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87 Cards in this Set

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All Sympathomimetics, whether indirectly or directly increase activity of?
Adrenergic receptors. They are adrenoreceptor-activating drugs. They increase the activity of adrenergic receptors.
Explain the two mechanisms of indirect-acting Sympathomimetic drugs.
1. Displacement of stored catecholamines from the adrenergic nerve terminal
2. Inhibition of catecholamines reuptake from the synaptic cleft back into the presynaptic neuron.
What is the overall effect of indirect-acting sympathomimetic drugs?
In both cases, the overall effect is an increase in concentration and duration of action of catecholamine released into synaptic cleft.
Which drug is selective for binding to alpha-1 adrenergic receptors?
Phenylephrine
Alpha-1 adrenergic receptors are coupled to ________ __ via __ _____.
Alpha-1 adrenergic receptors are coupled to phospholipase C via G proteins.
What results when there is stimulation of alpha-1 receptors?
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.
What is the overall effect of alpha-1 receptor stimulation?
contraction. For example, alpha-1 stimulation results in vascular smooth muscle contraction, pupillary dilator muscle contraction, prostate contraction, and cardiac contractile cell contraction.
TRUE/FALSE. Alpha-2 and Alpha-1 receptors play a significant role in the CNS.
FALSE. Only alpha-2 receptors play a significant role in the CNS.
Alpha-2 receptors are coupled to _____ ____ via an ______ __ _____.
Alpha-2 receptors are coupled to adenylyl cyclase via an inhibitory G protein.
What is the overall effect of alpha-2 adrenergic receptors?
Alpha-2 adrenergic receptors have the overall effect of inhbiting adenylyl cyclase, resulting in a decrease in intracellular levels of cyclic AMP (cAMP).
Explain the autoinhibiton of neurotransmitter release which is an important effect of alpha-2 receptors.
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)
What occurs in the endocrine system when alpha-2 receptors are stimulated?
Stimulation of alpha-2 receptors in the endocrine system:
-leads to a decrease in insulin secretion and renin secretion
What occurs in the GI tract when alpha-2 receptors are stimulated?
-leads to a decrease in muscle activity indirectly by functioning as autoreceptors on presynaptic adrenergic nerve terminals that prevent release of catecholamine neurotransmitters.
Beta-adrenergic receptor have a biochemically opposite effect of which receptors?
alpha-2 adrenergic receptors
Beta receptors are coupled to ____ _____ by a ________ __ _____.
Beta receptors are coupled to adenylyl cyclase by a stimulating G protein.
The effect of decreasing cAMP in alpha-2 receptors depends on?
The tissue site where alpha-2 receptors are stimulated.
Stimulation of beta receptors leads to the synthesis of?
second messenger molecule cAMP
The effect of cAMP synthesis secondary to beta receptor stimulation depends on?
Both the tissue site and the subtye of beta receptor that is stimulated.
Both beta-1 and beta-2 stimulation in the heart lead to?
influx of calcium into cells, causing an increase in both cardiac pacemaker cell activity (positive chronotrophic effect) and cardiac contractility (positive inotrophic effect).
In the respiratory, uterine, and vascular tissues which receptors (beta-1, beta-2, or both) relaxes smooth muscle?
beta-2 receptors
What are two sympathomimetic drugs that are also endogenous compounds?
Epinephrine and norepinephrine
Most sympathomimetics are chemical variations of which two drugs?
epinephrine and norepinephrine. For all of these agents, the parent compound may be considered to be phenylethylamine.
Chemical substitution of phenylethylamine alters what 3 things?
-Duration of action, receptor selectivity, and susceptibility of sympathomimetics to metabolism by MAO and COMT.
Hydroxyl substitution at the 3 and 4 positions of phenylethylamine results in drugs with?
High affinity for adrenergic receptors but a relatively short duration of action dur to rapid inactivation by COMT
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?
This increases the selectivity of the resulting drug for beta-receptors.
Which endogenous compound has higher selectivity for beta-receptors due to the addition of a carbon chain onto the amine position of phenylethylamine?
epinephrine
What happens when there is chemical substitution at the alpha carbon on phenylethylamine?
It decreases susceptibility of the resulting drug to degradation by monoamine oxidase (MAO). Overall, this chemical substitution increases the duration of action of sympathomimetics.
If there is replacement of one of the hydroxyl groups of the catecholamine with a hydroxymethyl group what happens?
This increases beta-2 selectivity and prevents metabolism by COMT.
Name 2 drugs which are beta-2 selective agonsts, they replaced one of the hydroxyl groups of the catecholamine with a hydroxymethyl group.
Albuterol and Levalbuterol
What happens when the position of the hydroxyl groups moves on the catecholamine ring.
This renders the drug non-catecholamine and prevents metabolism by COMT.
Which beta-2 selective agonist hydroxyl group is at a different position on the catecholamine ring.
Metaproterenol
What happens when there is an addition of a long carbon-based chain onto the amine position? Name one?
This results in a ver long-acting beta-2 selective agonist. For example: Salmeterol.
Which drug is marketed as a single enantiomer instead of a racemic mixture?
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.
How is albuterol marketed?
racemic mixture. R- (acitve) and S-enantiomers (inactive).
Vascular smooth muscle of the cardiovascular system contains which receptor types?
Alpha and beta-2 adrenergic receptors.
What does acitvation of alpha receptors by pure alpha agonist cause?
vasoconstriction, leading to an increase in arterial resistance
What does an increase in arterial resistance lead to?
An increase in arterial resistance typically leads to a dose-dependent rise in blood pressure.
