20.6h Pharmacodynamics - Actions of Medications

pharmacodynamics

When we consider a medication’s pharmacodynamics, or effects on the body, we are specifically interested in its mechanisms of action and the relationship between its concentration and its effect.

four

Medications can act in (?) different ways.

receptor site

They can bind to a (?), change the physical properties of cells, chemically combine with other chemicals, or alter a normal metabolic pathway.

physiochemical interaction

Each of these actions involves a (?) between the medication and a functionally important molecule in the body.

receptor

Most medications operate by binding to a (?); almost all medication receptors are glycoprotein molecules on the surfaces of cells (cell membranes).

normal regulatory stimulation/inhibition function

They are part of the body’s (?) and can be stimulated or inhibited by chemicals.

Channel-linked receptors

(?) are located on cell membranes and bind a ligand (a substance that forms a complex with a biomolecule to serve a biological purpose) and opens a channel through the membrane that allows specific ions to pass through.

acetylcholine

Examples of substances that use these channels include (?), nicotine, and gamma-aminobutyric acid (GABA).

Enzyme-linked receptors

(?) are cell-surface receptors with intracellular domains that are associated with an enzyme.

signal

When a ligand binds to the extracellular portion, a (?) is transferred through the membrane that activates the enzyme and initiates a chain of events within the cell that eventually leads to a response.

insulin receptor

An example of enzyme-linked receptors is (?).

nuclear hormone receptors

Responsible for detecting steroid and thyroid hormones and certain other molecules, (?) receptors receptors then interact with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.

G-protein-linked receptors

(?) have three components: a receptor, a G protein (a type of protein that acts as a molecular “switch” inside cells), and an effector (i.e., enzyme or ion channel).

activated G-protein

The (?) then interacts with either an ion channel or an enzyme in the membrane.

adrenergic medications

Many substances including (?), opiates, and many others utilize these receptors.

medication

Each different receptor’s name generally corresponds to the type of (?) that stimulates it.

opioid receptor

For example, if an opiate stimulates the receptor, it is an (?).

generic name

When multiple medications stimulate the same receptor, standard practice is to use the (?).

affinity

The force of attraction between a medication and a receptor is their (?).

greater the affinity

The (?), the stronger is the bond.

strength

Different medications can bind to the same type of receptor site, but the (?) of their bond can vary.

shape

The binding site’s (?) determines its receptivity to other chemicals whether they are medications or endogenous substances.

specific

These binding sites are relatively (?)—a nonopiate medication generally does not affect an opiate binding site, although occasionally a medication with a similar receptor binding site unexpectedly cross reacts.

subtypes

Receptors can also have (?).

adrenergic receptors

At least five subtypes of (?), for example, are important to prehospital practice.

efficacy

A medication’s pharmacodynamics also involve its ability to cause the expected response, or (?).

efficacies

Just as different medications can have different affinities for a site, they can also have different (?); that is, medication A can cause a stronger response than medication B.

Affinity and efficacy

(?) are not directly related.

stronger response

Medication A can cause a (?) than medication B even though medication B binds to the receptor site more strongly than medication A.

chemical change

When a medication binds with its specific type of receptor, a (?) occurs that ultimately leads to the medication’s effect.

stimulate or inhibit

In most cases, medications either (?) the cell’s normal biochemical actions.

new function

In fact, a medication cannot impart a (?) to a cell.

receptor

Some medications can interact with a (?) and directly result in the desired effect.

second compound

Other medications, however, can interact with a receptor and cause the release or production of a (?).

second messenger

This secondary compound, or (?), includes such compounds as calcium or cyclic adenosine monophosphate (cAMP), which is the most common second messenger.

multitude of effects

It has a (?) inside the cell.

endocrine system

These secondary messengers are particularly important in the (?) because they occur principally in endocrine glands.

cAMP

Once (?) is formed inside the cell, it activates still other enzymes, usually in a cascading action.

cascading action

That is, the first enzyme activates another enzyme, which activates a third enzyme, and so forth.

amplifies

This is important because the cAMP (?) the action so that even a small amount of a medication (or hormone) acting on the cell surface can initiate a powerful, cascading, activating force for the entire cell (Figure 20-8).

number of receptors

The (?) on a target cell usually does not remain constant on a daily basis or even from minute to minute.

receptor proteins

This is because the (?) are often destroyed during the course of their function.

remanufactured

At other times, they are either reactivated or (?) by the protein-manufacturing mechanism of the cell.

available receptors

Binding a medication (or hormone) to a target cell receptor causes the number of (?) to decrease.

down-regulation of the receptors

This process known as (?) results in a decreased responsiveness of the target cell to the medication or hormone as the number of available active receptors decreases.

up-regulation

In other cases, but less commonly, a medication (or hormone) can cause the formation of more receptors than normal.

up-regulation

This process, (?), increases the target tissue’s sensitivity to the particular medication or hormone.

agonists and antagonists

Chemicals that stimulate a receptor site generally fall into two broad categories—(?) .

