Principles of Pharmacology Flashcards
Pharmacology
The scientific study of the actions of drugs and their effects on a living organism
The WHO estimates that as many as _% of people in developing countries are entirely dependent on herbs or plant-derived medicinals
80%
What is the focus of neuropharmacology
Drug-induced changes in the functioning of cells in the nervous system
What is the focus of psychopharmacology?
Drug-induced changes in mood, thinking, and behaviour
What is the focus of neuropsychopharmacology?
Identifying chemical substances that act on the nervous system to alter behaviour that is disturbed because of injury, disease, or environmental factors
Drug action
The specific molecular changes produced by a drug when it binds to a particular target site or receptor
Drug effects
The more widespread changes in physiological or psychological function as a result of drug action
Therapeutic effects
The drug-receptor interaction produces the desired effect
Side effects
All non-therapeutic effects
Specific drug effects
Those effects based the physical and biochemical interactions a drug with a target site in living tissue
Nonspecific drug effects
Those effects that are based on certain unique characteristics of the individual, rather than the chemical activity of a drug-receptor interaction
What is an example of a nonspecific drug effect?
A placebo
Placebo
A pharmacologically inert compound
Bioavailability
The amount of drug in the blood that is free to bind at specific target sites to elicit drug action
Is bioavailability more important than dosage? Why or why not?
Yes, because many different factors are involved
Pharmacokinetic factors
Factors that contribute to bioavailability
What are 5 pharmacokinetic components of drug action?
- Routes of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
What is determined by the route of administration?
How quickly and how completely the drug is absorbed into the blood
What happens once the drug is in the blood plasma?
Some drug molecules move to tissues to bind to active target sites (receptors) or to plasma proteins or may be stored temporarily in bone or fat, where it is inactive
Depot binding
Type of drug interaction involving binding to an inactive site
Drug inactivation occurs primarily as a result of what?
Metabolic processes in the liver
The amount of drug in the body is dependent on what?
The dynamic balance between absorption and inactivation
Inactivation influences what?
The intensity and duration of side effects
What are the two major categories of administration methods?
Enteral and parenteral
Enteral methods use what route?
The gastrointestinal (GI) tract
Agents administered by which method are generally slow in onset and produce highly variable blood levels of drug?
Enteral
What is the most common enteral method?
Oral
Why is oral administration (PO) the most popular route?
- Safe
- Self-administered
- Economical
- Avoids complications and discomfort of injection methods
In order for orally administered drugs to be effective, what needs to happen?
- Must dissolve in the stomach fluids and pass through the stomach wall to read blood capillaries
- Must be resistant to destruction by stomach acid and enzymes
What is an example of a drug that cannot be administered orally? Why?
Insulin, because it can be destroyed by digestive processes
Absorption
Movement of the drug from the site of administration to the blood circulation
Most drugs are not fully absorbed until they reach what part of the GI tract?
The small intestine
First-pass metabolism
Phenomenon in which the liver metabolizes some of a drug before it can circulate through the body
What must be done for drugs that show extensive first-pass effects?
Must be administered at higher doses or in an alternative method
Why is the first-pass metabolism beneficial?
Potentially harmful chemicals/toxins can be chemically altered before passing to the heart for circulation throughout the body
Rectal administration
The placement of a drug-filled suppository in the rectum, where it melts or dissolves, releasing the drug to be absorbed into the blood
Why is bioavailability of drugs administered rectally hard to predict?
Depending on the placement of the suppository, the drug may avoid some first-pass metabolism
What happens with drugs absorbed from the lower rectum into the hemorrhoidal vein?
They bypass the liver
What happens with drugs placed deeper in the rectum?
They are absorbed by veins that drain into the portal vein, going to the liver before circulation
What is the most rapid and accurate method of drug administration?
Intravenous (IV) injection
Why is IV injection so effective?
A precise quantity of the agent is placed directly into the blood and passage through cell membranes is eliminated
Why is the quick onset of IV administered drugs also a hazard?
It leaves little time for corrective measures and cannot be removed from the body
Why is the IV administration of street drugs particularly dangerous?
- Drugs that are impure or poor quality provide uncertain doses and reactions are likely
- Lack of sterile equipment can lead to infection
- Users may attempt to dissolve drugs that have insoluble filler materials, which, when injected, may become trapped in the small blood vessels in the lungs, leading to reduced respiratory capacity or death
What is the advantage of intramuscular (IM) injection?
