Pharmacology - Intro To Ans

Front 1

two main neurotransmitters that operate in the autonomic system

Back 1

acetylcholine
noradrenaline

Front 2

all motor fibers leaving CNS release ___ which acts on ___ receptors

Back 2

acetylcholine
nicotinic

Front 3

all postganglionic parasympathetic fibers release ___, which acts on ___ receptors

Back 3

acetylcholine
muscarinic

Front 4

all postganglionic sympathetic fivers (with one exception:___) release ___, which may act on either ___ or ___.

Back 4

(exception: sympathetic innervation of sweat glands - ACh acting on muscarinic receptors)
-noradrenaline - alpha or beta adrenoreceptors

Front 5

inotropy

Back 5

contractility

Front 6

Voluntary nervous system -neurotransmitter
-agonist
-antagonist

Back 6

Neurotransmitter: ACh
Agonist: nicotine
Antagonist: curare

Front 7

Parasympathetic nervous system
-neurotransmitter
-agonist
-antagonist

Back 7

Neurotransmitter: ACh
Agonist:
-at ganglion: nicotine
-at SM, glandular cell: muscarine
Antagonist:
-at ganglion: hexamethonium (C6)
-at SM, glandular cell: atropine

Front 8

Sympathetic nervous system
-neurotransmitter
-agonist
-antagonist

Back 8

Neurotransmitter:
-at ganglion: ACh
at SM, glandular cell: noradrenaline
Agonist:
-at ganglion: nicotine
-at SM, glandular cell: alpha, beta agonist
Antagonist:
-at ganglion: hexamethonium (C6)
-at SM, glandular cell: alpha, beta antagonist

Front 9

Co-transmitters

Back 9

Additional substances that are packaged with original neurotransmitter and released when we stimulate nerves. ATP is one important substance. It acts as a neurotransmitter in it’s own right.

Front 10

Neuropeptide Y

Back 10

36 amino acid peptide neurotransmitter found in brain and ANS
augments vasoconstrictor effects of noradrenergic neurons

Front 11

Vasoactive Intestinal Peptide

Back 11

28 amino acids
parasympathetic actions of vasodilation in GI tract, sweat, salivary glands, penis

Front 12

Tyrosine Hydroxylase

Back 12

an oxygenase, found in the cytosol of all cells containing catecholamines is the enzyme that catalyzes the rate-limiting step in the production of catecholamines

converts tyrosine to DOPA, which is then converted to dopamine, which is then converted to norepinephrine

Front 13

AAADC

Back 13

Aromatic Amino Acid Decarboxylase
catalyzes decarboxylation reaction that converts DOPA to dopamine, and 5-HTP to serotonin

Front 14

VMAT

Back 14

Vesicular Monoamine Transporter
Transport protein located in presynaptic cells that works on synaptic vesicles.

Front 15

DBH

Back 15

Dopamine Beta-Hydroxylase
Will convert dopamine to norepinephrine. When DBH is not present, the neurotransmitter will be dopamine.

Front 16

Catecholamines

Back 16

chemical compounds derived from the amino acid tyrosine - most abundant catecholamines are epinephrine, norepinephrine and dopamine
these are hormones that are released by the adrenal glands in situations of stress such as psychological stress or low blood sugar levels

Front 17

VMAT1

Back 17

-transports the monoamine neurotransmitters into synaptic vesicles
-in chromaffin cells, it is responsible for transporting newly synthesized epinephrine from cytosol back into chromaffin granules in prep for release
-also ships NE out of granules of chromaffin cells so that it can be acted upon by PNMT in the cytosol

Front 18

Chromaffin Cells

Back 18

-neuroendocrine cells found in the medulla of the adrenal gland
-secrete epinephrine, norepinephrine
-where the enzyme dopamine-hydroxylase catalyzes the conversion of dopamine to noradrenaline

Front 19

PNMT

Back 19

Phenylethanolamine N-methyltransferase
-an enzyme found in the adrenal medulla that converts Norepinephrine Epinephrine

Front 20

Activation of the nicotinic receptors on the adrenal medulla will___.

Back 20

Activate and release adrenaline.

Front 21

Adrenaline is made by:

Back 21

adding another methyl group to noradrenaline, done by PMNT in the cytosol of the adrenal medulla

Front 22

Norepinephrine (noradrenaline)

Back 22

-a catecholamine with dual roles as a hormone and a neurotransmitter
-synthesized from dopamine by dopamine β-hydroxylase
-released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons
-along with epinephrine, underlies flight-or-flight response

Front 23

Reserpine

Back 23

Blocks VMAT, which normally transports free norepinephrine, serotonin, and dopamine from the cytoplasm of the presynaptic nerve into vesicles for subsequent release into the synaptic cleft. The unprotected neurotransmitters are then metabolized by MAO and therefore never reach the synapse.

Front 24

MAO

Back 24

Monoamine oxidases are enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. This deactivates the neurotransmitters.

