Term
| Direct cholinergic agonists produce effects via ___ __ of ___ receptors. |
|
Definition
- direct activation
- muscarinic |
|
|
Term
| Acetylcholine acts on __ and ____. But direct cholinoceptor agonists only act on ___ receptors, not ___ recptors. |
|
Definition
- acetyl choline > muscarinic and nicotinic receptors
- muscarinic not nicotinic receptors |
|
|
Term
| types of muscarinic receptors: |
|
Definition
|
|
Term
| M1 receptors are on ___ and work through the ___ ___ system. This receptor is ___. |
|
Definition
- nerves
- IP3 DAG
- excitatory |
|
|
Term
| M2 receptors are ___ and work via ___ which ___ ___ levels. Thus these are ___ receptors. |
|
Definition
- cardiovascular
- K+
- decreases cAMP
- inhibitory |
|
|
Term
| M3 receptors are ___ and work through ___ and ___. These are ___ receptors. |
|
Definition
- glandular
- IP3 and DAG
- excitatory |
|
|
Term
| All ___ receptors are blocked by atropine. |
|
Definition
|
|
Term
| Nm receptors are on ___ ___ and work via __ and ___. They are blocked by ____. |
|
Definition
- skeletal muscle
- Na+ and K+
- curare |
|
|
Term
| Nn receptors are on ___ and work through __ and ___ and are blocked by ____. |
|
Definition
- nerves
- Na+ and K+
- mecamylamine |
|
|
Term
| M2s relax things and slow them down. They are in the __ and __ __ and in the ___ ___. |
|
Definition
- SA and AV nodes
- veins
- bladder sphincter |
|
|
Term
|
Definition
| sweat glands and intestines, etc. |
|
|
Term
| NICOTINE AS THE DOSE GOES UP, RESPONSE GOES UP UNTIL CERTAIN SPOT, THEN NO EFFECT. NICOTENE DEPOLARIZES CELL, SO HAS TO BE AT LOW ENOUGH CONCENTRATION TO ALLOW CELLS TO REPOLARIZE. |
|
Definition
|
|
Term
| parasympathetic stimulation of SA node causes a ___ in ___ ___ ___, meaning it has a ___ ___ effect. Acetylcholine does the same thing. |
|
Definition
- decrease in spontaneous diastolic depolarization
- negative chronotropic |
|
|
Term
| Parasympathetic stimulation of the AV node causes ___ ___ ___, which is a ____ ___ effect, and ___ ___ ___. Acetylcholine does the same things. |
|
Definition
- decreased conduction velocity
- negative dromotropic
- increased refratory period |
|
|
Term
| Parasympathetic stimulation of the atrial muscle results in __ ___ ___ and ___ ___ ___. Acetylcholine does the same thing. |
|
Definition
- decreased contractile strength
- decreased refractory period |
|
|
Term
| Acetylcholine on the AV node causes ___ refractory period, while acetylcholine on the atrial muscle causes ___ refractory period. |
|
Definition
- acetylcholine> AV node> increased refractory period
- acetylcholine> atrial muscle> decreased refractory period |
|
|
Term
| Vessels have ___ to __ parasympathetic innervation. But acetylcholine would act on them to cause ___. |
|
Definition
|
|
Term
| cholinergic innervation to SA, AV, atrial muscle and Purkinje tissue is present. Innervation of the ventricular myocardium is sparse. |
|
Definition
|
|
Term
| parasympathetics to SA node: |
|
Definition
| SA node decreased depolarization current (If) increased repolarization |
|
|
Term
| there are some __ receptors in veins, so don't put meds here b/c cause drop in blood pressure |
|
Definition
|
|
Term
| The vagus ___ resting membrane potential and ___ rate of rise of spontaneous depolarization, thus it ___ the heart rate. Sympathetics do the opposite. |
|
Definition
- decreases resting membrane potential
- slows rate of rise of depolarization
- decreases heart rate |
|
|
Term
| With parasympathetic stimulation to the heart ___ permeability is ___ resulting in ___, which leads to ___ spontaneous depolarization, and a ___ of the action potential ___, a ___ in the refractory period, and a ___ repolarization. |
|
Definition
- K+ permeability is enhanced
- hyperpolarization
- slower spontaneous depolarization
