Term
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Definition
nCite the classification of sympathomimetics
nIdentify the pharmacokinetics of sympathomimetics
nDefine the mechanism of action (MOA) of sympathomimetics
nCompare and contrast the organ system effects of sympathomimetics
nList the clinical uses of sympathomimetics
nRelate toxic effects of sympathomimetics |
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Term
What does the Adrenergic Neuron do?
Where is it found?
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Definition
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Term
| ****NT's at Adrenergic neurons**** |
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Definition
-
Synthesis
-
storage
-
release
-
receptor binding
-
removal
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Term
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Definition
Tyrosine is transported by Na+ linked carrier into the axoplam
*Hydroxylation of Tyrosine is the RATE LIMITING STEP |
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Term
Storage
What are the NT's involved?
Where are they transported to?
What forms Epi?
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Definition
•Neurotransmitters Dopamine & Norepinephrine transported to synaptic vesicles
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Term
Release
What triggers influx of Ca++?
Then what happens? |
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Definition
- Action potential arriving at nerve jxn triggers Ca++ influx
- Ca++ causes the vesicles inside of the cells to fuse w/ cell membrane
- The contents are then expelled into the synapse
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Term
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Definition
•Diffuses across synaptic space
•Binds to either post synaptic receptor on the effect or organ or to the pre synaptic receptor on the nerve ending
•Triggers cascade of events involving second messengers
•Adrenergic receptors use both cyclic AMP second messenger system and phosphatidylinositol cycle to transduce signal to effect |
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Term
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Definition
•May diffuse out of the synaptic space
•Be metabolized
•Recaptured by an uptake system
•Reuptake is inhibited by tricyclic antidepressants or by cocaine |
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Term
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Definition
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Term
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Definition
•May be taken up into vesicles
•Persist in a protected pool inside the cell
•May be oxidized and excreted in urine as vanillylmandelic acid, metanephrine or normetanephrine (inactive metabolites)
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Term
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Definition
•Several classes of receptors
•ά and β
•Initially identified on response to epinephrine, norepinephrine and isoproterenol
•Molecular identities of a number of subtypes |
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Term
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Definition
•Selectivity means that a drug may preferentially bind to one subgroup of receptors at concentrations too low to interact extensively with another subgroup |
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Term
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Definition
•Show a weak response to isoproterenol
•Responsive to naturally occurring catecholamines
•Subdivided into two subgroups based on affinities for agonist and blocking drugs |
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Term
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Definition
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Term
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Definition
•Present on the post synaptic membrane of effector organs
•Originally designated as α adrenergic – involving constriction of smooth muscle
•Activation of α1 initiates a series of reactions:
- G protein activation causing release of Ca++ from the endoplasmic reticulum into the cytosol |
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Term
Alpha 1 and Alpha 2 Receptos
Fig6.5 pg 69 understand |
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Definition
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Term
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Definition
•Located on presynaptic nerve endings
•Located on βcell of the pancreas
**•Control adrenergic mediator and insulin output
•Portion of the released norepinephrine cycle backwards and reacts with the α2 receptors on the neuronal cell membrane
•This causes a feedback inhibition of the ongoing release of norepinephrine
•Modulating mechanism |
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Term
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Definition
•α1 A B C
• α 2 A B C D
•Different drugs target different receptors
•Example tamsulosine selective α1A antagonist use to treat BPH α1A are located primarily in the urinary tract |
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Term
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Definition
•Responses different form α
•Strong response to isoproterenol
•Less sensitivity to epinephrine, norepinephrine |
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Term
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Definition
•Two major subgroups β1 and β2
•β1equal affinities for epinephrine and norpinephrine
•β2 have a higher affinity for epi than norepi
•Tissues with a β2 predominance are particularly responsive to hormonal effects of circulating epi released by the adrenal; medulla epi |
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Term
Distribution of receptors |
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Definition
•Organs tend to have a predominance of one type of receptor, some are mixed
•Vasculature to skeletal muscle have both but β2 predominate
•Heart contains predominantly β1 |
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Term
Distribution of Adrenoceptors
Alpha 1 |
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Definition
•Alpha 1
–Tissue: Vascular smooth muscle
•Action: Constriction
–Tissue: Pupillary dilator muscle
•Action: contraction – dilates the pupil
–Tissue: Pilomotor smooth muscle
•Action: erects hair
–Tissue: Prostate
–Tissue: Heart
•Action: increases force of contraction |
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Term
Distribution of Adrenoceptors
Alpha 2 |
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Definition
•Alpha 2
–Tissue: Postsynaptic CNS adrenoceptors
•Action: Multiple
–Tissue: Platelets
•Action: Aggregation (increase clotting)
–Tissue: Adrenergic and cholinergic nerve terminals
•Action: Inhibition of transmitter release
(modulating action of the receptors)
–Tissue: Some vascular smooth muscle
•Action: contraction
–Tissue: Fat cells
•Action: inhibition of lipolysis (inhibition of fat breakdown)
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Term
Distribution of Adrenoceptors
Beta 1 |
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Definition
–Tissue: heart
–Action: Increase force & rate of contraction |
