Area 4 – Clinical Sciences

Evidence-Based Practice

Pharmacist roles

Pharmacists have had ever-expanding important roles in healthcare.  These include: 1) Maintaining a leadership position in medicine safety and efficiency in drug distribution. 2) Increasing roles in direct patient care as well as improving patient care. 3) Keeping up to date information of drug evidence-based guidelines to improve safety and efficacy of therapies.  4) Improving the balance between patients, insurance companies and physicians; lowering costs; and improving therapy of patients. 5) Taking more proactive approaches in triaging a patient to a physician or hospital. 6) Managing and counseling patients on important laboratory tests.

As a pharmacist, it is very likely that you will field many questions related to not only medications, but also to various diseases. You will often recommend over-the-counter (OTC) medications for common ailments such as colds and coughs. It is vital to have a great understanding of all OTC medications. It is also vital to know proper dosing of all cold OTC medications for children. While you can suggest OTC medications for common ailments, you are not legally licensed or trained to make diagnostic decisions about a patient. If you are ever concerned that a patient needs to be seen by a doctor for further tests, you should immediately counsel the patient to see his physician as soon as possible. If you are concerned that the patient needs immediate attention, you should dial 911.

Pharmacist specialization

As of now, pharmacists take care of a lot of different healthcare aspects when dealing with diseases and patients.  However, as the needs of the population increase and healthcare needs increase, the expectations for pharmacists will also need to increase.  In the future, to maintain a successful healthcare system, with increased patient care and decreased medical error, pharmacists will need to become increasingly focused, maintaining care for certain disease states, certain patient subsets, and certain types of drug regimens, much more so than is done today.  This will keep the workload for the pharmacist to a feasible level and allow for better patient care with longer time with each patient, which will increase health and safety of a certain drug therapy.

Pharmacist shortage

One big issue in the field of pharmacy is the lack of pharmacists.  The population of the United States is expanding at an incredible degree, and more and more drugs are being prescribed to this ever growing population every day.  It is becoming extremely difficult for States to fill the need for pharmacists to match the increasing number of prescriptions.  It is thought that the number of pharmacists in the upcoming years will only increase marginally in relationship to the amount of prescriptions being filled.  The need for pharmacists is demanding, however, to increase the number of pharmacists to match the need can lead to several problems including a greater chance of licensed pharmacists being under-qualified for the position they hold, allowing for a greater chance for medical error.  Additionally, by increasing the number of pharmacists, the salary for pharmacists will begin to decline, which could have an effect on the amount of people wanting to take this job, because the salary would not match what is required from the pharmacists, thus creating a catch-22 situation.

OBRA 90

Omnibus Budget Reconciliation Act of 1990 (OBRA 90) has a few main components that address pharmacy regulations. The components include regular and proper drug utilization reviews (DUR’s), collecting data on drug safety and efficacy, and patient counseling. The first main goal of OBRA 90 relates to improving drug therapy and medication safety through the DUR’s and proper drug interaction reviews. The second main goal of OBRA 90 relates to patient counseling. According to OBRA 90, proper patient counseling must be given to patients when a new prescription is dispensed. Patient medication counseling includes items such as proper administration of medications and possible medication, diet, and herbal drug interactions.

The OBRA 90 act proposed new federal laws requiring pharmacists to counsel on new prescriptions and new refills.  Each state has its own requirements as well.  It is good for pharmacists to familiarize themselves with federal laws as well as counseling laws from the states they wish to be licensed.  OBRA 90 proposes that a pharmacist will need to discuss various counseling points: the name of the drug, description of the drug, special instructions for the administration of the drug, possible adverse reactions, possible interactions and contraindications, as well as how many refills are left on the prescription and directions in case a dose of the medicine is missed.

Stages of clinical trials

Phase I trials—first human studies performed after successful preclinical animal studies of a given compound has shown some benefit.  Phase I trials involve a small group of healthy volunteers to determine the toxicity and metabolism of the drug.

Phase II trials—provided to a larger population, the therapeutic efficacy and the required therapeutic dose of the drug are assessed.  Safety assessment studies are continued during this time as well.

Phase III trials—performed to assess the effectiveness of the newly developed drug, in an unbiased controlled environment.  Drug is tested in double blind study, in which test subjects are given either a placebo (a fake drug) or the drug being tested.  The exact nature of the drug given to patients during the trial is hidden from both patient and physician.  This is done to remove any possible bias during the experiments.  If approved by the FDA, the drug can be put on the market.

Phase IV trials—post market safety surveillance.  Companies that developed the new drug must monitor the drug’s safety and efficacy in the larger population of patients and assess any possible long-term toxicity that the drug might possess.

NCE and NME

An NCE (new chemical entity) and NME (new molecular entity) are compounds, which have been developed and show therapeutic potential against a particular disease state or target in preclinical trials, but have not yet been studied in humans.  As defined by the Food and Drug Administration, and NCE and NME, is a compound by which the region of the molecule responsible for the physiological changes or effects has not been approved by the FDA.  Development of an NCE or NME is one of the first steps in drug development.  Once preclinical trials are completed, the next step in drug development would be to begin studying the effects of the compounds on humans in phase I, phase II, and phase III clinical trials.  If all goes well, following FDA approval, the compound can go to market.

Placebo response

The placebo response is a phenomenon of clinical trials, in which pharmacologically inert sugar pills or other compounds that are used as controls, shows apparent beneficial biological effects.  It is thought that the placebo drugs have this apparent beneficial response for numerous reasons, such as doctors, who do want their patients to feel better, inadvertently and subconsciously skew the data.  Additionally, patients who feel that they might be receiving the experimental drug rather than an inert compound may feel they are feeling better due to a rather strong power of suggestion.  The exact reason for a placebo response, however, is not entirely understood.

Nocebo response

The nocebo response is the counterpart to the placebo response.  It is not a term that is used as frequently as the placebo response.  Nocebo is a pharmacologically inert compound that leads to apparent unwanted side effects.  Some causes of the nocebo effect can be possible allergies to the fillers used in making the nocebo compound.  It is thought that the nocebo response may have a more psychological basis, in that the patients could be using the power of suggestion (worrying too much) to make themselves sicker. The exact reason for a nocebo response, however, is not entirely understood.

Drug interactions

Drug interactions are dangerous and sometimes hard to recognize because the interactions may resemble a disease or new health problem, but may not necessarily be associated with a drug interaction.  Drugs can interact with other drugs, which can lead to lower or higher bioavailability of the drugs; additionally a combination of drugs might lead to a separate dangerous side effect.  Drugs can also interact with certain types of food.  Food, similar to the drug interactions, can lead to changes in bioavailability and efficacy of the drugs.  Drugs can also inhibit the absorption of necessary vitamins, nutrients, etc. from food.  Many factors can regulate interactions, and as a pharmacist, these specific interactions must be well understood in order to properly counsel a patient on a particular prescription or prescriptions.

Dosage terms

Loading dose—is an initial dose that is given to a patient to reach therapeutic levels of the drug rapidly, before the dose is tapered off to normal levels.  Depends on the particular drug.  A loading dose is common for anti-seizure medications, anticoagulants and some antibiotics.

Maintenance dose—the minimum dose of a drug that is needed after initial loading dose to maintain an effective therapeutic level in the blood stream.

Replacement dose—dose administered as replacement of a missed dose of a drug.  A replacement dose depends on a particular drug and may or may not be necessary.

Abbreviations

These important abbreviations should be understood by the pharmacist and translated into general easily understood directions for the patient.

Drug interactions

Ethanol and metronidazole interactions

Flagyl, also known as metronidazole, is an anti-microbial agent that is commonly prescribed for various disorders including giardia.  Ethanol absolutely should not be ingested for several days after administration of Flagyl, due to a potentially fatal drug interaction.  Mixing Flagyl and ethanol can lead to a disulfiram-like reaction.  This is caused by blocking acetylaldehyde dehydrogenase, leading to an increased level of acetylaldehyde in the blood.  This increased level of acetylaldehyde can lead to signs of a hangover such as: headache, extreme nausea and vomiting, and flushing of the skin.  This interaction can also occasionally lead to severe cardiac and liver toxicity.  It is vital as a pharmacist to make sure that a patient taking Flagyl knows this potentially dangerous interaction no matter the age of the patient, as even a small amount of alcohol (such as that found in cough syrup or mouthwash) can cause a reaction.

Ethanol/acetaminophen interactions

Acetaminophen (Tylenol) is metabolized by one of two ways.  The majority of acetaminophen is broken down in the liver by glucoronidation and sulfation and excreted from the body.  Approximately 5% of the drug is converted by the P4502E1 cytochrome enzyme (CYP2E1) into a hepatotoxic compound known as N-acetyl-p-benzoquinoneimine (NAPQI).  Under normal therapeutic doses, this toxic compound is quickly sequestered by glutathione.  Heavy alcohol consumption (binge drinking, chronic alcoholism) can lead to an upregulation of the CYP2E1 enzyme.  This up-regulation of CYP2E1 can lead to an increase of acetaminophen being metabolized into the cytotoxic NAPQI compound.  If the level of NAPQI is too great, glutathione stores will be used up and the remaining NAPQI will not be able to be fully metabolized leading to potentially severe liver damage.  The damage to the liver can be acute as well as chronic.  An alcoholic should not consume more than 2 grams of acetaminophen a day.

Crushed forms of drugs

There are too many drugs to memorize which should not be crushed.  As a pharmacist it would be best to read all package inserts, use common sense (if a drug is extended release for example, it should not be crushed, or it can lead to a possible overdose) when counseling a patient.  Additionally, it would be best to have a list of drugs that shouldn’t be crushed, which can be found sometimes as a poster in the pharmacy that can be easily referenced.

Home diagnostic tests

Home diagnostic kits are used to determine pregnancy, ovulation, blood pressure, blood-glucose levels, and glucose urine levels.  Several other diagnostic tools have become increasingly popular, easy to use, and easy to purchase.  These devices can offer quick diagnostic views and can be used for many purposes such as an early warning for other possible more serious diseases.  They are considered a nice alternative to visiting a doctor for simple tests, with not only lower costs, but less time is wasted waiting for the doctor.  However, these home diagnostic kits can also be troublesome: they can be misinterpreted, thus causing unneeded worry, and important problems that might be present might be missed and ignored.  These diagnostic kits might also be used in lieu of visiting the doctor, and while some home remedies might exist to treat whatever disease may be present, these kits should never be used as an alternative to a doctor’s appointment.

SOAP notes

SOAP notes are a form of documentation used by pharmacists, physicians, and various other healthcare personnel to write and communicate about a patient.  SOAP (subjective, objective, assessment and plan) notes are used to organize diagnostic results, physician and pharmacist orders, and other important notes about a patient or certain medical problems of a patient.  Subjective data are problems and symptoms of a disease as described by the patient.  Objective data are observations of a disease, symptoms, lab tests, etc. that are made by healthcare personnel about a disease.  Assessment data consists of the judgment about a disease based on the objective and subjective data by the healthcare personnel (physicians).  The plan of the soap note is the therapy action chosen based on the assessment of the disease.  SOAP notes provide a quick and organized way to asses and treat a patient, which is vital when working in a hospital with many diverse patients.

