Pharm Ch. 18 (For Exam 1)

Adverse effects of beta-adrenergic drugs

mild tremors, headache, nervousness, dizziness

Adrenergic agonists

Drugs that stimulate and mimic the actions of the sympathetic nervous system. Also called sympathomimetics.

Sympathomimetics

Drugs used therapeutically that mimic the catecholamines epinephrine, norepinephrine, and dopamine. Also called adrenergic agonists.

Catecholamines are metabolized by what enzymes?

MAO and COMT -MAO breaks down cat. in the nerve ending -COMPT breaks down cat. outside of the nerve ending at the synaptic cleft -Reuptake also halts catecholamine mechanism (active trasnport)

Toxicity and management of adrenergic OD

Toxic effects of adrenergic drugs are an extension of their common adverse effects (e.g. seizures from excessive CNS stimulation, hypotension or hypertension, dysrhythmias, palpitations, nervousness, dizziness, fatigue, malaise, insomnia, headache, tremor, dry mouth, and nausea). In the acute setting seizures can be effectively managed w/ diazepam. Intracranial bleeding can also occur, often as the result of an extreme elevation in blood pressure. Such elevated BP poses the risk of hemorrhage not only in the brain but elsewhere in the body as well. Best treatment is to lower the BP using a rapid-acting sympatholytic drug.

Alpha-adrenergic receptors

a class of adrenergic receptors that are further subdivided into alpha1 and alpha2 adrenergic receptors

Alpha 1 and Alpha 2 receptors control the release of ________________

neurotransmitters

Selective agonists

only affect one receptor subtype

Noncatecholamine adrenergic drugs

phenylephrine, metaproterenol, and albuterol. - Structurally dissimilar to the endogenous catecholamines and have a longer duration of action than either the endogenous or synthetic catecholamines; show similar patterns of activity.

Where are alpha 1 receptors located?

postsynaptic effector cells (the tissue, muscle, or organ that the nerve stimulates).

Where are alpha 2 receptors located?

presynaptic nerve terminals

Adrenergic receptors

receptor sites for the sympathetic neurotransmitters norepinephrine and epinephrine

What effect do beta 2 receptors have on the uterus?

relaxation

Where are beta 2 receptors located?

smooth muscle fibers of the bronchioles, arterioles, and visceral organs

Vasoactive Sympathomimetics

support the cardiovascular system during cardiac failure or shock -effects seen on various alpha and beta receptors -effects directly related to specific dose of adrenergic drug

The ANS is divided into _______ and _________.

sympathetic and parasympathetic

Catecholamines produce a ______________ response

sympathomimetic

T/F: Adrenergic compounds include several exogenous (synthetic) and endogenous (produced in the body naturally) substances

true

T/F: The beta-adrenergic receptors are ALL located on postsynaptic effector cells

true

Alpha 1 receptors (vasodilate/vasoconstrict) blood vessels

vasoconstrict

What is the predominant adrenergic agonist response?

vasoconstriction and CNS stimulation

Beta 2 receptors (vasodilate/vasoconstrict) blood vessels

vasodilate -also increases heart rate/contractility

The Peripheral Nervous System (PNS) is divided into what?

Somatic and Autonomic

Catecholamines

Substances that can produce a sympathomimetic response. They are either endogenous catecholamines (such as epinephrine, norepinephrine, and dopamine) or synthetic catecholamine drugs (such as dobutamine).

Synaptic Cleft

The space either between two adjacent nerve cell membranes or between a nerve cell membrane, and an effector organ cell membrane (also called synapse).

Where are beta 3 receptors located?

human urothelium muscle and detrusor muscle

Ophthalmic drugs

-similar to nasal congestants; just on the surface of the eye -stimulate alpha receptors and cause constriction -ex. epinephrine, naphazoline, phenylephrine, and tetrahydrozoline

What three things happen when beta 1 adrenergic receptors are stimulated by an adrenergic drug?

-Positive Inotropic effect (force of contraction) -Positive chronotropic effect (heart rate) -Positive dromotropic effect (SA and AV conduction)

Dopaminergic receptors dilate which blood vessels (resulting in increased blood flow)?

-Renal -Mesenteric -Coronary -Cerebral

Stimulation of alpha-adrenergic receptors result in:

-Vasoconstriction of blood vessels -Relaxation of GI smooth muscles (decreased motility) -Constriction of bladder sphincter -Contraction of uterus -Male ejaculation -Contraction of pupillary muscles of the eye (dilated pupils)

Common vasoactive adrenergics

-dobutamine -dopamine -ephedrine -epinephrine -fenoldopam -midodrine -norepinephrine -phenylephrine

What are the only usual contraindications to the use of adrenergic drugs?