- decrease in action potential duration
- decrease in the refractory period
- faster repolarization |
|
|
Term
| parasympathetics> Decrease in slow calcium current in heart cells |
|
Definition
|
|
Term
| Net physiological effect in the heart depends on the local concentrations of the agonist in the heart and in the vessels, and on the level of reflex responsiveness |
|
Definition
|
|
Term
| parasympathetic stimulation to the bronchioles causes: |
|
Definition
contraction
you don't want to let flies in when sleeping with mouth open |
|
|
Term
| Parasympathetic stimulation to the GI tract causes: |
|
Definition
- increased tone and motility
remember rest and digest |
|
|
Term
| parasympathetics to the urinary bladder causes: |
|
Definition
- contraction of the destrusor
- relaxation of the sphincter |
|
|
Term
| parasympathetics to the eye causes: |
|
Definition
- miosis (pupils constrict) via contraction of iris sphincter muscle
- accomodation via ciliary muscle contraction |
|
|
Term
| The eye has ___ receptors. |
|
Definition
|
|
Term
| parasympathetic stimulation to gland causes: |
|
Definition
- increased secretion
Bronchial
GI
Salivary
Lacrimal
Sweat glands |
|
|
Term
| Cholinoceptor agonists groups: |
|
Definition
1. Choline esters (direct agonists): bethanechol
2. Alkaloids (direct agonists): muscarine pilocarpine
3. Other (direct agonists): cevimeline |
|
|
Term
| Choline esters are ___ ___ ___. ___ is a type of this. This works on __ and __ receptors. |
|
Definition
- direct cholinorecptor agonists
- Bethanechol
- M2 and M3 |
|
|
Term
| Alkaloids are a ___ ____ ___. ___ ___ is a type of this. |
|
Definition
- direct cholinoreceptor agonists
- muscarine pilocarpine |
|
|
Term
| Cevimeline is a ___ ___ ___ and works on ___ recptors. |
|
Definition
direct cholinoreceptor agonist
M3 |
|
|
Term
| Bethanechol is not metabolized by __ ___ so it is ___ acting. |
|
Definition
|
|
Term
| Therapeutic uses of Bethanechol: |
|
Definition
- postoperative or neurogenic urinary retention
- postoperative atonic bowel (without obstruction)
- GERD
- lazy bladder syndrome |
|
|
Term
| After cystoscope if can’t urinate they give Betanechol. Beth does not cross membranes, well it is very polar, so it is give subcu and is slowly absorbed into system and causes vasodilation, but not profound. But b/c its so polar it accumulates in the kidney> m2 stimulated > relaxes, stimulates M3> bladder contracts> pee. |
|
Definition
|
|
Term
Reflux esophagitis caused by lower esophageal sphincter incompetence; bethanechol increases motility of sphincter and esophageal smooth muscle
symptoms, chest pain when lying down on full stomach |
|
Definition
|
|
Term
| Therapeutic uses of Pilocarpine: |
|
Definition
- glaucoma - lower IOP
(not popular, nearly historic for primary open angle glaucoma) Students should understand mechanism for reduction of IOP |
|
|
Term
| Pilocarpine side effects: when you stimulate ciliary muscle> fibers relax> eye rounds and you can’t see farther than foot in front of you. Old treatment. |
|
Definition
|
|
Term
| current treatment for glaucoma: |
|
Definition
miotics increase outflow via canal of schlemm
epinephrine increases outflow via uveoscleral pathway
beta blockers decrease aqueous production
Narrow angle glaucoma (angle closure) treat with laser iridectomy (surgery). Lower IOP with combination beta blocker and alpha agonist to control before surgery is possible |
|
|
Term
| Cevimeline therapeutic uses: |
|
Definition
| - oral med for Sjogren's syndrome aka dry mouth |
|
|
Term
| Cevimeline is a ___ ___ agonist and is __ selective. It is resistant to ___ and has little to no CNS effects, minimal bowel side effects, and minimal vascular side effects. |
|
Definition
synthetic muscarinic
M3
choline esterases |
|
|
Term
