Sympathomimetics

Front 1

All Sympathomimetics, whether indirectly or directly increase activity of?

Back 1

Adrenergic receptors. They are adrenoreceptor-activating drugs. They increase the activity of adrenergic receptors.

Front 2

Explain the two mechanisms of indirect-acting Sympathomimetic drugs.

Back 2

1. Displacement of stored catecholamines from the adrenergic nerve terminal
2. Inhibition of catecholamines reuptake from the synaptic cleft back into the presynaptic neuron.

Front 3

What is the overall effect of indirect-acting sympathomimetic drugs?

Back 3

In both cases, the overall effect is an increase in concentration and duration of action of catecholamine released into synaptic cleft.

Front 4

Which drug is selective for binding to alpha-1 adrenergic receptors?

Back 4

Phenylephrine

Front 5

Alpha-1 adrenergic receptors are coupled to ________ __ via __ _____.

Back 5

Alpha-1 adrenergic receptors are coupled to phospholipase C via G proteins.

Front 6

What results when there is stimulation of alpha-1 receptors?

Back 6

Stimulation of alpha-1 receptors results in activation of the G coupling protein, which in turn activates phospholipase C leading to release of IP3 (inositol 1,4,5-triphosphate). IP3 stimulates the release of stored calcium, leading to activation of calcium-dependent kinases.

Front 7

What is the overall effect of alpha-1 receptor stimulation?

Back 7

contraction. For example, alpha-1 stimulation results in vascular smooth muscle contraction, pupillary dilator muscle contraction, prostate contraction, and cardiac contractile cell contraction.

Front 8

TRUE/FALSE. Alpha-2 and Alpha-1 receptors play a significant role in the CNS.

Back 8

FALSE. Only alpha-2 receptors play a significant role in the CNS.

Front 9

Alpha-2 receptors are coupled to _____ ____ via an ______ __ _____.

Back 9

Alpha-2 receptors are coupled to adenylyl cyclase via an inhibitory G protein.

Front 10

What is the overall effect of alpha-2 adrenergic receptors?

Back 10

Alpha-2 adrenergic receptors have the overall effect of inhbiting adenylyl cyclase, resulting in a decrease in intracellular levels of cyclic AMP (cAMP).

Front 11

Explain the autoinhibiton of neurotransmitter release which is an important effect of alpha-2 receptors.

Back 11

Alpha-2 receptors are located on the presynaptic nerve endings of the nervous system, and stimulation of these receptors leads to a decrease in release of neurotransmitter from the nerve ending (this type of receptor is called an autoreceptor)

Front 12

What occurs in the endocrine system when alpha-2 receptors are stimulated?

Back 12

Stimulation of alpha-2 receptors in the endocrine system:
-leads to a decrease in insulin secretion and renin secretion

Front 13

What occurs in the GI tract when alpha-2 receptors are stimulated?

Back 13

-leads to a decrease in muscle activity indirectly by functioning as autoreceptors on presynaptic adrenergic nerve terminals that prevent release of catecholamine neurotransmitters.

Front 14

Beta-adrenergic receptor have a biochemically opposite effect of which receptors?

Back 14

alpha-2 adrenergic receptors

Front 15

Beta receptors are coupled to ____ _____ by a ________ __ _____.

Back 15

Beta receptors are coupled to adenylyl cyclase by a stimulating G protein.

Front 16

The effect of decreasing cAMP in alpha-2 receptors depends on?

Back 16

The tissue site where alpha-2 receptors are stimulated.

Front 17

Stimulation of beta receptors leads to the synthesis of?

Back 17

second messenger molecule cAMP

Front 18

The effect of cAMP synthesis secondary to beta receptor stimulation depends on?

Back 18

Both the tissue site and the subtye of beta receptor that is stimulated.

Front 19

Both beta-1 and beta-2 stimulation in the heart lead to?

Back 19

influx of calcium into cells, causing an increase in both cardiac pacemaker cell activity (positive chronotrophic effect) and cardiac contractility (positive inotrophic effect).

Front 20

In the respiratory, uterine, and vascular tissues which receptors (beta-1, beta-2, or both) relaxes smooth muscle?

Back 20

beta-2 receptors

Front 21

What are two sympathomimetic drugs that are also endogenous compounds?

Back 21

Epinephrine and norepinephrine

Front 22

Most sympathomimetics are chemical variations of which two drugs?

