Week 2: Pharmacology Key Concepts Flashcards
Distribution
Transportation of drugs throughout the body to target tissues. Several factors affect drug distribution:
- Blood flow: drugs may enter the circulatory system but may not be able to get to the target area (or have reduced impact) or increased blood flow = more drug reaching target tissues
- Drug solubility
- Drug-protein complexes: blood or plasma proteins cannot cross plasma into cells; may have a reversible attraction to free drugs - protein bound drugs cannot enter the cell but can reverse and leave too much free drug in the body
- Ability to pass through membranes
Absorption
The movement of a drug from site of administration, across membranes, to circulation. Can be affected by:
- **route **(i.e., oral, buccal, sublingual)
- physical form (i.e., tablet, gel cap, liquid)
- size of drug molecule (impacts how easily it can pass into blood steam)
- degree of ionization (if it needs to give up electrons)
- solubility (most cell membranes are made up of lipids, so the drug needs to be lipid soluble to pass through the membrane and made water soluble to be excreted)
- vascularity of the area
- digestive motility, pH, co-morbidities, etc.
Metabolism
The process by which structure (and function) of drugs, nutrients, vitamins, and minerals is altered. Also called biotransformation, where the liver is the primary site of metabolism. Metabolism usually makes a drug more water soluble and excretable (hydrophilic). May be impacted by:
- life span changes: decreased metabolism in infants and older adults
- genetic variations in CYP enzymes (cytochrome P450) that determines speed at which drug is metabolized
Excretion
The kidneys are the primary site for excretion but there is also pulmonary, glandular, fecal/bile excretion. The rate of excretion influences concentration of a drug in the blood.
In renal excretion, most drugs (not attached to albumin) are filtered into the nephron but the pH of urine can influence reabsorption of a drug from the nephron. Drugs that are highly bound to plasma proteins are not filtered because they are too big.
Agonist
Mimics or enhances action of a receptor eliciting a response that may be greater than that of endogenous substances (i.e., morphine has a greater response than endorphins or enkephalins)
Partial Agonist
Displays both agonist and antagonistic effects - will produce a weaker response than endogenous substances
Antagonist
Prevents a response through inhibition or blocking by competing with endogenous substances or competing with a drug agonist for receptor binding sites (i.e., naloxone). Can be competitive or non-competitive.
- Competitive: competes with agonist drug for the same receptor site
- Non-competitive: binds to a different receptor site but still inactivates agonist receptor
Synergistic
When drugs administered together interact, so combined effects exceed that of each individual drug’s effects
Example: diuretics and ACE inhibitors both decrease BP so when given together the effects are greater than when given alone
Two different drugs that have different mechanisms of action work together to target the same issue and result in an improved therapeutic response!
Additive
When drugs used together so that smaller doses of each drug can be give, and toxic effects avoided while adequate drug action is maintained
Example: acetylsalicylic acid and codeine for analgesia
Two drugs can be given together at lower doses for improved therapeutic impact with less risk for adverse effects.
Drug to drug interactions
- Compete for CYP (enzymes used in metabolism of drugs)
- Inhibit CYP enzymes - might reduce the metabolism of another drug and lead to toxicity
- Induce CYP enzymes - could increase metabolism of another drug and reduce amount of functional drug
- Compete for binding sites on plasma proteins
Indications of use
The reason the drug is prescribed
Mechanism of Action
How the drug works in the body to achieve the desired effect
Desired effects
What the effect is we are trying to achieve with therapy
Adverse effects
Negative side effects that are unintended or unwanted
Pharmacokinetics
What the body does to a drug; includes the movement of a drug through the body (ADME)
- As drug enters blood (Absorption)
- As drug moves to target tissues (Distribution)
- As drug is metabolized (Metabolism)
- and as drug is removed from the body (Excretion)
The drug must reach target tissue at a high enough concentration to produce a desired/therapeutic effect
Pharmacodynamics
What the drug does to the body to create a response. It is related to:
- The mechanism of action of a drug
- How a drug interacts with target tissues
- Altering activity of a cell through interactions with the receptor
- Altering activity of an enzyme
What drug forms are most soluble? List most to least
- Liquid
- Suspension Solution
- Powder
- Capsule
- Tablet
- Coated Tablet (coating slows down release)
- Enteric coated tablet
Bioavailability
Amount of the drug absorbed into systemic circulation that is physiologically available to reach target cells to produce an effect and is always expressed as a percentage from 0%-100%
Enteral Medication
Oral delivery. Medication is swallowed (non sublingual or buccal) and enters the digestive system. The liver will process whatever is digested and may start to remove some drugs (first pass effect) it may do this before the drug even enters the blood stream. The portal vein connects the stomach and liver, and the drugs must pass through these systems prior to entering the systemic circulation and reaching the target tissues.
