Intro and Anti-psychotics Flashcards
Pharmacokinetics
How a drug is absorbed, distributed, metabolized, excreted. What the body does to a drug. Liberation, Absorption, Distribution, Metabolism, Excretion.
Pharmacodynamics
Mechanism of action of a drug. What the drug does to the body.
Enteral/Oral administration
via the GI tract: safest, easiest route; must pass through the GI tract (w/stomach acid, enzymes) and enter portal circulation for 1st pass metabolism (1st pass effect)
1st-pass metabolism
absorbed in GI tract, enters portal vein to liver, metabolized, then enters general circulation. eventually sent back to liver by arterial circulation for more metabolism. PO takes 1-3 hours for 75% of dose of most psychoactive drugs to enter blood, depending on lipid solubility.
Parenteral/Inhalation
Avoids GI tract, 1st-pass metabolism, inhaled to lungs. Fastest drug effects (8-10 seconds) b/c lungs have largest surface area, avoids most of 1st-pass metabolism, blood goes from lungs to left side of heart and pumped out to arterial system (to brain very fast).
Why are smoking drugs of abuse (when inhaled) very reinforcing?
Partially due to very fast effects.
Transmucosal
Across mucous membranes, directly into bloodstream. Sprayed into nose/snorted. Drug effects in 2-3 minutes for cocaine.
Buccal (sublabial)
Between cheek and gums (nicotine gum)
Sublingual (SL)
Under tongue (nitroglycerine-for heart pt; alprazolam-xanax)
Intravenous (IV)/Injected
Very fast drug effects (15-30 seconds)
Intramuscular (IM)
Drug effects in 10-20 minutes.
Depot form
Intramuscular (IM): allows slow, controlled release over weeks (e.g., Risperdal Consta, Haldol Decanoate)
Intravenous/IV Advantages
Emergency; Dose titration; Irritating substances when diluted
Intravenous/IV Disadvantages
Risk of adverse drug reactions (ADRs); Cannot give highly lipid drugs; Vein collapse with frequent repetitions.
Subcutaneous (SC, SQ, subcut)
Injected just under skin, not into the vein: Drug effects in 15-30 minutes, or hours to months. Examples: vaccines, insulin, TB skin test.
Subcutaneous Advantages
Better for highly lipid drugs, implantation of solid pellets
Subcutaneous Disadvantages
Possible pain, tissue damage from irritating substances
Transdermal
Through skin by patch
Transdermal Advantages
Slow, controlled release over hours to days
Transdermal Disadvantages
May get irritation, sometimes inconsistent absorption, must avoid heat and rubbing
Transdermal Examples
nicotine patch for addiction, hormonal patches, methylphenidate (daytrana) for ADHD, rivastigmine (exelon) for dementia, selegiline (emsam) for depression, scopolomine for motion sickness
Liberation
release of drug from its dosage form
Absorption
movement of drug from administration site into the blood
Distribution
movement of drug from intravascular to extra-vascular space
Metabolism
transformation of drug into compounds that are easier to eliminate
Excretion
elimination of drug or metabolite via renal, biliary, or pulmonary processes
Absorption in the stomach considerations
many drugs are absorbed better in the stomach than in intestines (and vice versa). You can reach a desired concentration level faster when taken on an empty stomach. Some pills are enteric-coated to decrease irritation of the stomach lining, and may delay absorption until intestine for those drugs that are better absorbed in intestine. Bottom line: take drugs as instructed.
Immediate release (IR)
drug is released with no time lapse
Controlling release, absorption
Sustained-release (SR); Sustained-action (SA); Extended-release (ER, XR, XL); Controlled-release (CR); and Time release technology (TR)
Benefits of Delayed Release
Decreases side effects, (possibly) improves therapeutic effects by smoothing out peaks, troughs. Often may be sprinkled on applesauce (in insert says so).
Caution with Delayed Release
Should not be chewed or crushed (unless insert states otherwise)
Metabolism
Drugs are metabolized by enzymes primarily in the liver, but also intestines. The drug is usually inactivated, easier to excrete.
Prodrug
A drug that is initially inactive, but becomes active when absorbed or metabolized.
Excretion
Mainly in urine, but also in feces, sweat, mammary milk, or exhaled air.
