Month: April 2017

Clinical Skills – Cluster the Clinical Findings

April 18, 2017 Clinical Skills, Differential Diagnosis, History Taking No comments

It is often challenging to decide whether clinical data fit into one problem or several problems. If there is relatively long list of symptoms and signs, and an equally long list of potential explanations, one approach is to tease out separate clusters of observations and analyze one cluster at a time. Several clinical characteristics may help.

Patient age: The patient’s age may help; younger adults are more likely to have a single disease, whereas older adults tend to have multiple diseases.

Timing of symptoms: The timing of symptoms is often useful. For example, an episode of pharyngitis 6 weeks ago is probably unrelated to the fever, chills, pleuritic chest pain, and cough that prompted an office visit today. To use timing effectively, you need to know the natural history of various diseases and conditions.

Involvement of different body systems: Involvement of the different body systems may help group clinical data. If symptoms and signs occur in a single system, one disease may explain them. Problems in different, apparently unrelated, systems often require more than one explanation. Again, knowledge of disease patterns is necessary.

Multisystem conditions: With experience, you will become increasingly adept at recognizing multi system conditions and building plausible explanations that link manifestations that are seemingly unrelated. To explain cough, hemoptysis, and weight loss in a 60-year-old plumber who has smoked cigarettes for 40 years, you would rank lung cancer high in your differential diagnosis. You might support your diagnosis with your observation of the patient’s cyanotic nailbeds. With experience and continued reading, you will recognize that his other symptoms and signs fall under the same diagnosis. Dysphagia would reflect extension of the cancer to the esophagus, pupillary asymmetry would suggest pressure on the cervical sympathetic chain, and jaundice could result from metastases to the liver. Related risk factors should be explored promptly.

Key questions: You can also ask a series of key questions that may steer your thinking in one direction and allow you to temporarily ignore the others. For example, you may ask what produces and relieves the patient’s chest pain. If the answer is exercise and rest, you can focus on the cardiovascular and musculoskeletal systems and set the gastrointestinal (GI) system aside. If the pain is more epigastric, burning, and occurs only after meals, you can logically focus on the GI tract. A series of discriminating questions helps you analyze the clinical data and reach logical explanations.

The Comprehensive Adult Health History

April 16, 2017 Clinical Skills, EHR/EMR, History Taking, Practice No comments , , , ,

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Initial Information

Data and Time of History

The date is always important. Be sure to document the time you evaluate the patient, especially in urgent, emergent, or hospital setitngs.

Identify Data

These include age, gender, marital status, and occupation. The source of history or referral can be the patient, a family member or friend, an officer, a consultant, or the clinical record. Identifying the source of referral helps you assess the quality of the referral information, questions you may need to address in your assessment and written response.


Document this information, if relevant. This judgment reflects the quality of the information provided by the patient and is usually made at the end of the interview. For example, “The patient is vague when describing symptoms, and the details are confusing,” or, “The patient is a reliable historian.”

Chief Complaint(s)

Make every attempt to quote the patient’s own words. For example, “My stomach hurts and I feel awful.” If patients have no specific complaints, report their reason for the visit, such as “I have come for my regular check-up” or “I’ve been admitted for a thorough evaluation of my heart.”

Present Illness

This Present Illness is a complete, clear, and chronologic description of the problems promoting the patient’s visit, including the onset of the problem, the setting in which it developed, its manifestations, and any treatments to date.