What will happen to the heart to compensate for the increase in arterial pressure sensed by the brain.
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.
Activation of beta-2 receptors in the vasculature in the cardiovascular system results in?
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.
What happens to the heart when there is activation of beta-receptors.
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).
How do beta-1 and beta-2 agonist activity effect peripheral resistance?
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.
How do alpha adrenergic agonists affect the eye?
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.
How do beta-adrenergic agonists affect the eye?
Increase the production and secretion of aqueous humor into the eye, resulting in increased intraocular pressure
Which type of receptors are in the upper respiratpry tract?
Alpha receptors
What do Alpha agonist cause in the upper respiratory tract?
vasoconstriction, which is a useful effect for relieving upper respiratory tract congestion (e.g, nasal congestion)
Which receptors are in the lower respiratory tract?
Beta-2 receptors
Stimulation of beta-2 receptors by beta agonists cause what to occur in the upper respiratory tract?
bronchodilation, an effect that is very useful in the pharmacological treatment of airway diseases such as asthma.
Stimulation of both alpha (especially alpha-2 receptors) and beta receptors in the GI tract leads to?
relaxation of smooth muscle
Which receptor causes the majority of sympathomimetic activity in the GI tract.
alpha-2 receptor stimulation
Which receptors are found in the Genitourinary tract?
alpha-1 and beta-2 receptors
Which receptors leads to the overall effect of increasing urinary continence?
alpha-1 receptor stimulation
Which receptors results in bladder wall relaxation?
Beta-2 receptor stimulation. These receptors are found in the bladder wall.
TRUE/FALSE. Sympathomimetic drugs decrease glycogenolysis in the liver.
FALSE. Sympathomimetic drugs increase glycogenolysis in the liver, leading to an increase in blood sugar. (beta receptors)
In the pancreas, insulin secretion is promoted by____ _____ _____ and inhibited by ________ _____ ________. Renin secretion is also stimulated by _______ ______ and inhibited by _______ _____ ________.
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.
What are the two groups that alpha agonist can be divided into?
Peripheral alpha agonist (due mostly to alpha-1 adrenergic receptors) and central alpha agonist
In the CNS which alpha receptors predominate?
alpha-2 receptors
Which type of alpha agonist is phenylephrine?
Phenylephrine is a potent peripheral-acting alpha-1 agonist, which causes increase in blood pressure.
Which type of alpha agonist is clonidine?
Clonidine is a centrally-acting alpha-2 agonist, and has overall effect of decreasing blood pressure.
Name two drugs which have mixed-selectivity (alpha and beta agonist activity) with direct or indirect central effects.
Amphetamine and methamphetamine
What is one of the most potent vasopressor agents known.
Epinephrine (potent stimulator of all adenergic receptors)
When epinephrine is given as an IV or IM bolus dose what does this produce?
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.
When epinephrine is given as a slow IV infusion or as a subcutaneous injection what is the response?
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.
Which receptors does norepinephrine stimulate?
Norepinephrine is more selective for a vasopressor effect, and does not significantly increase cardiac output. Norepinephrine stimulates alpha and beta-1 receptors.
Which receptors does epinephrine stimulate but norepinephrine doesn't.
beta-2 receptors, therefore, vasodilation at lower or waning doses does not typically occur in norepinephrine
Which drug is selective for direct stimulation of alpha-1 adrenergic receptors? What does this drug cause? What is it used for?
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.
Name 2 non-selective alpha adrenergic agonist. What are they used for?
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.
Name a centrally-acting alpha-2 receptor agonist.
Clonidine and Tizanidine.
Describes Clonidine's overall effect.
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.
Describe Tizanidine's overall effect.
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.
What do nonselective beta adrenergic agonist cause?
both inotrophic and chronotrophic effects
Name a beta-1 selective adrenergic agonist. What does it cause? What is it used for?
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.
The beta-2 selective agonist were especially impt. for the management of?
lower airways disease, such as asthma
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)?
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.
Name 3 short-acting beta-2 selective agonist.
Albuterol, Levalbuterol, and pirbuterol
Name 1 long-acting beta-2 selective agonist.
salmeterol
Amphetamine and Methamphetamine
CNS stimulants that promote the release of norepinephrine from presynaptic storage vesicles.
What is Amphetamine used for?
ADHD and narcolepsy
Methlphenidate is used for?
ADHD
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?
pseudoephedrine which promotes the release of norepinephrine from presynaptic vesicles and does not bind to adrenergic receptors directly.
Pseudoephedrine is a popular?
decongestant in both prescription and OTC cold and allergy medications
TRUE/FALSE. Most of the adverse effects are related to sympathomimetics are direct extension of their pharmacodynameic effect.
TRUE.
What is a potential toxicity of several alpha agonists?
Supine hypertension
What are the toxicities of the centrally-acting agonists (alpha-2 selective agonists such as clonidine)drugs?
dry mouth, sedation, especially when therapy is intiated
Which sympathomimetics cause tolerance?
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.
What toxicities do beta-2 selective agonst may cause?
tachycardia, especially when given systemically by oral dosing rather than by inhalation in aerosol form. They also may cause muscle tremors.
How can muscle tremors be avoided when taking a beta-2 selective agonist?
In patients taking albuterol, muscle tremor may be avoided by switching them to levalbuterol, which contains only the single active enantiomer of albuterol.
What are the common adverse effects of most centrally-acting sympathomimetics (excluding alpha-2 selective antagonist)?
Nervousness, hyperactivity, insomnia, and other symptoms of general CNS stimulation