PHARMACY TECHNICIAN

PHARMACY TECHNICIAN CHAPTER TWENTY NINE

The Endocrine System • A “communication” system for the body • Major components of the endocrine system are: • Hypothalamus • Pituitary gland

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

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

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)

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

Female hormones Drug Products • MOA: replaces estradiol in females • Indications: menopausal Sx, prevent osteoporosis, Contraception, maintenance of pregnancy Remember: Federal Law mandate for OC OC are contraindicated in women with a history of TE disorders, strokes and breast cancer DepoProvera is an IM injection used for birth control that lasts for 3 months

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

Male Sex Hormone Drug Products • MOA: replaces testosterone levels in men • Indications: hormone replacement therapy, treatment of anemia in cancer patient (no used for this anymore) • Contraindications: history of liver disease, and prostate cancer Side effects: weight gain, muscle hypertrophy, viriziling effects, priapism, hepatitis and blood filled cysts in liver (oral more than IM), long term use results in sexual problems, gynecomastia Because of abuse in sports, federal schedule 3

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.

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

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

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

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 • Avoid Alcohol • Glipizide (Glucotrol®) • Glyburide (Diabeta®) • Tolbutamide (Orinase®) • Glimepiride (Amaryl®) • Biguanides • Inhibits hepatic gluconeogenesis during fasting • Metformin (Glucophage®) • Caution: with people with kidney disease can result in a fatal reaction called Lactic acidosis

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

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

Thyroid Disease • Thyroid gland is responsible for secreting thyroid hormone, T4. • T4 basically controls metabolic functions in the body • More T4 equals a higher basal metabolic rate • Less T4 equals a lower basal metabolic rate • Hypothyroidism is a condition where thyroid gland does not secrete adequate T4 • Condition products slow BMR, slow heart rate, electrolyte abnormalities, lipid disorders • Tx: Levothyroxine (synthroid ®, Levoxyl ®) • Hyperthyroidism is a condition of to much T4 • Can produce a dangerous heart condition called Atrial Fibrillation • Tx: Methimazole (Tapazole®), Propylthiouracil (PTU) • SSKI (super saturated potassium iodide) used in the emergency tx of “thyroid storm”

Corticosteroids • Adrenal gland naturally produces cortisol and other “corticosteroids” • These hormones are very important in priming the body to deal with stress. They control artery’s and heart’s sensivity to norepinephrine, blood pressure, water clearance by the kidney and many others • A loss of cortisol secretion by the adrenal gland produces “adrenal crisis” which is a medical emergency Severe side effects: immune suppression, osteoporosis, elevated blood glucose, cataracts, growth suppression in children With Inhalation products like Advair® tell patients to rinse mouth after the dose

PHARMACY TECHNICIAN CHAPTER THIRTY ONE

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

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

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

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

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

Neuron • Smallest unit of the nervous system • Brain is composed of approximately 100 billion neurons • Highly differentiated from other cells

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

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

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®) • Sertraline (Zoloft®) • Citalopram (Lexapro) • SNRI • Duloxetine (Cymbalta®) • Safer in overdose than TCA’s

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

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 • Treated with dopamine receptor antagonists Major side effects: Abnormal heart arrhthymias, hypotension, sedation, Extrapyramidal symptoms (Parkinson’s like) movement disorders

Second Generation Antipsychotics • The previous list of Antipsychotics had major side effects of hypotension, sedation, weight gain, erectile dysfunction, cardiac arrhythmias (Long QT) and EPS (Extra pyramidal Symptoms) • EPS is a movement disorder that is similar to Parkinson’s disease • Second generation drugs were developed to avoid EPS • A major side effects to these drugs are: risk of drug induced diabetes and weight gain. • Ziprasidone has the risk of cardiac arrhythmias (long QT) • Clozapine has the risk of fatal blood condition called agranulocytosis • (Very low white blood cell count) • FDA REMS requires registries set up to monitor this risk

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)

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®)

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

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.

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

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

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

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

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

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.

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

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

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®)

Protease Inhibitors • Kaletra ® (lopinavir/Retrovir) • Reyataz ®(atazanavir) • Aptivus® (Tipranavir) • Prezista ® (Darunavir) • Lexiva ® (fosamprenavir) • Inhibits viral enzyme HIV protease which assists in viral assembly

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

PHARMACY TECHNICIAN