Pharmacology Principles (Exam 1) Flashcards
Three Phases of Drug Action
- Pharmaceutic Phase
- Pharmacokinetic Phase
- Pharmacodynamic Phase
When anyone takes a single medication that drugs has to go through all three of these process
Phase 1: Pharmaceutic Phase
-Dissolution of the drug occurs so it can be used and absorbed
-Tablet to granules to smaller particles to solution to be absorbed into the blood.
-Only occurs with oral drugs
2 stages of the Pharmaceutical Phase
Disintegration phase
Dissolution phase
Phase 2: Pharmacokinetic Phase
What the body does to the drug.
4 phases of the Pharmacokinetic Phase
- Absorption
(After dissolution in the stomach, it moves to the small intestines so it can be absorbed into blood) - Distribution
(The drug leaving the blood by passing through the cell membrane to intended to carry out its affect) - Metabolism/Biotransformation
(Liver metabolizes the drug to lipid soluble metabolite to water soluble metabolite - Excretion
(Then travels so the kidney can excrete the drug)
Giving a drug IV
The drug starts the the distribution phase of the phramacokinetic phase. There is no absorption because it is being injected directly into the blood stream
What organ metabolizes
The liver
What organ excretes
The kidney
Phospholipid Layer
Semipermeable Layer
Tightly packed together
Drug can pass through if it is lipid soluble. (Can pass through lipid layer)
Water soluble drugs might require transport carriers
First Pass Effect
-Absorption effects the metabolism of drug before systemic circulation
-% of drug broken down in the liver
-It is the liver taking a toll or tax which affects the bioavailability of the drug
-If you take 40 mg of drug orally it is not 100% bioavailability because the liver will take a percentages
Bioavailablity
The amount of drug left after first pass
Bioavailibitly of PO varies
Bioavalibilty of IV is 100%
Three routes of Absorption
Enteral
Parenteral
Topical Transdermal
Enteral Route of Absorption
-By way of the GI tract. (oral/gastric mucosa, small intestine, rectum)
EC intended to break down in small intestine NOT stomach. First Pass
PO break down starts in stomach absorbed in small intestine. First Pass
SL, Buccal, Rectal all highly vascularized tissue. NO first pass effect. By-passess the liver
Parenteral
-SQ, IM IV intrathecal (into spinal canal), epidural (the space around the spinal cord)
-IV is the fastest (no barriers to absorption, often irreversible)
-Does not go through the first-pass effect
Topical (Transdermal)
-Application of meds to body surfaces
-Eyes, skin, ears, nose, lungs
-Localized so no first pass
Pharmacokinetic Phase: Distribution
-The movement of the drug through the body
-Process by which the drug molecules leave the blood stream and arrive at site of action
-Depends largely on adequacy of blood circulation
Decreased blood flow equals
Decreased distribution
If someone has peripheral vascular disease, abscesses, or tumors it decrease the blood flow to that area which results in the drug not being able to reach that area
Distribution: Blood Brain Barrier (BBB)
Affects distribution
Cells in the capillary wall in the brain with even more tight junctions which prevent drug passages
Only drugs with a transport system or EXTREMELY lipid soluble can pass through the BBB
Distribution: Blood Brain Barrier (what can cross)
Alcohol can cross the BBB
Glucose can cross the BBB (energy)
Not fully developed in infants
Distribution: Protein-Binding Effect.
-Temporary storage of the drug molecule that allows drug to be available for a longer period of time
-Drug Ratio of bound to unbound (free) molecules varies
-Binding is reversible (a rapid process)
-Only the ubound drugs is active and free to exert effects
Distribution: The goal when we have a medication that has a high protein binding effect
-Maintain a steady state of free drug concentration aka steady state because only ubound drugs are free to exert effects
Distribution: What effects protein-binding?
