ANS Pharmacology - Beardsley - Exam 1 Flashcards
Muscarinic receptors found on:
- Organs innervated by _____ nerves
- Tissues innervated by ACh ____ nerves (eg, sweat glands)
- CNS
Muscarinic receptors found on:
- Organs innervated by parasympathetic nerves
- Tissues innervated by ACh sympathetic nerves (eg, sweat glands)
- CNS
Pesticides are often anti-___ inhibitors.
•Carbamates is a pesticide that is:
–Reversible
–Treat with __ (anti-____) alone
•Organophosphates
–“Age” to gradually become ____
–Treat with ___ + ____ (an agent that displaces organophosphate and reactivates ACh-esterase)
Pesticides are often anti-cholinesterase inhibitors.
•Carbamates
–Reversible
–Treat with atropine (antimuscarinic) alone
•Organophosphates
–“Age” to gradually become permanent
–Treat with atropine + pralidoxime (an agent that displaces organophosphate and reactivates ACh-esterase)
Muscarinic receptors found on:
- Organs innervated by ___ nerves
- Tissues innervated by ACh __ nerves (eg, sweat glands)
- ___
Muscarinic receptors found on:
- Organs innervated by parasympathetic nerves
- Tissues innervated by ACh sympathetic nerves (eg, sweat glands)
- CNS
Drugs that mimic or augment the action of ACh are called ___. How do they act?
Name 4 drugs that are direct acting.
Name 4 drugs that are indirect acting. Which one is the shortest action time? Which ones haev a quaternary structure and why is this important? Which one treat ileus?
What are organophosphate?
Drugs that mimic or augment the action of ACh are called cholinomimetics.
Cholinomimetics can be direct agents or infirect agents.
They can be selective for N or M, but they cannot hit specific subtypes (cannot hit M1, and not hit M2, it will hit both, Or, it cannot hit Nm without hitting Nn).
- Direct
- Bind and activate muscarinic or nicotinic receptor
- Can be selective for N or M, but not subclass within N & M
Drugs that are direct acting:
BP CM
Bethanechol – muscarinic agonist
Pilocarpine – muscarinic, penetrates CNS
Carbachol – both muscarinic and nicotinic (mostly used as eye drops for glaucoma)
Muscarine-containing mushrooms
I went to the bethroom in chols and saw a pilbug sitting on the head (CNS) of a muskrat. Both were eating carbs and smoknig nicotine (carbophol targets M and N). Crumbs got into their eyes (carbophol is used as eye drops in glaucoma)
It can also act indirectly:
- Indirect - inhibits AChesterase.
- Vary by distribution (eg, into CNS)
- Amplify endogenous ACh so ACh swims in the synaptic cleft longer.
4 indirect drugs:
NEPP - ACHesterase inhibitors
Neostigmine - treats ileus (know this!)
Edrophonium
Pyridostigmine
Physostigmine
At chols, they indirectly sell foods so Eddie and Phy bought new piruoettes.
The shortest one is Edrophonium (earliest in thea alphabet).
All have a quarternary structure except physostigmine.
Significance of structure shape?
- Quaternary agent: These are CHARGED. Anything that is polar or charged won’t pass membranes. Poor CNS penetration, poor absorption (oral dose >> parenteral dose). It won’t be absorbed well and it won’t hit the CNS very well. Thus, if you give oral dose, you need to give a A LOT compared to IV.
- Tertiary amine: better absorption and CNS penetration
Organophosphates - causes cholinergic toxicity. They are GREAT insectisides. They are distributed everywhere – CNS toxicity is the worst
Actions of Indirect ACh Agents
Targets:
- CNS – at high doses causes ___,___
- Eye, respiratory, GI, and urinary tracts – similar to direct agents
- Heart – predominantly ____ actions (like direct agents)
- Vasculature – ____ vascular resistance via ganglionic stimulation of SNS
- Summary: like direct except vasculature effects
Slide 23: Actions of Indirect ACh Agents
- CNS – at high doses: convulsions, coma
- Eye, respiratory, GI, and urinary tracts – similar to direct agents
- Heart – predominantly vagal actions (like direct agents)
- Vasculature – increased vascular resistance via ganglionic stimulation of SNS
- Summary: like direct except vasculature effects
Uses of Cholinomimetics
Tagets:
- ___ – glaucoma (covered in eye lecture)
- GI – post-operative ___ (drug used is called ____) & ___ mouth (drug used is called ___)
- GU – post-op _____ retention; neurogenic bladder (____)
- Musc-skeletal – see future lectures
- Treat ____ drug intoxication
CNS – Alzheimer’s disease covered elsewhere
Uses of Cholinomimetics
- Eye – glaucoma (covered in eye lecture)
- GI – post-operative ileus - when their (neostigmine) & dry mouth (pilocarpine)
- GU – post-op urinary retention; neurogenic bladder (bethanecol)
- Musc-skeletal – see future lectures
- Treat antimuscarinic drug intoxication
CNS – Alzheimer’s disease covered elsewhere
Pesticides are often anti-___ inhibitors.
•Carbamates is a pesticide that is:
–Reversible
–Treat with ___ (an ___ drug) alone
•Organophosphates - these are bad.
–As they bind to AChesterase and “Age” to gradually become __
–Treat with ___ + __ (an agent that displaces organophosphate and reactivates____)
Pesticides are often anti-acetylcholinesterase inhibitors.