Insulin storage

Insulin is an important polypeptide that regulates glucose levels in the blood. In type I diabetes mellitus, insulin levels are lower than normal or absent, and thus replacement insulin must be injected subcutaneously in order for the patient to be able to survive.  Glucose is the central component of ATP synthesis and is very necessary for cellular function.  Originally porcine insulin was used to treat type I diabetes.  Now however, insulin is made synthetically, by transfecting the human insulin gene into bacteria.  There are also many types or analogs of insulin that have been developed including a fast-acting analog known as Lispro.  Insulin should be kept in the refrigerator before use.  When using insulin, it will remain fresh at room temperature for a month.  Check insulin for unusual cloudiness or particulates.  Some insulin is cloudy and some is clear, therefore it is important to counsel a patient about what their specific insulin should normally look like.  Do not use insulin past the expiration date.

Serotonin-Reuptake Inhibitors

Selective Serotonin Reuptake Inhibitors (SSRIs) are a type of drug that are used to treat depression, anxiety and other chemical imbalances that might lead to other mental illnesses such as personality disorders.  This class of antidepressants inhibits enzymes that lead to the reuptake of serotonin into the presynaptic cleft of the neuron, which leads to an increase of extracellular serotonin levels and increased binding of serotonin to its receptor.  This leads to selective activation of serotonin neurons, which is why it is thought that SSRIs tend to show fewer side effects than other antidepressants.  It is thought that lower levels of neuron activity can lead to increased depression and anxiety, although exact causes of these mental disorders is not entirely understood.  Side effects of SSRIs include nausea, drowsiness, changes in weight, changes in libido, possible panic attacks and liver and kidney problems.  SSRIs can also lead to various cardiac events such as arrhythmias, tachycardia, etc.  These drugs include citalopram, escitalopram, paroxetine, and fluoxetine.

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) were the first generation of antidepressants.  First used in the 1950s, TCAs’ mechanism of action is not entirely understood, but it is thought that it might inhibit the reuptake of numerous neurotransmitters including norepinephrine, dopamine and serotonin by neurons.  Due to its non-selectivity, these antidepressants, have numerous side effects and are used less now than other antidepressants.  Adverse reactions include severe cardiac problems, and overdose of the drug is often fatal.  Other side effects include difficult urination, constipation, dry mouth and blurred vision.  TCAs are used sparingly to treat depression, neuronal-based pain and chronic bed-wetting.  The TCA class includes imipramine, desipramine, trimipramine, clomipramine, lofepramine, amitriptyline, nortriptyline, protyptyline and doxepin.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are used to treat depression, but can be used to treat other disorders such as Parkinson’s disease.  MAOIs inhibit the activity of the enzyme monoamine oxidase.  Monoamine oxidase breaks down neurotransmitters including melatonin, serotonin, epinephrine, dopamine and norepinephrine.  MAOIs have numerous side effects, including, when taken by mouth, they can lead to the down-regulation of important metabolic pathways and can lead to a dangerous hypersensitivity event.  MAOIs interact with numerous drugs and have important side effects including anxiety, euphoria, urine retention, rashes, and hypernatremia.  MAOIs include isocarboxazid, moclobemide, phenelzine, tranylcypromine, selegiline, and tolaxotone.  Many food products and natural products have MAOI activity, which can interact with many drugs and should be taken with caution.  It is important to counsel patients about which foods (such as certain types of cheese) can potentially interact with MAOIs.

Digoxin

Digoxin is a pressor/inotrope and is often used to treat congestive heart failure, atrial fibrillation and paroxysmal atrial tachycardia.  Digoxin acts by binding to and inhibiting the Na⁺/K⁺ pump on myocytes of the heart, which leads to an increase of intracellular Na⁺, and this in turn can lead to an increase of intracellular calcium through an increase of Na⁺/Ca⁺ exchange.  This increase in calcium leads to an increase in contractions of the heart muscle.  Digoxin also increases activity of the vagal nerve, which increases AV node activity.  Adult doses generally range between 0.125 to 0.5 mg a day by mouth, with a loading dose of 0.75 to 1.25 mg, or a dose ranging from 0.1 to 0.4 mg by IV with a loading dose of 0.5 to 1mg.  For pediatrics, doses are much lower; proper doses should be reviewed.  Adverse effects that signal digoxin toxicity include severe headache, severe tiredness, irregular heart rates, abnormally slow or fast heart rate, hallucinations, and vision problems.  More common adverse effects include decreased appetite, mild fatigue, dizziness, decreased libido, and enlarged breasts in males.

Pancrelipase

Pancrelipase is a prescription drug that combines three digestive enzymes: lipase, protease, and amylase.  Normally produced in the pancreas, these enzymes are important for digestion.  During periods of decreased pancreas functionality, this drug can be administered as replacement for the normal enzymes to facilitate digestion.  Pancrelipase is often administered in patients with cystic fibrosis or inflammation of the pancreas.  This drug is administered by mouth and should not be crushed or broken.  Side effects of this drug can include diarrhea, abdominal pain, nausea, and pain surrounding the anus.  Other side effects can include mild anemia, hyperuricemia, and mouth ulcers.

Haloperidol

Haloperidol (Haldol) is one of the first of the major antipsychotics to be developed and is used to control mental/emotional disorders such as schizophrenia, Tourette’s syndrome, and involuntary muscle spasms and tics.  Haloperidol belongs to the group of the butyrophenone compounds which are known to block dopamine receptors.  There are many other forms of drugs in this class of drugs including droperidol, benperidol, triperidol, melperone, lenperone and domperidone.  Haloperidol is probably the most widely used.  Haloperidol deaconate is a long acting form of haloperidol which can be injected once every four weeks at a dose between 50 to 300 mg.  Oral drugs can also be administered at a dose of 100 mg per day.  Adverse effects include development of tardive dyskinesia, which is a neurological disorder that may occur in response to the long use of dopamine receptor antagonists which can lead to an increase in involuntary movement such as Parkinson-like symptoms. Other side effects include neuroleptic malignant syndrome which can be fatal.  Other side effects can include weight gain, drowsiness, muscle-cramps, and severe depression.

Penicillins

Penicillins are a class of β-lactam antibiotics, named in response to the β-lactam ring moiety found in the chemical structure of these antibiotic compounds.  Penicillins bind important proteins in the bacterial cell wall, known as penicillin binding proteins (PBPs), inhibiting the synthesis of the cell wall, leading to lyses of the bacteria.  There is a large class of penicillins including natural penicillins (Penicillin G, penicillin V), penicillinase-resistant penicillins (methicillin, oxacillin, nafcillin, cloxacillin, dicloxacillin), Aminopinicillins (ampicillin, amoxicillin, bacampicillin), carboxypenicillins (carbenicillin, ticarcillin), and ureidopenicillins (azlocillin, mezlocillin, piperacillin).  Additionally β-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) are used with penicillins to treat resistant bacteria.  These drugs have a wide range of activity against different bacterial species.  Adverse reactions include severe allergy, nausea, seizures, hypokalemia, hyponatremia, cholestatic jaundice, and hemolytic anemia. Penicillins interact with several drugs such as aminoglycosides and oral contraceptives.

Adherence

Adherence (compliance) refers to a patient’s ability to adhere to a specific diagnosed drug regimen as suggested by the doctor or pharmacist.  Improper drug adherence can cause many healthcare issues including an ineffective treatment of the patient’s disease.  Poor adherence can also lead to societal healthcare issues, such as improper use of antibiotics has led to the formation of more resistant bacterial strains.  Errors in adherence can be due to many reasons, including forgetfulness, the purpose of the treatment not being clarified properly to the patient and the patient being too embarrassed to ask questions, lack of effect perceived or otherwise, side effects real or imagined, or the patient started to feel better and felt that taking the remainder of the drug was unnecessary.  Ways to improve adherence include more effective counseling on drug regimens.  Make sure patients understand the course of treatment and the importance of following this treatment until finished, unless due to awful side effects.  Ultimately however, it is the patient’s choice to adhere or not to a drug regimen and they will do as they please.

iPLEDGE

iPLEDGE is a risk management computer program which was developed to decrease the potential teratogenic effect of Accutane (isotretinoin) on unborn fetuses. Approved by the FDA, it requires that all healthcare personnel (physicians and pharmacists), all wholesale distributors and all patients prescribed isotretinoin, must be registered with iPLEDGE.  Before a patient is given their prescription each month, they must be counseled of certain risks and must also meet certain criteria.  Women have additional criteria that they must pass including two pregnancy tests with negative results before they are given their first prescription of isotretinoin and they must pass an additional pregnancy test each subsequent month before their prescription is refilled.  Furthermore, it is suggested that women should use two birth control methods such as condoms and birth control pills, if sexually active while on the drug.

Clinical Pathophysiology

Classes of diseases

These categories are generalizations, and diseases can easily fall under one or more category types.

1. Infectious diseases—caused by foreign microbial agents such as bacteria, fungi, and viruses.
   
2. Allergic/autoimmune disorders—caused by hypersensitivity reactions (I, II, III, IV) of the immune system; can lead to disorders such as asthma, allergic rhinitis, and arthritis.
   
3. Metabolic disorders—caused by errors in the metabolic pathways; can lead to some serious health problems.  An example of this can be seen with people who suffer from phenylketonuria (PKU) and cannot metabolize phenylalanine.  Metabolic disorders can be caused by important dietary deficiencies, genetically inherited, or be symptoms of other underlying diseases.
   
4. Neoplastic disorders—caused by numerous environmental and genetic insults, leading to uncontrolled growth of tissue, leading to the development of tumors
   
5. Toxic disorders—caused by toxins and toxicants to the body.  An example of this could be cirrhosis of the liver in response to chronic ethanol consumption.
   
6. Psychiatric disorders—described as chemical imbalances; deals with alterations in brain signaling, such as changes in dopamine levels, which can lead to various mental disorders, including depression and schizophrenia.

Important terms

Carcinoma—Generally the most common types of cancer by which malignant tumors form in epithelial cells of the organ tissue.

Lymphoma/leukemia—malignant tumors that develop from leukocytes, blood and bone marrow cells.

Sarcoma—occurs due to tumors developing in connective and supportive tissues, including the bone, muscle, blood vessels, adipose tissue, and soft tissue (tissue that surrounds and supports the internal organs).

Mesothelioma—specific tumors derived from the protective membrane lining (mesothelia) of organs, most commonly found in the outer-linings of the chest cavity and lungs, but could be found in the abdomen as well.

Glioma—tumors that form from abundant neuronal cells of the central nervous system known as glia.

Gerimonoma—are tumors of the germ (reproductive) cells found in the ovaries and testis.

Choriocarcinoma—an aggressive type of malignant cancer that originally forms in the placenta

Diabetes insipidus—a disorder that leads to excessive thirst and loss of fluids through dilute urine.  It is largely caused by a deficiency/decrease in vasopressin secretion in response to some injury to the pituitary gland (i.e. tumor growth).  Treatment includes regulation of fluids, prevention of dehydration.  Synthetic vasopressin or drugs that induce vasopressin (i.e. Chlorpropamide) can be given as a treatment.

