Intro to Clinical Pharmacology Flashcards
Pharmacology
The study of drugs and their interaction in living systems
Drug
Any chemical that can affect living processes
Clinical pharmacology
Study of drugs in humans
Therapeutics
Use of drugs to diagnose, prevent, and treat disease or to prevent pregnancy
Properties of an Ideal Drug
- Effectiveness: elicit the responses for which it is given
- Safety: drug cannot produce harmful effects
- Selectivity: elicits only the response for which it is given
Factors that determine the intensity of drug responses
Administration, pharmacokinetics, pharmacodynamics, sources of individual variation
Pharmacokinetics
Impact of body on the drugs; absorption, distribution, metabolism, excretion, time course of drug responses
Application of pharmacokinetics in therapeutics
By applying knowledge of pharmacokinetics to drug therapy, we can help maximize beneficial effects and minimize harm
Absorption
Movement of a drug from its site of administration into the blood
Rate of absorption
Determines how soon effects will begin
Amount of absorption
Helps determine how intense the effects will be
Factors affecting drug absorption
Rate of dissolution, surface area, blood flow, lipid solubility, pH partitioning
Distribution
Movement of drugs throughout the body
How is drug distribution determined? (3 factors)
- Blood flow to tissues
- Exiting the vascular system
- Entering cells
Blood Flow to Tissues
- Drugs are carried by the blood to tissues and organs of the body
- Blood flow determines rate of delivery
Abscesses and tumors (reg. blood flow to tissues)
- Low regional blood flow impacts therapy
- Pus-filled pockets, not internal blood vessels
- Solid tumors have limited blood supply
Blood-Brain Barrier (BBB)
Tight junction between the cells that compose the walls of most capillaries in the CNS
-Drugs must be able to pass through cells of the capillary wall; only drugs that are lipid soluble or have a transport system can cross the BBB to a significant degree
Placental Drug Transfer
Membranes of the placenta do NOT constitute an absolute barrier to the passage of drugs; movement determined in the same way as other membranes
Risk with placental drug transfer
Birth defects: mental retardation, gross malformations, low birth weight; mother’s use of habitual opioids: birth of drug-dependent baby
Protein Binding
Drugs can form reversible bonds with various proteins; Plasma albumin is the most abundant and important > large molecule that always remains in the bloodstream; impacts drug distribution
Entering cells
- Some drugs must enter cells to reach the side of action
- Most drugs must enter cells to undergo metabolism and excretion
- Many drugs produce their effects by binding with receptors on the external surface of the cell membrane > do not need to cross the cell membrane to act
Drug Metabolism
Biotransformation; the enzymatic alteration of drug structure > most often takes place in the liver
P450 System
Most drug metabolism that takes place in the liver is performed by the hepatic microsomal enzyme system; metabolism doesn’t always result in a smaller molecule
Special Considerations in Drug Metabolism
Age, induction of drug-metabolizing enzymes, first-pass effect, nutritional status, competition between drugs
Excretion
Removal of drugs from the body; drugs and their metabolites can exit the body through urine, sweat, saliva, breast milk, or expired air
Renal routes of drug excretion
Glomerular filtration, passive tubular reabsorption, active tubular secretion (kidneys)
Factors that modify renal drug exretion
pH-dependent ionization, competition for active tubular transport, age
Nonrenal routes of drug excretion
Breast milk, bile, lungs (especially anesthesia), sweat/saliva
Pharmacodynamics
Study of biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced; study of what drugs do to the body and how they do it
Sources of individual variation
Physiologic variables (age, gender, weight) Pathologic variables (diminished renal and liver function) Genetic variables (can alter drug metabolism) Drug interactions (no two patients alike)
Half life
Time required for the amount of drug in the body to decrease by 50%; determines the dosing interval
Controlled Substance Act (Landmark Drug Legislation)
Established categories into which controlled substances are placed; Schedule I-V
Schedule I drugs
No accepted use in US and have high potential for addiction (ie. heroin, LSD, cigarette marijuana)
Schedule II drugs
Accepted medical use, high abuse potential; written prescription needed/no refills allowed (ie. dilaudid, cocaine, dura morph, codeine)
Schedule III drugs
Medical use, less abuse potential (ie. marinol, vicodin)
Schedule IV drugs
Phenobaritol, ambien, lorazepam
Schedule V drugs
Lomotil, robitussin AC (codeine)
New Drug Development
Pre-clinical testing (animal testing): toxicity, pharmacokinetics, useful effects
Clinical testing (2-10 years)
-Phase I: healthy volunteers (check toxicity)
-Phase II/III: patients (on sick patients, adverse effects)
-Phase IV: Aftermarket surveillance (once drug has been approved)
Drug Names
Chemical, generic (nonproprietary), trade (brand)
Consequences of drug-drug interactions
Intensified effects, increased therapeutic effects, increased adverse effects
Basic mechanisms of drug-drug interactions
Direct chemical or physical interaction; pharmacokinetic interactions: altered absorption, altered distribution, altered metabolism, altered renal excretion, interactions that involve P-glycoprotein
Ways to reduce medication errors
Replace handwritten medication orders with a computerized order entry system; have a senior clinical pharmacist accompany physicians on rounds; use a bar-code system
Individual variation in drug responses
Gender, race, failure to take medicine as prescribed, drug interaction, diet
Efficacy
Maximum effect that a drug can produce, regardless of dose
Potency
Amount of a drug tat is needed to produce a given effect
Drugs
Chemicals that produce effects by interacting with other chemicals
Receptors
Special chemicals in the body that most drugs interact with to produce effects
Important properties of receptors
- Receptors are normal points of control of physiologic processes
- Under physiologic conditions, receptor function is regulated by molecules supplied by the body
- Drugs can only mimic or block the body’s own regulatory molecules
- Drugs cannot give cells new functions
Agonists
Molecules that activate receptors
Antagonists
Preventing receptor activation; noncompetitive and competitive
Partial agonists
Agonists that only have a moderate intrinsic activity; maximal effect that a partial agonist can produce is less than that of a full agonist. Can act as antagonists as well as agonists
Noncompetitive antagonists
Bind irreversibly to receptors, reduce the maximal response that an agonist can elicit, impact not permanent
Competitive antagonists
Compete with agonists for receptor binding, bind reversibly to receptors; equal affinity: receptor occupied by whichever agent is present in the highest concentration
Interpatient variability in drug responses
Initial dose of a drug is necessarily an approximation, subsequent doses must be “fine tuned” based on the patient’s response
ED50
Effective dose in 50% of the population tested
LD50
Average lethal dose to 50% of the animals treated
Therapeutic Index
Measure of drug’s safety; ratio of drug’s LD50 to its ED50. Higher the therapeutic index, the safer the drug; lower the therapeutic index, less safe the drug
Drug-drug interations
Interactions occur whenever a patient takes more than one drug; some are intended and others are undesired
Consequences of drug-drug interactions
Intensification of effects (increased therapeutic/adverse effects), reduction of effects, creation of a unique response
Clinical significance of drug-drug interactions
- Potential to significantly impact the outcome of therapy
- Responses may be increased or reduced
- Risk for serious drug interaction is directly proportionate to the number of drugs a patient is taking
- Interactions are especially important in drugs w/ low therapeutic index
- Many interactions are yet to be identified
Grapefruit juice effect
Inhibits metabolism of certain drugs; raises the drugs’ blood levels
Timing of drug administration
Some drugs are better tolerated on an empty stomach, others should be taken with food esp. for nausea
