Term
| Which postganglionic sympathetic neurons are not adrenergic |
|
Definition
Those that release Dopamine and sympathetic innervation of the eccrine (thermoregulatory) sweat glands,
which is cholinergic! |
|
|
Term
| Dopamine can act on what type of receptors |
|
Definition
| D1, D2 and alpha and Beta receptors |
|
|
Term
| What enzyme catalyzes the reactions of L-Dopa to dopamine |
|
Definition
| aromatic amino acid decarboxylase |
|
|
Term
| What enzyme catalyzes the reaction of NE to epinephrine |
|
Definition
| phenyl-N-methyl-transferase |
|
|
Term
| What enzyme catalyzes the step of dopamine to NE |
|
Definition
|
|
Term
| Primary means of inactivation of catecholamines |
|
Definition
| Reuptake into nerve terminals |
|
|
Term
| Catechol-O-Methyl-Transferase (COMT) |
|
Definition
is located extracellularly on
membranes throughout the body. It can therefore metabolize released
catecholamines into inactive metabolites. |
|
|
Term
|
Definition
Critical alpha-1 distribution is in the radial muscle of the iris, the
vasculature, and the genitourinary (α-1a) and gastrointestinal sphincters.
Activation of these receptors causes contraction of the muscle. |
|
|
Term
|
Definition
1. Also located in the vasculature, although they play a less critical role
than the alpha-1.
2. Located on NE nerve terminals. So function as inhibitory
autoreceptors. That is, activation of these receptors decreases the
amount of NE released.
3. Located in the brainstem where activation leads to decreased
sympathetic and increased parasympathetic nervous system
activation.
** Points 2 and 3 are important for understanding why alpha-2 agonists
are considered anti-adrenergic. |
|
|
Term
| Relative affinities of b2 for epi and NE |
|
Definition
| 100 fold greater affinity for Epi |
|
|
Term
|
Definition
receptors are important because of their localization to cardiac muscle.
1. Activation leads to increased conduction and contractility in the heart.
2. Therefore, beta-1 receptor activation increases cardiac output. |
|
|
Term
|
Definition
| Mediate vasodilation in skeletal muscle, bronchiodilation, and relaxation of bladder and uterine walls |
|
|
Term
|
Definition
| Increase GFR, Sodium excretion and renal blood flow. causes vasodilation in renal, cardiac, cerebral, and mesenteric vasculature. |
|
|
Term
What is the Main autonomic determinant
of vascular tone/total peripheral resistance. |
|
Definition
| Alpha 1 activation which causes vasoconstriction |
|
|
Term
| Parasympathetic effects on total peripheral resistance |
|
Definition
Parasympathetic nervous system activation will not
alter total peripheral resistance, but direct-acting muscarinic agonists can. |
|
|
Term
| What effect does alpha1 activation have on intraocular pressure |
|
Definition
decreases blood flow to ciliary body and trabecular
network. Decreases production and increases outflow of aqueous humor. |
|
|
Term
| What effect does alpha 2 activation have on intraocular pressure |
|
Definition
| decreases production of aqueous humor and increases outflow of aqueous humor. |
|
|
Term
| What effect does beta 1 activation have on intraocular pressure |
|
Definition
| increases the production of aqueous humor |
|
|
Term
| What effect does beta 2 activation have on intraocular pressure |
|
Definition
| increases aqueous humor production and increases outflow of aqueous humor |
|
|
Term
| What effect does muscarinic activation have on intraocular pressure |
|
Definition
causes contraction of ciliary muscle. Tension on trabecular network leads to increased outflow of aqueous humor
through the network. |
|
|
Term
| What mediates sympathetic Regulation of the Bronchioles and what effects does it have |
|
Definition
| Beta-2 mediated. 1. Bronchodilation 2. Incresed cilial beat frequency 3. decreased vascular permeability 4. Inhibits release of inflammatory mediators from mast cells |
|
|
Term
| Effects of parasympathetic Regulation of the Bronchioles |
|
Definition
| Constricts bronchioles and increases mucous secretions |
|
|
Term
| Effects of sympathetic Regulation of the Urinary Bladder |
|
Definition
Alpha 1a - Constricts sphincter and prostate as well as prostate capsule
Beta 2 - Relaxtion of bladder wall (detrusor muscle) |
|
|
Term
| Parasympathetic Regulation of the Urinary Bladder |
|
Definition
| Muscarinic activation causes relaxation of sphincter and contraction of bladder wall |
|
|
Term
| What are the majority of cholinergic receptors in the CNS |
|
Definition
| 95% Muscarinic, 5% Nicotinic Nueral |
|
|
Term
| What is the response to Cholinergic CNS stimulation |
|
Definition
| Mimics peripheral sympathetic effects, Increase blood pressure, heart rate, pupil dilation. Cognitive -- confusion, altered memory, coma. Motor -- Initial tremors followed by convulsion |
|
|
Term
|
Definition
| Rapidly degraded <20 sec. Stimulates both nicotinic and muscarinc receptors. Clinically usefeul in settings where rapid stimulation/degradation is necessary i.e. cataract surgery. |
|
|
Term
|
Definition
(1) Synthetic carbamoyl choline ester.
