ANS - just the drugs and targets Flashcards
What are the 7 important Cholinergic Agonists?
Pilocarpine - M bethanechol - M (the rest are ache inhibitors) neostigmine pyridostigmine edrophonium donepezil organophosphate nerve gas
What are the 10 important Cholinergic Antagonists?
7 are antimuscarinics
atropine, scopolamine, benztropine, oxybutynin, tolterodine, ipratropium, tiotropium
3 are antinicotinics (NMJ)
atracurium, rocuronium, succinylcholine
Propantheline is what type of drug?
- Semisynthetic antimuscarinic
* Quaternary ammonium and thus relatively greater effect on GI motility
Glycopyrrolate is what type of drug?
- Semisynthetic antimuscarinic
* Quaternary ammonium and thus relatively greater effect on GI motility
Benztropine is what type of drug?
- Semisynthetic antimuscarinic
* Tertiary amine compounds so there is potential for CNS involvement
Oxybutynin is what type of drug?
- Semisynthetic antimuscarinic
* Tertiary amine compounds so there is potential for CNS involvement
Tolterodine is what type of drug?
- Semisynthetic antimuscarinic
* Tertiary amine compounds so there is potential for CNS involvement
Scopolamine is what kind of drug?
• A naturally occuring, alkaloid antimuscarinic
Hexamethonium is considered what type of drug?
• Ganglionic blocker, antinicotinic, anticholinergic
Atropine is considered what type of drug?
• Non selective antimuscarinic anticholinergic
Pralidoxime is considered what type of drug?
• Cholinesterase regenerator, anticholinergic (indirect)
Pirenzepine is considered what type of drug?
• M1 selective antimuscarinic anticholinergic
What does the drug Edrophonium do?
• Reversible, short acting ache inhibitor
what is special about pilocarpine?
It is highly lipophilic and can distribute anywhere, CNS or periphery
- that means any muscarinic receptor in the body is a target for pilocarpine
- also it is not ache degraded, only secreted by kidneys and trapped by acidic urine
What are the 8 important adrenergic agonists?
Each has a different receptor profile Epinephrine - alpha1, alpha2, beta1, beta2 Norepinephrine - alpha1, alpha2, beta1 isoproterenol - beta1, beta2 albuterol - beta2 phenylephrine - alpha1 pseudoephedrine - indirect agonist dobutamine - beta1 dopamine - D1 (important for renal vasculature), also an indirect SNS agonist
What are the 9 important adrenergic antagonists?
Doxazosin, Terazosin, Prazosin - alpha1 Metoprolol, Atenolol - beta1 Propanolol - beta1, beta2 Labetalol, Carvedilol - alpha1, beta1, beta2 Clonidine - alpha2 AGONIST
When an alpha2 adrenergic receptor is bound, what happens?
- Alpha2 receptor = Gi protein.
- cAMP is decreased as AC is inhibitied
- K channel opening is also a possible event
- When you see any Gi for neuro, think hyperpolarization
- The nerve terminal will be LESS ACTIVE
What kind of GPCR is the beta2 adrenergic receptor?
- Gs - increases AC, increasing cAMP (probably closing the K channel)
- End result is a positive nerve terminal response
What kind of GPCR is the beta1 adrenergic receptor?
- Gs - increases AC, increasing cAMP (probably closing the K channel)
- End result is a positive nerve terminal response
- Also Beta1 stimulation increases Ca conductance through L and N type Ca channels
What kind of GPCR is the alpha2 adrenergic receptor?
- Gi - inhibits AC, reducing cAMP and often opening a K channel
- End result is hyperpolarization of the nerve terminal
What kind of GPCR is the alpha1 adrenergic receptor?
• Gq - active PLC, release IP3 and DAG, releasing intracellulr calcium and activating PKC
For adrenergic agonists, what is the most common mechanism of indirect-acting agonists?
• At peripheral synapses, increasing the storage and release of NE/EPI is the most common mechanism of increasing SNS output by indirect means
What determines absorption by oral route of SNS agonists?
- Ability to resist first pass metabolism
- MAO and COMT in the liver
- Methyl group on alpha-carbon helps - escape MAO
- Non-catechols helps (no OH groups on phenyl ring) - escape COMT
Due to the molecular properties of SNS agonist drugs, what is the end result of their bioavailability?
- Catecholamine NT (NE and EPI) are not effective orally
- They also don’t enter the brain well
- Have short durations of action
- If you design a drug you have to strategically overcome these issues
What property of adrenergic SYMPATHOLYTIC antagonists greatly LIMITS their clinical utility?
