Pharm 5 Lecture Flashcards
What is the main sympathetic nervous system neurotransmitter?
Norepinephrine
What is released from the adrenal medulla (when stimulated by SNS) as a HORMONE?
Epinephrine
Catecholamines
hormones made by the adrenal glands, release when a person is under physical or emotional stress, high potency, quick duration, does not penetrate BBB, easily broken down, can’t be taken orally
What are some examples of catecholamines?
Norepinephrine (Noradrenaline)
Epinephrine (adrenaline)
Dopamine
Dobutamine
What are the 6 steps of adrenergic neurotransmission?
- Synthesis of norepi
- uptake into storage vessicles
- release of neurotransmitter
- binding to receptor
- removal of norepi
- metabolism
What is the rate-limiting step of the synthesis of norepinephrine?
Hydroxylation of tyrosine into DOPA (dihyro-Phenoxyalanine)
What is the main precursor to epinephrine?
Dopamine
When is dopamine converted to norepinephrine?
Inside the vessicle; where it is protected from degradation
What inhibits transport of dopamine into the vessicle?
Reserpine
What causes fusion of the vesicle containing norepi with the cell membrane in a process known as exocytosis?
Influx of calcium causes the fusion
What blocks the release of the vesicle containing norepi?
Guanethidine and bretylium
What prevents reuptake of norepinephrine?
Cocaine and imipramine
What metabolizes norepineprhine?
Methylated by Catecol-O-methyl transferase (COMT)
Oxidized by Monoamine oxidase (MAO)
DOPA
dihydro-Phenoxyalanine
How does DOPA –> Dopamine?
Dopa is decarboxylated
Isoproteronol
A direct acting synthetic catecholamine
Alpha Adrenoceptors in order of affinity
Highest Affinity: Epinephrine
Norepinephrine
Lowest: Isoproterenol
Beta Adrenoceptors in order of affinity
Highest affinity: Isoproterenol
Epinephrine
Lowest: Norepinephrine
What are the names of the dopaminergic receptors?
D1, D2, D3, D4, D5
A1 receptors have a relatively high affinity for….
Norepinephrine
A2 receptors have a high affinity for….
Clonidine (Catapres), an antihypertensive drug
What does alpha 1 innervate?
Smooth muscle of most non-cardiac origin
What are the effects of stimulating alpha 1?
vasoconstriction; increased bp
mydriasis (dilation of pupils)
increased bladder tone
increased tension in prostate
What are the effects of stimulating alpha 2?
Creates negative feedback loops (prejunctional nerve terminals)
Some GI and digestive effects
Where are alpha 2 receptors located?
Prejunctional nerve terminals
Why would we stimulate alpha 2?
Increasingly used in human cardiovascular surgery as a sedative as part of multi-modal anesthesia
What are some advantages to stimulating alpha 2 during srugery?
Modulates DPB-induced inflammatory responses better than glucocorticoids (such as a cortisol)
Sympatholytic effects help ameliorate unwanted CV reflexes post-op
less respiratory depression postop than other options
What is the one alpha 2 drug used in humans?
Dexmedetomidine (precedex)
What has affinity for Beta 1 receptors?
Equal affinity for norepinephrine and epinephrine (both less than isoproterenol)
What has affinity for Beta 2 receptors?
More affinity for epinephrine than norepinephrine
Both again, have more affinity than isoproterenol
What are Beta 3 receptors involved in?
Lipolysis
What tissues have beta 1 receptors?
Many, but mostly in the heart!
What are the effects of beta 1 stimulation?
Positive chronotrope
Positive ionotrope
Increased lipolysis (triglycerides feed heart)
Kidneys release more renin (vasoconstriction, increase bp)
What do beta 2 receptors mostly affect?
lungs
What are the effects of beta 2 stimulation?
Mostly relaxation of pulmonary smooth muscle
vasodilation in skeletal muscles and liver and some organs
insulin release (energy jolt)
uterine muscle relaxation
increased liver output metabolic food via glycogenolysis
What is the effect of stimulating dopaminergic receptors?
Positive chronotrope
Positive ionotrope
vasoconstriction (at high doses)
increased blood flow to the kidneys
What acts as both a hormone and neurotransmitter?
Epinephrine
What does epinephrine stimulate?
alpha and beta; the archetypical adrenergic response
What are the effects of epinephrine?
Positive inotrope and chronotrope (B1)
Kidneys release renin, results in vasoconstriction, bp (B1)
Increased CO and O2 consumption
Dilates arterioles to liver and skeletal muscle (B2)
Bronchodilation (B2)
Pancrease releases glucagon; increase gluconeogenesis; the creation of glucose; hyperglycemia (B2)
Constricts arterioles to mucous membranes, viscera, skin (A1)
What does epi affect at low doses?