Agonists

(?) bind to the receptor and cause it to initiate the expected response.

Antagonists

(?) bind to a site but do not cause the receptor to initiate the expected response.

agonist–antagonists

Some medications, (?) (also called partial agonists), can do both.

Nalbuphine (Nubain)

(?), for instance, stimulates some of the opioid agonists’ analgesic properties but partially blocks others such as respiratory depression (Figure 20-9).

lock

Receptor-mediated medication actions work like a (?) (the receptor) and key (the agonist).

key

Putting the (?) in the lock and turning it opens the lock.

antagonist

An (?) is like a key that fits into the lock but cannot turn and cannot open it.

maximal effect

Target tissues generally have many receptors, so to take the analogy another step, imagine that to get (?) , a single key (agonist) must move around and open many doors (trigger many biochemical responses).

agonist–antagonist

An (?) would be a key that unlocks and opens a door but gets stuck in the lock.

blocks

That is, the medication causes the expected effect, but that medication also (?) another medication from triggering the same receptor.

competitive antagonism

This (?) is considered surmountable because a sufficiently large dose of the agonist can overcome the antagonism.

Noncompetitive antagonism

(?) can also occur.

door is barred

Continuing the lock, key, and door analogy, imagine that the (?).

insurmountable

This antagonism would be (?); no amount of agonist could overcome it.

different site

Noncompetitive antagonism occurs because the binding of the antagonist at a (?) causes a deformity of the binding site that actually prevents the agonist from fitting and binding.

Irreversible antagonism

(?) can also occur when a competitive antagonist permanently binds with a receptor site.

no amount of agonist

When this occurs, (?) will stimulate the receptor.

new receptors

For the effects of such an antagonist to wear off, the body must create (?).

antagonists

Two medications can appear to be (?) while actually acting independently.

physiologic antagonism

This (?) can occur when one medication’s effects counteract another’s.

net effect

Although neither agent chemically affects the other, their (?) is antagonistic.

opiate receptor

An example of a receptor, agonist, antagonist, and agonist–antagonist can be described using an (?).

natural endorphins

These receptors occur naturally in the brain and respond to (?).

Morphine sulfate

(?) acts as an agonist.

pain relief

It binds to the opiate receptor and causes the expected response of (?).

Naloxone (Narcan)

(?) acts as an antagonist.

pain relief

It binds to the opiate receptor but does not initiate the (?).

blocks

It prevents morphine sulfate from binding to the site and thus effectively (?) the morphine and its response.

nalbuphine (Nubain)

If the patient is given (?), an agonist–antagonist, it binds to the opiate receptor and relieves pain, but it is less efficacious than morphine.

nalbuphine

The (?) blocks morphine from the receptor like an antagonist but stimulates the receptor on its own like an agonist, although to a lesser extent.

physical properties

Some medications change the (?) of a part of the body.

osmotic balance

Medications that change the (?) across membranes are good examples of this type of medication action.

mannitol (Osmotrol)

The osmotic diuretic (?), for instance, increases urine output by increasing the blood’s osmolarity, or osmotic “pull.” This increased osmolarity triggers the normal regulatory systems to decrease water reabsorption in the renal tubules, thereby reducing the total amount of water in the body.

chemical reactions

Medications that participate in (?) that change the chemical nature of their substrates (the chemical or substance on which a medication acts) play a large role in EMS practice.

isopropyl alcohol

For example, (?), which is often used to disinfect skin before percutaneous needle insertion for phlebotomy or IV cannulation, denatures the proteins on the surface of bacterial cells.

bacteria

This ruptures the cells, destroying the (?).

Antacids

(?) are another example.

chemically neutralizing

They act by (?) the hydrochloric acid in the stomach.

sodium bicarbonate

Given intravenously, (?), chemically neutralizes some of the acids in the bloodstream, effectively making the blood more alkalotic.

chemical analogs

Some anticancer and antiviral medications are (?) of normal metabolic substrates.

counterfeit incorporation mechanism

In a process that has been dubbed a (?), these medications can be incorporated into the products of metabolism of cancer cells.

expected substrate

Because these medications are not really the (?), the anticipated product either cannot form or, if formed, is substantially or completely inactive.