Front 25

NET/NAT

Back 25

Neuroepinephrine Transporter
-monoamine transporter that transports the neurotransmitter noradrenaline from the synapse back to its vesicles for storage until later use

Front 26

Uptake 1

Back 26

presynaptic uptake
high-affinity
saturable
Na-dependent
Substrates: NA>A
Inhibitors: Imipramine, cocaine

Front 27

Uptake 2

Back 27

location: cell membranes of non-neuronal cells
low-affinity
not saturable
not Na-dependent
Substrates: A>NA
Inhibitors: corticosteroids

Front 28

COMT

Back 28

Catechol-O-methyl transferase
-an intracellular enzyme located in the postsynaptic neuron involved in the inactivation of the catecholamine neurotransmitters
-introduces a methyl group to the catecholamine

Front 29

Pheochromocytoma

Back 29

-neuroendocrine tumor of the adrenal medulla (originating in the chromaffin cells), or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually epinephrine and norepinephrine
-can be detected by testing metanephrines in urine (product of COMT)

Front 30

Tyramine

Back 30

-monoamine compound derived from tyrosine
-can cause the release of stored monoamines, such as dopamine, norepinephrine, and epinephrine

Front 31

Amphetamine

Back 31

-a group of drugs that act by increasing levels of norepinephrine, serotonin, and dopamine in the brain
-has been shown to both diffuse through the cell membrane and travel via the dopamine transporter (DAT) to increase concentrations of dopamine in the neuronal terminal

Front 32

Phenelzine

Back 32

Monoamine oxidase inhibitor (MAOI) used as an antidepressant drug
-similar to other substrates of MAO
-MAO tries to oxidize phenelzine, which then binds covalently to the enzyme, thus inactivating it irreversibly

Front 33

MAO-A

Back 33

-preferentially deaminates norepinephrine and serotonin
-inhibited by clorgiline and befloxatone

Front 34

MAO-B

Back 34

-preferentially degrades benzylamine and phenylethylamine
-inhibited by: selegiline (deprenyl), rasagiline

Front 35

Adrenergic Receptors
-two main groups?
-subtypes?

Back 35

-class of G protein-coupled receptors that are targets of the catecholamines
-ligands are adrenaline and noradrenaline and are activated by these
-main groups: alpha and beta
-subtypes of alpha: alpha1 and 2
-subtypes of beta: beta1, 2, and 3

Front 36

α1 receptor mechanism

Back 36

α1 couples to Gq, which results in increased intracellular Ca2+ which results in e.g. smooth muscle contraction

Front 37

α2 receptor mechanism

Back 37

α2 couples to Gi, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction.

Front 38

β receptor mechanism

Back 38

β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis

Front 39

β1 agonist action

Back 39

heart muscle contraction

Front 40

β2 agonist action

Back 40

smooth muscle relaxation

Front 41

β3 agonist action

Back 41

enhance lipolysis

Front 42

Alpha receptors cause vaso___
Beta receptors cause vaso___

Back 42

alpha = vasoconstriction
beta = vasodilation

Front 43

Prazosin

Back 43

-alpha-adrenergic blocker, which lowers blood pressure by relaxing blood vessels
-prazosin, specifically, is selective for the alpha-1 receptors on vascular smooth muscle. These receptors are responsible for the vasoconstrictive action of norepinephrine, which would normally raises blood pressure. By blocking these receptors, prazosin reduces blood pressure.

Front 44

Phentolamine

Back 44

-Regitine
-reversible, nonselective alpha-adrenergic antagonist
-primary action is vasodilation due to α1 blockade
-primary application is the control of hypertensive emergencies, most notably due to phaeochromocytoma

Front 45

Isoprenaline

Back 45

-structurally similar to epinephrine but acts selectively on beta receptors, activating β1 and β2 receptors equally
-primary use is for bradycardia or heart block. By activating β1-receptors on the heart, it induces positive chronotropic, dromotropic, and inotropic effects.

Front 46

Propranolol

Back 46

-a non-selective beta blocker mainly used in the treatment of hypertension
-blocks the action of epinephrine on both β1- and β2-adrenergic receptors

Front 47

How does Clonidine lower blood pressure?

Back 47

1. Presynaptic effect and reduced NE release from sympathetic post-ganglionic neurons.
2. CNS effect: activation of alpha-2 receptors in cardiovascular regulatory sites in medulla --> reduced sympathetic tone.

Hint 47

alpha-2 agonist

Front 48

Phenylephrine

Back 48

an α1-adrenergic receptor agonist causing vasoconstriction and smooth muscle contraction

Front 49

Yohimbine

Back 49

-A selective competitive α2 adrenergic receptor antagonist. The α2 receptor is responsible for sensing adrenaline and noradrenaline and telling the body to decrease its production as part of a negative feedback loop. Blocking α2 causes an increase in the release of NE.
-Yohimbine helps to raise libido.

Front 50

Salbutamol (Albuterol)

Back 50

A short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease.

Front 51

Dobutamine

Back 51

Direct stimulation of β1 receptors of the sympathetic nervous system. Specifically of the heart, increasing contractility and CO. Since it does not act on dopamine receptors to induce the release of NE (another α1 agonist), dobutamine is less prone to induce hypertension than is dopamine.

Front 52

Atenolol

Back 52

A β1 receptor selective antagonist, a drug belonging to the group of β-blockers.

Front 53

Location of β1-Adrenergic receptors

Back 53

mainly in the heart and in the kidneys

Front 54

Location of β2-Adrenergic receptors

Back 54

located mainly in the lungs, GI tract, liver, uterus, vascular smooth muscle, and skeletal muscle (note that there is a small population on the heart)

Front 55

Location of β3-Adrenergic receptors

Back 55

fat cells

Front 56

Prazosin

Back 56

Prazosin is an α-adrenergic blocker, selective for α1 receptors on vascular smooth muscle. These receptors are responsible for the vasoconstrictive action of NE, which would normally raise bp. By blocking these receptors, prazosin reduces blood pressure.