IV Drugs are considered to be bioavailable by what percentage? Why?
100% and it is because they are delivered directly to the tissues
What should the nurse consider for a client with acute kidney injury or chronic kidney disease?
With liver disease the molecule may not be metabolized for excretion; with kidney disease the molecule may be metabolized but may not be excreted - may hang around, so a lower dosage of drug should be administered.
Enterohepatic Recirculation
Lipid soluble drugs can be reabsorbed with bile via enterohepatic recirculation, resulting in a decreased rate of excretion.
Minimum effective concentration
The minimum amount of drug that can be given to produce a therapeutic effect
Toxic concentration
The amount of drug given that will no longer result in a therapeutic effect but a toxic effect
Therapeutic Index
The index of safety for a drug (i.e., 50-100 mg), it is the ratio between the amount of drug that is toxic to 50% of the population (TD50) and the amount of drug that is effective to 50% of the population (ED50) A larger therapeutic index is preferred.
Drug half-life
The amount of time for the drug to lose its concentration by half, provides an estimate of duration of action. It is the time it takes for plasma concentration to be reduced to 50%. Drugs with a short half life can be given more frequently to maintain the drug in therapeutic range - drugs with longer half lives are given less frequently.
Loading doses
The initial dose that may be more concentrated to induce a response more quickly. Larger dose leads to more rapid absorption and shorter onset of action.
Maintenance dose
Used to maintain a drug within the therapeutic range. repeated dosing is required to maintain steady plasma concentration of drug. The next dose is given before plasma concentration dips out of therapeutic range.
Therapeutic range
The difference between the minimum effective concentration and the toxic concentration- it is the window of safety within the therapeutic index.
Receptor
Most drugs influence biological response through interactions with cellular receptors:
- Intrinsic activity: ability of drug to bind to receptor and produce an effect
- Affinity: degree of attraction
Prodrugs
Medications that require metabolism to produce their therapeutic actions
Enzyme induction
Some drugs can increase metabolic activity in the liver
Therapeutic Index
LD50/ED50 = safe range to give a medication. LD50 is the lethal dose for 50% of the population; ED50 is the effective dose for 50% of the population. The TI is a measure of the drug’s safety margin: the higher the value, the safer the medication.
Margin of Safety
is calculated as the amount of drug that is lethal to 1% of animals (LD1) divided by the amount of drug that produces a therapeutic effect in 99% of animals (ED99). In general, the higher the MOS value, the safer the medication. Of course, this considers only the lethality of the drug and does not account for non-lethal, though serious, adverse effects that may occur at lower doses
Potency
A drug that is more potent will produce a therapeutic effect at a lower dose compared with another drug in the same class.
Efficacy
the magnitude of maximum response that can be produced from a particular drug.
Agonist
A drug that produces the same type of response as the endogenous substance
Partial Agonist
describes a medication that produces a weaker, or less effi-cacious, response than an agonist. Key properties of partial ago-nists is that they display both agonistic and antagonistic effects.
Antagonist
A second possibility is that a drug will occupy a receptor and
prevent the endogenous chemical from acting.
Functional Antagonist
Inhibit the effects of an agonist, not by competing for a receptor but by changing pharmacokinetic factors. For example, antagonists may slow the absorption of an agonist, resulting in less pharmacological effect. An antagonist may change the pH of the surrounding fluid and neutralize the agonist before it is even absorbed.
Side effects
types of drug effects that are predictable and
that may occur even at therapeutic doses. Side effects are less serious than adverse effects.
Teratogens
Drugs that cause birth defects
