What is an agonist?
Molecule found in nature/made in lab
binds to specific receptor –> elicit same response as endogenous compound would when bound
What is an antagonist?
Molecule found in nature/made in lab
incompletely binds to specific receptor
blocks usual response from occurring
can also observe opposite response –> dry mouth instead of salivation
Can the dose amount of agonist/antagonist alter observed effects? If so why?
higher doses can engage in more receptors or more receptor types –> exaggerated response + signs of toxicity (more pathways triggered)
What are the 2 types of Cholinergic antagonists?
What is another name for a cholinergic antagonist?
What is another name for a muscarinic antagonist?
What does a muscarinic antagonist do?
Block effects of parasympathetic autonomic discharge
What are 2 examples of muscarinic antagonists?
What are the 2 types of nicotinic antagonists and what do they do?
Ganglionic Blockers - block ALL outflow past ganglionic level
Neuromuscular Blockers - prevent skeletal muscles from working properly
What are some examples of Nicotinic Antagonists?
What is another name for Atropine?
Where does atropine come from?
Origianally isolated from plants –> Atropa belladonna
Derivatives synthesized in lab
What is atropine?
classic cholinergic antagonist
What are some other drugs that have similar structures and produce similar effects as Atropine?
What are the actions of atropine?
Resversible block muscarinic receptors –> prevents ACh from binding to those sites
Will Atropine block actions of exogenously administered cholinergics or endogenous acetylcholine?
Typically blocks actions of EXOGENOUSLY administered cholinergics
Which tissues are most sensitive to Atropine?
What other tissues are effected by Atropine?
What are the CNS effects of anticholinergics and why do they produce those effects?
Atropine –> minimal CNS effect; can’t cross BBB
Scapolamine –> drowsiness/amnesia; can cross BBB
What are some signs of scopolamine toxicity?
Which antimuscarinic is used in Parkinson’s and what is it treating?
Why would you use antimuscarinics to treat Parkinson’s?
In parkinson’s there is to much ACh
Benztropine will block ACh effects
How would you treat motion sickness and how would you administer the drug?
Injection, orally, transdermal patch
What are the effects of Antimuscarinics on the Eye?
block cholinergic stimulation of pupillary constrictor muscle –> mydriasis (unopposed sympathetic dilation)
prevent contraction of ciliary muscle –> cycloplegia (loss of accommodation) –> unfocused near vision –> blurry vision
Reduce lacrimal secretion –> dry eye
can DANGEROUSLY worsen narrow angle glaucoma (lack of outflow of aqueous humor)
What are the therapeutic uses of antimuscarnics on the eye?
used for opthamologists to view the retina –> mydriasis and cycloplegia = good in this case
But not commonly used anymore
How are antimuscarnics administered in the eye?
What are the low does effects of antimuscarinics ( .5 mg atropine) on the cardiovascular system?
atropine block M1 receptors only –> bradychardia; ACh still can bind to M3
What are the effects of moderate to high doses of antimuscarinics (1-5 mg atropine) on the cardiovascular system?
block M2 receptors in SA/AV nodes that USUALLY slow HR –> tachycardia
like inhibiting brakes on HR
What are the effects of toxic doses of antimuscarinics (>10 mg atropine) on the cardiovascular system?
intraventricular condition block –> inhibits electrical pulse generation in pacemaker nodes
Why does antimuscarinics (atropine) have little effect on BP?
There are minimal innervations from parasympathetic system
What are the therapeutic uses of antimuscarinics (atropine) in CV disorders?
During acute MI or SA/AV node function –> bradycardia; so you want to give moderate dose of antimuscarinic (atropine) –> block M2 receptors –> increase HR
What are the effects of anticholinergics on the Respiratory System?
Bronchodilation –> better air flow
What are some anticholinergic drugs used for respiratory disorders and how are they given?
Ipratropium (Atrovent) and Tiotropium (Spiriva)
given as inhaler or nebulizer –> bronchodilation
What are Ipratropium (Atrovent) and Tiotropium (Spiriva) used to treat?
What are some other uses of atropine or scopolamine regarding the respiratory system?
Dry upper/lower respiratory secretions prior to surgery or in mechanically vented patients
What are the effects of antimuscarinics on the GI tract?
reduced motility –> prolong gastric emptying time/slowing intestinal transit time
reduce salivary secretion –> dry mouth (common side effect)
reduce gastrointestinal secretions
What are some therapeutic uses of atropine in GI disorders?
reducing GI secretions (BUT NOT ACID IN STOMACHE)
What is Lomotil and what is it used for?