Beta affects predominate
What does epi affect at high doses?
alpha effects
How is epinephrine administered?
IV, IM, SQ, endotracheally (not orally)
What degrades epinephrine?
Monoamine oxidase
catechol-o-methyl transferase
CPR dose of epinephrine
1mg IV/IO every 3-5 min
What is epi used for?
Hypotension and shock
Anaphylaxis and shock Type I hyeprsensitivities
Asthma /bronchoconstriction
In conjunction with local anesthetics (like lidocaine)
What are the perfusion doses of epinephrine for an adult?
2-10 ug bolus PRN to effect
1-10 ug/min infusion given to effect
What are the perfusion doses of epinephrine for a ped?
- 05-10 ug/kg bolus
0. 05-0.5 ug/kg/min infusion
What adrenoreceptors does norepi affect?
Alpha and Beta 1
little effect on beta 2
What are some other names for norepinephrine?
Noradrenaline
Norepinephrine
Levarternol
What are the cardiovascular effects of norepi?
Profound vasoconstriction (Alpha) w.o B2 effects
Both systolic and diastolic BP’s increase
increase SVR
Positive inotrope (B1) but little chronotrope
Why is there little chronotropic effect of norepinephrine?
Baroreceptor reflex arcs; increase parasympathetic stimulation which decreases HR, decreases sympathetic stimulation which decreases HR and SV. Vasodilation decreases HR and SV and tried to bring BP to normal
How is norepinephrine administered?
Generally given by bolus or more commonly, infusion
short half life
What is the adult dose of norepinephrine?
0.5- 12.0 mcg/min titrated to effect
Why can’t you give norepinephrine Sub Q?
Causes necrosis
What do high doses of dopamine affect?
Alpha receptors, arterial and venous vasoconstriction
What do low doses of dopamine effect?
Beta receptors; vasodilation to kidneys, brain and viscera
What are the effects of dopamine?
Positive inotrope and chronotrope (B1)
Vasoconstriction at high doses (A1)
Increase renal blood flow (D receptors)
Increased visceral perfusion (D receptors)
What do medium doses of dopamine effect?
increased cardiac output
What are the high, medium, and low doses of dopamine?
Low: 1-2 mcg/kg/min
Medium: 2-10 mcg/kg/min
High: >10 mcg/kg/min
What is the drug of choice for cardiogenic or septic shock?
Dopamine
What is dopamine used to treat?
Cardiogenic or septic shock
Renal failure
Hypotension (particularly low output renal failure)
CHF (particularly low output renal failure)
What is the synthetic analog of dopamine?
Dobutamine (Dobutrex)
What receptors does dobutamine work on?
B1 selective agonist
How does dobutamine compare to dopamine?
Dobutamine has greater inotropic and less chronotropic effect than dopamine (increases SV, CO)
What is the half life of dobutamine?
10 minutes with IV infusion; short half life
What is the dobutamine dose?
2-20 mcg/kg/min to effect (with HR not increasing >10% above baseline) in adults
2.5-10 mcg/kg/min in pediatrics
What is an advantage of dobutamine?
Causes less increase in myocardial O2 demand than the other catecholamines mentioned so far
What is dobutamine used for?
Short-term support of patients with CHF, as in struggling to separate from bypass
What is like dobutamine, but a PARTIAL B1 selective agonist?
Prenalterol
Both PO and IV used with a long duration of action (unlike isoproternol)
Isoproterenol (Isuprel)
Synthetic catecholamine B1 and B2 selective agonist
What are the effects of Isuprel?
Strong positive chronotrope and positive inotrope and a potent vasodilator B2)
Increases CO and decreases afterload
When is Isuprel used?
Mostly used as a cardiac stimulant in emergency situations (usually as a 2nd-line drug)
Neo
Relatively alpha 1 selective agonist
Potent vasoconstrictor, raises SBP/DBP, increase SVR
Causes reflex bradycardia
Can treat SVT
Why does neo have a longer DOA?
not a catecholamine derivative therefore not inactivated by COMT
Why is Neo commonly used as a nasal spray decongestant?
Phenylephrine decreases nasal congestion by acting on alpha 1 adrenergic receptors in the arterioles of the nasal mucosa to produce constriction.
What is dose of neo?
Adult: 50-200 ug repeated and given to effect
Peds: 0.05-0.5 ug/kg
“Mixed Action” Adrenergic Agonists
Ephedrine (vasopressor) and Pseudoephedrine
Sympathomimetics: cardiac stimulation, elevated systolic and diastolic BP’s, CNS stimulation, bronchodilation
What drug is metabolized into dopamine?
Levodopa (which doesnt cross the BBB)
What are dopaminergic agonists used for?
treating Parkinson’s Disease, cause by degeneration of dopamine- producing cells in the brain
