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