Muscarinic antagonists part 2

Question 1

what are some clinical uses on muscarinic antagonists?

Answer 1

• COPD
• asthma
• Parkinson’s
• overactive bladder
• mydriatics (ophthalmic exams)
• IBS-D (to stop diarrhea)

Question 2

what are CNS adverse effects of muscarinic antagonists?

Answer 2

confusion, hallucinations, delirium, and possibly a coma

Question 3

what are peripheral adverse effects of muscarinic antagonists?

Answer 3

dry eyes, constipation, tachycardia, dry skin, decreased urination (DECREASED SLUD)

Question 4

what are structural features of the structures of the CNS anti-muscarinic drugs?

Answer 4

they all have tertiary nitrogens because the quaternary are always ionized so they will never be able to get through the blood brain barrier

Question 5

what two drugs are interactions with muscarinic antagonists? why?

Answer 5

benedryl and antitriptaline because they are competitive antagonists for the same receptor

Question 6

why are muscarinic antagonists used as mydriatic agents?

Answer 6

they paralyze ciliary eye muscle which causes the lens to be incapable of bending to accommodate for light

Question 7

when should mydriatic agents be avoided in the patient?

Answer 7

if they are already taking other antimuscarinics because it could be too much if they were given one to dilate they’re eye (cycloplegia)

Question 8

what is the suffix of drugs that do not have CNS effects?

Answer 8

“ium”

Question 9

what happens when you relax the sphincter muscle of the eye?

Answer 9

it causes dilation

Question 10

what happens when you relax the ciliary muscle of the eye?

Answer 10

it causes the lens to flatten and the inability to see far

Question 11

what should you always be aware of when you go to the doctor to get your eyes dilated?

Answer 11

if you’re on any other muscarinic antagonists

Question 12

Which type of receptor is involved in vestibular nausea?

Answer 12

M1

Question 13

How can we use the M1 receptor to prevent nausea?

Answer 13

We can use an M1 antagonist to prevent the nausea before it occurs

Question 14

can muscarinic antagonist treat all forms of OAB?

Answer 14

no, only some forms

Question 15

How does urination work?

Answer 15

when sufficient urine is in your bladder, your stretch receptors fire which causes the parasympathetic neurons to fire and the motor neurons that are holding the internal sphincter together to relax. Then the smooth muscle contracts and you relax your external sphincter to release the urine when you’re ready.

Question 16

What structure is present in all of the drugs used in COPD?

Answer 16

they have a quaternary ammonium compound

Question 17

what structure is present in all of the drugs used in Parkinson’s?

Answer 17

they all have a tertiary ammonium compound that is able to penetrate the CNS

Question 18

does dicyclomine that is used to treat IBS-D have to potential to cause CNS adverse effects?

Answer 18

yes because it only has a tertiary amine

Question 19

what is mydriasis?

Answer 19

dilation of the eye

Question 20

can muscarinic blockers cause mydriasis?

Answer 20

yes

Question 21

is scopolamine good at treating nausea after it is already onset?

Answer 21

no, it is only a preventative medication

Question 22

of all the drugs we were given to treat OAB, do they all have the same effectiveness? what makes them different?

Answer 22

relatively, the only thing that changes is the amount of ADRs from use which is due to the amount of times the medication has to be taken. this is because longer-use drugs flatten out the AUC and decrease the probability of reaching toxic levels.

Question 23

what is good about drugs for OAB that are more specific for M3?

Answer 23

they will not cause bradycardia in the patient by binding the the M2 receptors in the heart

Question 24

what is functional selectivity?

Answer 24

for some reason when the drug is taken in the human it has more attraction for receptors on a certain tissue than the same receptors on the other and we are not sure why

Question 25

when do we see functional selectivity in antimuscarinics? what drug?

Answer 25

when M3 antagonists for some reason bind to M3 receptors in the bladder more than M3s in the salivary galnds
-solifenacin

Question 26

which two drugs would be primarily be affected by 3A4 inhibitors?

Answer 26

solifenacin and darifenacin because they are highly metabolized by 3A4 in the liver

Question 27

which drug would be most affects by genetic polymorphisms of 2D6?

Answer 27

darifenacin because it is primarily metabolized by 3A4 and 2D6 in the liver

Question 28

which drug for OAB can you not give to old people and why?

Answer 28

Oxybutynin because it is very very lipophillic and only has a tertiary amine. this means it will very easily get through the blood brain barrier, expecially those of old people because theirs is starting tho wear down. if it gets into their brains it could cause the decreasee of ACh and the increase of dopamine which would cause major issues.

Question 29

which two drugs for OAB are prodrugs for 5-HMT? are they still pharmacologically active molecules as prodrugs?

Answer 29

fesoterodine and tolterodine.. YES

Question 30

what side affects would you see in someone that had poor 2D6 metabolism versus overactive 2D6 metabolism in regards to fesoterodine and tolterodine?

Answer 30

because both the active metabolite and the prodrug are active molecules, they will see no difference in effect. however the poor metabolizer would have more prodrug and the good metabolizer would have more metabolite

Question 31

why is fesoterodine more predictable than tolterodine?

Answer 31

because tolterodine has to be hydroxylated on a methyl group and fesoterodine is activated by taking off an ester and replacing it with an alcohol

Question 32

since fesoterodine and tolterodine are basically the same, how do we tell which one will have more affect than the other?

Answer 32

by which ever one is less protein bound, that drug will have more effect