| ___ has no therapeutic use. It is the toxin responsible for mushroom poisoning. |
|
Definition
|
|
Term
| contraindications for cholinorecptor agonist use: |
|
Definition
- bronchial asthma
- bladder, small intestine, or bowel obstruction
- peptic ulcer b/c these meds would increase HCl |
|
|
Term
| toxicity of cholinorecptor activating drugs: |
|
Definition
- syncope caused by sudden bradycardia
- orthostatic hypotension
- cardiac bradyarrhythmias b/c decreased refractory period
- gut or urinary urgency (big one)
- diaphoresis
- sialogogic effects= salivation (big one)
- abdominal cramping |
|
|
Term
| 2 main categories of anticholinesterases: |
|
Definition
- Carbamates
- Organophosphates |
|
|
Term
| Malathion is an ___ _____ that is toxic to bugs, but not humans. |
|
Definition
| - organophosphate anticholinesterase |
|
|
Term
|
Definition
|
|
Term
| potential sites of action for anti-cholinesterases: |
|
Definition
- all autonomic ganglia (N)
- all postganglionic parasympathetic neuroeffector junctions (M)
- Postganglionic sympathetic cholinergic sites (sweat glands-M)
- adrenal medulla (N)
- skeletal neurtoransmitter junction (N)
- central nervous system
death by skeletal muscle paralysis- depolarizing block of diaphragm |
|
|
Term
| Clinical importance of anticholinesterases |
|
Definition
Few therapeutic uses
Some chemicals (from agricultural or military sources) are themselves significant sources of poisoning.
Ophthalmologic applications. |
|
|
Term
| mechanism of cholinesterase inhibition: |
|
Definition
Stability of the inhibitor/AChE complex is primary determinant of duration of action.
Carbamates: bind covalently with active site. Carbamoylated enzyme is relatively resistant to removal (0.5 to 6 h duration)
Organophosphates: bind covalently; phosphorylated enzyme very resistant to removal (100 + h)
Aging: phosphorylated complex is strengthened with time. |
|
|
Term
| only reversible cholinesterase: |
|
Definition
| only one truly reversible agent, edrophonium, is an alcohol, half life is 2-10 minutes. |
|
|
Term
| Neostygmine and Pyridostigmine are ____ ____. Explain them. |
|
Definition
- carbamate antichoinesterases
Quaternary ammonium compounds: variable absorption from p.o.; is devoid of CNS effects.
Uses:
Improvement of muscle strength in myasthenia gravis
Toxicities are predictable from distribution of AChE and distribution pattern for the drug. |
|
|
Term
| Thymic abnormalitiy is found in 75% pateints under 45 (either hyperplasia or thymoma). Primary therapy is either surgical or immunosuppressive. If not controlled, then Neostigmine or another quaternary anticholinesterase agent will be used to treat symptoms. |
|
Definition
|
|
Term
| Note that use in gastric atony and urinary retention is limited to conditions in which innervation is present. Atony or UR that is neurological in origin may not respond. |
|
Definition
|
|
Term
| characteristics of organophosphate anticholinesterases: |
|
Definition
Highly lipid soluble (except echothiophate)
Bind covalently to and inhibit cholinesterases.
Have muscarinic and nicotinic actions
Readily penetrate the CNS (except echothiophate)
Absorbed by all routes
Hydrolyzed slowly in the body
insects metabolize these to toxic things, humans do not |
|
|
Term
| clinical uses of organophosophates |
|
Definition
In insects, malathion to malaoxon.
Mammals can preferentially oxidize these chemicals to less toxic compounds. Malathion is preferentially toxic to insects.
Nerve gas (soman, tabun, sarin & others)
Developed for volatility, potency, rapid absorption and “aging” |
|
|
Term
WITH WAR GAS YOU DIE OF MUSCARINIC POISON- DIE IN OWN SECRETIONS. MILITARY CARRY SIRINGE WITH ANTIMUSCARINIC DRUG AND BLOCKS EFFECT OF MUSCARINIC. BUT THEN TOO MUCH ACETYL CHOLINE ON NICOTINIC RECEPTORS> CAN’T BREATHE.