Cretinism (congenital hypothyroidism)—a disorder in children due to decreased levels of thyroid hormones, that if left untreated can lead to stunted growth and severe intellectual disability.  Treatable if caught in time by providing thyroxine to the patient.

Goiter is an enlargement of the thyroid gland, often a symptom of more serious disease of the thyroid.  Goiter can be caused by low iodine in the diet, or a sign of Grave’s disease, in which the thyroid is hyper active. An unusual growth in the neck is a common sign of a goiter. Treatment often includes surgical removal of the thyroid, in part or totally, and hormone replacement therapy.

Tumors

Tumor grade is a system to classify neoplastic cells by how abnormal the cells appear beneath a microscope compared to normal tissue.  Generally performed after a biopsy of a tumor, the tissue is given to a pathologist to study, who determines if the tumor is benign or malignant.  The pathologist will also determine the degree of malignancy, by grading the cancer cells.  Well-differentiated cells have an appearance that is close to that of normal tissue, while poor or undifferentiated cells have little to no discernable features that are similar to normal tissue. There are five stages of grading: Gx- grade cannot be determined; G1- well-differentiated tumor; G2-moderately differentiated tumor, G3-poorly differentiated tumor, G4-undifferentiated tumors. G1 represents a low grade tumor, G2 represents an intermediate grade tumor, G3 and G4 represent a high grade tumor.  Higher tumor grade and poorer differentiation often correlates to increased cancer aggression.

The first stage of tumor progression involves cells that have bypassed normal growth restraints, leading to increased proliferation of cells as well as decreased apoptosis.  This stage is known as dysplasia.  As growth continues unheeded, the amounts of mutations increase, due to the lack of the proper checks and balances necessary in cellular growth.  The cells and tissues become oddly shaped, and show an apparent difference compared to normal cells.  This stage is known as hyperplasia.  As the cells continue to grow, they develop pre-invasive primary tumors, such as carcinomas, in which the cells are encapsulated within the tumor.  As the cancer progresses, cells begin to escape from the tumor, by invading into surrounding tissue as well as blood vessels, giving rise to metastases.  As invasive cells of the primary tumor reach the blood, they can reach distant organ sites, creating secondary tumors, inhibiting the function of important organ systems.  It is the development of these secondary tumors that often lead to increased patient mortality.

A proto-oncogene is a gene that during cancer progression has a high likelihood of becoming an oncogene, a gene that becomes expressed and or overtly active greater than normal in response to mutation or changes in cellular signaling.  Oncogenes are one component necessary for cells to bypass normal host restraints that govern proliferation, apoptosis, and migration, allowing tumors to grow and cancers to thrive.  An example of an oncogene is Ras, a small protein that regulates essential cellular pathways.  Up-regulating Ras can transform some normal cells into malignant cancer cells.  Tumor suppressor is a gene or protein that is generally lost during the cancer progression.  Tumor suppressors, if transfected and expressed at high levels in a cancer cell, will generally retard growth, increase cell death, and decrease migration.  Tumor suppressors are lost for many reasons, including genetic mutations as well as epigenetic factors, such as increased methylation of the gene promoter, which would inhibit transcription of the gene.  A prime example of a tumor suppressor is p53.

Developmental defects

Common causes leading to developmental defects include:

·         Chromosomal defects—occurs usually early during development, commonly an extra chromosome exists known as trisomy.  Trisomy 13 has been linked to the disease holoprosencephaly, which is due to the lack of forebrain development, which can cause severe facial and brain deformities

·         Infectious diseases—certain diseases can lead to various abnormal developments of the fetus.  Rubella can cause Congenital Rubella syndrome (CRS) in unborn fetus.  CRS can lead to abnormal heart, eye and brain development.  Children are generally intellectually disabled, underweight and have smaller heads.

·         Teratogenic drugs—certain drugs can lead to abnormal development of the fetus.

·         Deficiencies—of certain vitamins are hormones often can lead to abnormal fetal development.  One example is folic acid; increased folic acid levels can decrease chances in developing neural tube defects.

·         Radiation—can lead to various severe developmental deformities depending on time frame of pregnancy exposure occurred and length of exposure.

During the first two weeks of gestation, the fertilized zygote divides, and implementation occurs in the uterus.  During these approximately first two weeks, the basic developmental properties that give rise to the more complex organ development are formed.  Teratogenic drugs and other insults to the fetus at this point rarely lead to developmental disorders, however, they can lead to spontaneous abortion, sometimes before the mother even realizes she is pregnant.  During the next six-seven weeks, the heart, limbs and ears develop.  Eyes develop from four to thirty-eight weeks, while the central nervous systems and peripheral nervous systems develop from three to thirty-eight weeks.  Teratogenic drugs, radiation, infectious agents and other fetal damaging agents can potentially harm fetal development throughout the pregnancy.

Symbiotic host-parasite relationships

There are three different types of symbiotic host-parasite relationships.  The first is mutualism.  In this case, the host-parasite relationship is beneficial to both organisms.  An example of this could be the many types of bacteria we have in our GI tract that aid us in digestion and breaking down some of our nutrients.

Commensalism occurs when there may be a benefit to one of the organisms, usually the parasite, but it does not injure the host, nor does it offer any apparent help.  An example of this includes insects that use larger animals not as a source for food, but as transportation.  It helps the insect, but does not cause any real harm to the host animal.

Parasitism occurs when organism thrives through the expense of another organism.  An example of this could be seen with infectious microbial agents.  They need other organisms to thrive, however, this leads to disease and sometimes death to the host.

Respiratory alkalosis and acidosis

Respiratory alkalosis is caused by hyperventilation, which leads to excessive CO₂ excretion from the lungs.  This leads to decreased plasma levels of CO₂, which leads to increased bicarbonate and increased pH levels.  Respiratory alkalosis is often associated with increased anxiety and can also be caused by going from a low altitude to a high altitude.  Changes in pressure can lead to increased CO₂ ventilation.  Symptoms include rapid uncontrollable breathing.  It can also lead to numbness as well as a tingling sensation in the skin.  Treatment can include a paper bag, to increase the likelihood of re-breathing in CO₂ and returning the pH to normal.

Respiratory acidosis occurs in response to decreased CO₂ excretion.  Plasma CO₂ levels are increased as well as levels of carbonic acid, leading to a decrease in pH levels.  Compensation can include increased bicarbonate formation.  Symptoms include shortness of breath, dizziness, and confusion.  Treatment can include oxygen replacement and the use of bronchodilators to open airway passages if, for example, the underlying cause is asthma.  Often respiratory alkalosis is a symptom of an underlying disorder.

Metabolic alkalosis and acidosis

Metabolic alkalosis occurs in response to lower levels of hydrogen ions in the blood.  It is commonly associated with uncontrolled vomiting, which can lead to increased level of bicarbonate in the body, increasing pH.  The body undergoes hypoventilation in order to attempt to return pH levels back to normal.  Increased excretion of bicarbonate by the kidneys can also help in returning pH levels back to normal.  Symptoms include slow deep breathing as well as periods of apnea or lack of breathing.  If untreated it can lead to irregular heart rhythm, nausea, and irritability.  Treatment can include addition of saline solution by IV.

Metabolic acidosis occurs in response to an increased level of hydrogen ions in the blood.  This can be caused by increased production of hydrogen atoms as well as decreased ability of kidneys to form bicarbonate, a necessary sequestration agent of hydrogen ions in the body.  Symptoms include shallow breathing, headaches, and lack of energy.  Treatment includes replacement of fluids and electrolytes, dialysis if due to kidney failure, or replacement by sodium bicarbonate.

Vitamin deficiencies

Symptoms of vitamin A deficiency include dry inflamed eyes, dry skin, and decreased night vision.  It can also lead to increased susceptibility to respiratory infections and can decreased growth in children.

Vitamin C deficiency symptoms include increased nose bleeding, weakness and fatigue if mild.  If severe, deficiency can lead to scurvy, which can lead to excessive bleeding, severely swollen gums, and poor healing.

Vitamin E deficiency is rare.  Symptoms include anemia, decreased coordination, muscle weakness, inability to feel position of limbs in relationship to torso. Vitamin A deficiency can also lead to massive brain hemorrhaging in infants.

Cold treatments

The common cold is often a highly contagious viral infection, leading to respiratory distress.  Symptoms can include a low fever, soar throat, cough, nasal congestion, and general lethargy.  Possible nonprescription drug suggestions can include decongestants (to relieve sinus pressure and mucous build-up and to make breathing easier), anti-histamines to decrease runny noses and allow for easier sleep, NSAIDs and other analgesics for pain, headaches and fever, and local numbing agents (topical anesthetics to treat the soar throat).  Common decongestants include phenylephrine, pseudoephedrine; common anti-histamines can include diphenhydramine, loratadine; common analgesics include aspirin, ibuprofen, acetaminophen, local numbing agents/anesthetics include benzocaine, menthol and phenol.

Osteoarthritis

Osteoarthritis is a disease that leads to the degenerative breakdown of the cartilage in joints.  Cartilage protects our joints by acting as a cushion and can protect the wearing of our bones.  When the cartilage degrades, this protection of the joints is lost, leading to stiffness and pain.  Osteoarthritis is known to affect the hips, hands, feet, knees and spine.  Osteoarthritis is often a component of age; the joints become increasingly inflamed which can lead to pain and swelling.  In advanced cases, total loss of cartilage can occur, severely limiting mobility of the patient.  Other causes of osteoarthritis include obesity, surgery on the joints, diabetes, and gout.  Treatment exists for limiting pain, with such medicines as acetaminophen and aspirin.  Weight loss can limit progression.

Poison ivy, oak, and sumac

Poison Ivy, poison oak, and poison sumac can lead to allergic skin reactions known as rhus dermatitis.  Most people are sensitive to the sap from the leaves, stems, and roots of the rhus family of plants, but like any allergy, it is acquired.  Generally the allergy occurs due to direct contact of the sap on the skin.  Rashes can range from mild to severe.  Rashes are usually itchy, and painful fluid filled blisters generally form on the skin.  Rash may appear a few hours up to a week after exposure, and symptoms can last nearly a month.  Rash can spread to other parts of the body in response to itching.  These rashes are not contagious.  They will clear up after a few weeks untreated if mild.  Other treatments can include OTC local anesthetics, hydrocortisone products, and agents that dry oozing blisters and dry up rashes (calamine lotion, aluminum sulfate, zinc oxide, etc.)  Cool compresses can also be useful.

Traveler’s diarrhea

Traveler’s diarrhea is a very common occurrence when a patient travels, especially to developing nations.  In fact, up to 50% of people traveling experience some type of diarrhea.  The risk of traveler’s diarrhea can be reduced by not drinking tap water and only eating cooked food or fruits that have been personally peeled.  It is also important to remind patients to use bottled water for brushing teeth and to avoid swallowing any water in the shower.  If a patient does develop traveler’s diarrhea, it is usually self-limiting and can be improved by staying hydrated and by taking 4mg Loperamide.  If a patient has a fever or is experiencing bloody stools, they should not take Loperamide and will most likely need antibiotic therapy.  Fluoroquinolones are often used with very good success and are only needed for about 3 days.