(2) Long acting-NOT hydrolyzed by ChEs
(3) Only stimulates muscarinic |
|
|
Term
|
Definition
(1) synthetic carbamoyl choline ester
(2) Long acting-NOT hydrolyzed by ChEs.
(3) Stimulates BOTH muscarinic and nicotinic
(4) causes release of ACh from synapses |
|
|
Term
|
Definition
(1) Recently (2000) approved
(2) Selective for M3
receptors |
|
|
Term
|
Definition
(1) Plant alkaloid
(2) only muscarinic |
|
|
Term
| ChE inhibitors act by what mechanism |
|
Definition
ChE inhibitors, except the organophosphates, are competitive
inhibitors of ChE. |
|
|
Term
| Edrophonium and Ambenonium |
|
Definition
ChE inhibitors (1) Brief duration min (Edrophonium) to hrs (Ambenonium)
(2) electrostatic forces and hydrogen bonding.
(3) reversible |
|
|
Term
Neostigmine,
physostigmine,
pyridostigmine |
|
Definition
| ChE inhibitors. Binding mechanism similar to ACh. Longer duration 0.5-6 hrs. |
|
|
Term
Organophosphates—Isoflurophate and
echothiophate |
|
Definition
(1) phosphorylate active site of ChE forming a phosphoryl-enzyme
complex
(2) very slowly reverses (hundreds of hours).
(3) With time bond strength increases -“ages”, and the phosphoryl-
ChE link becomes essentially irreversible.
(4) Need synthesis of new ChE. |
|
|
Term
| Which ChE inhibitors do not cross the BBB |
|
Definition
| Neostigmine, edrophonium, pyridostigmine, & ambenonium & Echothiophate |
|
|
Term
| Which ChE inhibitors do cross the BBB |
|
Definition
| Physostigmine, Isoflurophate, insecticides, & nerve gases |
|
|
Term
| Which drugs would be used to treat myasthenia gravis |
|
Definition
Long-Term Oral Rx Is With ChE Inhibitors that Don’t cross the BBB:
Neostigmine (short duration [2-4 hr])
Pyridostigmine (3-6 or 6-8 hr [sustained release])
Ambenonium (3-8 hr) |
|
|
Term
| Drugs used for treatment of Glaucoma |
|
Definition
| (1) topical (pilocarpine, carbachol) or (echothiophate, 2nd choice due to side effects) |
|
|
Term
| Drugs used to treat xerostomia (dry mouth) |
|
Definition
(1) Pilocarpine-
(2) Cevimeline- M3 selective, longer lasting, fewer side effects |
|
|
Term
| Treatment of choice for urinary bladder atony |
|
Definition
Treatment-cholinomimetic or ChE Inhibitor
(1) bethanecol- M3 selective
(2) neostigmine- relatively short duration (2-4 hr) |
|
|
Term
| Neuromuscular blockade during surgery |
|
Definition
Treatment- ChE Inhibitor of moderate duration
(1) Neostigmine- increases ACh in neuromuscular junction to
overcome competitive blockade |
|
|
Term
| treatment for Intoxication by Antimuscarinic Agents i.e. (1) Poisoning with atropine, antihistamines, tricyclic antidepressants |
|
Definition
Physostigmine is the drug of choice
(a) crosses the blood-brain barrier
(b) reverse many of the central and peripheral effects of poisoning
by atropine and related antimuscarinic agents.
(c) can cause seizures. |
|
|
Term
| What are the four drugs used to treat alzeimers |
|
Definition
| Tacrine, Donepezil, Rivastigmine, Galantamine |
|
|
Term
|
Definition
Used to treat alzeimers disease (a) modest increase in cognitive function.
(b) can cause reversible liver damage (30-50%)
(c) Cholinergic side effects that they can also limit use.
(d) no longer widely used in clinical practice. |
|
|
Term
|
Definition
produces modest improvement in some
measures of cognitive function in patients with Alzheimer’s disease.
(a) more selective to CNS ChE, less toxic
(b) long duration of action – single dose/day is possible |
|
|
Term
| Rivastigmine and galantamine |
|
Definition
Recently FDA approved to treat alzeimers. (b) Long-acting, but given twice daily
(c) Pattern of toxicities is less severe, like donepezil, but still
includes nausea, vomiting, diarrhea, and insomnia.