-The amount of protein in a persons blood
-Albumin is the primary plasma protein
Hypoalbuminemia (Malnutrition or liver disease)
-More free drug is available for distribution to tissue site
-Possibility of overdose and toxicity
Protein-Binding Example
warfarin/Coumadin
-Drug used to decrease coagulation (Blood thinner)
-Very highly protein bound (97-99%), leaves 1-3% free to exert effect
-A client with low albumin = less bound warfarin and more free warfarin
-More free warfarin can exert effect which increases the risk of toxicity and increase bleeding
Pharmacokinetic Phase: Metabolism
-Aka- Biotransformation
-Method by which drugs are INACtivated or biotransformed into a metabolite
-Live is the major site for drug metabolism. It can convert lipid-soluable drugs into water soluble metabolites. Kidney can excrete these metabolites.
What enzyme is responsible for turning lipid soluble drugs into water soluble drugs
Cytochrome P-450
If your liver isn’t working than you can have drug toxicity why?
Because you can not break drug down into inactive and have to much drug build up within the system
Metabolism: CYP450
-A group of isoenzymes that metabolize drugs
-About half of all drugs are metabolized by this system
-Drug-drug interactions can occur when drugs metabolized by the same isoenzyme are taken concurrently
Metabolism: CYP450: Clinical Significance
-Substrate: If a drug uses CYP450 system for metabolism. Pro-drug: is a substrate that uses the CYP450 system to convert to an active form
-Inducer: Speeds up metabolism of the CYP450 system. Reduces the amount of drug in the body. Reduces the therapeutic effect
-Inhibitor: slows down metabolism of the CYP450 system. Increases the amount of drug in the body. Increases risk of toxicity
If a drug is a CYP450 inhibitor
It can cause of build of medications in the liver because they are not being brokendown
If a drug in a CYP450 Inducer
It can cause a decrease in the amount of drug in the body because the liver is working overtime. this reduces therapeutic effect.
CYP450 Inhibitor Example
-Grapefruit juice is a CYP450 inhibitor. Taking grapefruit juice with another drug that uses the CYP450 system can cause an increase in the amount of drug in the body. This leads to toxicity
Pharmacokinetic Phase: Excretion
-How the drugs are complete removed from the body. Must be water soluble.
-Hydrophilic drugs can be excreted effectively
-Kidney is the major site. Through glomerular filtration. Tubular secretion. Tubular reabsorption
Pharmacokinetic Phase: Excretion. Reabsorption and Secretion
-Some of the drug is secreted
-Some of the drug in reabsorbed
Important in maintain a steady state while in excretion
90% of Penicillin G is excreted through the kidney so very little is reabsorbed so the drug would need to be given more frequently to maintain steady state
To maintain steady state
You can give high dose of drug or give drug more frequently
Pharmacokinetic Phase: Excretion. Kidney disease
Decreased excretion = drug build up and cause toxicity
Renal labs = blood urea nitrogen (BUN), creatinine
Best measure of kidney fuction
GFR. Glomerular filtration rate.
Calculated from the creatinine level, age, body size, and gender.
Elimination: Half-Life
-Serum half-life. (T 1/2) is time required for the serum concentration of a drug to decrease by 50%
-Takes 5 half-lives for 97% of drug to be eliminated.
Takes about _____ half lives for steady state to occur
4-5
When does steady state occur?
When intake of drug equals amount metabolized/excreted
One time dose of morphine 10 mg is given at 12:00. T 1/2 is 3 hours
1500 = 5 mg
1800 = 2.5 mg
21 = 1.25 mg
2400 = 0.625 mg
0300 = 0.313 mg
Around the Clock Dosing (ATC)
-Goal is to maintain 50% concentration in body
ATC Example: Morphine 10 mg given every 3 hours (ATC)
-After about 4 does there would be a constant level or “steady sate” of 5 mg at all times
-Serum concentration maintained at 50%
Onset, Peak, Duration
-Onset: time it takes for drug to elicit therapeutic response (latent period)
-Peak: time it takes for drug to reach its maximum therapeutic effect
-Duration: Time drug concentration is sufficient to elicit a therapeutic response
Phase 3 of Drug Action: Pharmacodynamic Phase
What the drug actual does to the body.