Meningitis

Meningitis can be caused by numerous microbial organisms, including gram negative organisms such as E.Coli, as well as Group B streptococci such as Haemophilus influenzae, Neisseria meningitides, Streptococcus pneumoniae and listeria monocytogenes.  Meningitis occurs when the protective membranous layer surrounding the central nervous system known as the meninges becomes inflamed.  A spinal tap is often performed to measure levels of white blood cells in the cerebrospinal fluid.  An excess of white blood cells can indicate meningitis.  Patients will often have a fever, aversion to light, nausea, diarrhea, and change in mental acuity.  Initial treatment of meningitis, before actual diagnosis is known, which is known as empiric therapy differs with age.  Treatment of meningitis usually consists of a regimen of cefotaxime or ceftriaxone alone or in combination with vancomycin, or a combination regimen of ampicillin with aminoglycoside or vancomycin. Generally these antibiotics do not readily get to the sight of infection, and thus the highest safe dose of the antibiotic is generally given.

Endocarditis

The most common cause of endocarditis is Streptococcus and Staphylococcus, which can cause infections in the protective lining of the heart.  This type of infection is more common in patients already suffering from some heart damage and may have had some heart surgery in the past.  Patients will be fatigued and feverish, and generally diagnosis will occur through visual inspection.  Treatment can depend on the causative microbial agent that led to the infection.  In streptococcus, penicillin G alone or in combination with gentamycin can be given.  Additionally Ceftriaxone can also be given.  In staphylococcus infections, nafcillin, oxacillin, and cefazolin can be given alone or in combination with gentamycin.  In both cases of streptococcus and staphylococcus infections, vancomycin can also be given if penicillin offers potential complications.

Heart failure

New York Heart association functional guidelines of heart failure:

·         Functional Class I—patients with heart disease that does not hinder activity at all.

·         Functional Class II—patients with heart disease that shows minor hindrance of physical activity, increased tiredness, increased odd heart rate, fluttering of the heart, and increased chances of chest pain and angina.

·         Functional Class III—patients with moderate to severe hindrance of physical activity of patients, there are no obvious symptoms of heart disease except at rest.

·         Functional Class IV—patients with heart disease/heart failure symptoms are present at all times, including at rest.

Heart failure management guidelines from the American College of Cardiology/American Heart Association:

·         Stage A—There are no symptoms or presence of heart failure, however, patients have a high risk of contracting disease (i.e. genetics, obesity, and hypertension)

·         Stage B—patients develop physical signs/damage to the heart as an indicator of heart failure, but do not show other symptoms of the disease

·         Stage C—patients that have current symptoms of heart disease or past symptoms with underlying structural damage to the heart.

·         Stage D—patients with severe damage to the heart and severe symptoms of heart disease.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) can present clinically with abdominal pain, diarrhea and/or constipation, heartburn, nausea, cramps, increased urination, and decreased sexual desire.  IBS is one of the most common diseases of the digestive system.  IBS is also more common in women.  First line therapy in patients with a mild case of IBS includes antimuscarinic and anticholinergic drugs such as dicyclomine and hyoscyamine.  Laxatives can help with constipation, but does not affect other IBS symptoms.  Loperamide is a drug that is used to treat against diarrhea, but does not affect other IBS symptoms.  Other drugs used to treat this disorder include selective serotonin reuptake inhibitors and tricyclic antidepressants.  Tegaserod is a serotonin agonist which can relieve various IBS symptoms, including bloating and pain, and helps in constipation IBS. Alosetron was a serotonin antagonist that was used to treat IBS with diarrhea, but was pulled from the market due to a possible connection to increased cardiac distress.  Tricyclic antidepressants and antimuscarinic and anticholinergic drugs can lead to depression of the central nervous system, constipation, decreased sweating, urine retention and decreased urination.  Tegaserod can lead to increased nausea, headache, and abdominal pain.  Laxatives can lead to cramping and if overused can lead to the loss of important bacterial colonies from the gut, as well as damage to the GI tract.

Gout

Gout is a disease that occurs in response to high levels of uric acid that deposit in the joints, leading to pain and inflammation.  Gout is caused by hyperuricemia.  The incidence of gout has been reported for millennia and is known to occur in 1% of the population.  Symptoms generally begin with pain in the joints of the feet.  During an arthritis attack the patient can experience a fever, and the affected area can be very inflamed and tender to the touch.  Treatment against a gouty arthritis attack may include colchicine.  Colchicine acts as an anti-inflammatory agent and acts by inhibiting leukocyte phagocytosis of uric acid crystals.  Diarrhea and cramping can occur, and patients should be counseled to stop taking this drug once it occurs.  This drug can also cause bone marrow depression.  Indomethacin and corticosteroids can also be used to treat acute gouty arthritis.

Generalized seizures

Generalized seizures occur on both sides of the brain and include: Absence seizures—these are subtle seizures that last only a few seconds, include a loss of awareness, but usually not complete unconsciousness.  People with this disorder will often stare blankly, completely unaware of their surroundings.  Often occurring in children, these seizures are hard to diagnose, and will often go unnoticed for years. Atonic seizures—lead to a complete loss of muscle strength or tone, often causing the victim to collapse suddenly.  There is little warning, and protective helmets and clothing are often worn in case the patient falls.  Myoclonic seizures—are rapid whole body muscle contractions.  Contractions are brief and usually occur on both sides of the body at the same time (e.g., arms or legs).  Tonic clonic seizures—also known as grand mal seizures, are the most common seizure type.  Often affecting the entire body, first the body stiffens (tonic) and becomes very rigid, next severe muscle contraction and jerking occurs (clonic). Loss of respiratory function can also occur.

Partial seizures

Partial seizures are the most common seizures attributed to patients suffering from epilepsy.  Partial seizures are generally caused by a disturbance in the electrical activity of a specific region in the brain.  There are two types of partial seizures: simple partial seizures and complex partial seizures.  During simple partial seizures, patients do not lose consciousness; the seizure can originate at one point in the body, leading to rapid contraction of muscles but can eventually spread to be a more general-like seizure.  These seizures are often attributed to unusual sensations of taste, touch, smell, hearing and sight.  They can also bring about odd exaggerated emotional states including fear, rage, anger and even joy. A person having complex seizures may appear conscious, however, they do not remember anything that has occurred during the seizure, what was said, or what was felt.  Complex partial seizures largely affect the temporal lobe of the brain and affect more of the brain function than simple partial seizures.

Peptic Ulcer Disease

Peptic Ulcers are a general classification of lesions of the GI tract usually due to excessive acid or other digestive enzymes.  Ulcers can also be caused by infections from the Helicobacter pylori, gram-negative bacteria, NSAIDs and stress.  Clinically, symptoms often occur after eating and pain is relived by antacids or other drugs such as PPIs.  Pain can exist from hours to months, depending on how serious and large the ulcer is.  Pain can be relatively acute and can lead to chronic pain.  Treatment includes relieving symptoms and underlying causes/infections.  For helicobacter pylori infections, antibiotic drug regimens can be used.  For NSAID induced peptic ulcers, removal of NSAID use will often help.  Antacids can also be used; other drugs such as proton pump inhibitors (PPI) and H2-receptor blocker are drugs that can be used to inhibit release of gastric juices, allowing ulcers to heal. Drug regimens of these drugs can often be chronic.

Ulcerative colitis

Ulcerative colitis (UC) is a type of inflammatory bowel disease.  It affects the colon and rectum.  The most common clinical symptom of ulcerative colitis that generally appears first includes bloody diarrhea, as well as a painful and frequent need to defecate.  UC is often caused by inflammation and ulcers.  UC severity (mild, moderate, severe and fulminate) are diagnosed by endoscopy, tissue biopsy, and bacterial studies of feces.  UC is considered mild if defecation occurs less than four times a day, marred with or without blood and with a normal erythrocyte sedimentation rate.  Moderate UC has more than four defecations a day with signs of toxicity (little bleeding, low levels of infection, etc.)  Patients with severe UC suffer from six or more defecations with noticeable systemic symptoms including fever, anemia, infection, etc.  Fulminate UC occurs if there are ten or more defecations a day with significant levels of systemic symptoms, including abdominal distention, continuous bleeding and may need numerous blood transfusions.  Treatment can include drugs as well as surgery.

Crohn’s Disease

Crohn’s disease (CD) is a type of irritable bowel disease which leads to inflammation of the GI tract which can affect any part of the GI tract, from the mouth to the anus.  CD is chronic, although symptoms may go into remission for periods of time. Certain factors that might lead to CD may be bacterial infection or overeating, however, the exact cause is not entirely understood.  Symptoms of CD can include chronic diarrhea, frequent bouts of diarrhea at night, and increased levels of abdominal pain.  CD is marred by lesions of the GI tract.  Other symptoms can include fever, excessive bleeding from the rectum, and may lead to weight loss as well as excessive fatigue.  CD also can also have non-GI related symptoms including the development of arthritis, formation of painful nodules on the limbs, fatty liver, hepatitis, and gallstones.  Treatment can include drugs as well as surgery.

Alopecia

Androgenic alopecia (male pattern baldness) occurs in the presence of excessive androgen, a common component of aging in males.  Other types of alopecia can occur in response to chemotherapy, hereditary and other underlying diseases, but these often are untreatable.  Minoxidil (Rogaine®) and finasteride (Propecia®) can be used to treat male pattern baldness.  The mechanism of action of minoxidil is not understood; it may stimulate hair follicle cellular growth and may also increase blood flow to hair follicles encouraging growth.  Minoxidil is applied in 1 ml doses, twice daily and must be applied continuously for continuous hair growth.  Adverse effects include excessive hair growth all over the body, possible increased heart rate, and should not be used on a pregnant female.  Finasteride was originally used to treat benign prostatic hyperplasia and prostate cancer.  Finasteride inhibits 5-α-reductase by inhibiting testosterone conversion to dihydrotesterosterone.  DHT is important in hair loss.  Finasteride is usually taken once a day for three months to see if it works.  Side effects include breast enlargement, skin rashes, erectile dysfunction, decreased sex drive and can be teratogenic.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that causes the immune system to attack the joints.  As the disease progresses, the pain and loss of mobility can be severe, and other tissues including the heart, lungs and muscles may be affected.  Rheumatoid arthritis has an incidence of 1% and usually affects women more than it does men between the ages of 30-60.  Clinical symptoms can progress unpredictably.  Ten to twenty percent of patients with this disease have a short disease, with a long remission; seventy to eighty percent have a moderate form of the disease with continual cyclical outbreaks.  For ten to twenty percent of patients, the disease will continue to progress into a rather destructive disease.  Patients meet at least four criteria: morning stiffness that lasts at least 1 hour, swelling of three or more areas of soft tissue around the joints with systemic arthritis, positive rheumatoid factors which are antibodies that collect in joints, erosion of bones around joints, or nodules that form over points of arthritic joints but beneath the skin.