Back 22

epinephrine and norepinephrine. For all of these agents, the parent compound may be considered to be phenylethylamine.

Front 23

Chemical substitution of phenylethylamine alters what 3 things?

Back 23

-Duration of action, receptor selectivity, and susceptibility of sympathomimetics to metabolism by MAO and COMT.

Front 24

Hydroxyl substitution at the 3 and 4 positions of phenylethylamine results in drugs with?

Back 24

High affinity for adrenergic receptors but a relatively short duration of action dur to rapid inactivation by COMT

Front 25

What happens when there is an addition of a short carbon chain, such as a methyl or isopropyl group, onto the amine position of the phenylethylamine?

Back 25

This increases the selectivity of the resulting drug for beta-receptors.

Front 26

Which endogenous compound has higher selectivity for beta-receptors due to the addition of a carbon chain onto the amine position of phenylethylamine?

Back 26

epinephrine

Front 27

What happens when there is chemical substitution at the alpha carbon on phenylethylamine?

Back 27

It decreases susceptibility of the resulting drug to degradation by monoamine oxidase (MAO). Overall, this chemical substitution increases the duration of action of sympathomimetics.

Front 28

If there is replacement of one of the hydroxyl groups of the catecholamine with a hydroxymethyl group what happens?

Back 28

This increases beta-2 selectivity and prevents metabolism by COMT.

Front 29

Name 2 drugs which are beta-2 selective agonsts, they replaced one of the hydroxyl groups of the catecholamine with a hydroxymethyl group.

Back 29

Albuterol and Levalbuterol

Front 30

What happens when the position of the hydroxyl groups moves on the catecholamine ring.

Back 30

This renders the drug non-catecholamine and prevents metabolism by COMT.

Front 31

Which beta-2 selective agonist hydroxyl group is at a different position on the catecholamine ring.

Back 31

Metaproterenol

Front 32

What happens when there is an addition of a long carbon-based chain onto the amine position? Name one?

Back 32

This results in a ver long-acting beta-2 selective agonist. For example: Salmeterol.

Front 33

Which drug is marketed as a single enantiomer instead of a racemic mixture?

Back 33

Levalbuterol which consists of the active R-enantiomer of albuterol; in some patients, the adverse effects related to S-albuterol may be avoided by giving levalbuterol instead.

Front 34

How is albuterol marketed?

Back 34

racemic mixture. R- (acitve) and S-enantiomers (inactive).

Front 35

Vascular smooth muscle of the cardiovascular system contains which receptor types?

Back 35

Alpha and beta-2 adrenergic receptors.

Front 36

What does acitvation of alpha receptors by pure alpha agonist cause?

Back 36

vasoconstriction, leading to an increase in arterial resistance

Front 37

What does an increase in arterial resistance lead to?

Back 37

An increase in arterial resistance typically leads to a dose-dependent rise in blood pressure.

Front 38

What will happen to the heart to compensate for the increase in arterial pressure sensed by the brain.

Back 38

The heart will slow down. Therefore, peripherally-actiing alpha agonist do not always cause a brisk rise in blood pressure, especially in patients who are already hypotensive.

Front 39

Activation of beta-2 receptors in the vasculature in the cardiovascular system results in?

Back 39

Relaxation of vascular smooth muscle which will lower blood pressure, and may result in reflex tachycardia as the heart rate rises to compensate for the fall in blood pressure.

Front 40

What happens to the heart when there is activation of beta-receptors.

Back 40

Activation of beta-receptors in the heart causes an increase in contractility (positive inotrophic effect) and an increased firing rate of pacemaker cells (positive chronotrophic effect).

Front 41

How do beta-1 and beta-2 agonist activity effect peripheral resistance?

Back 41

Sympathomimetics with significant beta-1 and beta-2 agonist activity will increase the heart rate (beta-1 activity in the heart) but decrease peripheral resistance (beta-2 activity in the vasculature), leading to an overall effect of maintaining or slightly increasing systolic BP while significantly decreasing diastolic BP due to diastolic runoff.

Front 42

How do alpha adrenergic agonists affect the eye?

Back 42

1. Mydriasis (pupil dilation) caused by activation of alpha receptors in the pupillary dilator muscle of the iris (contraction of this muscle dilates the pupil)
2. Increase in the outflow of aqueous humor from the eye, leading to decrease intraocular pressure, and
3. vasoconstriction of blood vessels in the eye, resulting in a decongestant effect in the eye.