•Carbamates os a pesticide that is:
–Reversible
–Treat with atropine (treat with an antimuscarinic) alone
•Organophosphates
–“Age” to gradually become permanent
–Treat with atropine (which treats the symptoms right away) + pralidoxime (an agent that displaces or bumpbs the organophosphate and reactivates ACh-esterase)
Cholinoceptor blocking drugs
•____ is prototypical cholinoceptor blocking drug.
It is found in belladonna (deadly nightshade) & other plants.
•Variation in effect
–PK (eg, CNS penetration: scopolamine >> atropine)
–Receptor specificity (for various M subgroup)
•Lots of drugs have “anticholinergic” effects (not just the “pure” agents we discuss here)
Cholinoceptor blocking drugs
- Atropine is prototype
- Found in belladonna (deadly nightshade) & other plants
- Variation in effect
- PK (eg, CNS penetration: scopolamine >> atropine)
- Receptor specificity (for various M subgroup)
- Lots of drugs have “anticholinergic” effects (not just the “pure” agents we discuss here)
Antimuscarinic Drug Actions
- CNS – _____ (agitation, hallucinations, coma in high dose); tx __ __
- Eye – _____; cycloplegia (can’t ___); __“sandy” eyes
- Cardiovascular – ____
- Respiratory – broncho____ & secretions
- GI – ___ mouth; secretions & motility
- GU – ____ smooth muscle of ureters & bladder & slows voiding
- Sweat glands –____thermoregulatory sweating
Name the 5 anti-muscarinic drugs to know:
Slide 29: Antimuscarinic Drug Actions
- CNS – sedation (agitation, hallucinations, coma in high dose); tx motion sickness
- Eye – mydriasis; cycloplegia (can’t accommodate); dry “sandy” eyes
- Cardiovascular – tachycardia
- Respiratory – bronchodilation & secretions
- GI – dry mouth; secretions & motility
- GU – relax smooth muscle of ureters & bladder & slows voiding
- Sweat glands – suppresses thermoregulatory sweating
- Atropine
- Scopolamine
- Ipratropium
- Glycopyrrolate
- Oxybutynin
A troop of anti-M’s, IPRA’s (int. professional rodeo association) glyded on their scooter instead of taking an ox.
Anti-muscarinic drugs treat:
- Parkinson’s disease (more later)
- Motion sickness (____)
- Eye exams (more later)
- Asthma & COPD (inhaled ___)
- Bradycardia (___)
- Overactive bladder & spasms (____)
- decrease secretions (____)
- Counteract muscarinic effects when neostigmine is used to reverse muscle relaxants (____)
- Treat cholinergic toxicities (____)
Anti-muscarinic drugs treat:
- Parkinson’s disease (more later)
- Motion sickness (scopolamine) •Eye exams (more later) –> motion sickness on a scooter
- Asthma & COPD (inhaled ipratropium) –> pargue has lots of smokers
- Bradycardia (atropine) –> dmitri atropine playing britten cello concerto.
- Overactive bladder & spasms (oxybutynin) –> oxy clean man who has an overactive bladder and is spastic)
- decrease secretions (glycopyrrolate) –> give glyc if you can’t gleak”
- Counteract muscarinic effects when neostigmine is used to reverse muscle relaxants (glycopyrrolate)
- Treat cholinergic toxicities (atropine)
Excess cholinergic blockade results is:
Excessively cool blind man (ray charles) had red hot full lips but dry elbows.
- Mad as a hatter – CNS delirium, irritability
- Blind as a bat – sympathetic mydriasis (with light sensitivity) and blurry vision from the loss of accommodation reflex (lens out of focus)
- Dry as a bone –loss of sweating, dry mouth, decreased tear production
- Hot as a pistol – loss of sweating and temperature control
- Red as a beet – vasodilation in response to temp
- Full as a flask – urinary retention
Anti-cholinergic side effects is a big problem – especially in elderly
–Probably #1 cause of delirium
–Also associated with dementia & agitation
–They have enough trouble with vision
- Dry mouth, etc.
- Sedation
- Urinary retention in those with mechanical problems (contraindicated in men with BPH)
Anti-cholinergic side effects is a big problem – especially in elderly
–Probably #1 cause of delirium
–Also associated with dementia & agitation
–They have enough trouble with vision
- Dry mouth, etc.
- Sedation
- Urinary retention in those with mechanical problems (contraindicated in men with BPH)
Beta-2 promotes __ uptake
potassium
•Alpha-1: contraction
–We care most about effects on ____, ___, & ____ tract
•Alpha-2: inhibition
–Predominant effect is from central alpha-2 receptors which ___ sympathetic tone and ___ BP
•Beta-1: Increase ___ rate
–Positive ___tropic, ____tropic, & __tropic effect
•Alpha-1: contraction
–We care most about effects on vasculature, eye, & urinary tract
•Alpha-2: inhibition
–Predominant effect is from central alpha-2 receptors that reduce sympathetic tone and decrease BP
•Beta-1: Go heart!
–Positive chronotropic, dromotropic, & inotropic effect
Beta-2: makes you ___
–All effects from table are important
Dopamine: dilates renal vessels
–Most important DA receptors are in the brain
Beta-2: makes you relax.
–All effects from table are important
Dopamine: dilates renal vessels
–Most important DA receptors are in the brain
The second one. It is irreservisible!
