with contaminated sewage and
water contaminated with bacteria
 Streptococcal exotoxin activates T cells to produce
massive damage to muscle and skin
 IV high dose antibiotics are required
40
Viral Infections
 Virus are non living things who primary reason for
existence is to make more copies of themselves
 Infect various cells. Each virus may have its own
preference called a virus’ trophism
 Can be a DNA or RNA virus
 Antibiotics can not be used to treat these infections
 Antiviral Drugs



Acyclovir
Gancyclovir
Ribavirin
 These drugs usually acted on a viral DNA or RNA
polymerase blocking its action
41
Serious viral infections
 Hepatitis B
 DNA virus
 Causes acute and chronic disease of the liver
 Even with therapy, infection is life long
 Results in cancer or cirrhosis of the liver
 Ebola Hemorrhagic Fever
 Caused by the marburgviridae family of viruses
 Originally found near a region near the Ebola river in the
congo in 1970’s
 New species of virus
 Infects primates and bats (most likely vector)
 Can be spread by airborne droplets and infect body fluids
 Characterized by coagulalopathy which massive bleed and
shock
42
HIV infection
 Target of HIV is the CD4 lymphocyte
 HIV also shows trophism to the macrophage and a cell
in the CNS called a microglial cell
 RNA virus that replicates inside of CD4 cell
 CD4 cells die as virus is released and starts a new
round of infection.
 Infection can not be cured; the virus spread to
macrophages which can live for years provides a life
long viral reservoir.
43
Natural History of HIV infection
 Exposure to blood or bodily fluids through sexual
contact and/or use of needles
 Prodromal stage
 Initial stage of infection: about 4 weeks patient develops
signs of flu like symptoms
 Before this period no antibodies against HIV can be
deteched
 After this febrile flu like state passes, patient is said to be
seroconverted (i.e. will show detectable antibodies)
 Clinical latency
 The immune system temporarily subdue infection
 Can last between 2-10 years
 As virus replicates in CD4 cells, these cells die by
rupture, apoptosis or attack by the CD8 cell
 As CD4 levels decline, opportunistic infection sets in
44
Acquired Immunodeficiency
Syndrome
 Final Stage
 Occurs when CD4 levels have fallen to less than 200
cells/microliter
 And patient has one of the following





Pneumocystic Pneumonia caused by a protozoan,
Pneumocytis Jirovecci
Esophageal candidiasis
MAC infection
Kaposi Sarcoma
Burkitt’s Lymphoma
 Patient will usually die from one of these cancers or
infections
45
Drugs used in HIV infections
 Reverse transcriptase inhibitors
 Block RNA reverse transriptase (NRTI)





AZT, Zidovudine (Retrovir®)
Abacavir (Ziagen®)
Lamivudine (Epivir®) Approved for both HIV and HBV
Emtricitabine (Emtriva®) also called FTC
Tenofovir (Viread®) approved for both HIV and HBV
 These drugs also come in various combinations

Combivir (AZT and Lamivudine)
 NNRTI


Efavirenz (Sustiva®)
Etravirine (Intelence®)
46
Protease Inhibitors
 Kaletra ® (lopinavir/Retrovir)
 Reyataz ®(atazanavir)
 Aptivus® (Tipranavir)
 Prezista ® (Darunavir)
 Lexiva ® (fosamprenavir)
 Inhibits viral enzyme HIV protease which assists in viral
assembly
47
Fusion Inhibitors
 Prevent HIV from attaching to CD4 cells
 Pharmacology is very complex
 Prevents “fusion” of virus with the cell
 Drugs include:
 Enfurvirtide (Fuzeon®) a drug given by subcutaneous
injection
 Maraviroc (Selzentry®) oral drug
48