Chapter 4: PRINCIPLES OF PHARMACOLOGY Flashcards
What is psychopharmacology?
The study of the effects of drugs on the nervous system and behaviour.
What are the two major aspects of drug influence?
- drug effects
- sites of action
What are drug effects?
Observable changes in an individual’s physiology and/or behavior.
What are sites of action?
The locations where drug molecules interact with molecules on or in cells to affect biochemical processes.
What are pharmacokinetics?
The process by which drugs are absorbed, distributed within the body, metabolized, and excreted.
What hapenns during absorption?
Drug is administered and absorbed through tissues. eg. intramuscular absorption
What happens during distribution?
drug is distributed throughout body and blood.
What happens during metabolism?
Drug is changed to an inactive form by enzymes, usually in liver.
What happens during excretion?
Drug is excreted in urine by kidneys.
What is the fastest route of administration of drugs?
- Intravenous injection (IV injection)
- Reaches brain in a few seconds
What are the disadvantages of IV injection?
- required skills
- entire dose reaches bloodstream at once: if sensitive individual, little time to counteract the drug.
How does intraperitoneal injection work?
-injected through the abdominal wall into the peritoneal cavity
What is intramuscular injection (IM)?
intramuscular: directly into large muscle. drug absorbed into bloodstream through capillaries that supply muscle.
What is subcutaneous injection?
-space beneath the skin
What is the most common way of administering drugs?
- Oral administration
- Some drugs cannot be administered orally because they are destroyed by stomach acid or digestive enzymes. (ex: insulin)
- sublingual: under the tongue
Does inhalation have rapid effects?
Yes because the route from the lungs to the brain is very short.
What is topical administration?
- directly through the skin
- for steroid hormones, nicotine
- insufflation is a type of topical administration: contact with the nasal mucosa, rapid effect.
Where are most of sites of action located ?
-on or in cells of the CNS
What is the most important factor that determines at which rate the drug enters the nervous system?
-lipid solubility: the ability of fat-based molecules to pass through the cell membrane
Why is the blood brain barrier not effective for drugs?
-blood-brain barrier is only for water-soluble molecules
Is heroin or morphine more lipid soluble?
-Heroin is more lipid-soluble than morphine: IV injection of heroin will produce more rapid effects than morphine
How is the drug metabolized and deactivated ?
-liver plays especially active role in enzymatic deactivation, but some deactivating enzymes also found in the blood, and brain.
What happens in the case where the drugs become even more active during metabolisation?
- enzymes transform molecules of a drug into other forms that are biologically active.
- Transformed molecule can become even more active that the drug that is originally administered.
- Drug effects then have very long duration (ex: fluoxetine (prozac))
What is a dose-response curve?
A graph of the magnitude of an effect of a drug as a function of the amount of drug administered.
Why do we use the dose-response curve?
- Because drugs vary widely in their effectiveness
- The effects of a small dose of a relatively effective drug can equal or exceed the effects of larger amounts of a relatively ineffective drug
What happens after the maximum effect point is reached?
Increasing the dose of the drug will not produce any more effect.
What other effect than analgesia do opiates have?
-depress activity of neurons in the medulla that control heart rate and respiration.
What is the margin of safety for opiates?
The distance between the dose-response curve for the analgesic effect of morphine and the dose-response curve for the depressive effect of morphine on respiration.
What is the therapeutic index?
- The ratio between the dose that produces the desired effect in 50 percent of the animals and the dose that produces toxic effects in 50 percent of the animals.
- The lower the ratio the more careful you should be
What are the two main reasons why drugs vary in their effectiveness?
- sites of action
- affinity of a drug with it’s site of action.
What is the site of action of oxycodone?
-suppresses the activity of neurons in spinal cord and brain that are involved in pain perception
What is the site of action of aspirin?
-reduces the production of a chemical involved in transmitting information form damaged tissue to pain-sensitive neurons.
What is affinity?
- The readiness with which two molecules join together.
- high affinity: drug can be prescribed at relatively low dose
- low affinity: drug has to be prescribed at higher doses in order to function
What’s the most desirable drug’s characteristics in terms of sites of action and affinity?
- high affinity for sites of action that produces desirable effects
- low affinity for sites of action that produce toxic effects.
What is tolerance?
A decrease in the effectiveness of a drug that is administered repeatedly.
What is sensitization?
An increase in the effectiveness of a drug that is administered repeatedly.
What happens if someone who develops tolerance of a certain drug stop taking it suddenly?
-withdrawal symptoms:
opposite of drug effects (dysphoria, agitation…)
What mechanisms of responsible for tolerance?
- Normally, most systems in body are regulated so that they stay at or near an optimal value
- Effects of drugs alter these systems for a prolonged time.
- Compensatory mechanisms begin to produce the opposite reaction.
- When stop taking the drug compensatory systems are not opposed by drug effects, and that’s what produces withdrawal symptoms.
What is physical dependence ?
Compensatory changes following repeated use of a drug that results in withdrawal symptoms when the drug is no longer taken.
What is receptor downregulation?
-Compensatory mechanism that involves a decrease of the binding of drugs with receptors.
What are the two scenarios of downregulation?
- receptors become less sensitive to the drug do affinity of drug decreases
- receptors decrease in number
What is the second compensatory mechanism other than receptor downregulation?
- involves the process that couples the receptors to ion channels in the membrane or to the production of second messengers.
- after prolonged stimulation of the receptors, one or more steps in the coupling process become less effective.
What are the effects of barbiturates and do they cause tolerance or sensitization?
- cause sedation and also depress neurons that control respiration.
- the sedative effects show tolerance but the respiratory depression does not.
What can repeated injections of cocaine produce?
- more and more likely to produce movement disorders and seizures
- euphoric effects of cocaine do not show sensitization
What is a placebo?
An inert substance that is given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug.
Is it correct to say that placebo have absolutely no effect because they are inert substances ?
- No it’s not correct
- If a person expects that a placebo can have a physiological or psychological effect, then it may actually produce that effect.
What can placebo responses be the result of ?
- Changes in motivation
- Expectation
- Forms of learning (eg. classical conditioning)
