Download Psychopharm Notes pp 1-99

Drugs, Kinetics, etc. Notes pp 1-99
Ch 1
Drug: any chemical that can affect living processes.
Pharmacology: the study of drugs and their interactions with living systems.
Clinical Pharmacology: the study of drugs in humans
Theraputics aka pharmacotheraputics the use of drugs to diagnose, prevent, or treat
disease or to prevent pregnancy.
An idea drug: effectiveness, safety and selectivity. Additionally: reversibility,
predicatibility. Ease of administration, freedom from drug interaction, chemical stability,
low cost, possession of a simple generic name.
But NO DRUG IS SAFE.
The theraputic objective: maxium benefit with minimum harm.
Factors that determine the intensity of drug responses:
 Administration route
 Pharmacokinetics (how much of an administered drug gets to its site of
action)
 Pharmacodynamics (impact of drugs on the body)
 sources of individual variation (drug interactions, age, gender, wt,
pathologies, genetics).
Ch 2
Five Rights of Drg Administration: Give the Right Drug to the Right Patient in the
Right dose by the right route at the right time. Sixth: Right Documentation.
Application of Oarmacology in Pt Care
Steps:
Preadministration Assesment:
 Collect baseline date
 Id high risk pts
 Assess capacity for self care
Dosage and Administration
 Read the order, verify if needed
 Verify the ID of pt
 Read the Med label. Verify the id of drug, strength/dose, and suitability
for intended route.
 Verify dosage calculations
 Implement special handling, if needed.
 DON’T administer the drug if you do not understand the reason for it’s
use.
Evaluating and Promoting Theraputic effects
 Evaluating theraputic response,
 Promoting Pt Adherence
 Implementing nondrug measures
Minimizing adverse Effects
 Reduce adverse effects
o ID high risk pts
o Ensuring proper administration through pt education
o Warning pts about activities that might lead to adverse effect
 Know how to remedy adverse effects
o Hypoglycemia – glucose
o Know the major side effects, early signs of an adverse rxn, when rxn’s are
likely to occur.
o Know interventions to minimize discomfort and harm.
Minimizing Adverse Interactions
 Taking a thourough hx
 Pt education
 Being alert for known interactions and possible interactions.
...
Ch 3
Drug Legistation
Federal Pure Food and Drug Act of 1906: weak, Drugs must be “free of adulterants”
Nothing about safety or effectiveness.
Food, Drug and Cosmetic Act of 1938: required drug testing for toxicity to be reviewed
by the FDA and only drugs deemed safe by FDA would be approved for marketing.
1962 Harris Kefauver Amendments to FDCA: (Response to thalidomide in europe)
Strengthen all aspects of the earlier law. First law that required drugs to be effective.
Established rigorous new testing procedures.
1970 Controlled Substances Act -- Schedule 1 (Heroin, LSD) no approved medical uses
and high potential for abuse. Schedules II –V have medical uses.
1992 FDA permitted accelerated approval for AIDS and cancer drugs. Drug
manufacturers can market prior to Phase III, with rigourous Phase IV follow up.
Problems: manuf. Often fail to follow up, and no clear mechanism for removing the drug
from the market if they fail to confirm a clinical benefit.
Prescription Drug User Fee Act: drug sponsors pay $500,000 per drug to pay for
additional reviewers and a strict timetable for review. Result: drugs get to market faster.
FDA Modernization Act (FDAMA) of 1997
P 16 . . . .
Stages of New Drug Development
Preclinical: 1-5 years -- animal testing for toxicity, pharmacokinetic properties, and
potentially useful biologic effects.
Clinical Testing I-IV
Phase I: Healthy Volunteers, unless the drug will have severe side effects (cancer drugs)
then it’s tested by people with the disease. Goals: evaluates drug metabolism,
pharmacokinetics, and biologic effects.
Phases II and III: Patients. Determine theraputic effects, dosage range, safety, and
effectiveness. Only 500-5000 pts receive the drug, only a few hundred take it for more
than 3-6 months.
Phase IV: Post matketing surveillance. Drug is released for general use so that they can
observe it’s effects on a large population.
Pre 1990’s very little testing was done in women and children – effectively barring all
women of child bearing age from phase I and II trials (concerns for fetal safety). Now
the pop of women in trials reflects the population in general. Same with children.
NAMING p 19
Trade names are easy to remember, but there are multiple trade names for each drug, also
the drug manufacturer can change the formulation at will. Generic names are long and
complicated, but more precise. Use Generic name.
OTC Drugs:
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Americans spend $20 BILLION per year on OTC
60% of all doses administered
40% of Americans take at least one OTC every 2 days.
4x as many consumers treat illness at home with OTC than visit a prescriber.