Slower, more even absorption over a period of time
Drugs administered by IM injection are typically absorbed within how long?
10-30 minutes
How can absorption be slowed with IM injection?
By combining it with a second drug that constricts blood vessels
What is a disadvantage of IM injections?
Sometimes the solution can be very irritating and cause significant muscle discomfort
What method of administration is the most common route for small lab animals?
Intraperitoneal (IP) injection
How are drugs administered in IP injection?
The drug is administered through the abdominal wall into the peritoneal cavity
Peritoneal cavity
The space that surrounds the abdominal organs
Which route of administration allows for drugs to be absorbed at a rate that is dependent on the blood flow to the site?
Subcutaneous (SC) administration
Why is the effect on the brain so rapid with inhalation methods?
Because the blood has a short distance to travel to the heart
What are the disadvantages of inhalation methods?
- Irritation of nasal passages
- Damage to lungs
Intranasal administration
Topical administration of a drug to the nasal mucosa
What method can allow a drug to skip first-pass metabolism and bypass the blood-brain barrier?
Intranasal topical administration
What method of administration allows for a controlled and sustained delivery of a drug at a pre-programmed rate?
Transdermal administration
What are some advantages to transdermal administration?
- Don’t have to remember pills
- Painless
- Avoids first-pass effect
What method of administration is preferable in cases of mass vaccination campaigns?
Transdermal administration
What is the disadvantage of transdermal administration?
Only a limited number of drugs are able to penetrate the skin
What is possibly the most important factor in determining plasma drug levels?
The rate of passage through cell layers between the site of administration and the blood
Phospholipids
Lipid molecules that are major constituents of the cell membrane; composed of a polar head and two lipid tails
Movement across the membranes is always in what direction?
From higher to lower concentration
The larger the concentration difference on each side of the membrane, the….
More rapid the diffusion
Does lipid solubility increase or decrease the absorption of drug into the blood?
Increase
What determines how readily a drug will pass the lipid barriers to enter the brain?
The lipid solubility
What is one way to predict the relative rate of movement of a drug through cell membranes?
Estimate its lipid solubility using its partition coefficient
How does one measure the partition coefficient?
- Mix the drug with water
- Combine it with the same volume of oil or a lipid solvent
- After settling, the oil and water form two distinct layers, which are then separated and the amount of drug found in each is compared
- The ratio of the amount of drug dissolved in oil divided by its concentration is the oil/water partition coefficient
A higher concentration of drug in the oil compared with that in the water indicates what?
Greater lipid solubility and more rapid passage through cell membranes
Why are most drugs not readily lipid soluble?
Because they are weak acids or weak bases that can become ionized when dissolved in water
The extent of ionization depends on what two factors?
- The relative acidity/alkalinity (pH) of the solution
- An intrinsic property of the molecule (pKa)
Regardless of the route of administration, once the drug has entered the blood, how long does it take to be carried throughout the body?
1 to 2 minutes
In general, which parts of the body will have the highest concentration of drug?
The parts of the body in which blood flow is greatest
Cerebrospinal fluid (CSF)
A clear, colourless liquid that fills the subarachnoid space that surrounds the entire bulk of the bran and spinal cord and also fills the hollow spaces (ventricles) and their interconnecting channels (aqueducts), as well as the central canal
What is the second barrier that is unique to women?
The placental barrier
Teratogens
Agents that induce developmental abnormalities in the fetus
The effect of teratogens are dependent on what?
The timing of exposure
What are some effects of drug depot binding on therapeutic outcome?
- Reduction in the concentration of drug at its site
- Slower onset
- Reduction in effects
- Higher than expected blood levels of the displaced drug, possibly causing greater side effects
First-order kinetics
Term used to describe exponential elimination of drugs from the bloodstream
Half-life
The amount of time required for removal of 50% of the drug in blood
Why is half-life important?
Because it determines the time interval between doses
Why is half-life important?
Because it determines the time interval between doses
Steady state plasma level
The desired blood concentration of drug achieved when the absorption/distribution phases is equal to the metabolism/excretion phase
For any given daily dose of a drug, the steady state plasma level is approached after a period of time equal to what?