What happens if a drug is delayed in its metabolism or elimination, or is ineffective?
It can reach toxic levels, or can cause GI, liver, kidney, or lung disease.
Cytochrome P450 (CYP)
System in the liver that is main system of enzymes that inactivate drugs. Different in every individual (ex: poor, extensive (normal), ultra rapid, or rapid metabolizers).
Variability in Cytochrome system (different metabolizers) - Elderly
Age-elderly may have decreased hepatic (liver), renal (kidney) function. They may get toxic levels, particularly if liver or kidney dysfunction. Dose usually halved. Polypharmacy often leads to many drug-drug interactions.
Variability in Cytochrome system (different metabolizers) - Supersensitivity (allergic)
Rash is most common reaction. Discontinue (D/C) drug immediately. Take antihistamine, topical corticosteroid. Call doctor. Some can become fatal. Must not try drug again.
Variability in Cytochrome system (different metabolizers) - General susceptibility factors
Less effective barriers to absorption (GI, blood-brain barrier); Increased body fat (keeps fat-soluble drugs in body longer); More sensitive receptors.
Impact of drug-drug interactions
Significant side effects (ex: excessive drowsiness with xanax and ambien)
What are the most common type of drug-drug interactions?
Those of addictive drugs.
Synergistic effects of drug-drug interactions
Two drugs are adding to one another or having an impact on one another for an additive effect. Ex: thyroid hormone added to antidepressant.
Antagonistic drug effects of drug-drug interactions
two drugs doing opposite things cancel one another out. Can lead to decreased therapeutic effect.
Drug-drug interactions: inhibition
a drug can inhibit an enzyme that metabolizes itself or other drugs
Drug-drug interactions: induce
a drug can induce an enzyme that metabolizes itself or other drugs
CYP enzymes
main system which inactivates drugs, found in liver and some in the intestines. Involved in drug-drug interactions by inhibiting or inducing metabolization of a drug. Psychotropics are infamous for being effected by, or effecting other drugs.
Drug Inhibition process
Drug A (a CYP-substrate) usually binds to CYP enzyme and is metabolized. Drug B (a CYP inhibitor) blocks the site and does not allow A to be metabolized. Increases level of “un-metabolized” drug A in blood plasma, which may increase side effects and toxicity.
Timeframe for Drug-drug interactions
occurs immediately, within hours to days. It doesn’t matter which drug is added first.
Drug Induction process
Drug A (a CYP-substrate) usually binds to CYP enzyme and is metabolized. Drug C (a CYP-inducer) induces a cell that makes the enzyme to make more. Increases metabolism of A, decreases plasma levels of A, and decreases drug effects. Can take days to weeks to develop if drug C is added second. Will occur immediately if drug C is already present for several days.
Effects of diet on drug metabolism
Grapefruit juice: inhibits 3A4, causing increased levels of 3A4-metabolized drugs. (85 drugs affected by DDIs- ex: ability, celexa). May cause death. One glass may have an effect for greater than 3 days.
Herbs: St. John’s wort induces 3A4. As a result, drugs like seroquel will had less effect.
How can you warn your patients?
instruct patients to ask their doctor or pharmacist about potential DDIs, including food, OTC drugs, herbs, supplements
Peak level
drug concentration at it’s highest
Trough level
drug concentration at it’s lowest
Half-life (T1/2)
Time required for plasma concentration to decline by 50% after 1 dose. After 1T1/2, 50% of drug is eliminated. After 2 T1/2, 75% is eliminated. After 3 T1/2, 87.5% is eliminated. Etc.
How long does it take for most of a drug to be entirely eliminated?
About 6 half-lives.
First-order kinetics
How a drug is eliminated slowly in the body (half-lives). The metabolism rate is a constant fraction of the remaining drug.
What drug does not follow the half-life rule?
Alcohol - zero-order kinetics: an absolute amount is eliminated per hour, regardless of the amount in the blood.
Steady state (SS)
Plasma drug concentration does not change with repeated (or continuous) same dose administration. Drug in rate = drug out rate. After 6 half lives, 98.4% of steady state is achieved - SS concentration is reached with regular-interval (or continuous) dosing after 6 half-lives.