(d) Efficacy similar to that of donepezil |
|
|
Term
| Three primary contraindications of cholinomimetics |
|
Definition
| Asthma, Coronary insufficiency and peptic ulcers. |
|
|
Term
| By what mechanism do antimuscarinics work? |
|
Definition
| Competitive antagonists at the muscarinic receptor. |
|
|
Term
| Prototypical antimuscarinic drugs |
|
Definition
| Atropine and scopolamine, atropine only crosses BBB at higher doses. |
|
|
Term
|
Definition
| antimuscarinic. Like a short acting atropine used in opthalmic exams to help dilate pupil. Lasts about 6 hours |
|
|
Term
| What drug is used in conjunction with antimuscarinic during opthalmic exams to help dilate the pupil. What receptor does it act upon |
|
Definition
| Phenylephrine. Alpha-adrenergic agonist. |
|
|
Term
| What use do antimuscarinics have in presurgery patients |
|
Definition
| Stops the heart rate from decreasing too much. Not routine. Used in patients in danger of cardiac slowing i.e. downs syndrome patients |
|
|
Term
| What are antimuscarinics used for in post surgical patients |
|
Definition
| ChE inhibitors are sometimes used to help stop neuromuscular blockade after surgery by increasing ACh at nicotinic and muscarinic synapses. In this case Antimuscarinic drugs can be coadministered to prevent unwanted side effects of muscarinic activation |
|
|
Term
|
Definition
| Used as a ChE reactivator from organophosphate poisoning. Must be applied within hours of poisoning |
|
|
Term
| Drug of choice for organophosphate poisoning |
|
Definition
| Atropine. Also given with Pralidoxime |
|
|
Term
|
Definition
| Selective M3 antagonist. Used for urinary urgency/incontinence and bed wetting. Relaxes detrusor and tightens sphincter. |
|
|
Term
|
Definition
| New drug, relatively selective for M3, used like Tolterodine but with less side effects (especially dry mouth)and a little more efficacy. |
|
|
Term
| Drug of choice for motion sickness and what side effects does it have |
|
Definition
Scopolamine patch. Can cause dry mouth, drowsiness Rare serious CNS effectsdepression,
amnesia, excitation, psychotic episodes |
|
|
Term
| Two drugs that can be used for Bronchospasms |
|
Definition
Ipratropium: inhalant antimuscarinic, not very selective. Not absorbed well so it doesn't produce many side effects. Lasts 4-6 hrs longer if given with an Alpha 2 agonist
Tiotropium: Like ipratropium but lasts longer 24 hr duration and is selective for M1 and M3 |
|
|
Term
| Treatment of Parkinsons disease |
|
Definition
| Usually levodopa or carbidopa but antimuscarinics were used prior to there development to decrease the cholinergic input and restore balance between excitatory and inhibitory signals. Still can be used in some populations to control tremors but mostly as a secondary treatment due to side effects. |
|
|
Term
| Antimuscarinic contraindications / precautions |
|
Definition
Glaucoma
Obstructive or paralytic GI disease
Myasthenia gravis
Antimuscarinics contraindicated in
pathological conditions where blockade of PSNS or skeletal muscle system receptors would worsen symptoms. |
|
|
Term
| Treatment for antimuscarinic toxicity and symptoms. |
|
Definition
| Treat with ChE inhibitors(physostigmine), remove source, gastric lavage, diazepam is used to reduce CNS mediated convulsions. Symptoms: Blind as a bat, dry as a bone, red as a beet, hot as a hare, and mad as a hatter |
|
|
Term
| By what mechanism do organophosphates work |
|
Definition
|
|
Term
|
Definition
Acetylcholine,
Bethanechol,
Carbachol,
Cevimeline,
Pilocarpine |
|
|
Term
| short acting AChesterase inhibitors |
|
Definition
|
|
Term
| Longer acting ACh esterase inhibitors |
|
Definition
Neostigmine,
Physostigmine,
Pyridostigmine, |
|
|
Term
| Irreversible ACh esterase inhibitors |
|
Definition
Isoflurophate,
Echothiophate |
|
|
Term
|
Definition
Tacrine(not used much),
Donepezil,
Rivastigmine,
Galantamine, |
|
|
Term
|
Definition
Atropine,
Scopolamine,
Tropicamide,
Tolterodine (used for urinary incontinence and bedwetting),
Solifenacin and Oxybutynin (urinary incontinence),
Ipratropium and Tiotroprium (Bronchospasms),
Glycopyrrolate |
|
|
Term
|
Definition
|
|
Term
| The Alzheimers drugs act by what mechanism |
|
Definition
| They are ACh esterase inhibitors |
|
|