PRILODOXINE COVALENTLY BINDS WAR GAS AND PULLS IT OFF RECEPTOR.BUT PRILODOXINE CAN’T REVRESE IT ONCE SECOND BOND OF POISON HAS OCCURRED. |
|
Definition
|
|
Term
| organophosphate toxicity manifestations: |
|
Definition
Muscarinic, Nicotinic and CNS manifestations:
Muscarinic Nicotinic CNS
Bronchoconstriction Muscular fasciculation Restlessness
Bronchial secretion Hypertension Insomnia
Sweating Tremors
Salivation Confusion
Lacrimation Ataxia
Bradycardia Convulsions
Hypotension Respiratory depression
Miosis Circulatory collapse
Blurring of vision
Urinary incontinence |
|
|
Term
Organophosphate toxicity:
Limited reversibility even if treated rapidly
Enzyme/drug bond becomes increasingly irreversible with time. “Aging” is related to formation of a second bond of the phosphate group binding the enzyme.
Treatment [Atropine; pralidoxime (2-PAM)]:
support respiration
large doses of atropine
cholinesterase reactivator pralidoxime |
|
Definition
|
|
Term
| Pralidoxime aka (2-PAM). The oxime moeity ___ the ____ bound enzyme. It also ___ the cholinesterase enzyme. This is most effective at ___ ___ __ b/c it cannot penetrate the ___. |
|
Definition
- destabilizes the organophosphate bound enzyme
- reactivate
- neuromuscular junctions
- cannot penetrate CNS |
|
|
Term
| Muscarinic cholinoreceptor antagonist occupy __ receptors and prevent action of ___ ___ or other ___ ___. |
|
Definition
- M recptors
- prevent action of endogenous acetylcholine or other muscarinic agents |
|
|
Term
| Atropine and Scopalamine are ___ ___ ___. These are in bella donna, women used to put them on eyes to make them dilate by blcoking the ___ nervous system. |
|
Definition
- alkaloid muscarinic antagonists
- parasympathetic |
|
|
Term
|
Definition
The actions of these drugs upon peripheral tissue/organ activity are similar to that which would occur following reduction of activity in postganglionic, parasympathetic and postganglionic cholinergic sympathetic nerves.
Both drugs also block CNS muscarinic receptors (“Mad as a hatter”) |
|
|
Term
| classic symptoms of bella donna poisoning: |
|
Definition
- hot as a hare (hyperthemia from decreased sweating)
- dry as a bone (inhibition of secretions)
- red as a beet (cutaneous vasodilation- not explained as antimuscarinic effect)
- blind as a bat (cycloplegia, blurred vision_)
- mad as a hatter (CNS effect)
- bloated as a toad (inhibition of GIT) |
|
|
Term
| bella donna cardiovascular effects at high doses: |
|
Definition
- increased heart rate
- often used to counteract bradycardia |
|
|
Term
| Difference between quaternary and non-quaternary antimuscarinics: |
|
Definition
| - quaternary compounds are not absorbed as well and do not have CNS actions |
|
|
Term
| QUATERNARY COPUNDS ARE FIXED SALTS THAT DON’T TRAVEL ACROSS MEMBRANES WELL, SO IF BREATHE IT IN LUNGS WE DON’T HAVE WORRY ABOUT IT GETTING INTO PERIPHEARY. |
|
Definition
|
|
Term
| overdose of a quaternary or non-quaternary anti-muscarinic is more likely to be fatal, why? |
|
Definition
| - quaternary b/c neuromuscular blockade |
|
|
Term
| not appropriate to give quaternary antidote to cholinergic agonist |
|
Definition
|
|
Term
| Therapeutic uses of anti-muscarinics: |
|
Definition
- respiratory disorders
- opthamology
- gastroenterology
- urological disorders
- motion sickness |
|
|
Term
| explain how antimuscarins are used for respiratory disorders. What are the names of the drugs used and what are they used for? |
|
Definition
- quaternary amines so no CNS effects
- Ipratropium and Tiotropium are inhaled to reverse bronchial constriction and block secretions
- used with severe asthma, emphysema, chronic bronchitis, COPD
- often used in combination with beta 2 agonist |
|
|
Term
| what are Ipatropium and Tiotropium: |
|
Definition
| - inhaled quaternay antimucarinics used to reverse bronchial constriction and block secretions in severe asthma, ephysema, and chronic bronhcitis |
|
|
Term
| How and why are antimuscarinics used in opthamology: |
|
Definition
- cause mydriasis and cycloplegia of long or short duration
- used for routine examination
- often combined with alpha adrenergic drugs |
|
|
Term
| How and why are antimuscarins used in gastroenterology |
|
Definition
- rarely used for PUD in U.S.
