ANS Drugs Flashcards
What happens when a nicotinic receptor is activated?
there is an influx of positive ions, which depolarize the cell
Describe the distribution, second messenger system, and effects of M1, M2, and M3 receptors.
- M1 are coupled to Gq and can be found in the CNS
- M2 are coupled to Gi and can be found in the SA node, AV node, and atria to reduce heart rate, AV conduction velocity, and atrial inotropy
- M3 are coupled to Gq and can be found in glands and smooth muscle where they mediate smooth muscle relaxation and gland activation
What effect does a low dose of IV cholinomimetic have? What is this effect dependent on?
- the cholinomimetic will active M3 receptors on endothelial cells, triggering release of NO, which causes smooth muscle relaxation and vasodilation
- this effect, then, is dependent on the presence of an intact endothelium
What is bethanochol?
a muscarinic agonist
What is pilocarpine?
a muscarinic agonist
What is varenicline?
a nicotinic agonist used for smoking cessation
What is carbachol?
a muscarinic and nicotinic agonist
What is methacholine?
a muscarinic agonist used as a “challenge” to test for asthma
What drugs end in the suffix “-stigmine”?
acetylcholinesterase inhibitors
What is the preferred treatment for myasthenia gravis?
pyridostigmine or neostigmine, long-acting acetylcholinesterase inhibitors that don’t penetrate the CNS
Describe the tensilon test.
- a test used to determine whether an individual with myasthenia gravis is being over or under treated
- when edrophonium is given, systems should improve if under treated and worsen if over treated
Why cholinesterase inhibitors don’t penetrate the CNS? Which do penetrate the CNS?
- the quaternary amines neostigmine, pyridostigmine, and edrophonium don’t enter the CNS
- the tertiary amines like physostigmine do
What is the mechanism of action of the curare drugs?
they are non-depolarizing NMJ blockers that directly inhibit nicotinic activity at the skeletal muscle end plate
What is succinylcholine used for?
it is a depolarizing NMJ blocker
How does succinylcholine compare to tubocurarine?
succinylcholine is a depolarizing NMJ blocker whereas tubocurarine is a non-depolarizing blocker, thus succinylcholine may cause an initial period of fasciculations and muscle soreness and can’t be readily reversed by acetylcholinesterase inhibitors
What is the preferred treatment for atropine poisoning?
physostigmine because it is an acetylcholinesterase inhibitor that penetrates the CNS
What are organophosphates?
acetylcholinesterase inhibitors that demonstrate aging
How is insecticide or organophosphate poisoning treated?
- pralidoxime is used to regenerate acetylcholinesterase in the periphery but doesn’t penetrate the CNS
- atropine is used to control the CNS effects
Name three acetylcholinesterase inhibitors used to treat Alzheimer’s disease.
- galantamine
- donepezil
- rivastigmine
What is atropine?
a muscarinic antagonist
Which two plants are known to contain natural atropine?
- atropa belladona (aka deadly nightshade)
- datura stramonium (aka jimsonweed)
What is scopolamine and it’s primary use?
a muscarinic antagonist used primarily for the treatment of motion sickness as a transdermal patch
What are ipratropium and tiotropium?
inhaled M3 antagonist used to reduce pulmonary secretions and bronchodilation in those with COPD
What are oxybutinin and tolterodine?
M3 antagonist with selectivity for receptors in the bladder and thus used to treat urgency incontinence
What are benztropine and trihexyphenidyl?
M1 antagonists used to treat the tremor and rigidity of Parkinson’s or the EPS effects of anti-psychotic medications
Describe the effects of activating a1 receptors, including the receptor cascade involved.
- a1 receptor activation triggers a Gq cascade
- this results in arterial and venous constriction
- as well as mydriasis and sphincter contraction
Describe the effects of activating a2 receptors, including the receptor cascade involved.
- a2 receptors are linked to a Gi cascade on presynaptic cells
- activation inhibits insulin release, lipolysis and fat mobilization, and aqueous humor production
- activation also inhibits neurotransmitter release
What is the effect of brimonidine?
it is an a2 receptor agonist used to reduce aqueous humor production for the treatment of chronic open angle glaucoma
Describe the effects of activating B1 receptors, including the receptor cascade involved.
- B1 receptors are linked to a Gs cascade
- they are located on cardiac myocytes and JGA cells
- activation leads to an increased heart rate, improved inotropy, and renin release
Describe the effects of activating B2 receptors, including the receptor cascade involved.
- B2 receptors are linked to a Gs cascade
- activation leads to bronchodilation and vasodilation in the lungs and skeletal muscle as well as coronary dilation
- activation also has many metabolic effects, stimulating gluconeogenesis, release of insulin, and lipolysis and fat mobilization
- B2 receptor stimulation also induces greater aqueous humor production
What is phenylephrine?
an a1 agonist, it is used as a nasal decongestant and can also be used to induce mydriasis
What is the effect of phenylephrine, an a1 agonist, on a pressure curve?
- because it constricts arteries and veins, it causes an increase in systolic, diastolic, and mean arterial pressure
- it will, however, also induce a reflex bradycardia
What is the selectivity of norepinephrine?
it has significant alpha activity and some B1 activity
What is the effect of norepinephrine on a pressure curve?
- it’s alpha activity causes arterial and venous constriction, raising systolic and diastolic pressure
- it’s beta1 activity increases inotropy, widening pulse pressure
- it induces a reflex bradycardia but increases systolic, diastolic, and mean arterial pressure
What is the selectivity of dobutamine?
it has primarily beta1 activity and some beta2 activity
Describe the effect of dobutamine on a pressure curve.