Front 43

How do beta-adrenergic agonists affect the eye?

Back 43

Increase the production and secretion of aqueous humor into the eye, resulting in increased intraocular pressure

Front 44

Which type of receptors are in the upper respiratpry tract?

Back 44

Alpha receptors

Front 45

What do Alpha agonist cause in the upper respiratory tract?

Back 45

vasoconstriction, which is a useful effect for relieving upper respiratory tract congestion (e.g, nasal congestion)

Front 46

Which receptors are in the lower respiratory tract?

Back 46

Beta-2 receptors

Front 47

Stimulation of beta-2 receptors by beta agonists cause what to occur in the upper respiratory tract?

Back 47

bronchodilation, an effect that is very useful in the pharmacological treatment of airway diseases such as asthma.

Front 48

Stimulation of both alpha (especially alpha-2 receptors) and beta receptors in the GI tract leads to?

Back 48

relaxation of smooth muscle

Front 49

Which receptor causes the majority of sympathomimetic activity in the GI tract.

Back 49

alpha-2 receptor stimulation

Front 50

Which receptors are found in the Genitourinary tract?

Back 50

alpha-1 and beta-2 receptors

Front 51

Which receptors leads to the overall effect of increasing urinary continence?

Back 51

alpha-1 receptor stimulation

Front 52

Which receptors results in bladder wall relaxation?

Back 52

Beta-2 receptor stimulation. These receptors are found in the bladder wall.

Front 53

TRUE/FALSE. Sympathomimetic drugs decrease glycogenolysis in the liver.

Back 53

FALSE. Sympathomimetic drugs increase glycogenolysis in the liver, leading to an increase in blood sugar. (beta receptors)

Front 54

In the pancreas, insulin secretion is promoted by____ _____ _____ and inhibited by ________ _____ ________. Renin secretion is also stimulated by _______ ______ and inhibited by _______ _____ ________.

Back 54

In the pancreas, insulin secretion is promoted by beta-receptor activation and inhibited by alpha-2 receptor activation. Renin secretion is also stimulated by beta receptor activation and inhibited by alpha-2 receptor activation.

Front 55

What are the two groups that alpha agonist can be divided into?

Back 55

Peripheral alpha agonist (due mostly to alpha-1 adrenergic receptors) and central alpha agonist

Front 56

In the CNS which alpha receptors predominate?

Back 56

alpha-2 receptors

Front 57

Which type of alpha agonist is phenylephrine?

Back 57

Phenylephrine is a potent peripheral-acting alpha-1 agonist, which causes increase in blood pressure.

Front 58

Which type of alpha agonist is clonidine?

Back 58

Clonidine is a centrally-acting alpha-2 agonist, and has overall effect of decreasing blood pressure.

Front 59

Name two drugs which have mixed-selectivity (alpha and beta agonist activity) with direct or indirect central effects.

Back 59

Amphetamine and methamphetamine

Front 60

What is one of the most potent vasopressor agents known.

Back 60

Epinephrine (potent stimulator of all adenergic receptors)

Front 61

When epinephrine is given as an IV or IM bolus dose what does this produce?

Back 61

This produces a rapid, short-term increase in BP. (EpiPen kit). This profound increase in BP is due to
1. myocardial stimulation leading to a positive inotrophic and chronotrophic effect and
2. vasoconstriction in the vascular beds.

Front 62

When epinephrine is given as a slow IV infusion or as a subcutaneous injection what is the response?

Back 62

The response is not as dramatic in terms of vasopressor effect. At lower doses, or as initial bolus dose is wearing off, epinephrine may actually cause overall vasodilation rather than vasoconstriction.

Front 63

Which receptors does norepinephrine stimulate?

Back 63

Norepinephrine is more selective for a vasopressor effect, and does not significantly increase cardiac output. Norepinephrine stimulates alpha and beta-1 receptors.

Front 64

Which receptors does epinephrine stimulate but norepinephrine doesn't.

Back 64

beta-2 receptors, therefore, vasodilation at lower or waning doses does not typically occur in norepinephrine

Front 65

Which drug is selective for direct stimulation of alpha-1 adrenergic receptors? What does this drug cause? What is it used for?

Back 65

Phenylephrine. This drug causes significant vasoconstriction when given locally or systemically. It may be used for treatment of life-threatening hypotension. Also, due to its ability to constrict blood vessels in the upper respiratory tract via stimulation of alpha-1 receptors, this drug is widely used as a nasal and ophthalamic decongestant in both OTC and prescription products.