  • Each principal symptoms should be well characterized, and should include the seven attributes of a symptom: 1) location; 2) quality; 3) quantity or severity; 4) timing, including onset, duration, and frequency; 5) the setting in which it occurs; 6) factors that have aggravated or relieved the symptom; 7) associated manifestations. It is also important to query the “pertinent positives” and “pertinent negatives” drawn from sections of the Review of Systems that are relevant to the Chief Complaint(s). The presence or absence of these additional symptoms helps you generate the differential diagnosis, which includes the most likely and, at times, the most serious diagnoses, even if less likely, which could explain the patient’s condition.
  • Other information is frequently relevant, such as risk factors for coronary artery disease in patients with chest pain, or current medications in patients with syncope.
  • The Present Illness should reveal the patient’s response to his or her symptoms and what effect the illness has had on the patient’s life. Always remember, the data flow spontaneously from the patient, but the task of oral and written organization is yours.
  • Patients often have more than one symptoms or concern. Each symptom merits its own paragraph and a full description.
  • Medications should be noted, including name, dose, route, and frequency of use. Also, list home remedies, nonprescription drugs, vitamins, mineral or herbal supplements, oral contraceptives, and medicines borrowed from family members or friends. Ask patients to bring in all their medications so that you can see exactly what they take.
  • Allergies, including specific reactions to each medication, such as rash or nausea, must be recorded, as well as allergies to foods, insects, or environmental factors.
  • Note tobacco use, including the type. Cigarettes are often reported in pack-years. If someone has quit, note for how long.
  • Alcohol and drug use should always be investigated and is often pertinent to the Present Illness.

Past History

  • Childhood illnesses: These include measles, rubella, mumps, whooping cough, chickenpox, rheumatic fever, scarlet fever, and polio. Also included are any chronic childhood illnesses.
  • Adult illnesses: Provide information relative to adult illnesses in each of the four areas: 1) medical: illnesses such as diabetes, hypertension, hepatitis, asthma, and human immunodeficiency virus; hospitalizations; number and gender of sexual partners; and risk-taking sexual practices; 2) surgical: dates, indications, and types of operations; 3) obstetric/gynecologic: obstetric history, menstrual history, methods of contraception, and sexual function; 4) psychiatric: illness and time frame, diagnoses, hospitalizations, and treatments.

Family History

Under family history, outline or diagram the age and health, or age and cause of death, of each immediate relative including parents, grandparents, siblings, children, and grandchildren. Review each of the following conditions and record whether they are present or absent in the family: hypertension, coronary artery disease, elevated cholesterol levels, stroke, diabetes, thyroid or renal disease, arthritis, tuberculosis, asthma or lung disease, headache, seizure disorder, mental illness, suicide, substance abuse, and allergies, as well as symptoms reported by the patient. Ask about any history of breast, ovarian, colon, or prostate cancer. Ask about any genetically transmitted diseases.

Personal and Social History

The personal and social history captures the patient’s personality and interests, sources of support, coping style, strengths, and concerns. It should include occupation and the last year of schooling; home situation and significant others; sources of stress, both recent and long-term; important life experiences such as military service, job history, financial situation, and retirement; leisure activities; religious affiliation and spiritual beliefs; and activities of daily living. Baseline level of function is particularly important in older or disabled patients. The personal and social history includes lifestyle habits that promote health or create risk, such as exercise and diet, including frequency of exercise, usual daily food intake, dietary supplements or restrictions, and use of coffee, tea, and other caffeinated beverages, and safety measures, including use of seat belts, bicycle helmets, sunblock, smoking detectors, and other devices related to specific hazards. Include sexual orientation and practices and any alternative health care practices. Avoid restricting the personal and social history to only tobacco, drug, and alcohol use. An expanded personal and social history personalizes your relationship with the patient and builds rapport.

