7: Cholinoceptor antagonists Flashcards
What are Nicotinic receptor antagonists also called?
Ganglion blocking drugs
–> Block transmission of whole autonomic devision at ganglion
Explain the mechanism of action, effect and use of Hexamethonium
Nicotinic receptor antagonist, first ever antihypertensive drug!
–> Ion channel block
- creates a use-dependant block
Effect:
- loss of function of the dominant autonomic NS
- e.g. at rest : increased HR, bronchodilation, hypotension –> vasodilation + less retention in Kidney
Also:
- pupil dilation (light sensitivity)
- constipation
- no bladder emptiying
- –> too unspecific, no clinical use anymore
What is a use-dependant block?
The more a channel/recptor etc, is used, the stronger its blocke
–> At high usage–> high blocking
e.g. at Ion channel blockers, where Ion channels need to be open (working) for blocking to go into channel and create effect
Explain the mechanism of action, effect and use of Trimetaphon
Trimetaphon: Nicotinic receptor antagonist
- receptor blocking antagonist
- half life of around 30 min
- effects same as Hexamethonium (dominant autonomic System functions are lost)
Used in controll of BP during surgery (as single dose shot)
Name two Nicotinic receptor antagonists (including their mechanism of action and effect
Hexamethonium
- ion channel blocker
- 1st ever hypertensive drug (no clinical use anymore)
Trimetaphon
- receptor blocker
- t1/2= 30min
- used in controll of BP during surgery
Effect:
- loss of function of dominant Autonomic system
- at high dosage: blocking of NMJ –> paralysis (many poisons)
What is the clinical use of Nicotinic receptor antagonists?
Barely any clinical use:
- drugs are too messy, too many side effects because all autonimic functions are blocked + interference with NMJ
Ony use
Trimetaphon to controll BP during surgery
What are the side effects of Nicotinic antagonist drugs?
Too messy: interfer with many systems
E.g. somatic (NMJ) –> used in animal poisons (alpha-bungarotoxin) leading to parlaysis
But also:
- hypotension
- light senstitivity
- constipation
- no bladder emptying
- etc.
What are the effects of Atropine and Hyoscine on the CNS?
Why?
Atropine;
- Normal dose – Little effect
- Toxic dose - Mild restlessness –>Agitation (normal effect of M-antagonists)
- (Less M1 selective)
Hyoscine;
- Normal dose – Sedation, amnesia
- Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain)
- (Greater permeation into CNS. Influence at therapeutic dose)
–> Difference not yet fully understood, probably because Hyoscine more lipophilic –> BBB maybe more M1 selective
What is the mechanism of action and use of Tropicamide
Tropicamide
Muscarenic receptor antagonist
Causing pupil dilation (relaxation of Spincter Pupillae) –> Mydriasis and blurred vision (paralysis of ciliary muscle of eye)
- Used for examination of the retina
Explain the clinical use of Muscarenic receptor antagonists in Anestehetic premedication
Hyoscine
Causes sedation
- blocks bronchioconstrition –> dilation (good for e.g. inhaled anesthetics)
- blocks glandular secretions (good e.g. to prevent aspiration of saliva)
- Blocks HR reduction (good because anesthetics generally decrease HR –> prevention of bradycardia)
Explain the clinical use of Hyoscine
Used as hyoscine patch in motion sickness
Normally: Auditory signals + visual sicknes are combined and when missmatch: transport to vomiting centre
When blocked: Pathway to vomiting centre blocked –> prevention of motion sickness
Explain the use of Muscarenic antagonists in Parkinsons disese
Problem in Parkinsons is: too little Dopamine
this can’t be changed but amount of dopamine receptor can be increased –> less dopamine needed for same effect
- Dopamine receptor is downregulated by M4 activity
- When blocking M4 –> less downregulation –> More Dopamine receptors
Explain the clinical use of muscarenic antatgonists in respiratory disease
Which drug is commonly used to achive this?
Blocking of Bronchioconstriction –> Bronchiodilation
- e.g. Ipratropium Bromide
- Atropine
Explain the clinical use of a Muscarenic antagonist in GI conditions such as Irritatable bowl syndrome
IBS: movement of GI tract causes pain
(Usually M3 selective antagonists)
With antagonist:
- Slows GI tract down
- motility and tone
- secretions
- –> reduction of symptoms of IBS
What are the side effects of Muscarenic Receptor Antagonists?
- Heat intolerance –> no thermoregulation via sweating
- Dry –> decreased secretions
- Blind –> Cyclopegia (cillary muscle paralysis)
- Mad –> CNS disturbance
Which drug would be used to treat Atropine poisoning?
Preferably: Physiostime –> reversible Anti-cholinesterase drug
Atropine: Blocks Muscarenic receptors (kompetitevely)
Physiostigme –> increases dose of available ACh
Explain the effect of Botolinum Toxin on the body
Extremely dangerous (only low dose required)
Blocks release of ACh out of vesicles
–> (by interfering with SNARE complex)
–> Paralysis of everythingn