-known drug allergy -severe hypertension

Characteristics of Adrenergic Drugs

-mimic the effects of NE, EPI, and DA (the catecholamines)

How do catecholamines work?

-produced in the SNS; stored in vesicles -when the nerve is stimulated, the vesicles move down the walls of the nerve ending towards the synaptic cleft and release their contents (the catecholamines). -the catecholamines then try to bind with receptors on the postsynaptic nerve and stimulate a response.

Autonomic Nervous System

A branch of the peripheral nervous system that controls autonomic bodily functions. It consists of the sympathetic nervous system and the parasympathetic nervous system.

Dopaminergic Receptor

A third type of adrenergic receptor (in addition to alpha-adrenergic and beta-adrenergic receptors) located in various tissues and organs and activated by the binding of the neurotransmitter dopamine, which can be either endogenous or a synthetic drug form.

Positive inotropic event

An increase in the force of contraction of the heart muscle (myocardium).

Positive dromotropic effect

An increase in the conduction of cardiac electrical impulses through the atrioventricular node, which results in the transfer of nerve action potentials from the atria to the ventricles. This ultimately leads to a systolic heartbeat (ventricular contractions).

Autonomic functions

Bodily functions that are involuntary and result from the physiologic activity of the autonomic nervous system. The functions often occur in pairs of opposing actions between the sympathetic and parasympathetic divisions of the autonomic nervous system.

Beta 1 receptors (increase/decrease) cardiac muscle contractility and (increase/decrease) heart rate of the SA and AV nodes

increase; increase

Indirect-acting sympathomimetic

Causes release of catecholamine from storage sites (vesicles) in nerve endings -then binds to receptors and causes a physiologic response -ex. Amphetamine and other anorexiants

Beta-adrenergic receptors

Receptors located on postsynaptic cells that are stimulated by specific autonomic nerve fibers. -Beta1-adrenergic receptors are located primarily in the heart, whereas beta2-adrenergic receptors are located in the smooth muscle fibers of the bronchioles, arterioles, and visceral organs.

Bronchodilators

adrenergic drugs that have an affinity for the adrenergic receptors located in the respiratory system -preferentially stimulate beta 2 receptors on the bronchial, uterine, and vascular smooth muscles

Common bronchodilators classified as predominantly beta2-selective adrenergics

albuterol, ephedrine, formoterol, levalbuterol, metaproterenol, pirbuterol, salmeterol, and terbutaline

What two adrenergic receptor types stimulate glycogenolysis in the liver? What receptor increases renin secretion in the kindeys?

alpha 1 and beta 2; beta 1

Positive chronotropic effect

an increase in heart rate

Beta 2 agonists are helpful in treating what respiratory conditions?

asthma and bronchitis

Overactive Bladder Indications

beta3 agonist (Myrbetriq) relaxes the detrusor muscle -leads to an increase in bladder storage capacity

Direct-acting sympathomimetics

binds directly to the receptor and causes a physiologic response -ex. Epinephrine

Mixed acting sympathomimetics

both directly stimulates the receptor by binding to it and indirectly stimulates the receptor by causing the release of the NT stored in vesicles at nerve endings -ex. Ephedrine

The CNS contains what?

brain and spinal cord

Glycogenolysis (Beta-adrenergic agonist response)

breakdown of glycogen to glucose

What does a beta-adrenergic agonist response usually result in?

bronchial, gastrointestinal (GI), and uterine smooth muscle relaxation; glycogenolysis; and cardiac stimulation

Nasal Decongestants: Indications

constriction of dilated arterioles and a reduction in nasal blood flow, which thus decreases congestion -stimulate alpha 1 receptors (little to no effect on beta receptors)

Alpha 1 (dilates/contricts) bladder sphincter

constricts

Alpha 1 (increases/decreases) GI muscle motility? What about any other receptor?

decreases (relaxation of gastrointestinal smooth muscle) -beta 2 also decreases motility

Alpha 1 does what to pupils?

dilate (mydriasis)

Beta 2 (dilates/constricts) bronchial muscles

dilates

Mydriasis

dilation of the pupil; whether drug or naturally induced

Dopaminergic receptors are stimulated by what?

dopamine

Ophthalmics

drugs that are used in the eye

What effect do alpha 1 receptors have on the penis/uterus?

ejaculation/contraction

examples of nasal decongestants

ephedrine, naphazoline, oxymetazoline, phenylephrine, and tetrahydrozoline

Nonselective agonists

have actions at both alpha and beta receptors

Adverse effects of alpha-adrenergic drugs

headache, restlessness, excitement, insomnia, and euphoria and some cardiovascular complications

Where are beta 1 receptors located?

heart