Disease Prevention and Population Health

Malnutrition

Malnutrition is caused by under-nutrition and obesity.  Under-nutrition occurs in response to starvation or a change in metabolism of nutrients, which might be caused by injury, in which the proper dietary needs are not being met.  Obesity occurs when there is too much caloric intake, which often coincides with lack of exercise.  Genetic traits can also increase chances of obesity.  There are three types of obesity; type I has a body mass index (BMI) greater than 30 but less than thirty-five; type II obesity are patients that have a BMI between 35 and 40, and types III, which has patients with a BMI over 40.  Other types of malnutrition include marasmus, which are patients that have low levels of fat and muscle, but otherwise appear healthy.  Kwashiorkor, are patients that have normal or slightly higher levels of fat and muscle, but show low immune response and low levels of important biochemical enzymes and proteins. People can also suffer a mixture of Kwashiorkor and marasmus in which fat, muscle, the immune response, and enzyme, protein and metabolic pathways are retarded.

Feeding tubes

Feeding tubes are given if for whatever reason a patient cannot eat on their own and a simple IV is considered insufficient.  A feeding tube is generally placed in the abdomen through the stomach directly or into the jejunum directly, although feeding tubes can also be placed through the nose, so nutrients can enter the esophagus and stomach.  The feeding tube is placed in patients who might be undergoing chemotherapy, in a coma, or undergoing radiation.  Feeding tubes can be painful if caught or rubbed against clothing; by taping the tube to the abdomen, while not in use, patients can perform everyday activities.  These tubes can lead to infection.  Feeding tubes can also lead to small cracks in the GI tract.  One of the most common side effects occurs when food is actually inhaled into the lungs.  More serious side effects can also occur, such as hemorrhaging of the GI tract as well as leakage of gastric fluids into the body.

Cholinergic crisis

The cholinergic crisis occurs in response to over-stimulation of the neuro-muscular junctions, excess acetylcholine leads to increased activation of the muscarinic receptors. This excess of acetylcholine is generally due to an inhibition of the acetylcholine esterase enzyme.  The acetylcholine esterase enzyme is important in the breakdown of acetylcholine.  With excessive acetylcholine, the muscarinic receptors become saturated and the muscles do not function with increasing levels of acetylcholine.  This can lead to a reduction in muscle tone, increased paralysis, and respiratory depression.  Cholinergic crisis can be caused by certain drugs as well as organophosphate poisonings.  The antidote of a cholinergic crisis is atropine.  Atropine is a competitive inhibitor of acetylcholine and can reverse the cholinergic crisis.

Renal insufficiency

Renal insufficiency occurs in response to kidney disease and failure, leading to lower clearance of various drugs, and thus new drug regimens must be designed for the patient.  The important steps required for creating a new drug regimen include: 1) obtaining a thorough patient medical history. 2) Determining creatinine clearance to estimate kidney function.  3) Reviewing present prescriptions and other medications of the patient.  4) Determining the correct dosing regimen of the prescriptions for the patient, the dosing regimen is individualized.  5) Monitoring clearance levels of the drugs during the new drug regimen as well as monitoring toxicity of the drugs.  6) Adjusting drug regimen based on findings of step 5, until optimal treatment is obtained.  Kidney function changes as the disease progresses, thus new drug regimens will need to be adapted.  State of drug clearance should constantly be monitored.

Nonpharmacological treatments

Acne Vulgaris is the most common form of acne, localized inflammation on the face.  Washing and scrubbing your face daily may be effective against acne, by drying and removing excess oil, dirt and bacteria.  A generous washing regimen can lessen the acne impact.

Psoriasis a common disorder leading to the reoccurrence of inflamed thickened plaques on the skin.  Psoriasis has a strong genetic factor.  UV light between the wavelength of 310-315 nm and emollients such as lotions and creams to keep the skin hydrated can reduce the risk of a psoriasis outbreak.

Atopic dermatitis (AD) is an itchy inflammatory disorder that is often triggered by allergens such as dust, food products, cleaning products, etc.  Non-pharmacological treatment includes reduced exposure to allergen trigger of AD and moisturizing skin during AD. Diligent washing and moisturizing of the can also be used as preventative measures against AD.

There are many ways a patient can treat osteoarthritis without using drugs.  The effectiveness for the treatment will be dependent on a case by case basis, however, drugs may be the best treatment for a certain individual.  Diet and exercise are an important means to treat osteoarthritis.  Obesity can lead to excessive wear and tear of the joints, leading to increased pain in people suffering from osteoarthritis.  Losing weight and remaining active can greatly help relieve joint pain and increase mobility.  Physical therapy is also an important treatment, in which stretching and joint specific exercises can increase mobility and relieve pain of the infected joints.

Nucleoside reverse transcriptase inhibitors

Nucleoside reverse transcriptase inhibitors (NRTIs) are some of the oldest drugs used to treat the HIV virus.  NRTIs inhibit HIV viral replication by hindering RNA-dependent DNA polymerase.  Drugs in the class include:  zidovudine (AZT), lamivudine (3TC), Abacavir (ABC), didanosine (ddI), stavudine (d4T), Zalcitabine (ddC), tenofovir (TDF) and emtricitabine (FTC).  NRTIs can cause lactic acidosis and hepatomegaly.  All NRTIs, except, abacavir, need to renally dose adjusted.  Compared to other HIV medication classes, NRTIs have few drug interactions.  3TC and FTC should not be used together.  Do not use AZT and d4T together as they can antagonize each other.  Typically, a patient has an HIV drug regimen that consists of two NRTIs and one other medication from either the non-NRTIs or protease inhibitor class.

Non-nucleoside reverse transcriptase inhibitors

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) stop HIV from replicating by binding to reverse transcriptase.  Unfortunately, the HIV virus can easily mutate in such a way that confers resistance to this entire class of drugs.  Drugs in this class include:  efavirenz (EFV), nevirapine (NVP), delavirdine (DLV).  All NNRTIs need to dose adjusted if a patient has any type of hepatic disease.  All drugs in this class are CYP 3A4 inducers or inhibitors and as such can interact with many drugs.  Drugs in the class can cause hepatic failure.  As a pharmacist, it is important to check and monitor for potential drug interactions when a patient is taking NNRTIs.

Protease inhibitors

Protease inhibitors (PIs) inhibit protease.  By inhibiting protease, the HIV virus cannot properly cleave polyproteins and instead of forming mature HIV particles, immature particles are formed.  The immature particles are considered non-infectious.  Drugs in this class include:  fosamprenavir (f-APV), amprenavir (APV), saquinavir (SQV), darunavir (TMC-114), tipranavir (TPV), ritonavir (RTV) and indinavir (ICV).  Protease inhibitors have many side effects that can be very distressing to a patient.  Common side effects include:  hyperglycemia, hyperlipidemia, hypertriglyceridemia, osteopenia, osteonecrosis (especially of the hip joints) and lipodystrophy.  Common laboratory values should be monitored every 4 weeks after the start of PI therapy.  All drugs in this class are CYP 3A4 inhibitors and as such can interact with many drugs.

HIV antiretroviral therapy in pregnancy

A woman who has HIV and becomes pregnant has a 30% chance of passing the HIV virus to the baby.  Antiretroviral therapy should be offered if the patient is not already taking any antiretroviral therapy.  Efavirenz is not to be taken by pregnant women.  Ideally, AZT should be one of the NRTIs being taken while pregnant.  Interestingly, AZT alone can reduce transmission of the HIV virus to the baby to less than 3%.  Pregnant women need to receive two doses of IV AZT during labor; this alone will reduce HIV transmission.  It is also recommended that the baby receive up to 6 weeks of AZT therapy after birth.

HIV post-exposure prophylaxis

Whenever there is an exposure event, it is always important to practice universal precautions.  In general, needle sticks make up the largest portion of infectious exposure.  If you are involved in an infectious exposure, always follow the post-exposure prophylaxis protocol at your healthcare institution.  Post-exposure HIV prophylaxis significantly reduces the already very slim chance of HIV infection from a needle stick. Typically HIV post-exposure prophylaxis involves two NRTIs and one other medication taken for four weeks.  Follow-up HIV testing is performed several times over the next year.

End-stage kidney disease

End-stage kidney disease can drastically change the volume of distribution of many drugs.  This change in volume of distribution can be due to variety of reasons including changes in drugs binding to various proteins, increased water weight gain, and other changes in the ratio of muscle to fat.  In general, this change in volume of distribution will not affect the drug response to a large degree.  For most medications, end-stage kidney disease increases the volume of distribution compared to a patient with normal kidney function.  A few medications such as digoxin, pindolol, methicillin and ethambutol actually have a decreased volume of distribution compared to a patient with normal kidney function.

End-stage kidney disease can increase or decrease how much drug is bound to proteins in the body.  Medications that are acidic, such as furosemide and phenytoin, generally are less protein bound.  This decrease in protein binding can be caused by several factors including toxins binding to proteins, leading to less protein binding sites available for acidic drugs; changes in the amount of albumin in the body; and physical changes to protein binding sites.  This is an important factor to keep in mind when checking kinetics for drugs such as phenytoin.  If a patient has kidney dysfunction, they will likely have a greater amount of unbound phenytoin and therefore will be therapeutic in a lower target range.

As a pharmacist, renally dosing medications is a common practice.  It is important to understand that a patient with end-stage kidney disease not only has significantly reduced drug renal elimination, but also potentially metabolizes those drugs through altered pathways.  Specifically, kidney disease has been shown to also alter how drugs are metabolized through the CYP P450 liver system.  While this may not be the case for every patient with kidney disease, it is an important factor to consider if a patient is exhibiting signs of drug toxicity or is reacting differently to a medication than expected.  If it appears that metabolism of a drug is being affected, you will most likely need to reduce the dosage or frequency of the medication.

Vitamin deficiencies

Vitamin B1 (thiamine) — deficiencies can lead to beriberi (a disorder of the nervous system) emotional problems, weakness and fatigue.  Thiamine deficiencies can also lead to cardiac arrest if severe enough.

Vitamin B2 (riboflavin) — deficiencies can lead to ariboflavinosis, which is a disorder that leads to a lower level of a protein important in energy metabolism.  Symptoms include inflammation of the throat and mouth, development of a magenta tongue, decreased red blood cell number, and various dermatological disorders and rashes.

Vitamin B3 (niacin)—deficiencies of this vitamin are generally associated with tryptophan deficiencies and can lead to Pellagra which has symptoms of photosensitivity, increased aggression, skin lesions, weakness, confusion, dementia and diarrhea.

Vitamin B5 (Pantothenic acid)—deficiencies of this vitamin have been associated with increased acne.  Vitamin B5 deficiencies can also lead to the development of paresthesia, a numbness of the skin.

Vitamin B6 (Pyridoxine)—can lead to increased depression, memory loss, hypertension, increased edema, and increased levels of homocysteine, which can lead to increased risk of heart disease and increased weakness of the bones.

Vitamin B7 (Biotin)—deficiencies in children can lead to stunted growth and various neurological problems.