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Term
Distribution of Adrenoceptors
Beta 2 |
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Definition
–Tissue: respiratory, uterine, & vascular smooth muscle
•Action: promotes smooth muscle relaxation
–Tissue: skeletal muscle
•Action: promotes K+ uptake
–Tissue: liver
•Action: activates glycogenolysis
(Note: If you have Bronchioconstrictino you want to effect Beta-2 receptors) |
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Term
Distribution of Adrenoceptors
Beta 3 |
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Definition
–Tissue: fat cells
–Action: activates lipolysis |
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Term
Distribution of Adrenoceptors
D1 |
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Definition
–Tissue: Smooth muscle
–Action: dilates renal blood vessels |
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Term
Distribution of Adrenoceptors
D2 |
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Definition
–Tissue: Nerve endings
–Action: Modulates transmitter release |
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Term
Organ System Effects
CV: Blood Vessels |
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Definition
CV
–Blood Vessels
•control peripheral vascular resistance
•Alpha receptors increase arterial resistance
•Beta 2 receptors promote smooth muscle relaxation
•Effect depending on anatomical site |
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Term
Organ System Effects
CV: Heart |
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Definition
•Cardiovascular
–Heart
•Largely Beta 1 receptors
•Activation results in Ca2+ influx
•SA node & purkinje fibers increase – positive chronotropic effect
•AV node – conduction velocity increases & refractory period decreases
•Intrinsic contractility is increased – positive inotropic effect and relaxation is accelerated
•Ejection time is decreased |
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Term
Organ System Effects
CV: Blood Pressure |
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Definition
•Cardiovascular
–Blood Pressure
•Alpha agonist
–increase peripheral vascular resistance
–decreases venous capacitance
–Leads to a rise in blood pressure which slows the heart
•Beta adrenoceptor agonist
–Decreases peripheral vascular resistance
–Increases cardiac output
–Vasodilates |
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Term
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Definition
–Pupillary dilator muscle
•Alpha receptors – mydriasis
•Alpha receptors – increases outflow of aqueous humor from the eye – reduces IOP
•Beta receptors decrease production of aqueous humor
–Ciliary muscle
•Beta receptors – decrease in accommodation |
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Term
Organ System Effects
Respiratory Tract |
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Definition
•Respiratory Tract
–Bronchial smooth muscle contain Beta 2 receptors – relaxation (bronchodilation)
–Blood vessels of upper respiratory tract contain alpha receptors |
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Term
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Definition
•Gastrointestinal Tract
–GI smooth muscle, both alpha & Beta – relaxation
–Alpha 2 receptors decrease salt and water flux into the lumen of the intestine |
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Term
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Definition
•Genitourinary (GU) Tract
–Uterus
•Contain alpha & Beta receptors
–Bladder, urethral sphincter & prostate
•Alpha receptors – mediate contraction – promotes urinary incontinence
•Beta 2 receptors – bladder wall relaxation
–Ejaculation (ductus deferens, seminal vesicles and prostate)
•Alpha receptors for activation |
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Term
Organ System Effects
Exocrine Glands |
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Definition
•Exocrine Glands
–Salivary glands
•Secretion of amylase & water
–Apocrine sweat glands (psychologic stress)
•Sweaty palms |
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Term
Characteristic Responses Mediated by Adenoreceptors |
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Definition
•Stimulation of α1produces vasoconstriction, increase in total peripheral resistance and BP
•Stimulation of β1 cause cardiac stimulation
•Stimulation β2 produces vasodilatation and bronchial relaxation |
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Term
Major effects mediated by alpha and beta adrenoreceptors
Fig 6.6 pg 69
*KNOW* |
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Definition
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Term
Receptor Regulation
What are the 3 types? |
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Definition
•Desensitization
•Homologous desensitization
•Heterologous desensitization |
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Term
Desensitization of Receptors
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Definition
•Desensitization – after a cell or tissue has been exposed for a period of time to an agonist, that tissue becomes less responsive to further stimulation
•Prolonged exposure to catecholamines reduces the responsiveness of the receptors
–Sequestration of receptors
–Down regulation
–Receptor phosphorylated (it's no longer active)
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Term
Receptor Regulation:
Homologous Desensitization
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Definition
•Homologous desensitization – loss of responsiveness exclusively of the receptor that has been exposed to repeated or sustained activation by a drug |
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Term
Receptor Regulation:
Heterologous desensitization |
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Definition
•Heterologous desensitization – loss of responsiveness of some cell surface receptors that have not been directly activated by the drug in question |
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Term
Characteristics of Adrenergic Agonist
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Definition
•Most adrenergic drugs are derivatives of β phenylethylamine
•Catecholamines
•Noncatecholamines |
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Term
Catecholamines
Epi Norepi Isoproterenol Dopamine |
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Definition
•High potency
•Rapid inactivation
•Poor penetration into CNS |
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Term
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Definition
•Not deactivated by COMT Catechol-O-methyl transferase
•Include phenylepherine, ephedrine, amphetamine
•Increase lipid solubility and permits greater access to CNS |
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Term
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Definition
•Direct Acting Agonist
•Indirect Acting agonist
•Mixed Acting Agonist |
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Term
Figure 6.8 Understand
pg 71
Sites of action of direct, indirect and mixed-acting adrenergic agonists |
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Definition
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Term
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Definition
