PSYC-2900 Chapter 4.1

psychopharmacology

the study of the effect of drugs on the nervous system and behaviour, including drugs of abuse, and therapeutic drugs

drug

exogenous chemical, not needed for normal cellular functioning, that alters function when taken in relatively low doses

drug effects

produce changes in physiological processes and in behaviour

sites of action

the locations where the drug molecules interact with other molecules in the body or with cells

pharmacokinetics

the life cycle of a drug as it moves through the body. comprised of 4 stages: absorption, distribution, metabolism, and excretion

absorption

the first stage of pharmacokinetics in which the drug is administered and absorbed through tissues (e.g. intramuscular injection)

distribution

the second stage of pharmacokinetics in which the drug is distributed throughout the body and blood

metabolism

the third stage of pharmacokinetics in which the drug is changed to an inactive form by enzymes, usually in the liver

excretion

the fourth and final stage of pharmacokinetics in which the drug is excreted in urine by the kidneys

intravenous (IV) injection

a type of route of administration in the absorption stage of pharmacokinetics. the drug is injected into a vein.

• fastest route, as the drug is absorbed and distributed immediately

• more invasive, increased care and need skill

• little time for correction if the individual is sensitive/reactive to the drug

intraperitoneal (IP) injection

a type of route of administration in the absorption stage of pharmacokinetics. the drug is injected into the peritoneal (abdominal) cavity.

• rapid absorption, but slower than IV

• commonly used as a method of drug delivery in small lab animals

intramuscular (IM) injection

a type of route of administration in the absorption stage of pharmacokinetics. the drug is injected directly into a large muscle (e.g. upper arm, thigh, glute).

• absorption is through the capillary beds in the muscle

subcutaneous (SC) injection

a type of route of administration in the absorption stage of pharmacokinetics. the drug is injected under the skin.

epidural

a type of route of administration in the absorption stage of pharmacokinetics. the drug is delivered directly into cerebrospinal fluid (CSF) to bypass the blood brain barrier (BBB)

intracerebral administration

a type of route of administration in the absorption stage of pharmacokinetics. a very small amount of drug is injected directly into a specific area of the brain to bypass the blood brain barrier (BBB)

• allows for more local distribution of the drug

intracerebroventricular (ICV)

a type of route of administration in the absorption stage of pharmacokinetics. the drug is injected directly into the ventricles of the brain to bypass the blood brain barrier (BBB)

• wider distribution through the brain

• rarely used in humans (e.g. antibiotics to treat certain infections)

oral administration

a type of route of administration in the absorption stage of pharmacokinetics. the drug travels through the digestive tract and is absorbed into the blood, sometimes undergoing first-pass metabolism.

• some drugs would be destroyed by stomach acid or digestive enzymes

first-pass metabolism

a process of absorbing drugs that takes place in the liver, in which some drug molecules are eliminated so that fewer are distributed to the body

sublingual administration

a type of route of administration in the absorption stage of pharmacokinetics. the drug crosses the mucous membrane that lines the mouth under the tongue

• faster than oral and less risk of digestive side effects

inhalation

a type of route of administration in the absorption stage of pharmacokinetics. the drug crosses to the blood stream through the lungs

• short route to brain and doesn’t involve first-pass metabolism

topical administration

a type of route of administration in the absorption stage of pharmacokinetics. the drug crosses an external membrane such as skin or mucous membrane of nasal passage (insufflation)

lipid solubility

the most important factor affecting the rate of drug distribution. it is whether or not the drug molecules can pass through the cells of the capillaries

e.g. compared to morphine, heroin has more of this, and therefore has faster effects

enzymes

metabolises and deactivates drugs in the body, sometimes transform molecules into more active versions

kidneys

excretes and removes drugs from the circulatory system

sites of action

a factor of drug effectiveness. the location of the body in which the neurons are suppressed by the drug provides greater/lesser effects

drug site of action interaction

a factor of drug effectiveness, including drug affinity, readiness with which two molecules join together.