60%-95% of illnesses are initially treated by the pt with self care – including
OTC.
 The average home medicine cabinet contains 24 OTC drugs.
Ch 4 p 25
Pharmacokinetics How a drug moves through the body. Includes absorption,
distribution, metabolism and excretion.
Absorption: the movement of a deuf from its site of administration into the blood.
Distribution: the movement from the blood into the interstitial spaces and into the
cells.
Metabolism: enzymatically mediated alteration of drug structure.
Excretion: movement of drugs and metabolites out of the body.
Elimination: combination of metabolism and exctretion.
Three ways to cross a cell membrane:
1 Direct penetration (most common)
2. Transport system
3. Channels and Pores (least common) only ions (sodium and potassium) and
molecules >200 amus.
Special Note: P-glycoprotein. Transports drugs OUT of many cells (liver, kidney,
braincapillaries, placenta, intestines)
Direct penetration is most common, drug must be lipid soluble. Polar molecules and
ions are not lipid soluble and cannot pentrate membranes.
Ions
Quaternary Ammonium Compounds like tubocurarine always have a positive charge.
Ph-dependent Ionization: weak acids and bases will carry a charge dependent on the
surrounding pH ( acids ionize in basic media, bases ionize in acidic media)
Ion trapping (pH Partitioning) because acids ionize in basic media and bases ionize in
acidic media – they get stuck there. The ions cannot cross back across the membrane.
When there is a pH gradient across a membrane, acidic drugs will accumulate on
the basic side and basic drugs will accumulate on the acidic side.
Clinical implications: by manipulating urinary pH we can use ion trapping to draw toxins
into the urine from the blood.
Factors affecting absorption:
1. Rate of dissolution
2. Surface area for absorption
3. Blood flow
4. Lipid solubility
5. pH partitioning absorption is enhanced when the difference bw the pH at the site
of administraion and the plasma makes the drug more likely to ionize in the
plasma (therefore be retained in the plasma)
P 30
Administration
 Enteral (via the GI tract)
 Parenteral (outside the GI tract) by injection: intravenous, sub Q,
intramuscular.
IV Advantages:
 no barriers to absorbtion.
 Abs is instantaneous and complete.
 Rapid onset of action.
 Precise control of med levels.
 Large fluid volumes (drugs with low solubility in water require a lot of
medium. IM cannot accommodate this volume, but the blood can.)
Permits use of irritant drugs ( free flowing IV line rapidly dilutes the drug
in the blood)
IV Disadvantages:
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High Cost
Difficulty
Inconveniece.
Irreversible. (To minimize risk, inject over one minute or more)
Possibility of Fluid overload (dangerous for hypertension, kidney disease,
heart failure)
 Infection possible failure of sterility
 Embolism (insertion of needle can form a thrombus, injection of
hypertonic or hypotonic solutions can destroy RBC, debris can produce
embolism, drugs that are not fully dissolved.) MUST NOT inject cloudy
or particulate solutions!!
 Formulation must be appropriate for the intended use:
o Insulin can only be “insulin injection”. Particulate suspentions are
not for IV use. Particulate is for Sub Q only.
o Epinephrine comes in different concentrations for different admin
routes. IV is dilute. Sub Q is concentrated. Wrong one could be
fatal.
Intramuscular and Sub Q Advantages:
 No significant barrier to abs.
 Absorption can be fast or slow based on water solubility (highly water soluble 1030 minutes) and blood flow to site of injection.
 Good for poorly soluble drugs, little harm from depositing a suspension of
undissolved drug in the interstitial space of muscle tissue.
 Good foor Depot preparations (drug is absorbed slowly over time)
Intramuscular and Sub Q Disadvantages:
 Discomfort
 Inconvenience
 Not good for bleeding risk pts (anticoagulants)
Oral
 Must pass through epithelial cells (usually in the Intestines)
 P-glycoproteins pump certain drugs out of epithelial cells and back into the lumen
of the intestine.
 Absorption is HIGHLY VARIABLE (due to drug solubility and stability, gastric
and intestinal pH, gastric emptying time, food in the gut, other drugs, coatings on
drug preparations.)
 Drugs absorbed in the GI tract go to the liver. (Some are passed through, some
undergo extensive metabolism some are recirculated “enterohepatic recirculation”
taken up in bile, secreted back into intestine, and reabsorbed.
Oral Advantages
 Easy, Convenient and inexpensive.
 Safer than injection. No risk of fluid overload, embolism or infection.
 Potentially reversible (activated charcoal)
Oral Disadvantages
 Variability
 Inactivation – ph of stomach, damaged by digestion.
 Requires a conscious cooperative pt.
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