Five half-lives
Zero-order kinetics
Term used to describe a constant rate of drug removal from the body, regardless of drug concentration in the blood
What is the most common reaction in biotransformation?
Oxidation
What does oxidation produce usually?
A metabolite that is less lipid soluble and less active
Type II/Phase II involve what kind of modification of the drug molecule?
Synthetic
Members of the cytochrome P450 (CYO450) class are responsible for what important activity?
Oxidizing most psychoactive drugs
Microsomal enzymes
Enzymes in liver cells responsible for metabolizing exogenous substances such as drugs
What can happen with increased numbers of enzyme molecules?
- The drugs speed up their own rate of biotransformation (2-3x)
- Increase the rate of metabolism of all other drugs modified by the same enzyme
What can happen with increased numbers of enzyme molecules?
- The drugs speed up their own rate of biotransformation (2-3x)
- Increase the rate of metabolism of all other drugs modified by the same enzyme
Enzyme induction
Increase in liver drug-metabolizing enzymes associated with repeated drug use
Genetic polymorphisms
Genetic variations among individuals that produce multiple forms of a given protein
Enzyme inhibition
Reduction in liver enzyme activity associated with a specific drug
Receptors
Large protein molecules located on the surface of or within cells, and are the initial sites of action of biologically active agents such as neurotransmitters, hormones, and drugs
Drug competition
Interaction between two drugs that share a metabolic system and compete for the same metabolic enzymes; bioavailability of one or both increases
Ligand
Any molecule that binds to a receptor with some selectivity
What types of molecules attach most readily to the receptor?
Those with the highest affinity
Dose-response curve
A method used to evaluate receptor activity which describes the extent of biological or behavioural effect (response) produced by a given drug concentration (dose)
Dose-response curve
A method used to evaluate receptor activity which describes the extent of biological or behavioural effect (response) produced by a given drug concentration (dose)
Affinity
Attraction between a molecule and a receptor
Receptor agonists
A neurochemical or drug that can bind to a particular receptor protein and alter the shape of the receptor to initiate a cellular response
Drug disposition tolerance/Metabolic tolerance
Occurs when repeated use of a drug reduces the amount of that drug that is available at the target tissue
Receptor antagonists
A molecule that interacts with a receptor protein and produces no cellular effect after binding, and also prevents an “active” ligand from binding
Partial agonists
Drug that acts as an agonist to some receptors, but an antagonist to others
Up-regulation
Increase in the number of receptors, which may be a consequence of denervation or of chronic antagonist treatment
Inverse agonists
Substance that activates a receptor but produces the opposite effect of a typical agonist at that receptor
Down-regulation
Decrease in the number of receptors, which may be a consequence of chronic agonist treatment
Cross-tolerance
Tolerance to a specific drug can reduce the effectiveness of another drug in the same class
Acute tolerance
Rapid tolerance formed during a single administration of a drug
Sensitization
The enhancement of particular drug effects after repeated administration of the same dose of drug
Noncompetitive antagonists
Drug that reduces the effect of an agonist, but does not compete at the receptor site
Physiological antagonism
Drug interaction characterized by two drugs reducing each other’s effectiveness in the body
Identify the five factors that affect drug action, and very briefly explain an example of how each one
- Route of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
What are the five gross categories of drugs?
- CNS stimulants
- CNS depressants
- Analgesics
- Hallucinogens
- Psychotherapeutics
What is an example of a CNS stimulant?
- Amphetamine
- Cocaine
- Nicotine
What is an example of a CNS depressant?
- Barbiturates
- Alcohol
What is an example of an analgesic?
- Morphine
- Codeine
What is an example of a hallucinogen?
- Mescaline
- LSD
- Psilocybin
What is an example of a psychotherapeutic?
- Prozac
- Thorazine
Describe a psychological effect of a CNS stimulant at a typical dose
Increased electrical activity in the brain and behavioural arousal, alertness, and a sense of well-being in the individual
Describe a psychological effect of a CNS depressant at a typical dose
Depress CNS function and behaviour to cause a sense of relaxation and drowsiness
Describe a psychological effect of an analgesic at a typical dose
Reduce the perception of pain
Describe a psychological effect of a hallucinogen at a typical dose
Alter one’s perceptions, leading to vivid visual illusions of distortions of objects and body image
Describe a psychological effect of a psychotherapeutic at a typical dose
Treat clinical disorders of mood or behaviour