Vitamin B9 (Folic acid)—folic acid deficiencies can lead to an up regulation of homocysteine. Folic acid deficiencies in pregnancy can lead to severe birth defects.  There is evidence that folic acid can be beneficial against cancer as well.  Folic acid deficiency can also lead to decreased RNA and DNA synthesis in red blood cells leading to increased red blood cell size and increased anemia.

Vitamin B12 (Cobalamin)—can lead to pernicious anemia, an anemia strictly associated with B12 vitamin.  It can also lead to decreased cognition and memory lapse, as well as decreased RNA and DNA synthesis in red blood cells, leading to increased red blood cell size and increased anemia.

Patient Assessment

Hypokalemia and hyperkalemia

Hypokalemia occurs in response to low potassium levels, generally levels less than 3.5 mEq/L.  Hypokalemia can be caused by decreased intake of potassium due to poor diet.  It can also be caused by increased loss of potassium due to drugs such as corticosteroids, diuretics, amphotericin B, and laxative abuse. Symptoms include cardiovascular (hypotension, differences in EKG), neuromuscular (cramps, weakness, lack of reflexes), and renal (unable to excrete concentrated urine, excess water loss) changes.

Hyperkalemia is due to high potassium levels, generally levels greater than 5.5 mEq/L.  Hyperkalemia can occur due to decreased effectiveness of potassium excretion, which can be due to renal dysfunction or certain drugs such as spironolactone.  Hyperkalemia can also be caused by excessive cellular breakdown, excessive intake due to supplements or IV fluids, and metabolic acidosis.  Symptoms include bradycardia and hypotension.

Hyponatremia and hypernatremia

Hyponatremia occurs when sodium levels fall below normal physiological levels, less than 125 mEq/L.  Hypernatremia, however, occurs when sodium levels are excessive, greater than 150 mEq/L.  Hyponatremia occurs in response to both increased fluid levels and dilution of fluids in response to various disease states including cirrhosis of the liver, congestive heart failure, renal failure and syndrome of inappropriate ADH.  It can also be caused by excessive sodium depletion due to kidney failure, sodium wasting, and severe decrease of sodium intake from the diet.  Symptoms include edema, cramps, confusion, dizziness, seizures and comas.  Hypernatremia is caused by dehydration which can be due to not drinking enough water; several drugs known as diuretics can increase sodium levels in the body.  Excessive intake of sodium through diet, drugs and IV fluids can also result in hypernatremia.  Symptoms include thirst, overactive reflexes, seizures, and even death.

Liver function tests

Liver function tests measure levels of liver enzymes in the blood.  Increased blood levels of these enzymes can be a sign of liver disease.  Alanine Transaminase (ALT) – synthesized specifically by liver cells, blood levels increase due to liver cell damage usually in response to inflammation, a common symptom of liver disease. Aspartate Transaminase AST, less specific than ALT for liver damage, AST is a protein found in the mitochondria of liver cells as well as cardiac, kidney, and brain cells.  When measured with ALT, however, a one to one ratio is often observed during liver damage.  Alkaline Phosphatase (AP) is elevated in many tissues and while it could be an indicator of liver disease, it is not specific.  This should send a warning sign to look at the liver and other tissues for further diagnosis.  Increased levels of albumin, bilirubin, Gamma-glutamyl transferase (GGT), and Lactate Dehydrogenase (LDH) can also indicate liver damage.

Home pregnancy tests

False positives are rare but can be caused by people who have had recent miscarriages in the last two months, childbirth in the last two months, or who are on fertility pills such as Profasi, which can alter gonadotropin or LH levels, thus giving a positive result in the pregnancy.  False negatives can be caused by taking the pregnancy test too soon after the missed period, urine not allowed to become warm if refrigerated, or dysfunction of the pregnancy test.

Inotropic and chronotropic drugs

Inotropic compounds are therapeutic drugs which affect the force of heart muscle contraction, positively (increasing force) or negatively (decreasing force).  Milrinone and digoxin are examples of positive ionotropes. While negative ionotropes include β-blockers and calcium channels blockers.  Chronotropic compounds are therapeutic drugs that affect the heart rate, positively (increasing) or negatively (decreasing) the rate.  Examples of a positive chronotope include atropine, while β-blockers are an example of a negative chronotrope.

Concordance

Concordance is a term that was recently coined describing the evolution of healthcare, particularly the relationship between patients, physicians and pharmacists in relation to the patients prescribed treatments.  Concordance, in many ways, is like an oral contract between a patient and their healthcare providers that they will adhere to prescribed therapy as directed.  This approach to healthcare makes patients more responsible for their well-being and not solely a responsibility of the physicians and pharmacists.

Migraine headaches

Migraines are a certain type of headache that is often associated with nausea, light sensitivity, audio sensitivity and sensitivity to smells.  Migraines are generally chronic and can last from a few hours to a couple of days.  Pain caused by migraines can differ from patient to patient and is often an intense throbbing.  Migraines can be associated with auras, which are neurological changes that occur about thirty minutes before the onset of the headache.  These auras are often visual changes such as hallucinations, blurry images, vision loss, lights, etc.  Some patients have migraines that are not associated with auras.  Migraine triggers are often patient specific, but can include allergies, food, too much or too little sleep and hormonal changes.  It is suggested that the pain of a migraine headache is due to excessive vasodilation in the blood vessels of the brain.  This increased pressure in the head, leads to this pain, although the exact causes of a migraine are not entirely understood.

Besides the normal migraines with or without an aura, other types of migraines also exist such as abdominal migraine, basilar type migraine, familial hemiplegic migraine and acephalgic migraine.  Abdominal migraines often affect children and are associated with nausea, abdominal pain, as well as flushing of the skin or draining of the skin, loss of appetite and can last up to 72 hours.  Treatment can include anti-nausea medicine (promethazine), tryptans (anti-migraine), NSAIDs, and other anti-migraine medicine.  Basilar artery migraines occur in response to a malfunction within the brainstem, due to errors in vasodilation of the basilar artery, which can lead to headache, dizziness and loss of muscle coordination.  Treatment can include vasoconstrictors and tryptans.  Acephalgic (headache-free) migraines occur when a patient experiences normal migraine symptoms including photosensitivity, audiosensitivity, nausea, and auras, but do not experience a headache. These will often gradually become a more classical migraine with a headache.  Treatment can include anti-nausea medicine (promethazine), tryptans (anti-migraine), NSAIDs, and other anti-migraine medicine.

Mania and depression

Manic episodes have several characteristics which include increased hyperemotional states which can include feelings of increased euphoria and joy, rapid and quick speech, increased agitation, as well as increased energy.  Often people experiencing manic episodes also suffer from mild to severe insomnia depending on the severity of the manic episode.  People suffering from mania often cannot function properly in life or at work and may experience psychotic episodes.  Depression has several symptoms that include fatigue, increased sleep as well as insomnia, altered appetite, feelings of helplessness, increased unwarranted feelings of guilt, hopelessness, and anxiety.  Often depressive episodes involve suicidal thoughts.  People who suffer from bipolar disorders will suffer from varying cyclical bouts of mania and depression.

Patient history

There are several things that should be covered when obtaining a comprehensive patient history.  Identifiers such as name, date of birth, sex, the name of their family physician, race and nationality should be recorded.  When obtaining a history it is important to be respectful and polite, if a patient is comfortable, they are more willing to provide private information.  Complaints (reasons for the patients visit), how long the symptoms have progressed, current and past medical care, allergies, present drug prescriptions, as well as OTC medication that the patient may be on should also be recorded.  Additionally, data from the system review (body temp, heart rate, blood pressure, etc.) should also be recorded.  Having a comprehensive history can make therapy easier, with fewer possible medical errors occurring.

Assessment techniques

A pharmacist must know and utilize basic healthcare assessment techniques.  Palpation is the measurement of swelling or injury of a particular area by touch, such as looking for swelling of the lymph nodes which often occurs during infection.  Percussion is performed when part of the body is tapped with a finger and the reverberations of sound are used to determine the presence of underlying illness.  An example of this is used to listen to listen for alterations in lung function, for example.  Auscultation is a technique in which a stethoscope is used to listen to sound within the body, such as heart beat.  This technique is also used simultaneously with an aneroid sphygmometer, which is important in measuring blood pressure.  Other techniques include checking body temperature (optimal temp~98.6 F°) and reflexes.  It is important to be thorough and accurate when inspecting a patient: their life may be at stake.

Life support

Basic life support consists of techniques to treat and sustain life long enough for the patient to reach the hospital.  These techniques include first aid to treat bleeding, shock, as well as cardiopulmonary resuscitation (CPR).  CPR can be used to rescue patients from cardiac and pulmonary arrest.  CPR can be used to provide oxygen to the lungs of the unconscious patient by transferring oxygen mouth to mouth from one person to that of the lungs of the patient.  Additionally, by providing firm chest compressions, the provider of CPR allows for blood to pump from the heart to other important organs.  CPR is used as a way to sustain life until paramedics arrive, as well as possibly returning a functional heart respiratory rate to the patient.  CPR has a high failure rate and patients that survive may have organ damage.  CPR is meant for life support until further treatment can be performed, not a replacement for treatment.

Advanced life support is performed as complementary treatment to basic life support.  While anyone can provide basic life support, advanced life support is specific to trained healthcare professionals.  Advanced life support involves the use of important medical devices including respiratory ventilators, electrocardiograms, and administration of important IV drugs.  Other important advanced life support actions include administration of tracheal tubes to aid in breathing, chest tubes to drain excess fluids, repair of collapsed lungs, etc.  A defibrillator is used to shock an irregular heartbeat back to a normal heart rate.  Drugs that are commonly used include epinephrine and atropine, which both can cause an increase in heart rate.  It is thought that chest compressions should be provided concomitantly with any provided advance life support.

Glucose tolerance tests

Glucose tolerance tests are used to measure glucose levels to determine if a patient has diabetes (type I, type II, or gestational).  After a period of fasting, the blood glucose levels are measured.  Baseline fasting blood glucose levels are generally between 70-105 mg/dL, after 30 minutes the level of glucose in the blood should range between 110-170 mg/dL, which should increase to 120-170 mg/dL after 60 minutes.  The fasting blood glucose levels after 90 minutes begins to drop to a range of 100-140 mg/dL and after 120 min, the level of fasting blood glucose should drop to a level between 70-120 mg/dL.  These levels are optimal, and if there are deviations from these ranges, this could indicate the presence of diabetes or other underlying disorders.

Chronic pancreatitis

Chronic pancreatitis (CP) is usually caused by structural damage to the pancreas and is often associated with chronic inflammation.  The patient may show symptoms of malnutrition.  Additionally, CP is often associated with liver disease brought on by chronic alcoholism.  Symptoms of pancreatitis include deep dull pain in the abdomen with nausea and vomiting.  CP is often associated with excessive weight loss and excessive loss of fat and protein through the feces (steatorrhea and azotorrhea respectively).  The use of analgesics such as aspirin, acetaminophen, and ibuprofen are used as treatment for the pain while anti-inflammatory drugs such as NSAIDS and COX-2 are used for the inflammation of the pancreas.  Non-pharmacological treatment includes stopping alcohol ingestion and the introduction of a fat reduced diet.