- inhibit GI motility, used in combo with opioid antidiarrheal
drug: propantheline |
|
|
Term
| How and why are antimuscarins used with urological disorders: |
|
Definition
- used in detrusor hyperreflexia, incontinence in the eldery
- increase bladder capacity
- decrease bladder pressure
drugs: oxybutynin, tolterodine |
|
|
Term
| what are oxybutynin and tolterodine? |
|
Definition
| - antimuscarins used in bladder incontinence in institutionalized elderly |
|
|
Term
| How are antimuscarins used to treat motion sickness? |
|
Definition
| - Scopolamine is useful in prophylactic treatment via CNS action in vestibular nuclei and reticular formation |
|
|
Term
| how are antimuscarinics helpful with muscarin poisoning: |
|
Definition
- treat poisoning from muscarin mushrooms or anticholiesterases
drugs: bella donna alkaloids or propantheline |
|
|
Term
| contraindications to antimuscarinics: |
|
Definition
- glaucoma
- protatic hypertrophy
- urinary retention
- dementia |
|
|
Term
| drugs with anti-cholinergic side effects |
|
Definition
- antihistamines
- Antiparkinson drugs |
|
|
Term
| drugs acting on striated muscle: |
|
Definition
| - neuromuscular blockers used in anesthesiology act at the nicotenic receptor site= nondepolarizing blockers |
|
|
Term
| Neuromuscular blocking drugs: |
|
Definition
Nondepolarizing blockers: competitive antagonists at NM cholinoceptors; prevent muscle contraction
Depolarizing blockers: first activate NM receptors briefly, and then cause sustained depolarization that results in muscle paralysis
Learn: Therapeutic applications and toxicity |
|
|
Term
| WITH NONDEPOLARIZING DRUG – USED IN SURGERY TO RELAX MUSCLES, BUT DEPOLARIZING AGENTS PREFERRED |
|
Definition
|
|
Term
| Non-depolarizing neuromuscular blocking drugs are ___ ___ at the ___ ___ receptor. They prevent ___ ___. |
|
Definition
- competitive antagonists
- Nm
- prevent muscle contraction |
|
|
Term
| Depolarizing blockers neuromuscular blocking drugs first briefly __ ____ receptors and then cause sustained ___ that causes ___ ___. |
|
Definition
- activate Nm cholinergic
- depolarization
- muscle paralysis |
|
|
Term
| SUCCINYLCHOLINE= 2 ACETYL CHOLINES JOINED TOGETHER, BLOCK STIRATED MUSCLE NICOTENIC MUSCLE RECEPTOR BUT DOES NOT EFFECT GANGLIA SO BP IS NOT EFFECTED. IT IS HYDROLYZED BY ESTERASE BUT NOT ACETYL CHOLINESTERASE. |
|
Definition
|
|
Term
| non-depolarizing neuromuscular blocking drugs occupy __ sites on __ __ ___ ___ thus blocking ___ access. These have ___ __ of duration. |
|
Definition
- Nm
- skeletal muscle end plates
- blocking acetyl choline access
- several hours |
|
|
Term
| Depolarizing neuromuscular blocking drugs have same effects as ___ but they are more resistant to ____ ___. Thus, membranes remain ___ b/c ___ is prevented. Initially this causes ____, but is followed by ____. |
|
Definition
- acetylcholine
- acetylcholine esterase
- depolarized
- repolarization
- fasiculations
- paralysis |
|
|
Term
| The neuromuscular blockade is facilitated by anticholinesterase. Thus, the neuromuscular blockade cannot be reversed pharmacologically |
|
Definition
|
|
Term
| with depolarizing neuromuscular blocking drugs WHEN STOP DRIP YOU DON’T HAVE TO HAVE MECHANICAL RESPIRATION ANYMORE. |
|
Definition
|
|
Term
| Succinylcholine, mivacurium - hydrolyzed rapidly by plasma cholinesterase. Short duration of action (5-10 min). However, there is a sub-population of slow metabolizers |
|
Definition
|
|