Review of Systems

  • General: Usual weight, recent weight change, clothing that fits more tightly or loosely than before, weakness, fatigue, or fever.
  • Skin: Rashes, lumps, sores, itching, dryness, changes in color; change in hair or nails; changes in size or color of moles.
  • HEENT: 1) head: headache, head injury, dizziness, lightheadedness; 2) eyes: vision, glasses or contact lenses, last examination, pain, redness, excessive tearing, double or blurred vision, spots, specks, flashing lights, glaucoma, cataracts; 3) ears: hearing, tinnitus, vertigo, earaches, infection, discharge. If hearing is decreased, use or nonuse of hearing aids; 4) nose and sinuses: frequent colds, nasal stuffiness, discharge, or itching, hay fever, nosebleeds, sinus trouble; 5) throat: condition of teeth and gums, bleeding gums, dentures, if any, and how they fit, last dental examination, sore tongue, dry mouth, frequent sore throats, hoarseness.
  • Neck: “Swollen glands,” goiter, lumps, pain, or stiffness in the neck.
  • Breasts: Lumps, pain, or discomfort, nipple discharge, self-examination practices.
  • Respiratory: Cough, sputum (color, quantity; presence of blood or hemoptysis), shortness of breath (dyspnea), wheezing, pain with a deep breath (pleuritic pain), last chest x-ray. You may wish to include asthma, bronchitis, emphysema, pneumonia, and tuberculosis.
  • Cardiovascular: “Heart trouble”; high blood pressure; rheumatic fever; heart murmurs; chest pain or discomfort; palpitations; shortness of breath; need to use pillows at night to ease breathing (orthopnea); need to sit up at night to ease breathing (paroxysmal nocturnal dyspnea); swelling in the hands, ankles, or feet (edema); results of past electrocardiograms or other cardiovascular tests.
  • Gastrointestinal: Trouble swallowing, heartburn, appetite, nausea. Bowel movements, stool color and size, change in bowel habits, pain with defecation, rectal bleeding or black or tarry stools, hemorrhoids, constipation, diarrhea. Abdominal pain, food intolerance, excessive belching or passing of gas. Jaundice, liver, or gallbladder trouble; hepatitis.
  • Peripheral vascular: Intermittent leg pain with exertion (claudication); leg cramps; varicose veins; past clots in the veins; swelling in calves, legs, or feet; color change in fingertips or toes during cold weather; swelling with redness or tenderness.
  • Urinary: Frequency of urination, polyuria, nocturia, urgency, burning or pain during urination, blood in the urine (hematuria), urinary infections, kidney or flank pain, kidney stones, ureteral colic, suprapubic pain, incontinence; in males, reduced caliber or force of the urinary stream, hesitancy, dribbling.
  • Genital: Male: Hernias, discharge from or sores on the penis, testicular pain or masses, scrotal pain or swelling, history of sexually transmitted infections and their treatments. Sexual habits, interest, function, satisfaction, birth control methods, condom use, and problems. Concerns about HIV infection. Female: Age at menarche, regularity, frequency, and duration of periods, amount of bleeding; bleeding between periods or after intercourse, last menstrual period, dysmenorrhea, premenstrual tension. Age at menopause, menopausal symp- toms, postmenopausal bleeding. If the patient was born before 1971, exposure to diethylstilbestrol (DES) from maternal use during pregnancy (linked to cervical carcinoma). Vaginal discharge, itching, sores, lumps, sexually transmitted infec- tions and treatments. Number of pregnancies, number and type of deliveries, number of abortions (spontaneous and induced), complications of pregnancy, birth-control methods. Sexual preference, interest, function, satisfaction, any problems, including dyspareunia. Concerns about HIV infection.
  • Musculoskeletal: Muscle or joint pain, stiffness, arthritis, gout, backache. If present, describe location of affected joints or muscles, any swelling, redness, pain, tenderness, stiffness, weakness, or limitation of motion or activity; include timing of symptoms (e.g., morning or evening), duration, and any history of trauma. Neck or low back pain. Joint pain with systemic symptoms such as fever, chills, rash, anorexia, weight loss, or weakness.
  • Psychiatric: Nervousness, tension, mood, including depression, memory change, suicidal ideation, suicide plans or attempts. Past counseling, psycho- therapy, or psychiatric admissions.
  • Neurologic: Changes in mood, attention, or speech; changes in orientation, memory, insight, or judgment; headache, dizziness, vertigo, fainting, black- outs; weakness, paralysis, numbness or loss of sensation, tingling or “pins and needles,” tremors or other involuntary movements, seizures.
  • Hematologic: Anemia, easy bruising or bleeding, past transfusions, transfusion reactions.
  • Endocrine: “Thyroid trouble,” heat or cold intolerance, excessive sweating, excessive thirst or hunger, polyuria, change in glove or shoe size.

