ANS - just the drugs and targets

Question 1

What are the 7 important Cholinergic Agonists?

Answer 1

Pilocarpine - M
bethanechol - M
(the rest are ache inhibitors)
neostigmine
pyridostigmine
edrophonium
donepezil
organophosphate nerve gas

Question 2

What are the 10 important Cholinergic Antagonists?

Answer 2

7 are antimuscarinics
atropine, scopolamine, benztropine, oxybutynin, tolterodine, ipratropium, tiotropium
3 are antinicotinics (NMJ)
atracurium, rocuronium, succinylcholine

Question 3

Propantheline is what type of drug?

Answer 3

• Semisynthetic antimuscarinic

* Quaternary ammonium and thus relatively greater effect on GI motility

Question 4

Glycopyrrolate is what type of drug?

Answer 4

• Semisynthetic antimuscarinic

* Quaternary ammonium and thus relatively greater effect on GI motility

Question 5

Benztropine is what type of drug?

Answer 5

• Semisynthetic antimuscarinic

* Tertiary amine compounds so there is potential for CNS involvement

Question 6

Oxybutynin is what type of drug?

Answer 6

• Semisynthetic antimuscarinic

* Tertiary amine compounds so there is potential for CNS involvement

Question 7

Tolterodine is what type of drug?

Answer 7

• Semisynthetic antimuscarinic

* Tertiary amine compounds so there is potential for CNS involvement

Question 8

Scopolamine is what kind of drug?

Answer 8

• A naturally occuring, alkaloid antimuscarinic

Question 9

Hexamethonium is considered what type of drug?

Answer 9

• Ganglionic blocker, antinicotinic, anticholinergic

Question 10

Atropine is considered what type of drug?

Answer 10

• Non selective antimuscarinic anticholinergic

Question 11

Pralidoxime is considered what type of drug?

Answer 11

• Cholinesterase regenerator, anticholinergic (indirect)

Question 12

Pirenzepine is considered what type of drug?

Answer 12

• M1 selective antimuscarinic anticholinergic

Question 13

What does the drug Edrophonium do?

Answer 13

• Reversible, short acting ache inhibitor

Question 14

what is special about pilocarpine?

Answer 14

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

Question 15

What are the 8 important adrenergic agonists?

Answer 15

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

Question 16

What are the 9 important adrenergic antagonists?

Answer 16

Doxazosin, Terazosin, Prazosin - alpha1
Metoprolol, Atenolol - beta1
Propanolol - beta1, beta2
Labetalol, Carvedilol - alpha1, beta1, beta2
Clonidine - alpha2 AGONIST

Question 17

When an alpha2 adrenergic receptor is bound, what happens?

Answer 17

• 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

Question 18

What kind of GPCR is the beta2 adrenergic receptor?

Answer 18

• Gs - increases AC, increasing cAMP (probably closing the K channel)
  
  • End result is a positive nerve terminal response

Question 19

What kind of GPCR is the beta1 adrenergic receptor?

Answer 19

• 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

Question 20

What kind of GPCR is the alpha2 adrenergic receptor?

Answer 20

• Gi - inhibits AC, reducing cAMP and often opening a K channel
  
  • End result is hyperpolarization of the nerve terminal

Question 21

What kind of GPCR is the alpha1 adrenergic receptor?

Answer 21

• Gq - active PLC, release IP3 and DAG, releasing intracellulr calcium and activating PKC

Question 22

For adrenergic agonists, what is the most common mechanism of indirect-acting agonists?

Answer 22

• At peripheral synapses, increasing the storage and release of NE/EPI is the most common mechanism of increasing SNS output by indirect means

Question 23

What determines absorption by oral route of SNS agonists?

Answer 23

• 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

Question 24

Due to the molecular properties of SNS agonist drugs, what is the end result of their bioavailability?

Answer 24

• 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

Question 25

What property of adrenergic SYMPATHOLYTIC antagonists greatly LIMITS their clinical utility?

Answer 25

• 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

Question 26

What are the two non-selective alpha adrenergic receptor blockers?

Answer 26

* Phentolamine and phenoxybenzamine | * Irreversible alpha1 and alpha2 blockers

Question 27

What does alpha2 receptor activation do?

Answer 27

• 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

Question 28

What does the ANS do in the eye?

Answer 28

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)

Question 29

What does the ANS do in the trachea and bronchioles?

Answer 29

beta2 adrenergic receptor - dilates the airways | muscarinic receptors - constricts airways, increases secretions

Question 30

What does the ANS do in the adrenal medulla?

Answer 30

nicotinic neruonal receptors - epinephrine and norepinephrine is secreted - has SNS effects, all adrenergic receptors are bound

Question 31

What does the ANS do in the kidney?

Answer 31

beta1 adrenergic receptor - secretion of renin | alpha1 adrenergic receptor - decreases secretion of renin

Question 32

What does the ANS do in the ureters and bladder?

Answer 32

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)

Question 33

What does the ANS do in the genitalia?

Answer 33

MALE muscarinic - stimulates erection alpha1 adrenergic receptor - stimulates ejaculation

Question 34

What does the ANS do in the lacrimal glands?

Answer 34

muscarinic only - stimulates tears

Question 35

What does the ANS do in the salivary glands?

Answer 35

alpha1 adrenergic receptor - thick viscid secretion | muscarinic receptor - copious, watery secretion

Question 36

What does the ANS do in the heart?

Answer 36

beta1 adrenergic receptor - increased rate, increased contractility M2 muscarinic receptor - decreased rate, decreased contractility

Question 37

What does the ANS do in the GI tract?

Answer 37

beta2 adrenergic receptor - decrease in muscle motility and tone alpha1 adrenergic receptor - contraction of sphincters muscarinic receptors - increased muscle motility and tone

Question 38

What does the ANS do in the genitalia (female)?

Answer 38

beta2 adrenergic receptor (SNS) | *relaxation of uterus

Question 39

What does the ANS do in the Blood vessels (skelatal muscle)?

Answer 39

beta2 adrenergic receptor (SNS) | *dilation and drop in TPR

Question 40

What does the ANS do in the blood vessels (skin, mucous membranes and splanchnic area)?

Answer 40

alpha1 receptor | *constriction - leads to a rise in TPR

Question 41

What is my mneumonic for remembering the 8 important adrenergic agonists?

Answer 41

``` Everybody - Epinephrine Noses - Norepinephrine In - Isoproterenol All - albuterol Possible - phenylephrine Personal - pseudoephedrine Dirty - dobutamine Details - dopamine ```

Question 42

What is my mneumonic for remembering the 9 important adrenergic ANTagonists?

Answer 42

``` Dinger - doxazosin Tries (to) - terazosin Poop - Prazosin Meticulously - metoprolol Avoiding - atenolol Popular - propanolol Locations, - labetalol Certainly - carvedilol California - clonidine ```

Question 43

What adrenergic receptor is predominant in uterine smooth muscle?

Answer 43

Beta2 receptor

Question 44

What adrenergic receptor is predominant in the urinary bladder sphincter?

Answer 44

alpha1 receptor - increases tone, or prevents urination

Question 45

What adrenergic receptor stimulates the release of renin?

Answer 45

Beta1 receptor - in balance with alpha1 receptor

Question 46

What adrenergic receptor is responsible for pupil dilation?

Answer 46

alpha1 receptor

Question 47

Which receptors are important for IOP?

Answer 47

IOP = intraocular pressure alpha1 = decrease IOP through outflow of humor Beta1, Beta2 = increase IOP through increased humor production

Question 48

according to French, which receptor blockade is best for relieving BPH-related urinary symptoms?

Answer 48

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)