• high affinity drugs produce effects at low concentrations (locating and binding to the site is fast/easy)

• low affinity drugs require higher concentrations

drug effectiveness

measured with a dosage response curve to find the maximum effect

therapeutic index

in drug effectiveness, measures the drug’s margin of safety, described as a ratio between doses that produce toxic effects in 50% of animals, and doses that produce desired effect(s) in 50% of animals

e.g. if the therapeutic index of a drug is 5.0, it is 5x more toxic than it is effective (larger numbers mean safer drug)

tolerance

a factor of drug effectiveness. a diminished effect due to repeated administration.

• larger doses needed to have an effect

• common in drugs of abuse

• receptor downregulation

receptor downregulation

a compensatory mechanism that is a decrease in receptor binding effectiveness, and a less effective coupling process

withdrawal symptoms

effects that occur with immediate cessation of repeated administration of drugs.

• effects are generally the opposite of the drug effects

sensitization

a more enhanced effect due to repeated drug administration

e.g. repeated injections of cocaine are more likely to produce movement disorders

placebo

an inactive substance that may have physiological or psychological effects

placebo effect

an effect caused by a person's expectations/belief in the treatment, not by the treatment itself

• must be accounted for in order to determine which effects are due to the actual drug

drug binding

occurs upon reaching the site of action, the drug produces an effect by binding to other molecules or cells

synaptic transmission

a process that is affected by drugs that affect behaviour. occurs in the pre and postsynaptic neuron

synaptic transmission in the presynaptic neuron

1. neurotransmitter is synthesized

2. neurotransmitter is stored in vesicles and eventually docks at the presynaptic membrane

3. an action potential travels down the axon, causing Ca²⁺ channels to open and interact with docking proteins, initiating neurotransmitter release into the synaptic cleft

synaptic transmission in the postsynaptic neuron

4. the neurotransmitter crosses the synaptic cleft and binds with receptors on the postsynaptic membrane, causing ion channels to open (leading to excitatory postsynaptic potential (EPSP) or inhibitory postsynaptic potential (IPSP))

5. the neurotransmitter is removed from the synaptic cleft through reuptake or enzymatic deactivation

agonist (AGO)

drugs that facilitate postsynaptic effects by binding with proteins and triggering the release of neurotransmitters

antagonist (ANT)

drugs that block or inhibit postsynaptic effects by preventing the release of neurotransmitters from the terminal button

competitive binding

when drugs use the same receptor site as the neurotransmitter. these drugs include direct agonists and direct antagonists

direct agonist

a drug that participates in competitive binding and binds directly to the receptor site of a neurotransmitter and acts like the neurotransmitter

direct antagonist

a drug that participates in competitive binding by blocking the neurotransmitter receptor site and preventing a) opening of the ion channel and b) triggering intracellular events

noncompetitive binding

when binding sites allow other substances (e.g. neuromodulator drugs) to bind to the postsynaptic membrane, including indirect agonists and indirect antagonists

indirect agonist

a drug that participates in noncompetitive binding by facilitating the opening of ion channels, but also allows binding of the neurotransmitter

indirect antagonist

a drug that participates in noncompetitive binding by preventing ion channels from opening, but still allows binding of the neurotransmitter

reuptake and deactivation

with neurotransmitters, a drug effect on synaptic transmission by

• the drug attaching to the terminal membrane transporters and blocking reuptake

• the drug binding to enzymes, preventing neurotransmitter deactivation

production alteration

with neurotransmitters, a drug effect on synaptic transmission by the drug acting as a precursor (AGO) or inactivating enzymes needed for synthesis (ANT)

storage and release alteration

with neurotransmitters, a drug effect on synaptic transmission by

• blocking vesicle transporters so that they cannot refill with neurotransmitters

• preventing release from the terminal button

• triggering release

indirect/direct binding

with neurotransmitters, a drug effect on synaptic transmission by stimulating or blocking receptor actions

binding of autoreceptors

with neurotransmitters, a drug effect on synaptic transmission by modulating release by

• stimulation indicating there is a lot of the neurotransmitter, and slowing synthesis

• blockage interrupting the feedback loop, continuing synthesis