Supplement Documents

Principle Symptoms

  • Abdominal pain
  • Acid-base abnormalities
  • AIDS/HIV infection
  • Anemia
  • Back pain
  • Bleeding disorders
  • Chest pain
  • Cough, fever, and respiratory infections
  • Delirium and dementia
  • Diabetes
  • Diarrhea, acute
  • Dizziness
  • Dyspnea
  • Dysuria
  • Edema
  • Fatigue
  • GI bleeding
  • Headache
  • Hematuria
  • Hypercalcemia
  • Hypertension
  • Hyponatremia and hypernatremia
  • Hypotension
  • Jaundice and abnormal liver enzymes
  • Joint pain
  • Kidney injury, acute
  • Rash
  • Sore throat
  • Syncope
  • Weight loss, unintentional
  • Wheezing and stridor

Variability – Differ in Drug Response

April 13, 2017 Adverse Drug Reactions, Pharmacodynamics, Pharmacogenetics, Pharmacokinetics, Therapeutics No comments , , , , , , , , , , , , , ,

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Substantial differences in response to drugs commonly exist among patients. Such between or interindividual variability is often reflected by various marketed dose strengths of a drug. Because variability in response within a subject from one occasion to another (intraindividual variability) is generally smaller than interindividual variability, there is usually little need to subsequently adjust an individual’s dosage regimen, once well-established, unless the condition or treatment of the patient changes. Clearly, if intraindividual variability were large and unpredictable, finding and maintaining dosage for an individual would be an extremely difficult task, particularly for a drug with a low therapeutic index (e.g., warfarin).

Many patients stabilized on one medicine receive another for the treatment of the same or concurrent condition or disease. Sometimes, the second drug affects the response to the first. The change in response may be clinically insignificant for most of the patient population, with the recommendation that no adjustment in dosage be made. However, a few individuals may exhibit an exaggerated response, which could prove fatal unless the dosage of the first drug given to them is reduced. The lesson is clear: Average data are useful as a guide; but ultimately, information pertaining to the individual patient is all-important.

PS: Evidence for interindividual differences in drug response

  • Variability in the dosage required to produce a given response – daily dose of warfarin
  • Variability in pharmacokinetics – phenytoin’s wide scatter in plateau plasma concentration
  • Variability in pharmacodynamics – levels of endogenous agonists or antagonists

Clearly, variability exists in both pharmacokinetics and pharmacodynamics, and measurement of drug in plasma is a prerequisite for separating the two. The characterization of pharmacokinetic and pharmacodynamic variabilities within the population is called population pharmacokinetics and population pharmacodynamics, respectively.

The dependence on dose and time in the assignment of variability is minimized by expressing variability not in terms of observations but rather in terms of the parameter values defining pharmacokinetics and pharmacodynamics, that is, in F, ka, Cl, and V for pharmacokinetics, and in Emax, C50, and the factor defining the steepness of the concentration-response relationship for pharmacodynamics.