• Lack of specificity
• They work at all adrenergic synapses
*thus we use adrenergic receptor blockers more than sympatholytic drugs
*these drugs work by modulating pre-synaptic nerve terminal thus they lose specificity
What are the two non-selective alpha adrenergic receptor blockers?
- Phentolamine and phenoxybenzamine
* Irreversible alpha1 and alpha2 blockers
What does alpha2 receptor activation do?
• CNS - stimulation of postsynaptic cells in the brain stem vasomotor center
○ Reduced peripheral SNS activity
• SNS - preferentially stimulates peripheral alpha2 (presynaptic) receptors
○ Reduces NE release from sympathetic neurons
• Overall, alpha2 receptors reduce SNS activity
What does the ANS do in the eye?
alpha1 adrenergic receptor - contraction of iris radial muscle, dilates the pupil
muscarinic receptor - contraction of iris sphincter muscle (pupil contracts), contraction of ciliary muscle (lens accommodates for near vision)
What does the ANS do in the trachea and bronchioles?
beta2 adrenergic receptor - dilates the airways
muscarinic receptors - constricts airways, increases secretions
What does the ANS do in the adrenal medulla?
nicotinic neruonal receptors - epinephrine and norepinephrine is secreted - has SNS effects, all adrenergic receptors are bound
What does the ANS do in the kidney?
beta1 adrenergic receptor - secretion of renin
alpha1 adrenergic receptor - decreases secretion of renin
What does the ANS do in the ureters and bladder?
beta2 adrenergic receptor - relaxes detrusor, contraction of trigone and sphincter
alpha1 adrenergic receptor - relaxes detrusor, contraction of trigone and sphincter
muscarinic receptor - contraction of detrusor, relaxation of trigone and sphincter (micturate)
What does the ANS do in the genitalia?
MALE
muscarinic - stimulates erection
alpha1 adrenergic receptor - stimulates ejaculation
What does the ANS do in the lacrimal glands?
muscarinic only - stimulates tears
What does the ANS do in the salivary glands?
alpha1 adrenergic receptor - thick viscid secretion
muscarinic receptor - copious, watery secretion
What does the ANS do in the heart?
beta1 adrenergic receptor - increased rate, increased contractility
M2 muscarinic receptor - decreased rate, decreased contractility
What does the ANS do in the GI tract?
beta2 adrenergic receptor - decrease in muscle motility and tone
alpha1 adrenergic receptor - contraction of sphincters
muscarinic receptors - increased muscle motility and tone
What does the ANS do in the genitalia (female)?
beta2 adrenergic receptor (SNS)
*relaxation of uterus
What does the ANS do in the Blood vessels (skelatal muscle)?
beta2 adrenergic receptor (SNS)
*dilation and drop in TPR
What does the ANS do in the blood vessels (skin, mucous membranes and splanchnic area)?
alpha1 receptor
*constriction - leads to a rise in TPR
What is my mneumonic for remembering the 8 important adrenergic agonists?
Everybody - Epinephrine Noses - Norepinephrine In - Isoproterenol All - albuterol Possible - phenylephrine Personal - pseudoephedrine Dirty - dobutamine Details - dopamine
What is my mneumonic for remembering the 9 important adrenergic ANTagonists?
Dinger - doxazosin Tries (to) - terazosin Poop - Prazosin Meticulously - metoprolol Avoiding - atenolol Popular - propanolol Locations, - labetalol Certainly - carvedilol California - clonidine
What adrenergic receptor is predominant in uterine smooth muscle?
Beta2 receptor
What adrenergic receptor is predominant in the urinary bladder sphincter?
alpha1 receptor - increases tone, or prevents urination
What adrenergic receptor stimulates the release of renin?
Beta1 receptor - in balance with alpha1 receptor
What adrenergic receptor is responsible for pupil dilation?
alpha1 receptor
Which receptors are important for IOP?
IOP = intraocular pressure
alpha1 = decrease IOP through outflow of humor
Beta1, Beta2 = increase IOP through increased humor production
according to French, which receptor blockade is best for relieving BPH-related urinary symptoms?
alpha1 antagonist
- this surprised me as I thought Beta1 was more involved in the relaxing of detrusor and tightening trigone and sphincter
- just remember BPH urinary urgency, diminished stream, block alpha1 (-azosins like Doxazonsin, Prazosin, Terazosin)