Exam 2: Chapters 2-6 Flashcards
Psychopharmacology
The study of the effects of drugs on the nervous system and on behavior
Drug effects
The changes we can observe in an animal’s physiological processes and behavior
Sites of action
The points at which molecules of drugs interact with molecules located on or in cells of the body
- causes an effect on some biochemical processes of these cells
What contributions have psychopharmacology studies made to science?
- development of psychotherapeutic drugs
- tools to study functions of the cells of the nervous system/ behaviors controlled
What do molecules of drugs have to do to be effective?
Reach its sites of action
How do drug molecules reach their sites of action?
- Enter the body
- Enter the bloodstream
- Be carried to the organ/s they act on
- Leave the bloodstream to come into contact with molecules with which they interact
What happens to molecules of drugs that enter the body?
They are metabolized > broken down by enzymes
OR
Excreted in urine
What is the process by which drugs are absorbed, distributed within the body, metabolized, and excreted?
Pharmacokinetics
What is the most common route of administration in laboratory animals?
Injection
Fastest route of injection
Intravenous (IV) injection - injection into a vein
Disadvantages of IV injections
- Increased care and skill to complete
2. Entire dose reaches the bloodstream at once > if sensitive, there is little to do to counteract the effects
What is an intraperitoneal (IP) injection?
Drug is injected through the abdominal wall > into the peritoneal cavity
- most common route for small animals
What is an intramuscular (IM) injection?
An injection made directly into a large muscle, such as in the upper arm, thigh, or buttocks.
How are IM injections absorbed into the bloodstream?
The drug is absorbed through the capillaries that supply the muscle with blood
What is a subcutaneous (SC) injection?
An injection made into the space beneath the skin
> useful for small amounts of a drug
can be modified for slow administration through use of dry pellet
What is the most common form of administration of medicinal drugs to humans?
Oral administration
Sublingual administration
Accomplished by placing them beneath the tongue
> is absorbed by by capillaries that supply the mucous membrane that lines the mouth
ex: nitroglycerine (causes blood vessels to dilate)
How are suppositories administered?
Through intrarectal administration
> most commonly used to administer drugs that might upset a person’s stomach
not common for animals
Forms of inhalation drugs + benefits of inhalation
Vapor, fine mist, gases
> route from lungs to brain is very short, drugs have rapid effects
How can drugs be absorbed directly through the skin?
Through topical administration
> creams, ointments, patches, snorted cocaine is actually topical as well
What makes the sniffing of cocaine a topical administration?
It comes into contact with the nasal mucosa which is a rapid route for topical administration to the brain.
> is called insufflation NOT inhalation
What are the (2) ways that drugs can be administered directly into the brain?
- Intracerebral administration
2. Intracerebroventricular (ICV) administration
Intracerebral administration
A very small amount of drug is injected directly into the brain
Intracerebroventricular administration
Way of getting a widespread distribution of a drug in the brain > is conducted via injection into the cerebral ventricles
What is the most important factor that determines the rate at which drugs can be introduced into the body?
Lipid solubility of the drug
The blood-brain barrier is a barrier only for ______- soluble molecules.
Water
Inactivation and Excretion main points
- Drugs do not remain in the body indefinitely
- Many are deactivated by enzymes in the liver, blood, and brain
- All are eventually excreted, primarily but the kidneys
- Some enzymes transform drug molecules into even more active molecules
What is the best way to measure the effectiveness of a drug?
to plot a dose-response curve
How to plot a dose-response curve
Subjects are given various doses of a drug per body weight of the individual and effects are plotted
Heavier subjects require a _______ quantity of a drug to achieve the same concentration of a small subject.
Larger
Increasingly stronger doses of a drug cause increasingly _______ effects.
Larger
What is the point at which increasing the dose of a drug does not produce any more effect?
Point of maximum effect
What is the margin of safety?
Reflected by the difference between the dose-response curve for its’ therapeutic effects and that for its’ adverse side effects
How to calculate therapeutic index
The ratio of the dose that produces desired effects and the dose that produces toxic effects.
The _________ the therapeutic index, the more care must be taken in prescribing the drug.
Lower
Why do drugs vary in their effectiveness?
- Different drugs (even with the same effects) may have different sites of action.
- The drug’s affinity with its site of action.
What is affinity?
The readiness with which the two molecules join together
A drug with a high affinity will produce effects at a relatively _____ concentration.
Low
What is the most desirable drug?
High affinity for sites of action that produce therapeutic effects and low affinity for sites of action that produce toxic side effects.
Tolerance
When a drug is administered repeatedly, it’s effects will diminish
Sensitization
A drug becomes more and more effective
Withdrawal symptoms
If an individual stops taking the drug that they have become tolerant to, they will experience the opposite effects of the drug itself
What is tolerance the result of?
the body’s attempt to compensate for the effects of the drug
What are the types of compensatory mechanisms?
- Decrease in effectiveness of binding
- either the receptor’s affinity for the drug decreases OR there are less receptors
- prolonged stimulation of receptors causes one or more steps in the coupling process to become less effective
What is sensitization?
Repeated doses of a drug produce larger and larger effects (less likely)
What is a placebo?
An innocuous substance that has no specific physiological effect
What do placebos have the potentiality to do?