Why People Differ

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The reasons why people differ in their responsiveness to a given dose of a drug are manifold and include genetics, disease, age, gender, body weight, drugs given concomitantly, and various behavioral and environmental factors. Age, body weight, disease, and concomitantly administered drugs are important because they are measurable sources of variability that can be taken into account. Gender-linked differences in hormonal balance, body composition, and activity of certain enzymes manifest themselves in differences in both pharmacokinetics and responsiveness, but overall, the effect of gender is small. Although inheritance accounts for a substantial part of the differences in response among individuals for many drugs, much of this variability is still largely unpredictable, particularly in regard to pharmacodynamics.
Pharmaceutical formulation and the process used to manufacture a product can be important because both can affect the rate and extent of release, and hence entry, into the body. A well-designed formulation diminishes the degree of variability in the release characteristics of a drug in vivo.
Heavy cigarette smoking tends to reduce clinical and toxic effects of some drugs, including theophylline, caffeine, and olanzapine. The drug affected are extensively metabolized by hepatic oxidation catalyzed by CYP1A2; induction of this enzyme is the likely cause.
Although on average the body maintains homeostasis, many biological functions and many endogenous substances undergo temporal rhythms. The period of the cycle is often circadian, approximately 24 hr, although there may be both shorter and longer cycles upon which the daily one is superimposed. The menstrual cycle and seasonal variations in the concentrations of some endogenous substances are examples of cycles with a long period. Drug responses and pharmacokinetics may therefore change with time of the day, day of the month, or season of the year.
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Mass Balance

April 4, 2017 Pharmacokinetics No comments ,

The mass balance technique has been suggested as a more direct alternative to the iterative approach. The mass balance technique is relatively simple and can be best visualized by examining the relationship between the rate of drug administration and the rate of drug elimination. At steady state, the rate of drug elimination (RE) is equal to the rate of administration (RA) and the change in the amount of the drug in the body with time is zero.

RA – RE = Change in the Amount of Drug in the Body with Time = 0

Under non-steady-state conditions, however, there will be a change in the amount of drug in the body with time. This change can be estimated by multiplying the difference in the plasma concentration (deltaC) by the volume of distribution and divided by the time interval between the two drug concentrations.

Screen Shot 2017 04 04 at 8 21 29 PMBy substituting the appropriate values in the left equation, an estimate of clearance can be derived as follows:

RA – RE = (deltaC)(V) / t

(S)(F)(Dose/tau) – RE = (C2 – C1)(V) / t

(S)(F)(Dose/tau) – (C2 – C1)(V) / t = RE

(S)(F)(Dose/tau) – (C2 – C1)(V) / t = (Cl)(C ave)

Note that the average plasma concentration (C ave) is generally assumed to be the average of C1 and C2.

While this C ave is not the steady-state average, it is assumed to be the average concentration that results in the elimination of drug as the concentration proceeds toward steady state. Equation 65 is an accurate method for estimating clearance if the following conditions are met:

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1.t, or time between C1 and C2, should be equal to at least one but no longer than two of the revised drug half-lives. This rule helps to ensure that the time interval is not so short as to be unable to detect any change in concentration and yet not so long that the second concentration (C2) is at steady state.

2.The plasma concentration values should be reasonably close to one another. If the drug concentrations are increasing, C2 should be less than two times C1; if the plasma concentrations are dealing, C2 should be more than one-half of C1 (i.e., 0.5 < C2/C1 < 2.0). This rule limits the change in concentration so that the assumed value for V will not be a major determinant for the value of Cl calculated from Equation 65.

3.The rate of drug administration [(S)(F)(Dose/tau)] should be regular and consistent. This rule helps to ensure a reasonably smooth progression from C1 to C2 such that the value of C ave [(C1 + C2)/2] is approximately equal to the true average drug concentration between C1 and C2.

The mass balance approach is a useful technique if the above conditions are met. It is relatively simple and allows for the calculation of clearance under non-steady-state conditions by a direct solution process. There are certain situations in which the above conditions are not met but the mass balance technique still works relatively well. For example, if the time interval between C1 and C2 is substantially greater than two half-lives but the value of C2 is very close to C1, then Equation 65 approximates Equation 15 because the average plasma concentration approximates the average steady-state value.

The mass balance approach is most commonly applicable for drugs that are given as a continuous IV infusion, as a sustained-release product, or at a dosing interval that is much less than the half-life.