Clinical Pharmacology and Therapeutic Decision Making

Disease states induced by drug use

There are several disease states that can be induced by specific drug use:

Pancreatitis

·         occurs when the pancreas becomes inflamed

·         can be fatal if left untreated

·         can be induced by excessive imbibing of alcohol

·         can also be induced by the use of estrogens, acetylcholine esterase (ACE) inhibitors, statins, cancer chemotherapy drugs and various other drugs

Nephrotoxicity

·         a general term for kidney toxicity

·         can be induced by NSAIDs, cisplatin, and aminoglycosides

Pulmonary Disease

·         pulmonary fibrosis can be induced by amiodarone and bleomycin.  This occurs when scars form on the air sacs of the lungs and the ability to transfer oxygen into the blood is damaged.

·         Β-blockers can lead to constriction of the bronchiole tubes.  This can lead to difficult breathing, asthma.

Orthostatic hypotension

·         can be induced by numerous drugs, including α blockers, β-blockers, ACE inhibitors, antidepressants, nitrates, and phosphodiesterase inhibitors.

·         Orthostatic hypotension is when the blood pressure drops as the person stands up leading to severe dizziness and fainting.

Clinical definitions of pain

There are six different clinical definitions of pain:

·         Nociceptive pain— pain due to a stimulatory response of common pain receptors and pathways, e.g., slamming a finger in a door or reflex pain through the spinal cord due to touching a hot stove.

·         Somatic pain— pain in tissues that are of a somatic origin such as muscle and skin.

·         Superficial pain— local pain, which could feel like a burning sensation, a painful throbbing, could be due to sensitive skin, or a hypersensitivity to pain (hyperalgesia) for example.

·         Deep somatic pain— A localized dull ache, a painful throbbing sensation.

·         Visceral pain—not localized, dull aching pain that often occurs at the onset of a disease

·         Neuropathic— pain that is related to direct damage to the nervous system. Could be due to injury of the peripheral nervous system or central nervous system.

Non-drug related pain management

The use of drugs in pain management is important, however, there are many non-pharmacological methods to regulate pain as well.  These can include the use of heating pads or ice packs to relieve pain and inflammation at a site of injury.  Physical therapy is also important in dealing with pain and in the healing process.  Other alternative therapies which have shown benefit in the regulation of pain can include meditation, massage, and acupuncture.  Alone or in combination with drugs, these alternative pain management techniques can provide a great deal of benefit to patients.

PQRST

P = Palliative (painkilling) factors of pain—What can be used to relieve the patients suffering/pain? Provoking (painful) factors of pain—what can be done to make the pain worse?

Q = Quality of pain.  This really involves the patient’s description of the pain, the general sensations that are being felt.

R = Radiation or location.  Where is the pain located in the body?

S = Severity = How painful is it compared to other pains the patient may have felt before?  Pain is very subjective.  A scale ranging from 0-5 helps measure the severity of pain that a patient is suffering.  0 = no pain, 5 = severe pain.

T = Temporal factors.  Does time affect the pain?  As time increases does pain decrease?  Is this pain temporary, a sign of nerve damage (numbness)?  Does the pain increase with time?  Is the pain getting worse?

These are some of the questions you need to ask when assessing pain, as well as assessing the underlying causes of the pain, allowing for a better, more effective treatment.

Acute and chronic pain

Acute pain generally occurs due to an apparent injury; onset is rapid and can range from minor to severe, however, pain is relatively short lasting.  Amount of pain is often proportional to the severity of the tissue damage.  Acute pain is generally easier to treat since the tissue damage is generally more easily diagnosed than chronic pain.  Chronic pain is generally considered pain that continues after apparent healing of damaged tissue has occurred.  Chronic pain is difficult to manage, as the underlying causes of chronic pain are not fully understood.  Also chronic pain can become resistant to normal medical treatments.  Chronic pain is also difficult to diagnose because there is often little or no obvious indications of the pain, unlike acute pain, where the tissue damage might be obvious. Doctors are a little more hesitant to treat chronic pain, due to some people attempting to get pain medications such as vicodin to use for their drug addictions, rather than being in actual pain.

Birth control

Five different types of birth control:

·         Condoms: made of latex, fit snugly over the penis.  A condom acts as a barrier to the sperm, which collects in a reservoir at the condom tip.  Condoms block pregnancy by 88% and STDs by 85%.  They are easy to use, cheap, and relatively effective; however, allergies can develop against latex.

·         Diaphragm: latex or silicone barrier placed in the vagina, blocking sperm from reaching the cervix, inhibiting pregnancy.  Diaphragms are expensive and must be fitted.  They have approximately a 90% success rate in blocking pregnancy if used correctly. They provide little protection against STDs, are uncomfortable, and can increase chances of UTI.

·         Coitus interruptus: the withdrawal method, in which the penis is removed before climaxing.  This method has a high pregnancy failure rate and does not protect against STDs.

·         IUD: highly effective birth control device that is placed in the uterus and causes the release of leukocytes and other components that are deadly to sperm. It is not effective against STDs.

·         Oral contraceptives pills: using hormones, regulates menstruation and ovulation, blocks pregnancy by inhibiting follicle formation and ovulation.  They provide no protection against STDs, and risks of taking oral contraceptives include migraines, breast cancer, hypertension, and strokes.

Tests

The PTT test stands for the partial thromboblastin time test and it is also known as the activated PTT test.  It is a diagnostic test to measure the length of time blood needs before it clots.  This test is often performed at the same time as the PT test.  The test is performed for a variety of reasons, but in particular to measure causes of excessive or unusual bleeding.  The test is also performed to assess the presence of bleeding disorders such as hemophilia and can also be used to measure excessive clotting, which can be dangerous and fatal, if not caught in time.  The test is performed to measure blood-clotting time before and after surgery.  This test can be used to measure the effects of heparin, an anti-clotting agent that is often given to patients after surgery to lower the chances of developing dangerous blood clots.  When the blood is taken, clotting is arrested with the addition of citrate.  When the test is performed, an activator of clotting is added to the blood and the time it takes for clotting to occur is measured.

Prothrombin time (PT) is a test to measure clotting of the blood often in relation to warfarin therapy, vitamin K levels, and overall liver damage/disease.  PT test provides two separate measurements including the prothrombin ratio (PR) and the international normalized ratio (INR).  Thromboblastin (tissue factor) is added to the sample blood and control blood and the time for clotting is calculated. The PR is calculated by (PT of sample)/PT of control.  INR is calculated by (PT of sample/PT of control)^ISI.  ISI is the international sensitivity index of the tissue factor that is provided by the manufacturer.  It compares their tissue factor with the international standard for tissue factor and is usually between 1 and 1.5.  Normal range of PT (time for blood to clot after tissue factor addition) is often 12-15 seconds.  The normal INR ratio is about 0.8-1.2.

Beers Criteria

The Beers criterion is a list of medications that have been deemed inappropriate and unhealthy to give geriatric patients because the risks generally outweigh the benefits.  Drugs on this list include:

Giardiasis

Giardia Lamblia is a parasitic protozoan that affects the gastrointestinal system and is the most common cause of diarrhea.  Giardia is usually caused by ingesting water contaminated with fecal matter.  The low pH of the stomach causes the release of the trophoziote, a protozoan with flagella, which can reproduce and colonize in the small intestine and can cause numerous problems of the gastrointestinal system including excessive edema, destruction of cilia, which severely decreases the absorption of nutrients, inducing severe diarrhea and dehydration.  Can also lead to abdominal pain, gas, nausea, and can cause malnutrition.  Diagnosed patients should be treated with metronidazole (250 mg TID for 7 days), furazolidone (100 mg QID for 7days), or paromomycin (25-30 mg a day for 7 days).  Pediatric doses differ: metronidazole (15 mg TID for seven days), furazolidone (6 mg/kg QID for seven days), and nitrozoxamide suspension (100 -200 mg every 12 h for three days).  Another pediatric drug that can be used is albendazole (400 mg daily for a week).

Scabies

Scabies occurs due to an infestation of the Sarcoptes scabiei mite, an insect that can cause severe itching of the skin.  Scabies is usually transmitted from person to person, and since they can live up to 36 hours on the human host, infestation can occur by touching clothes or bed sheets that may be infested, while not actually touching a person.  At the beginning mild itching is common, which quickly intensifies particularly at night.  Eczema and rashes can also form.  These mites usually make burrows into the skin, creating small little scratch-like marks on the skin which is often used for diagnosis.  Treatment includes OTC products such as permethrin which can kill the mites.  Oral medication known as ivermectin has shown to be effective in curing scabies.  Diphenhydramine, an OTC antihistamine medication can ease itching.

Lice

Three species of lice can infest the human host: head (Pediculus humanus capitis), body (Pediculus humanus corporis) and pubic (pthirus pubis).  Head lice are the most common forms of infestation and are mostly found in the hair on top of the head. Head lice can be found on anyone, cleanliness does not necessarily matter.  Body lice are more common in poverty stricken nations and people.  Body lice are found in clothing, but use the body as a food source.  Pubic lice, also known as crab lice, are generally found in the pubic hair, which can also travel to the eyebrows and eyelashes.  Pubic lice are a sexually transmitted disease.  Most common symptoms are itching, possible formation of welts from the biting insects and rash formation.  Treatment for lice includes OTC treatments of permethrin (a plant derivative that has several forms of chrysanthemiuc and pyrethic acid which is deadly to the lice).  For NIX resistant lice, another OTC product known as Ovide (malathione) could be used.

Megaloblastic anemia

Megaloblastic anemia is also known as B₁₂-deficiency anemia.  It often occurs in response to a decreased level of vitamin B_12, leading to decreased nucleic acid synthesis, which can decrease DNA synthesis of red blood cell (RBC) precursors known as megaloblasts.  This in turn leads to stunted RBC maturation, thus causing anemia.  This anemia can often be treated with introduction of B₁₂ by diet or dietary supplements. Several drugs have been associated with the development of megaloblastic anemia such as asazathioprine, chloramphenicol, colchicine, cyclophoshamide, cytarabine, 5-fluorodeoxyuridine, 5-fluoracil, hydroxyurea, 6-mercaptopurine, methotrexate, oral contraceptive pills, p-aminosalicylate, phenobarbital, phenytoin, primidone, pyrimethamine, sulfasalazine, tetracycline, and vinblastine.

Aplastic anemia

Several drugs have been linked to inducing aplastic anemia.  Drugs that are thought to show a strong likelihood of inducing aplastic anemia include: acetazolamide, captopril, chloramphenicol, chloroquine, chlorothiazide, chlorpromazine, dapsone, felbamate, lisinopril, lithium, pentoxifylline, quinidine, sulindac, and ticolpidine.  Other drugs that seem to have some connection to aplastic anemia, although they have not been studied as extensively, include carbamazepine, diclofenac, furosemide, indomethacin, methimazole, phenobarbital, phenothiazines, phenytoin, propylthiouracil, and sulfonamides.  Patients on these drugs should be monitored for signs of aplastic anemia.

