Study Set Content:
is an acute (sudden) decrease in the response to a drug after its administration.
Tachyphylaxis
TWO MAJOR CATEGORIES OF DESENSITIZATION
Homologous Desensitization
Heterogenous Desensitization
Refers to loss of responsiveness exclusively of the receptors that have been exposed
Homologous Desensitization
Refers to the process by which desensitization of one receptor by its agonists also results in desensitization of another receptor that has not been directly activated by the agonist in question.
Heterogenous Desensitization
is the principal route by which this occurs.
The norepinephrine transporter (NET
It is particularly efficient in the synapses of the heart, where up to ____ is removed by the NET.
90% of released norepinephrine
Remaining synaptic norepinephrine may escape into the extrasynaptic space and enter the bloodstream or be taken up into extraneuronal cells and metabolized by
catechol-o- methyltransferase (COMT).
where synaptic structures are less well developed, removal may still be 60% or more by NET. The NET, often situated on the presynaptic neuronal membrane, pumps the synaptic norepinephrine back into the neuron cell cytoplasm.
Vasculature,
In the cell, this norepinephrine may reenter the vesicles or undergo metabolism through monoamine oxidase (MAO) to
dihydroxyphenylglycol(DHPG).
Commonly used drugs such as antidepressants, amphetamines, and cocaine target monoamine ____ transporters with different potencies.
(norepinephrine, dopamine, and serotonin)
A shows the mechanism of reuptake of norepinephrine (NE) back into the noradrenergic neuron via the norepinephrine transporter (NET), where a proportion is sequestered in presynaptic vesicles through the
vesicular monoamine transporter [VMAT).
show the effects of amphetamine and cocaine on these pathways
B and C
may be considered the parent compound from which sympathomimetic drugs are derived (Figure 9-4).
Phenylethylamine
This compound consists of a
benzene ring with an ethylamine side chain.
Substitutions may be made:
ubstitution by -OH groups at the 3 and 4 positions yields sympathomimetic drugs collectively known as
(1) the benzene ring.
(2) the terminal amino group
(3) the a or ß carbons of the ethyl amino chain. catecholamines.
have prominent cardiovascular effects because of widespread distribution of and ß adrenoceptors in the heart, blood vessels, and neural and hormonal systems involved in blood pressure regulation.
Sympathomimetics
Any effect these agents have on blood pressure is counteracted by compensatory baroreflex mechanisms aimed at
restoring homeostasis
The endogenous catecholamines, ____, have complex cardiovascular effects because they activate both a and 3 receptors. A. Effects of Alpha 1 -Receptor Activation
norepinephrine and epinephrine
are widely expressed in vascular beds, and their activation leads to arterial and venous vasoconstriction.
Alpha 1 receptors
A relatively pure a agonist such as ____ increases peripheral arterial resistance and decreases venous capacitance. The enhanced arterial resistance usually leads to a dose-dependent rise in blood pressure (Figure 9-6).
phenylephrine
