ANS pharmacology Flashcards
What is the basic cycle of ACh being created and used between neurons?
What are the birth-to-death steps for ACh activation of muscarinic/nicotinic receptors?
- ‘Acetyl-CoA + Choline synthesizes to ACh.
- ACh is stored in synaptic vesicles, waiting for release.
- When stimulated, ACh is released into the synaptic cleft.
- It binds to post-synaptic nicotinic or muscarinic receptors.
- In the cleft, Acetyl-cholinesterase (AChE) breaks down ACh into acetate and choline. The choline is reabsorbed into the ACh neuron.
The basic pattern is: synthesis, storage, release, metabolism (breakdown), and activation of the receptor.
What are the primary neurotransmitter and primary receptors of the parasympathetic system?
The primary neurotransmitter is ACh.
The primary receptors are muscarinic and nicotinic.
Describe the transmitters and receptors in Adrenergic neurons.
How is NE formed in the pre-synaptic neuron?
What are the roles of MAO and COMT?
- In adrenergic neurons, NE binds with alpha-1, alpha-2, beta-1, and beta-2 receptors.
- Tyrosine forms DA which forms NE
- MAO and COMT metabolize NE.
What are the six ways we can manipulate the ANS?
What are the two primary categories of cholinergic stimulants/agonists?
What are other categorical distinctions for these drugs.
Q: What are the two primary categories of cholinergic stimulants?
A: direct-acting (on receptor) and indirect-acting (prevent breakdown of ACh).
Direct acting drugs, depending on where they are and what they are doing, will bind to muscarinic receptors to activate nerves, heart and smooth muscles, and glands and endothelium; or they can activate nicotinic receptors which will activate meuromuscular end plate and skeletal muscles, and the autonomic ganglion cells.
These same effects can be achieved by indirect acting drugs which simply increase ACh by blocking acetylcholinesterase and preventing ACh breakdown.
The direct-acting drugs are divided into alkaloids and choline esters. THe indirect-acting drugs are divided into reversible (permanently bind to AChE) or reversible. Each of these is divided into drugs that target muscarinic or nicotinic receptors.
What are some clinical uses of cholinergic drugs?
myasthenia gravis = autoimmune disease related to thymus; edrophonium is a short-acting medication that is diagnostic for the disorder
What are the symptoms of cholinergic toxicity?
SLUDGE
MTWTF (weekdays)
Trivia: Insecticides are often cholinergic and are the cause of many cases of cholinergic toxicity.
What are clinical uses of anti-cholinergics?
- mydriasis = pupil dilation
- imipramine = a tricyclic antidepressant with anti-cholinergic properties that is used for incontinence
- When prescribing drugs to reduce secretions (e.g. in respiratory tract), but by dessicating the secretions, this can also make them more gummy and difficult to move, so be careful
- Atropine is useful in treating bradycardia and to decrease GI motiflity
- Glycopyrrolate is used to treat incontinence
What are the 5 symptoms of anti-cholinergic toxicity?
H
D
M
R
B
Hot as a hare in the desert (altered thermoregulation)
Dry as a bone (decreased exocrine gland secretion)
Mad as a hatter (altered mental status)
Red as a beat (flushing)
Blind as a bat (dilated pupils, loss of accommodation)
See diagram of cholinergic agonists and antagonists.
… prof it unsure why nicotine is both antag/ag here.
What are the types of action of adrenergic agonists (sympathomimetic drugs)?
Adrenergic Agonists (sympathomimetic drugs that mimic the sympatnetic nervous system)
Similar to cholinergic agonists, different adrenergics can either directly stimulate receptors in the SNS or indirectly activate it by enhancing NE and E neurotransmitters.
Types of indirect action can be increasing pre-synaptic release, preventing NE or E reuptake, or inhibiting breakdown of NE or E.
What are the clinical uses of adrenergic /sympathomimetic drugs?
What determines their effect?
The effect of a sympathommimetic is determined by the receptor it targets (e.g. Alpha 1 or Alpha 2).
Alpha 1 (vascular smooth muscle that constrict on activation)
- treats hypotension via peripheral vascular constriction (phenylephrine, midodrine)
- Oxymetazoline (OTC decongestants)
Alpha 2 (decreases sympathetic tone through central inhibition, increasing dilation)
- Treats hypertension
- Clonidine, methyldopa treat HTN
- Guanfacine also treats ADHD
What is the primary action of activating an alpha 2 receptor with an agonist?
Alpha 2 agonists caause vasodilation by centrally inhibiting sympathetic tone. There is some peripheral vasoconstriction but this is minor. This is used to treat hypertension.
Common meds: clonodine, methyldopa, guanfacine
What is the primary action of an alpha-1 agonist? What does it treat?
Alpha-1 agonists cause peripheral vasoconstriction and can be used to treat HYPOtension.
Common meds: phenylephrine, midodrine, oxymetazoline
What are the major actions, uses, and common drugs of Beta-1, Beta-2, and dopaminergic agonists?
Beta-1 agonists
- Beta-1 receptors will increase chronotropy / inotropy (contractility of heart)
- Epinepherine and norepinepherine are naturally occuring agonists, also used as drugs
- Isoproterenol is useful for heart transplants to increase heart rate as body adapts to presence of the new heart
Beta-2 agonists
- Bronchodilation
- albuterol and epinepherine (epipen)
Dopaminergic
- Relaxation of renal, sphlancnic vasculature
- Renal dose dopamine are low doses (2-3 mcg/min). At higher doses of dopamine you get Beta-1 (heart) and then higher shows Beta-2 activity.
Review of Beta Adrenergic Agonists
What are the primary receptor affinities for isoproterenol?
What are the primary receptor affinities for dobutamine?
What are the primary receptor affinities for dopamine?
What are the primary receptor affinities for epinephrine?
What are the primary receptor affinities for norepinephrine?
What are the primary functions of binding an adrenergic antagonist to alpha-1 and alpha 2-receptors?
Alpha-1 adrenergic antagonism:
- lowers blood pressure (anti-hypertensive).
- relaxes smooth muscle in the prostate
- Common reversible alpha-1 antagonists are phentolamine and prazosin
- Common irreversible alpha-1 antagonist is phenoxybenzamine
- This can be given in heart surgery to relax the muscle, counterbalanced with beta meds
Alpha 2 adrenergic antagonists
- treats orthostatic hypotension
- Erectile dysfunction
What are the key decisions in choosing a beta blocker?
Choosing a beta blocker:
First: Choose its target receptor (B1, B2, or non-selective)
Second: +ISA or -ISA (intrinsic sympathomimetic activity = partial agonism)
Note: Carvedilol is most often used in HF
ANS drug and receptor chart (review)
CORE Q
What is the difference between PSNS and SNS?
What are their primary roles in regulation of the body?
What are the primary transmitters and receptors of each?
PSNS
- Purpose is rest and digest.
- Primary transmitter is ACh
- Primary receptors are muscarinic and nicotinic
SNS
- Purpose is fight or flight
- Primary transmitters are Norepinepherine, Epi, DA
- Receptors A-1, A-2, B-1, B-2, DA
- Alpha-1:
- Alpha-2:
- Beta-1:
- Beta-2:
- Dopamine:
