topic 21 Flashcards
What are nine examples of directly acting sympathomimetic agents (agonists)? What receptors do they work at?
α1, α 2, β1, β2, - epinephrine
α1,α2, β1 - norepinephrine
α1 - phenylephrine
α2 - clonidine
β1, β2 - isoproterenol
β1 - dobutamine
β2 - terbutaline; albuterol; metaproterenol
How do you differentiate between direct acting sympathomimetic agents, mixed acting, and indirect acting? What are examples of mixed acting and indirect acting? How do they work?
Direct acting agents action is not reduce by pretreatment with reserpine or guanthidine (deplete NE). In fact, it may be increased b/c reserpine could cause superselectivity (upregulation of receptors).
Indirect acting agents aciton is depleteed by pretreatment with reserpine or guanthidine b/c they simply cause NE to be released so they can’t work if there is no NE (Amphetamine and tyramine)
Mixed acting agents action is reduced by pretreatment with reserpine and guanthidine b/c they act directly and indirectly by releasing NE (ephedrine)
Where is the A1 receptor throughout the body? What effect does it have in general and at each location? What are some directly acting agonists of it?
In general, it leads to contraction or stimulation
Phenylephrine (A1 specific), NE, E
Arteries-contraction
Arterioles-contraction
Veins–contraction
Eye-contraction of dilator m.
Heart-increase force of -contraction
Uterus-contraction-Stimulation
Salivary Glands-Stimulation
Sweat Glands-Stimulation
Exocrine Pancreas-Stimulation
Growth Hormone-Stimulation
GI sphincters-contraction
Urinary bladder (trigone)-contraction
Spleen-contraction
Pilomotor SM-Erects hair
Where is the A2 receptor throughout the body? What effect does it have in general and at each location? What are some directly acting agonists for it?
Mainly inhibition in general.
Clonidine (A2 selective), NE
All Organs Receiving Adrenergic Innervation-inhibition of NE release
Pancreas ( Beta cells)-Inhibition
Some vascular smooth muscle (arteries; arterioles)-Contraction
Fat cell-inhibition of lipolysis
Platlets-aggregation
sympathetic ganglia-Inhibition of ganglionic release
Where is the B1 receptor throughout the body? What effect does it have in general and at each location? What are some directly acting agonists for it?
Stimulation in general
E, NE, Isoproterenol (Beta selective), Dobutamine (B1 selective)
Heart: Increased rate, force, conduction velocity, ventricular excitability, glycogenolysis
JG Cells: Increase renin release
Where is the B2 receptor throughout the body? What effect does it have in general and at each location? What are some directly acting agonists for it?
Relaxation/Inhibition ingeneral
E, Isoprorterenol, Terbutaline (B2 selective)
Arteries-releaxation
Arterioles-relaxation
Veins-relaxation
Ciliary muscle-relaxation
Bronchi; Bronchioles-relaxation
GI Tract-relaxation of smooth muscle
Urinary bladder (detursor)–relaxation
Secretions-Inhibition
Uterus-relaxation
Pancreas ( beta cells)-stimulation of insuli release
Growth Hormone-inhibition
Mast Cells-Inhibition of histamine release
Skeletal Muscle-promotes potassium uptake
Liver-activates glycogenolysis
Where is B3 receptor? What effect does it have there?
Fat cells-Activated lipolysis
What effect does epinephrine have metabolically? How does it bring that about? Which receptors does it use? Which receptor does it mainly use? What pathways are used?
EPI leads to increase FA, Lactic acid, and glucose in the blood.
It binds to beta receptors, mainly beta 2.
LIver: Upon binding, Adenylate cyclase converts ATP to cAMP—>cascade of phosphorylations—>active phosphorylase breaks down glycogen into glucose which is converted to glucose and put into bloodstream.
Muscle: Same thing but glucose-6P can’t be broken down into glucose, so lactic acid is forme and released.
Fat cells: Same thing, but a lipase is activated which converts TGs into FA which are released.
How are SM cells contracted and relaxed? What can be said of the affect of cAMP on SM cells?
Contracted: Ca channels lead to increase calcium which binds with calmodulin and then activates MLCK (myosin light chain kinase) which activates MLC allowing actin to bind—>contraction
Relaxed: Adenylate cyclase is activated, leading to more cAMP which activates a kinase which inactivates MLCK—>relaxation
cAMP in SM cells will always lead to relaxation.
What is the general structure of an agonist catecholamine? What kinds of changes happen to the general structure? What results in better beta activity? better alpha activity, exceptions? better CNS activity? Antagonists? Prolonged activity?