Front 66

Name 2 non-selective alpha adrenergic agonist. What are they used for?

Back 66

Oxymetazoline and naphazoline. They are used in OTC and prescription prodcuts for relief of nasal and ophthalamic congestion, and work by acting on agonist at alpha 1-receptors in the eye and both alpha-1 and alpha-2 receptors in the upper respiratory tract.

Front 67

Name a centrally-acting alpha-2 receptor agonist.

Back 67

Clonidine and Tizanidine.

Front 68

Describes Clonidine's overall effect.

Back 68

It has an overall effect of lowering peripheral BP by decreasing adrenergic sympathetic neurotransmission from the CNS, which leads to a decrease in vascular resistance. It is also used for treatment of hypertension.

Front 69

Describe Tizanidine's overall effect.

Back 69

It is useful more for its effects on reducing muscle spasticity due to presynaptic inhibition of motor neurons (via activation of alpha-2 autoreceptors). Overalls, this leads to a decrease in muscle tone and relief of muscle spasticity.

Front 70

What do nonselective beta adrenergic agonist cause?

Back 70

both inotrophic and chronotrophic effects

Front 71

Name a beta-1 selective adrenergic agonist. What does it cause? What is it used for?

Back 71

Dobutamine. This causes potent inotrophic effects without significant chronotrophic effects. It is used more often as a parenterally as a vasopressor drug for short-term emergency management of cardiac decomposition.

Front 72

The beta-2 selective agonist were especially impt. for the management of?

Back 72

lower airways disease, such as asthma

Front 73

Why is it important to give a patient a direct delivery of the beta-2 selective agonist drug by aerosol to the bronchial tissue (meter-dose inhalers)?

Back 73

Because beta-2 selective agonist are not 100% selective for beta-2 receptors, and at higher doses will stimulate beta-1 receptors (in other words, they are selective, but not specific, for beta-2 receptors.) Therefore, they had to find a way to enhance beta-2 stimulation in bronchial tissue but avoid beta receptor stimulation in the heart.

Front 74

Name 3 short-acting beta-2 selective agonist.

Back 74

Albuterol, Levalbuterol, and pirbuterol

Front 75

Name 1 long-acting beta-2 selective agonist.

Back 75

salmeterol

Front 76

Amphetamine and Methamphetamine

Back 76

CNS stimulants that promote the release of norepinephrine from presynaptic storage vesicles.

Front 77

What is Amphetamine used for?

Back 77

ADHD and narcolepsy

Front 78

Methlphenidate is used for?

Back 78

ADHD

Front 79

Ephedrine has two asymmetric carbon atoms and therefore has four optically active forms. What is the threo racemate form called? What does it promote the release of?

Back 79

pseudoephedrine which promotes the release of norepinephrine from presynaptic vesicles and does not bind to adrenergic receptors directly.

Front 80

Pseudoephedrine is a popular?

Back 80

decongestant in both prescription and OTC cold and allergy medications

Front 81

TRUE/FALSE. Most of the adverse effects are related to sympathomimetics are direct extension of their pharmacodynameic effect.

Back 81

TRUE.

Front 82

What is a potential toxicity of several alpha agonists?

Back 82

Supine hypertension

Front 83

What are the toxicities of the centrally-acting agonists (alpha-2 selective agonists such as clonidine)drugs?

Back 83

dry mouth, sedation, especially when therapy is intiated

Front 84

Which sympathomimetics cause tolerance?

Back 84

Alpha agonist that are used as intranasal decongestants (e.g., oxymetazoline, naphazoline). After tolerabce develops, when the patient discontinues the decongestant they will experience rebound nasal congestion.

Front 85

What toxicities do beta-2 selective agonst may cause?

Back 85

tachycardia, especially when given systemically by oral dosing rather than by inhalation in aerosol form. They also may cause muscle tremors.

Front 86

How can muscle tremors be avoided when taking a beta-2 selective agonist?

Back 86

In patients taking albuterol, muscle tremor may be avoided by switching them to levalbuterol, which contains only the single active enantiomer of albuterol.

Front 87

What are the common adverse effects of most centrally-acting sympathomimetics (excluding alpha-2 selective antagonist)?

Back 87

Nervousness, hyperactivity, insomnia, and other symptoms of general CNS stimulation