•Act directly on α or β receptors producing similar effects to those that occur stimulating the sympathetic nerves
•Norepi, epi, isoproterenol, phenylepherine |
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Term
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Definition
•Agents taken up in the presynaptic neuron and cause the release of norepi
•Norepi transverses the synapse and binds to receptors
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Term
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Definition
•Agonist such as ephedrine have the capacity to both stimulate the receptors and to release norepi from the adrenergic neuron |
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Term
Direct Acting Adrenergic Agonist |
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Definition
•Epinephrine naturally occurring interacts with both α and β receptors
•At low doses β effects (vasodilatation) predominate, at high doses α effects are strongest |
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Term
Actions of Direct Acting Adrenergic Agonist |
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Definition
•Cardiovascular strengthen contractility of myocardium and increases contraction rate
•Cardiac output increases
•Increase in systolic blood pressure secondary to arteriole constriction in skin and dilation of vessels going to liver and skeletal muscle |
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Term
|
Definition
EPI
•Powerful bronchodilation by direct action on bronchial smooth muscle
•Action relieves all bronchoconstriction
•Epi--Lifesaving in anaphylactic shock
•Relieves asthmatic attack
•Contraindicated in cardiac asthma
(b/c it increases the contraction rate, CO increases, Bronchoconstriction and wheezing --> if you give a Bronchodilator, they will NOT survive) |
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Term
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Definition
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Term
|
Definition
BP is increased in Hyperglycemics
•Epi causes hyperglycemia
•Increase glycogenolysis increase
•Increase release of glucagon
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Term
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Definition
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Term
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Definition
•Metabolizes by two pathways MAO and COMT
•Metabolites excreted in urine |
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Term
|
Definition
•Bronchospasm
•Epi is the primary drug in any emergency treatment of ANY condition of the respiratory tract
•Selective β2 agonist such as albuterol are preferred in treatment of chronic asthma |
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Term
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Definition
•2% Epi solution is used topically to reduce intraocular pressure
•Reduces the production of aqueous humor by vasoconstriction of cilliary body blood vessels |
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Term
****Anaphylactic Shock**** |
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Definition
| Epi is the drug of choice for type I hypersensitivity rxn |
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Term
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Definition
•Epi Increases the duration of local anesthetics
•Produces vasoconstriction at the injection site allowing the anesthetic to persist at tha injection site (when EPI is given w/ anesthetic will keep anesthetic their longer) |
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Term
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Definition
•Rapid onset but brief duration
•Given IV but may be used subcutaneously
•Oral administration is ineffective
•Inactivated by intestinal enzymes |
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Term
Know how Epi can be administered |
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Definition
IV-Subcutaneously
Aerosol
Topical
There is poor penetration into the CNS
Metabolites appear in the urine |
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Term
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Definition
- CNS distrubances
- Hemorrhage
- Cardiac arrhythmias
- Pulmonary edema
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Term
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Definition
- Anxiety
- Tremor
- Fear
- Headaches
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Term
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Definition
| May produce cerebral hemorrhage as a result of blood pressure elevation |
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Term
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Definition
Epi can trigger cardiac arrhythmias
Particularly if pt is on Digitalis (digoxin)
EPI is Contraindicated w/ digoxin |
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Term
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Definition
Epi can exacerbate or cause Pulmonary Edema |
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Term
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Definition
Epi has enhanced CV actions in pts w/ hyperthyroidism |
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Term
|
Definition
- In the presenceof cocaine Epi produces exaggerated CV actions
- Cocaine prevents reuptake of Catecholamines
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Term
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Definition
- NE
- Stimulates ALL adrenergic receptors
- when given in therapeutic doses to humans α receptors are the most affected
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Term
NE--Cardiovascular
What 3 things can occur? |
|
Definition
- Vasoconstriction
- Baroceptor reflex
- Atropine pretreatment (to avaoid baroreceptor reflex)
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Term
Vasoconstriction using NE |
|
Definition
NE causes greater vasoconstriction than Epi
due to weak β2 activityof NE
•Rise in peripheral resistance due to intense vasoconstriction
•Both systolic and diastolic Blood pressure increase
•Cause greater vasoconstriction than epi because it does not induce compensatory vasodilatation due to weak β2 activity
•No value in treatment of asthma (b/c very weak β2 activity) |
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Term
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Definition
•In vivo little cardiac stimulation is noted
•Due to increasing BP induces a reflex rise in vagal activity
•Vagal bradycardia overcomes the action of norepi
(pretreat w/ Atropine if want to use this drug) |
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Term
***Atropine pretreatment*** |
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Definition
*********KNOW**********
If Atropine is given prior to the NE, the Atropine BLOCKS the vagal effect and the result is Tachycardia |
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Term
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Definition
- Used to treat SHOCK
- Metaraminol is the drug of choice since it does NOT reduce blood flow to the kidney
NE has very LIMITED therapeutic use |
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Term
Isoproterenol
CV?