2 carbons connected to an amine group. the beta carbon connected to a benzene ring usually with OH groups on 3,4 carbons on benzene ring
Beta activity is increased by substitutions to amine and more hydroxyl groups.
Less substitutions to amine results in increased alpha activity (Epi and phenylepi have one methyl group there but still activate alpha)
Removal of 4 carbon OH results in prolonged activity (COMT)
Substitution at alpha carbon leads to prolonged activity (MAO)
Less hydroxyls—>more CNS activity
More than just alpha and beta carbons—>antagonist
What happens with baroreflex control of arterial blood pressure? What are 3 exceptions to these rules?
There are baroreceptors in the aortic arch and internal carotid arteries which send signals through the aortic and carotid sinus nerves which end up in the vagus and glossopharyngeal nerves respectively. These afferent signals become more frequent with increase in bp and less frequent with decrease in bp. These afferent signals meet up in the NTS (CNS) with efferent sympathetic and parasympathetic neurons. The parasympathetic neurons which travel in the vagus nerve are increased when the afferent signals increase and decrease when afferent signals decrease. Therefore, when bp is high, the parasymp will cause heart rate to decrease through the action of ACh on the M2 nerve at SA node. The opposite happens when bp is low. The sympathetic neurons are inhibited by afferent signals. There are two branches from these sympathetic neurons, the cardiac nerve and the vasoconstrictor nerve. When bp increases, afferent signals increase, symp. signals decrease and the heart rate is slowed, contractility decreases, and vasocontstriction decreases. The opposite happens when bp decreases. This is all short term, within minutes.
Exceptions: Isometric exercise (diastolic bp and hr increase), diving reflex (decrease in art. pressure and hr), defense reaction (increase in art. pressure and hr).
What is the effect of epi and norepi on the heart, bp, peripheral circulation, and metabolic effects?
Cardiac
heart rate-y:n,0 stroke volume-yyyy:yy Card output-yyy:0,n arrhythmias-yyyy:yyyy coronary flow-yy:yyy
BP
systolic arterial-yyy:yyy
mean arterial-y:yy
Diastolic arterial-y,0,n:yy
Peripheral
total peripheral resistance-n:yy cerebral blood flow-y:0 Muscle blood flow-yy:0,n Cut blood flow-nn:y,0,n renal blood flow-nnn:n Splanchnic blood flow-yy,0,n:0,y
Metabolic effects
02 consumption-yy:0,y
Blood sugar-yyy:0,y
Blood lactic acid-yyy:0,y
What are 2 non-specific alpha/beta andrenergic receptor agonists
epi and norepi
What receptors does epinephrine work at? What are its physiological effects? What are its therapeutic uses? How is it administered? How is it broken down? What are its untoward effects?
Potent agonist at A1, A2, B1, B2
Increase in heart rate, bp, card. output, contractility. Slight decrease in PVR. Vasoconstriction. Vasodilation at skel. muscle. Increase in blood glucose, lactic acid, FAs.
It is a substrate for COMT and MAO so it is quickly broken down
Administered parentally (IM, IV, SC, etc.)
Used in anaphylaxis, cardiac stimulant, glaucoma, with local anesthetics
Untoward effects: palpitation, cardiac arrythmias, cerebral hemorrhage, headache, tremor, restlessness
What receptors does norepinephrine work at? What are its physiological effects? What are its therapeutic uses? How is it administered? How is it broken down? What are its untoward effects?
Potent A1, A2, B1 agonist
It is a substrate for COMT and MAO so it is quickly broken down
Increase in syst. and diast. bp. Increase in PVR. Direct increase in HR, but indirect decrease in HR. Vasoconstriction.
Administered parentally (IM, IV, SC, etc.)
Used as a pressor, usually post cardiac surgery.
Untoward effects similar to EPI (palpitations, arrythmias, cerebral hemorrhage, headache, tremors, restlessness) + Hypertension.
What receptors does phenylephrine work at? What is its prominent physiological action? What are its therapeutic uses? How is it administered? How is it broken down? What are its untoward effects?
Potent A1 agonist
It is a substrate for MAO
Causes vasoconstriction
Administered parentally (IM, IV, SC, etc.), orally, locally
Used as a pressor, nasal decongestant, mydriasis w/o cycloplegia, glaucoma
Untoward: Hypertension, reflex bradycardia, dry mouth, sedation, rebound hypertension upon abrupt withdrawal
