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Psychopharm 6002


What IS Psychopharmacology? Study of the Mediation & Modulation of Behavior through both direct means (exogenous drugs) and indirect means (endogenous signaling substances)
Direct Means - Exogenous Drugs can directly mediate & modulate behavior through direct impact on CNS functioning
Indirect Means-Endogenous Signaling Substances Small Molecular Weight Molecules in the brain Hormones: Neurotransmitters, Neuromodulators Cellular Secondary Messengers: Specific enzymes needed to produce a specific substance
What is Goal of Psychopharmacology? Mediation & Modulation of behavior
What is Target Symptom Specific, precise, and individualized symptom (behavior) that can reasonably be expected to be improved or eliminated through medication use
Essential #1: History -Use open ended questions -Clarify (ie. when a client c/o poor sleep, ask specifics) -Obtain chronological symptom history -Identify Target Symptoms
Essential #2: Thorough Assessment -Physical Exam -Mental Status Exam -Standardized Rating Scales
Testing Mental Status Examination Write–a-Sentence Test Draw-a-Clock Test Copy-a-Three-Dimensional-Figure-Test Standardized Instruments (Zung Depression Scale, Beck Anxiety Scale, PANSS)
Mental Status Examination (MSE) It gives the clinician a better understanding of the client’s current status/ lvl of fx. Should be used at the initial eval & ea follow-up visit in order to assess response to treatment.
Essential #3: Laboratory Testing Complete Blood Counts, Thyroid function tests, Electrolytes, Glucose, Renal function, Hepatic function, Urinalysis, Urine drug screen, STD screen and hepatitis panel in high-risk populations, ****Pregnancy test
Complete Blood Count (CBC) Red blood cell count (RBC), Hematocrit (Hct), Hemoglobin (Hgb), Platelets, Mean Corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), Red cell distribution width (RDW), WBC, Differential: neutrophils, eosinophils, basophils, lymphocyte, monocytes
CBC cont. RBC: Males: 4.4 – 6.1 mil/mm3, Females: 4.2 – 5.5 Hct: Male: 40.7-50.5%, Female: 36.1-44.3% Hgb: Male: 13.8-17.2 gm/dl, Female: 12.1-15.1 gm/dl Platelets: 150-400 K/mm3
WBC Normal: 4,000-11,000 Variability: Increased WBC = Leukocytosis Shift to the left = increase in immature neutrophils called bands Shift to the right=increase in very mature neutrophils
WBC (Remember 500) Less than 500 WBC = panic Less than 500 neutrophils = bacterial infection Less than 500 lymphocytes = viral infection Less than 5.0 Hgb = heart failure and death
Why order a CBC? Used to detect: Polycythemia, Anemias, Infections, Monitor fluid status, blood loss, Inflammation, Need to conduct further tests such as bone marrow biopsy
Liver Function Tests Total bilirubin & direct bilirubin values are elevated in hepatocellular injury, variety of meds and substance use/abuse. Liver damage: abnormal LFT’s & may impair clearance of a drug, Increased LFTs may be seen with any drug that utilizes hepatolic metabolism
Liver Function Tests cont. Serum Enzyme: Alkaline Phosphate: 13-39 U/ml Aspartate aminotransferase (AST, was SGOT): 5-40 U/ml Alanine aminotransferase (ALT was SGPT): 5-35 U/ml Lactate dehydrogenase (LDH): 200-500 U/ml 5’-nucleotidase: 2-11 U/ml Gamma glumatic transpeptidase (GGT)
Liver Function Tests cont. ALT: increased when hepatic cells have been inflamed or died AST: Also reflects hepatic cell damage though less specific for liver disease (increased in MI) GGT: Meds/ETOH will cause increases in GGT
Thyroid Panel Thyroid hormone: thyroxine T4 or triodothyronine T3 Thyroid-releasing hormone (TRH) stimulates the release of TSH, TRH increases with exposure to cold, stress, decreased levels of T4 *Thyroid tests : TSH, T4 (free or total), T3 (free or Total)
TSH Thyroid-stimulating hormones (TSH) Increases release of stored thyroid hormones
Subclinical Hypothyroidism Subclinical Hypothyroidism: Normal free T3 &T4 Suppressed TSH
Essential #4: Explore client’s concerns about using medications -What are the client’s thoughts about medication use? -Clarify misconceptions &/or myths of med use -Discuss realistic expectations -Compliance issues
Essential #6: Follow-up -Schedule appropriate follow-up care -Give contact information
Essential #7: Make medication adjustments appropriately Know correct dosing of meds and when a dose change might be warranted
Essential 8 Polypharmacy Polypharmacy and off label use. Remember off label means using a medication that does not have FDA approval for it’s use in the disorder you want to treat.