Acute kidney disease (AKD)

Acute kidney failure is described as rapid loss of function of kidneys, which can lead to an increase or urea build-up, a shift in the acid-base homeostasis, and a shift in electrolyte balances.  Symptoms include altered levels of urination, hypovalemia, hypotension, rapid heart rate, edema, shortness of breath and it can also lead to hypertension, altered levels of electrolytes, etc.  AKD can be subdivided into Prerenal, Intrinsic, or Postrenal.  Prerenal AKD is often caused by lower blood perfusion into the kidneys, leading to a lower ability of kidneys to filter the blood properly.  It can be caused by numerous disorders such as dehydration or liver cancer, and certain drugs can induce this disorder.  Intrinsic AKD is caused by damage of the kidneys, which can be caused by inflammation, blood clots in the renal system, etc.  Postrenal AKD can be caused by any obstruction of urine flow from the kidneys.  This can be caused by kidney stones, an enlarged prostate, bladder cancer, etc.

Chronic kidney disease (CKD)

Chronic kidney disease (CKD) is diagnosed in someone who has less than a glomerular filtration rate (GFR) of 60 mL/min per area of 1.73 m² for at least three months.  It is generally caused by kidney damage.  Patients with Stage I CKD have kidney damage with normal GFR.  Patients with Stage II CKD have kidney damage and slightly decreased GFR levels.  Patients with Stage III CKD suffer from kidney damage and intermediately decreased GFR levels.  In Stage IV, patients suffer from a severe decrease in GFR level in response to kidney damage.  During Stage V, patients are in kidney failure.  Symptoms include foaming of urine due to higher levels of albumin, either microalbuminuria (albumin levels between 30-300 mg/d) or albuminuria (levels of albumin in urine exceed 300mg/d).  Other symptoms include hypertension, diabetes, edema, and anemia.

Acute organ rejection

Acute rejection is a major problem with solid organ transplants.  During the transplantation, the patient that is receiving the organ is immediately exposed to antigens from the donor organ.  The immune system of the organ donor does not recognize the antigens of the new organ, and an immune response occurs, leading to rejection of the transplanted organ.  While unpleasant and not desired, it is a normal response of the body to foreign tissue.  Many important factors can increase the chance for acute rejection of an organ including mismatched HLA between organ donor and organ recipient.  Acute rejection can increase in children and can increase with previous organ rejection, pregnancy, or if an organ was taken from a dead body.  Immunosuppressive drugs are used to lower the chance of acute rejection.  A drug regimen of immunosuppressants must be individualized and an important balance must be struck.  The use of immunosuppressants must be enough to treat rejection of the organ, but not too much that unwarranted infections occur and toxicity is kept at a minimum.

Hypercholestremia

Hypercholestremia is a symptom of a more serious underlying disorder and occurs due to increased levels of cholesterol in the blood.  It is closely related to hyperlipidemia, which is the increased level of lipids in the blood.  Increased cholesterol is associated with atherosclerotic plaques, which can impede blood flow leading to hypertension and have important deleterious effects leading to heart disease.  Total cholesterol levels below or equal to 200 mg per dL of blood are considered optimal.  200 – 239 mg/dL of cholesterol are considered marginally high, while cholesterol levels greater than 239 are considered overtly high.  The presence of lipoproteins such as LDL and HDL are associated with cholesterol levels and are also measured as cholesterol levels.  LDL in a healthy individual should remain lower than 100 mg/dL.  LDL levels between 100 to 189 mg/dl are considered moderately elevated to high level.  LDL over 189 is considered severely high.  HDL level between 40 -60 mg/dL is considered optimal, less than 40 is considered low, while greater than 60 is considered high.

Hypertriglyceridemia

Hypertriglyceridemia occurs when blood level of triglycerides are increased.  Triglycerides are usually the most abundant of the lipids that are found in the body and at reasonable levels are a good source of energy, but can lead to severe health problems if levels are increased including heart disease and diabetes.  Triglycerides in a healthy individual with low risk of developing heart disease and other disorders should be lower than 150 mg/dL in the blood.  Triglycerides between 150-200 mg/dL are considered slightly to intermediately high with increased risk of developing heart disease.  Levels between 200-499 mg/dL are considered high, while levels greater than 499 mg/dL are considered severely high, with a very high risk of developing heart disease.

Congestive Heart Failure

Congestive Heart Failure (CHF) occurs when structural or functional damage occurs to the heart that leads to a significant decrease in heart function.  This is often due to a lower force of the heart beat as well as incomplete filling of the heart with blood before each contraction, thus lowering the effectiveness of blood pumped to the body.  Failure of the left side of the heart can lead to shortness of breath, cough, confusion, excessive sweating, and excessive chilliness of the limbs. Failure of the right side of the heart can lead to excessive edema in the limbs and the abdominal cavity, nightly bouts of urination, excessive nosebleeds, and enlarged liver.  Drugs that are used to treat CHF include digoxin, ACE inhibitors, diuretics, β-blockers, and vasodilators.

Cystic Fibrosis

Cystic fibrosis is a heritable genetic disorder in response to a genetic mutation that leads to a mutated protein known as cystic fibrosis transmembrane regulator (CFTR), which is an important channel that is involved in the transport of water and electrolytes such as Cl^–.  This disease leads to excessive mucosal production which can cause severe defects in the function of various organs, including defects of the pancreas, intestine and lungs.  Cystic fibrosis can also lead to cirrhosis of the liver, arthritis, anemia, and diabetes.  In the lungs, excessive mucous production can lead to: increased bacterial infections, increased bacterial colonization, bronchiolitis and chronic blockage in the lungs.  Cystic fibrosis cannot be cured and treatment is focused on reduction of infections and reduction of chronic symptoms with the goal of prolonging life.  Treatments include pancreatic enzymes; insulin; N-Acetylcysteine, which can lower mucous levels; bronchodilators; anti-inflammatory drugs; etc.

Celiac disease

Celiac disease is an autoimmune disorder that affects the small intestine.  It occurs in people genetically disposed to the disease.  Often the disease is exacerbated by the presence of gliadin, a gluten glycoprotein found in wheat.  In response to the interaction of the protein tissue transglutaminase with gluten, an autoimmune reaction occurs, leading to inflammation of the small intestine.  This inflammation causes a decrease in nutrient absorption.  Symptoms can include weight loss, increased tiredness, excessive diarrhea and gas.  In children, the disease can lead to stunted growth.  Other symptoms can include abdominal pain and ulcer formations.  If gone unchecked, it can also lead to malnutrition and the development of cancer.  Blood tests are performed to measure levels of IgA antibodies which are common for celiac disease.  One of the most common and most effective treatments is the removal of gluten from the diet.  Sometimes, however, celiac disease becomes resistant to diet alone, and this is known as the refractory portion of the disease.  Steroids and immunosuppressants can be used for treatment.

Sickle cell anemia

Sickle cell anemia is a genetic disorder in which a point mutation of hemoglobin occurs, which can lead to blood cells taking on a sickle shape.  These sickle-shaped blood cells often have increased damage to the cellular membrane of the cells due to the warped shape.  Life expectancy is relatively less; however patients usually live a quality life.  Often patients will suffer from periodic painful sickle crisis.  Sickle cell crisis is often called vaso-occlusive crisis, which occurs when sickle blood cells clump and block important blood vessels to organs, leading to possible organ damage as well as pain.  A common type of vaso-occlusive crisis is known as acute chest crisis and includes chest pains, struggled breathing, and fever.  Symptoms often resemble pneumonia.  Treatment includes oxygen, and antibiotics as well as NSAIDS and other opioids.  Other sickle cell crises include aplastic crisis (exacerbation of anemia leading to increased paleness, irregular heart rate, and tiredness) and splenic sequestration crisis (acute enlargement of the spleen, often painful).

Acute pancreatitis

There are many risk factors associated with acute pancreatitis such as alcohol consumption, certain insect venoms and insecticides.  Infectious diseases, vascular problems including atherosclerosis and vasculitis, hypertriglyceridemia, hypercalcemia, gallstone disease, cystic fibrosis, inflammatory bowel disease, and peptic ulcer disease also are associated with acute pancreatitis.  Also many medications have been associated with acute pancreatitis, including 5-aminosalicyclic acid, asparaginase, azthioprine, didanosine, furosemide, mercaptopurine, methyldopa, metrondizole, pentamidine, sulfonamides, sulindac, tetracyclines, thiazides, and valproic acid .

BPH

Symptoms scores as related to severity of BPH according to the American Urological Association:

BPH (Benign Prostatic Hyperplasia) is a disorder of elderly men, a non-malignant growth of the prostate that can lead to discomfort, particularly during urination.  According to the American Urological Association a symptom score equal or less than seven equates to mild BPH.  Mild BPH is associated with a maximum rate of urination at 10 mLs per second and increased urinary retention (from 25mL up to 50mL).  Additionally, BUN levels and creatinine levels are increased in the serum.  Moderate BPH has a symptom level between 8 and 19.  Moderate BPH has symptoms of mild BPH with increased irritation and feelings of obstruction during urination.  A BPH AUA symptom score above 20 is considered severe, which includes the above symptoms along with other problems such as urinary tract infections, kidney damage and incontinence.

Anemia of Chronic Disease

Anemia of Chronic Disease (ACD) is one of the most common forms of anemia which has been connected to inflammation, tissue damage, as well as infectious diseases.  This anemia is marred shortened blood cell lifespan, decreased bone marrow, and decreased metabolism of iron.  Infections that are linked with ACD include tuberculosis, HIV, bacterial endocarditis, and chronic UTIs.  Chronic inflammatory diseases such as osteoarthritis, rheumatoid arthritis, gout, and lupus erythmatosus are also linked to ACD.  Cancer and other diseases such as alcohol induced liver disease, congestive heart failure and other heart disease can lead to ACD as well.

Gradual dose reduction

According to OBRA ’90, a gradual dose reduction (GDR) should always be attempted after a geriatric patient has been taking a psychotropic medication for longer than 4 months.  A GDR should be tried, at a minimum, of twice a year and if PRN dosing is also utilized, the patient’s care plan should be reviewed if PRN dosing is used more than twice a week.

There are certain exceptions to the GDR recommendation.  Specifically, patients with a documented psychiatric illness who have had recurrent psychotic episodes and who have stabilized on a maintenance dose are exempt from gradual dose reductions.  Additionally, patients with a documented psychiatric illness who have failed two previous gradual dose reductions within a year are also exempt from further gradual dose reductions.

Schizophrenia

There are generally five classifications of schizophrenia which include paranoid, disorganized, catatonic, undifferentiated, and residual.  Paranoid schizophrenia usually has symptoms of auditory and visual hallucinations, although mental acuity is more or less intact, and patients often have feelings of unwarranted paranoia and persecution.  Disorganized schizophrenia is marked with disorganized speech and thoughts, and may show inappropriate emotions and reactions to outward stimuli.  Catatonic schizophrenia is marked with problems in psychomotor skills, which can lead to catalepsy, excessive movement, or excessive rigidity.  Undifferentiated schizophrenia shows some symptoms of other types of schizophrenia such as paranoia, catalepsy, or disorganized thoughts.  Residual schizophrenia usually occurs when psychotic episodes occur between long periods (even years) without any noticeable symptoms.

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