Pulmonary?
Other effects? |
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Definition
-
CV: Intense stimulant (see Fig. 6.12)
-
Pulmonary: Profound rapid bronchodilation
-
Other effects: Not significantly significant
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Term
Isoproterenol
Therapeutic uses |
|
Definition
- Rarely USED as a bronchodilator
- Can be employed to stimulate the heart in emergency situations
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Term
Isoproterenol
Pharmokinetics |
|
Definition
- Absorbed sublingually
- More reliably absorbed given parentally
- Marginal substrate for COMT
- MAO stable
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Term
Isoproterenol
Adverse effects |
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Definition
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Term
|
Definition
- Immediate metabolic precursor to Norepi
- Can activate both alpha and beta receptors
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Term
**Know Action of Isoproterenol and DA
Fig 6.13 |
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Definition
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Term
Actions of Dopamine (DA)
CV |
|
Definition
•Cardiovascular
•Stimulatory effect on the β 1 receptors of the heart having both inotropic and chronotropic effects
•At very high doses activates the α receptors resulting in vasoconstriction |
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Term
Actions of Dopamine (DA)
Renal and visceral |
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Definition
•Renal and visceral
•Dilates renal and splachnic arterioles
•Increases blood flow to the kidneys |
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Term
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Definition
- SHOCK drug of choice for shock given by continuous infusion
- Raise the blood pressure stimulating the heart and more importantly increase blood flow to the kidneys
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Term
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Definition
•Overdose of dopamine produces the same effect as sympathetic stimulation
•Nausea, hypertension, arrhythmias |
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Term
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Definition
•Actions
•synthetic direct acting catecholamine
•Β1 receptor agonist
•Therapeutic uses
•Increase cardiac output in CHF
•Adverse effects
•Increases AV contraction |
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Term
|
Definition
•Direct acting synthetic adrenergic drug
•Binds to α and favors α1
•Not a substrate for COMT
•Raises systolic and diastolic BP no effect on heart
•Used topically as nasal decongestant (note: causes Rhinitis medicomatosa) |
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Term
|
Definition
•Direct acting synthetic adrenergic drug
•Binds primarily to α receptors with for α1
•Favored
•Raises blood pressure by stimulating α 1 receptors in arterioles
•Used to relieve attacks of paroxysmal supraventricular tachycardia
•Adverse effects hypertensive HA vomiting |
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Term
|
Definition
•Α2 agonist used to lower BP in essential hypertension
•Action is in the CNS
•Produces inhibition of sympathetic vasomotor centers |
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Term
|
Definition
•Not a catecholamine
•Administered orally or inhalation
•Produces dilatation of bronchioles
•Bronchodilator fo asthma |
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Term
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Definition
•Short acting β2 agonist
•Bronchodilators
•Good bronchodilator with few cardiac side effects |
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Term
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Definition
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Term
Indirect Acting Adrenergic Agonist
What are 2 agents? |
|
Definition
- Amphetamine (marked CNS stimulation and increase in BP)
- Tyramine (found in foods--cheeses, wines, beer, etc. fermented food--pts on MAOI-can precipitate effects, avaoid Tyramine)
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Term
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Definition
- Marked CNS stimulation
- Can increase blood pressure
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Term
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Definition
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Term
Mixed action Adrenergic agonist |
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Definition
•Ephedrine
•Not only releases stored norepi but stimulates both α & β receptors
•Ephedrine is a mild CNS stimulant |
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Term
***KNOW LIST OF DRUGS ON PG 81 FIG 6.17*** |
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Definition
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