Selective Toxicity using the best medication with the least side effects
Drugs fit into two large categories Agonists-produce effect (or turn on) Antagonists-block effect (or turn off) Partial Agonists
Pharmokinetics What happens between taking & leaving. Variable in how long trip through body it takes, how long till effect occurs, how long will effect last.
Drug Absorption As a drug is distributed in the body, it comes in contact with numerous membranes. Drugs pass some membranes but not others.
Drug Distribution Several factors influence drug distribution: Membrane permeability, Plasma protein binding, Depot storage
Membrane Permeability To enter an organ, a drug must permeate all membranes that separate the organ from the site of drug action. Ex. drugs that are lipophilic (fat loving) such as benzodiazepines, readily cross the blood-brain barrier
Plasma protein binding Binding of drugs to plasma protein such as albumin. Reduces the amount of free drug in the blood.
Depot Storage Lipophilic drugs accumulate in fat and released slowly from fat stores. Antipsychotics are highly lipophilic so they tend to hang around in your system for 1-3 months after they are discontinued.
Metabolism Elimination P450 system Some drugs are excreted after they have been metabolized while others are excreted unchanged.
Half Life Time required for the serum concentration of drug to decrease by one-half (how rapidly half the drug is excreted). Generally, 4-5 half lives = steady state Blood levels will be reliable generally after 5 half lives
Steady State Point at which a specific dose of drug given over a several-day period produces consistent blood level Predicts likely point therapeutic response
Half lives Medications with longer ½ lives take longer to reach steady state. The shorter the ½ life of antidepressants, the more likely patients will experience discontinuation symptoms.
Half lives cont. (ie. Effexor has a very short ½ life so it does cause discontinuation symptoms while the ½ life of Prozac is very long, therefore there are no discontinuation symptoms assoc. with Prozac.
Cmax: patient ingests a drug, it gets absorbed then reaches a peak concentration which is Cmax.
Tmax: the time required for a particular drug to reach Cmax is called Tmax.
Cmin after Cmax, the concentration of the drug graduallly comes down, eventually reaching a Cmin or trough concentration, just before the next dose is taken.
AUC (area under the curve): entire amount of drug that is present in the blood over a given period of time so AUC is a measure of the total amount of drug absorbed by the body
Area under the curve (AUC) cont. ER (extended release) formulation leads to an auc comparable to BID or TID dosing of IR (immediate release formulation).
Pharmacodynamics How do drug and receptors in body interact: Affinity: How much receptors like each other Dose-Response Curvature (3 curves, see next slide) Side-Effect, Interactions
Dose-Response Curvature Linear the more you take, the better you feel up to the point it can harm you. Meds with linear response can be increased if not seeing a therapeutic response.
Curving linear: Patients will improve and then max out; then the more they take, the worse they feel. For example, tricylic antidepressants have a curving linear response. If a patient is not responding to a tricylic, don’t increase the dose because it could make them feel worse.
Plateau: Patients will improve up until a certain point and then they will plateau, they will not get any better. Example: SSRI antidepressants
Hormetic Effect (Arndt-Shultz Law) Describes the relationship between dose and response Hormetic effect: there is not always a simple linear relationship between the dose of a drug and the clinical response
Hormetic Effect (Arndt-Shultz Law) cont It is not always the case that the higher the dose, the more effective the drug will be.
Hormetic Effect (Arndt-Shultz Law) cont Because of the hormetic effect, the higher doses beyond a certain point may actually be less effective. 50% of drugs demonstrate the hormetic effect
FDA Trials Phase I: test drug for safety in animals then in human volunteers. Phase II: test drug in groups of patients. Phase III: test drug in very large groups of patients
Bioequivalence (determined by administering drug to volunteers and obtaining average Cmax, half lives, and AUC.
Generic bioequialence 80%-125%: the bioequivalence of generic must be between 80-125% of original brand.
***please note many psychiatrists and patients complain about problems when switching from name brands to generic. Ie. Clozaril and Depakote
Created by: palmerag