- it has primarily beta1 activity but some beta2 activity
- beta1 activity increases heart rate and inotropy, increasing systolic arterial pressure and widening pulse pressure
- beta2 activity causes vasodilation and a drop in diastolic pressure
- together, the mean arterial pressure remains relatively unchanged although the pulse pressure is widened
What are the preferred treatments for distributive or hypovolemic shock and cardiogenic shock?
- distributive or hypovolemic shock: a1 agonists
- cardiogenic: B1 agonists
B2 agonists are useful in the treatment of what?
bronchoconstriction
Describe the selectivity of isoproterenol.
it has equal B1 and B2 activity
What is the effect of isoproterenol on a pressure curve?
- it has equal B1 and B2 activity
- in this case, the vasodilation caused by B2 outweighs the increase in heart rate and inotropy elicited by B1
- the result is a drop in diastolic pressure, a drop in MAP, a widened pulse pressure, and relatively unchanged systolic pressure
What is terbutaline?
a selective B2 agonist used to stop premature uterine contractions by relaxing smooth muscle
What is ritodrine?
a selective B2 agonist used to stop premature uterine contractions by relaxing smooth muscle
Describe the selectivity of epinephrine and it’s effect on a pressure curve.
- at low dose, it has greater beta activity and at higher dose it has greater alpha activity
- typically, it causes a rise in systolic pressure, a small drop in diastolic pressure
- thus, it increases MAP and widens pulse pressure
What is metyrosine?
a drug that blocks conversion of tyrosine to L-dopa and thus has a sympatholytic activity
What is reserpine?
a drug that blocks the VMAT and packaging of catecholamines into synaptic vesicles, thus is has a sympatholytic activity
What is atomoxetine?
an NET antagonist that maintains high synaptic levels of NE and is used to treat ADHD
Describe the mechanism of action and effects of cocaine.
- it blocks NET and DAT, keeping catecholamines in the synaptic cleft
- in doing so it causes mydriasis, tachycardia, hypertension, and CNS arousal
- long-term use is associated with atrophy of the nasal mucosa and septal perforation because it is vasoconstrictive
- it’s vasoconstrictive activity can also lead to MI and angina
Why should beta blockers never be used in those with cocaine in their system?
because it leads to unopposed alpha1 activity and hypertension
How do amphetamines work?
they displace catecholamines from synaptic vesicles, releasing them into the synaptic cleft
What is modafinil?
a stimulant used to treat narcolepsy
What vascular effects do D1 receptors mediate?
activation of D1 with an agent like fenoldopam leads to widespread vasodilation which uniquely includes the renal vasculature and can be used in hypertensive emergency
Dopamine agonists have what sympathetic activity?
- at low dose, D1 agonists bind D1 receptors and cause widespread vasodilation including in the renal and coronary vasculature
- at higher dose, they begin activating B1 receptors and stimulate the heart
- at even higher doses, they being activating a1 receptors and have a vasopressor effect
What is clonidine?
- a centrally-acting a2 agonist
- reduces sympathetic tone
- useful in the treatment of hypertensive urgency, ADHD, and tourette’s syndrome
What is a-methyldopa?
- a centrally-acting a2 agonist
- reduces sympathetic tone
- useful in the treatment of gestational hypertension
- may cause a lupus-like syndrome
What is tizanidine?
an a2 agonist that is useful as a muscle relaxant
What is phentolamine?
- a reversible a1 and a2 antagonist
- used in the treatment of cocaine-, tyramine-, and pheochromocytoma-induced hypertensive crisis
- may cause orthostatic hypotension with reflex tachycardia
What is phenoxybenzamine?
- an irreversible a1 and a2 antagonist
- used in the treatment of cocaine-, tyramine-, and pheochromocytoma-induced hypertensive crisis
- may cause orthostatic hypotension with reflex tachycardia
Which drugs end in the suffix “-osin”?
alpha1 antagonists (“o” for opera and “sin” for singer - phantom of the alpha)
What is prazosin?
- an alpha1 antagonist
- used in the treatment of hypertension and PTSD
- may cause orthostatic hypotension with reflex tachycardia
What is mirtazapine?
- an alpha2 agonist
- used to treat depression because it disinhibits presynaptic neurons and increases release of norepinephrine and serotonin
What is carvedilol?
a nonselective beta blocker that also has alpha1 antagonist activity
What is labetolol?
a nonselective beta blocker that also has alpha1 antagonist activity
Name two beta blockers with a1 antagonist activity as well.
carvedilol and labetolol
Name five B1-selective blockers.
those that are in the first half of the alphabet (A-BEAM)
- atenolol
- betaxolol
- esmolol
- acebutolol
- metoprolol
Name two beta blockers with partial agonist activity.
acebutolol and pindolol
How is beta-blocker over dose treated?
glucagon
What are the clinical uses for beta-blockers.
- treatment of hypertension and hypertensive crisis
- treatment of MI, reducing mortality
- management of chronic heart failure
- treatment of arrhythmias
- treatment of hypertrophic obstructive cardiomyopathy
- treatment of thyroid storm
- migraine prophylaxis
- treatment of essential tremor
What is labetolol?
- a non-selective beta blocker with alpha1 antagonist effects
- used for the treatment of gestational hypertension
- available IV for the treatment of hypertensive crisis and aortic dissection
Beta-blockers can exacerbate which two pre-existing conditions?
chronic pulmonary disease (COPD or asthma) and heart block