Diphenoxylate + atropine
slow down gut motility –> treat somache bugs
What are the effects of Antimuscarinics on the GU tract?
relaxation of smooth muscle in ureter/bladder wall –> reduces voiding
Why wouldn’t you want to give an antimuscarinic to a pt with benign prostatic hyperplasia (BPH)?
can worsen or causes urinary retention
What are some therapeutic uses of anticholinergics in urinary disorders?
urinary tract spasms associated w/ inflammation, surgery, or neurologic conditions
What is the classic anticholinergic used to treat urinary disorders?
How would you treat muscarinic toxicity?
How would you most likely get mushroom poisoning?
Eating wild mushrooms –> contain natural cholinergic agents
What are the 2 types of mushroom poisoning?
Describe rapid onset mushroom poisoning and how you would treat it?
Occurs w/ in 15 - 30 minutes after ingestion
muscarinic side effects
treat w/ atropine
Describe delayed onset mushroom poisoning and how would you treat it?
Occurs 6 - 12 hours after ingestions
muscarinic side effects + renal/hepatic toxicity
treat w/ supportive care (atropine = ineffective)
What type of sweat gland problem can be treated with muscarinic antagonists?
What is the name of the drug that could be used to treat eccrine hyperhidrosis?
What are some adverse side effects of anticholinergics?
Dry mouth (dry as a bone)
Mydriasis (blind as a bat)
Hot, Flushed skin (red as a beet)
Agitation (mad as a hatter)
Urinary retention (can’t pee)
Visual changes (can’t see)
Constipation (can’t shit)
What are some drugs that produce anticholinergic side effects?
What are 3 contraindications of anticholinergic use?
Gluacoma (especially narrow angle)
Elderly men with BPH (benign prostatic hyperplasia)
Why would glaucoma be a contraindication for anticholinergics?
anticholinergics cause angle closure –> prevent outflow of aqueous humor
Why is BPH a contraindication for anticholinergics?
can worsen or causes urinary retention
Why are gastric ulcers a contraindication for anticholinergics?
anticholinergics –> slowed gastric emptying –> aggregate ulcer symptoms
What does the toxin from clostridium botulinum do?
targets presynaptic proteins that block release of ACh
What is the result of the toxin from clostridium botulinum?
paralysis of skeletal muscle
decreased activity @ parasympathetic and sympathetic synapses
inhibition can last weeks –> months
What is the toxin from clostridium botulinum used to treat?
other focal muscle spasms
hyperhidrosis of palsm/axillae
cosmetic removal of wrinkles
What do ganglionic blocking agents do?
block ACh (and agonists) @ nicotinic receptors of parasympathetic/sympathetic ganglia
What is another name for ganglionic blocking agents?
Nondepolarizing competitive antagonists
What are some ganglionic blocking agents?
What kinds of effects of ganglionic blockers (sympathetic or parasympathetic)?
Mixed sympathetic/parasympathetic effects
What are some of the CNS effects of ganglionic blockers?
What are some of the ganglionic blocker effects on the eye?
Cycloplegia = Loss of accommodation
Moderate dilation of pupil
What are some of the ganglionic blocker effects on the CV system?
What are some of the ganglionic blocker effects on the GI tract?
What are the therapeutic uses of ganglionic blockers?
Really only used in pharmacological research
What do neuromuscular blockers do?
block neuromuscular transmission between motor end plate and nicotinic receptors on skeletal muscle
What are the 2 groups of neuromuscular blockers?
What do non depolarizing neuromuscular blockers do?
block ACh from binding nicotinic receptors
prevent depolarization of muscle fibers and inhibit contraction
result in very relaxed (paralyzed) muscle
Do nondepolarizing neuromuscular blockers bind competitively or noncompetitivelly?
How can you terminate the effect of non depolarizing neuromuscular blockers?
will increase ACh and overcome the competition for blocked receptors
When are non depolarizing neuromuscular blockers used?
during surgery –> muscle paralysis (relaxation)
How do non depolarizing neuromuscular blockers differ from each other?
differ by onset of action, half-life, means of elimination
What is a classic example of depolarizing neuromuscular blocker?
What does depolarizing neuromuscular blockers do?
binds to nicotinic receptors on skeletal muscle
acts like ACh
proivdes constant stimulation of receptor
Initially cause depolarization
Continued presence prevents transmission of further impulses
causes resistance to further depolarization –> paralysis
What are 2 advantages of depolarizing neuromuscular blockers?
short duration of action
give same effect as non polarizing antagonist
What are the therapeutic uses of depolarizing neuromuscular blockers like succinylcholine?
electroconvulsive shock therapy