Lect 5: adrenergic stimulants Flashcards
What is the rate limiting step in the conversion from tyrosine to NE
conversion of tyrosine to l-dopa
Where is NE converted to epinephrine
adrenal medulla
effect of tyramine and amphetamine on NE release
increase or cause the release of NE from the presynaptic terminal. Therefore these drugs have an effect only if noradrenergic innervation is intact.
antidepressants and cocaine effect on NE
block the reuptake of NE into the presynaptic terminal
- This is the main mechanism for termination of the action of NE in the synaptic cleft.
NE is metabolized by what two enzymes
monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).
List the steps from tyrosine to NE
Tyrosine -> L-DOPA-> dopamine -> NE
What are adrenergic receptors
alpha and beta receptors
differentiate between direct and indirect drugs
- direct: act on receptors to mimic sympathetic stimulation
- indirect: increase synthesis, cause release, or inhibit re-uptake/breakdown
what happens to effect of direct and indirect drugs with denervation
- abolish effect of indirect drugs
- may enhance effect of direct drugs
NE, epinephrine, and isoproterenol: list order of effect on alpha receptors
- epi > NE > > isoproterenol
what is phenylephrine
an alpha 1 agonist
alpha 1 acts via what G protein
- Gq
- excitatory
alpha 2 acts via what G protein
- Gi
- inhibitory
what is clonidine
alpha 2 agonist
which adrenergic receptor is responsible for constriction of blood vessels to skin, kidneym mucous membranes
alpha 1
which adrenergic receptor is responsible for the relaxation of BV to skeletal muscle
beta 2
which adrenergic receptor is responsible for relaxation of gut wall and bronchioles
beta 2
which adrenergic receptor is responsible for cardiac excitatory
beta 1
which adrenergic receptor is responsible for lipolysis in fat cells
beta 3
which adrenergic receptor is responsible for modulation of insulin and renin
beta 1
Which drug has a high affinity for all beta receptors
Isoproterenol
NE does not have much of an effect on which beta receptor
Beta 2
Epi and NE affinity for B1 receptors
same effect; but less than isoproterenol
what is dobutamine
beta 1 agonist
function of dobutamin on heart and renin secretion
- increase HR and contractility
- increase renin secretion
what is albuterol
a beta 2 agonist
function of albuterol on bronchiol smooth muscle, skeletal muscle BV, uterus, bladder, and GI muscle?
Relax
which adrenergic receptor is responsible for glycogenolysis/gluconeogenesis
beta 2
function of dopamine 1 receptors
- Dilate renal BV, increase renal blood flow
alpha receptor stimulation by NE effect on cardiovascular function
-
Skin and splanchnic blood vessels have mainly α receptors
- Smaller blood vessels are more densely innervated than larger ones, therefore the largest effect is on small blood vessels.
- Net effect is to increase blood pressure.
- Peripheral artery resistance is increased and venous capacity is decreased
- Increased blood pressure will stimulate baroreceptors, which then increase vagal input to slow the heart
what happens to cardiovascular response if atropine is given prior to norepinephrine
the vagal reflex is inhibited, the baroreceptor effect will not occur, and heart rate will increase
NE must be injected; why is it used only rarely, for severe hypotensive crisis
NE can cause severe vasoconstriction at the infusion site and can cause necrosis
NE has what strength of effect on alpha, beta 1 and beta 2 receptors?
stimulates α and β1 receptors, with little effect on β2 receptors
(α = β1>> β2)
epinephrine has what strength of effect on alpha, beta 1 and beta 2 receptors?
Epinephrine stimulates α, β1 and β2 receptors, which makes the effect complex
***the effect depends upon the dose administered
which receptors are most sensitive to epinephrine
- B2 receptors in blood vessels supplying skeletal muscle are more sensitive to epinephrine than alpha receptors
what effect does low dose epinephrine stimulation have on alpha, beta 1 and beta 2 receptors
-
beta1 receptors increase heart rate, conduction, contractility
- (inc systolic pressure)
-
alpha receptors constrict blood vessels in the skin, mucosa and kidney
- increased systolic
-
beta2 receptors relax blood vessels supplying skeletal muscle
- decrease in diastolic pressure
- pulse pressure increases
- since mean blood pressure is unchanged, there is little reflex slowing of the heart rate -> heart rate is increased
what effect does high dose of epinephrine have on systolic, diastolic, and mean arterial pressure
-
alpha receptors in blood vessels supplying skeletal muscle are stimulated
- diastolic pressure increases
-
increases blood pressure substantially
- both systolic and diastolic pressure will increase
-
mean pressure increases
- there is less increase in heart rate
epinephrine has a short duration of action and must be administered via
injection
Explain how an alpha block can be used to reverse the effect on high dose epinephrine and not norepinephrin
- taking out alpha receptors from high dose epinephrine leaves beta 2 receptor activation which causes vasodilation of BV to skeletal muscle and BP drops
- NE has no effect on B2 receptors
what are the primary uses of epinephrine
- bronchodilation in severe asthma attack via B2
- vasoconstrictor: decrease diffusion of injected drugs such as local anesthetics
- anaphylactic shock to restore blood pressure, decrease bronchospasm, decrease congestion and angioedema, and reverse cardiovascular collapse
what are some side effects of epinephrine
tremor, throbbing headache, increased blood pressure, tachycardia, angina
why is epinephrine contraindicated in people taking beta-blocker
unopposed effects on α receptors may lead to severe hypertension!
what is Ephedrine
- a drug that : stimulates α and β receptors similar to low-dose epinephrine, and also increases NE release
- long duration of action
- CNS stimulant
- bronchodilator
- taken off market due to deaths from high BP and stroke
