cholinoceptor antagonists

Question 1

agonists vs antagonists

Answer 1

both have affinity, but only agonists have efficacy

Question 2

where are nicotinic receptors- thus what are nicotinic receptor antagonists called

Answer 2

all ganglia of ANS, including adrenal gland (acts like a ganglion)

ganglion blocking drugs- both SNS and PNS

Question 3

hexamethonium and trimetaphan

Answer 3

these are nicotinic receptor antagonists- these drugs either block ion channel or block receptor- trimetaphan better at blocking receptor

Question 4

use-dependent block + comparison to competitive antagonist

Answer 4

relates to drugs blocking the ion channel- the more open the channels are, the more effective the antagonist is

unlike competitive antagonist (where the more agonist present, the less effective the drug), the more agonist present, the MORE effective the drug, as channel needs to be open for agonist to work

Question 5

feature of ion channel block

Answer 5

it is INCOMPLETE, sodium/potassium can still get through, just not very effectively

Question 6

do nicotinic receptor antagonist have affinity

Answer 6

yes if blocking receptor, no if blocking ion channel

Question 7

overall effect of nicotinic receptor antagonists

Answer 7

they block whole ANS ie both SNS and PNS, but effect it seems to have depends on which system is dominant a t the time, so if SNS dominant, will seem to have anti-SNS effect

Question 8

effects at REST after treatment of drug

Answer 8

anything that involves SNS, as at rest PNS is dominant (not blood vessels as only SNS effects that)

increased HR and bronchodilation

Question 9

effects of hexamethonium on BP

Answer 9

lowers BP- it cause dilation of BLOOD VESSELS, it stops production of renin from KIDNEY (less aldosterone+ ANG2), and although it increases HR in HEART, overall effect is lower BP

Question 10

side effects of hexamethonium

Answer 10

dilates pupil

saliva produces thick rather than watery secretion (thick due to SNS)

sweating goes down (only SNS has effect)

issues with gut motility and bladder

Question 11

hexamethonium vs trimetaphan uses

Answer 11

hexa used as anti-hypertensive, although not much anymore due to side effects

trimetaphan used for hypotension during surgery (as short acting)

Question 12

other nicotinic receptor antagonist+ effect

Answer 12

alpha-bungarotoxin (venom) is most powerful antagonist as permanently binds to receptor

main issue is somatic nervous system- paralyses you

Question 13

take home message for nicotinic receptor antagonists- thus difference for muscarinic receptor antagonists

Answer 13

too messy- have too many unwanted side effects as effect all parts of ANS

muscarinic less messy, as these receptors only found in PNS and sweat gland nerves

Question 14

main muscarinic receptor antagonists and effects of CNS+ possible reasons

Answer 14

atropine and hyoscine, both of which are very similar in structure, yet effect CNS differently

atropine has little effect with therapeutic dose, hyoscine causes sedation

atropin causes agitation at toxic dose, hyoscine causes CNS depression

may be because hyoscine more M1 selective (heavily targets one receptor), or hyoscine goes deeper into CNS

Question 15

muscarinic receptor antagonist for eye

Answer 15

tropicamide allows examination of retina- because PNS causes pupil constriction (smaller pupil), so harder to examine back of eye- tropicamide prevents this

Question 16

use as an anaesthetic premedication

Answer 16

PNS constricts BRONCHIOLES- by dilating it, anaesthetic can be better inhaled

PNS increases saliva- problem with anaesthesia is risk of inhaling saliva= choking, so this is prevented

PNS lower HR/contractility, combined with anaesthesia causes hypotension so drug prevents this

also has sedative effect eg hyoscine

Question 17

use to prevent motion sickness (what is it)

Answer 17

this is a sensory mismatch- visual info comes into eyes, and info relating balance/posture coming through ear via labyrinth- if they are telling different things, info goes via cholinergic nerve to vomiting center= nausea

hyoscine patch is very lipid soluble, so diffuses through skin into blood stream, and blocks muscarinic receptor in vomiting centre

Question 18

what is parkinsons disease

Answer 18

loss of dopaminergic neurones from substantia nigra to striata= loss of dopamine

D1 receptors respond to this dopamne to control fine muscle movement- lack of stimulation occurs in parkisons

Question 19

use in parkisons

Answer 19

muscarinic receptors (M4) surpress D1 receptors in case they are overactivated- by blocking these receptors, D1receptors are more sensitive= useful for parkisons

Question 20

respiratory use of muscarinic antagonists, and what drug used

Answer 20

asthma/COPD-prevents bronchoconstriction

ipratropium bromide used rather than atropine to prevent side effecs from systemic effects- ipratropium is charged, so not lipid soluble, so mainly effects lungs- atropine is not charged

Question 21

gastrointestinal use and type of drug

Answer 21

used in IBS, where there is a hyperreactive gut- hence less motility/secretion

M3 antagonist

Question 22

unwanted side effects of muscarinic

Answer 22

HOT- less sweating

DRY- less sweat, saliva and GI secretions

BLIND- cyclopegia where ability of lens to focus reduced= fuzzy

CRAZY- agitate due to CNS effect

Question 23

overdose of atropine treatment

Answer 23

too many anti-muscarinic symptoms, so physostigmine (anti-cholinesterase) given to prevent metabolism to ACH= outcompetes ACH

Question 24

effect of botulinum toxin

Answer 24

most toxic protein- prevents ACH going into vesicle (SNARE complex), thus prevent ACH leaving and binding to ANS/skeletal muscle

used to paralyse skeletal muscle in face to remove wrinkles, or as botox for sweating- but MUST be localised