Drugs my increase, decrease, inhibit, destroy, protect or irritate to create a response
Drugs can exert multiple effects on the body
Multiple Effects: Example
Drug name: Metaproternonal
MOA: Broncho dilator
Uses: Acute asthma attack or COPD
Adverse effects: Tachycardia and Palitations
Multiple effects: Desired is dilates bronchial passage. Not desired: tachycardia or palpitiations
Pharmacodynamics: Receptors
-Receptors are proteins located on cell surfaces
-Chemicals in the body that interact with drugs to produce effects
-These chemical bind with the drug = drug-receptor complex
When a drug binds with a receptor a drug receptor complex forms.
This complex initiates a physiochemical reaction
agonist = stimulates/activates
antagonist = inhibits/blocks
Receptor Theory of Drug Action: Agonist
-A drug that has the ability to INITIATE a desired therapeutic effect by BINDING to a receptor
Example: Isoproterenol = beta1 adrenergic AGONIST. So this binds to a beta receptor and causes vasodilation lowering peripheral vascular resistance
Receptor Theory of Drug Action: Antagonist
A drug that produces its acton NOT by stimulation receptors but PREVENTING or BLOCKING or INHIBITING other natural substances (ligands) from binding and causing a response
Examples:
Ranitidine/Zantac, an H2 ANATGONIST. Blocks the release of gastric acid
diphenhydramine, an H1 ANTAGONIST, blocks action of histamine
Receptor-Less Activation
Not all drug responses involve receptors
How do we determine what drug are worrisome or not?
-Therapeutic index is the measure of relative safety of drug.
NTI have a ratio of lowest concentration at which clinical toxicity commonly occurs. If it is 10 then 10.1 causes toxicity
Therapeutic levels checked to ensure the medication is dosed effectively but avoid toxicity
Black Box Warning
-Required by the FDA for drugs that are especially DANGEROUS
-Is the strongest safety warning a drug can carry and still remain on the market
-Black Box warning has to be present on package, label, and advertising
Adverse Drug Reaction and Medication Errors
-Med errors are a major cause of morbidity and mortality
-Third leading cause of death
Drug Drug interactions
-May be intended
-May be unintended
-Increased risk with polypharmacy and NTI drugs
-Drug FOOD interaction
-Drug HERB
-Drug DISEASE
How can the nurse minimize drug interactons?
-Minimize the number of drugs the patient receives
-Take a thorough drug history
-Be extra vigilant in monitoring when patient is taking drug with NTI
Drug interactions that INCREASE Therapeutic Effects
-Additive effects: 2 drugs taken with similar MOA. (2 antibiotics given together to treat a complicated infection)
Synergism/Potentiation: 2 drugs with DIFFERENT MOA but result in a combined drug effect greater than that of either drug alone
Activaiton of drug-metabolizing enzymes in the liver-decreases metabolism rate of the drug CYP450 system
Displacement: Displacement of one drug from plasma protein binding sites by a second drug — increases effect of displaced drug
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Drug interactions that decrease therapeutic effects.
Antidote: Drug given to ANTAGONIZE the toxic effects of another drug
Decrease Intestinal Absorption: If drug can not be broken down they will never get the therapeutic effects of the drug
Activation of drug-metabolizing enzymes in the liver—enzym inducers. Increase metabolism rate of the drug = quicker out of system. CYP450 system
Older Adults and Pharmacokinetic Consequences
Hepatic Changes. Drugs metabolized more slowly
Cardiac and Circulatory changes. Impaired circulation = decrease distribution of drugs
Gastrointestinal Changes = Decreased absorption of oral drugs
Renal Changes = Drugs excreted less completely
Decrease production of CYP 450 enzymes increase risk for drug interactions