To create the mind-body self-healing process
When do we use placebos?
When experimenters want to investigate the behavioral effects of drugs in humans they must use placebos so they can be sure that the behavioral effects they observe are caused by specific effects of the drug
Antagonists
Drugs that block or inhibit the postsynaptic effects
Agonists
Drugs that facilitate postsynaptic effects
Sequence of synaptic activity (1-5)
- Neurotransmitters are synthesized and stored in synaptic vesicles
- Synaptic vesicles travel to the presynaptic membrane
- Axon fires
- Voltage-dependent calcium channels open & allow calcium ions in
- Calcium ions interact with proteins in the synaptic vesicles and cause the release of neurotransmitter
Sequence of synaptic activity (6-8)
after release of neurotransmitter
- Molecules of the neurotransmitter bind with post-synaptic receptors & cause particular ion channels to open
- Opening of ion channels influences an excitatory or inhibitory postsynaptic potentials
- Neurotransmitters experience re-uptake or destruction by enzymes
Effects on production of neurotransmitters (+)
The rate of synthesis/release of a neurotransmitter is increased with the administration of a precursor
- the precursor serves as an agonist
What is a precursor?
Molecules readily available in the diet that only require a small amount of biosynthetic steps to be converted into neurotransmitters
Effects of production of neurotransmitters (-)
A drug my inactivate an enzyme needed to synthesize the neurotransmitter. Therefore the NT cannot be produced.
> drug is an antagonist
Effects on the storage of NT
Drug molecules may bind with a particular site on the transporter and inactivate it. Since the transporters are responsible for pumping NT across the vesicle membrane, there will be no NT in the vesicle when it eventually ruptures against the presynaptic membrane
Effects on the release of NT (-)
Drugs deactivate the proteins that cause synaptic vesicles to fuse with the presynaptic membrane and release their contents into the synaptic cleft
Effects of the release of NT (+)
Some drugs act as agonists and bind with proteins that cause synaptic vesicles to fuse with the membrane to directly trigger release of the NT
Explain how a drug can affect postsynaptic receptors
The drug can bind with a receptor, instead of the NT binding to it, and serve as either an agonist or antagonist
What is a direct agonist?
A drug that mimics the effects of a NT
> the drug attaches to the binding site where the NT usually attaches and opens ion channels
What is a direct antagonist?
A drug that binds with the receptors & do not open the ion channel. They occupy the binding site so that NT cannot bind
Non-competitive binding
Binding of a drug to a site on a receptor but does not interfere with the binding site for the principle NT
Indirect antagonist
A drug that attaches to a binding site on a receptor and interferes with the action of the receptor; does not interfere with the binding site for principle NT
Indirect agonist
A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding site of principle NT
Explain autoreceptors
- How can they be affected?
Autoreceptors regulate the amount of NT that is released
- They can be activated > less NT released
- They can be blocked > more NT released
Effects on reuptake of NT
Drugs can bind with transporter molecules responsible for reuptake and inactivate them > drugs stay in the synapse longer and create the effects of the drug for an extended period of time
Effects on the destruction of NT
The drug binds with the enzyme that normally destroys the NT
Effects on reuptake and destruction of NT are both _____.
Agonists
What are the two general effects of neurotransmitters?
- Depolarization (EPSP)
2. Hyperpolarization (IPSP)
Is glutamate excitatory or inhibitory?
Excitatory
Is GABA inhibitory or excitatory?
Inhibitory
All sensory organs transmit information to the brain through axons whose terminals release _______.
Glutamate
What is the difference between other neurotransmitters and glutamate/GABA?
These other neurotransmitters tend to activate or inhibit entire circuits of neurons involved in particular brain functions
- they are more of modulators than information-transmitters
Example of the modulator vs information-transmitter effect of glutamate/GABA and other NT
AcH activates the cerebral cortex and facilitates learning > the information learned/remembered is transmitted by neurons secreting GABA/glutamate
Where and by who is ACh secreted?
Secreted by efferent axons in the CNS
> found in the CNS, ganglia of the ANS, and the target organs of the parasympathetic branch of the ANS
What does ACh do?
All muscular movement is controlled by the release of ACh
What are synapses of ACh called?
Acetylcholinergic
Other functions of ACh
Dorsolateral pons - REM sleep
Basal forebrain - activating cerebral cortex/facilitating learning
Medial septum- electrical rhythms of hippocampus > formation of memories
What is acetylcholine made of?
- Choline
2. Acetate
How are choline and acetate joined to become ACh?
The acetyl group of acetyl-CoA is transferred to the choline molecule by the enzyme choline acetyltransferase (ChAT).
What are the products of the biosynthesis of acetylcholine?
- Acetylcholine
2. Coenzyme A (CoA)
What two drugs affect the release of AcH?
- Botulinum toxin
2. Black widow spider venom
Botulinum toxin big points
- Prevents the release of AcH (antagonist)
2. VERY toxic…one teaspoon of pure substance can kill entire human population
Black widow spider venom important points
- Stimulates the release of AcH (agonist)
2. Can be fatal but is much less toxic than botulinum toxin
A drug that affect acetylcholinesterase (AChE)
- Neostigmine