Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
61 Cards in this Set
- Front
- Back
Sympathetic pre-ganglionic neuron cell bodies
|
spinal cord segments T1-L3
|
|
Sympathetic post-ganglionic neuron cell bodies
|
prevertebral and paravertebral ganglia
|
|
Parasympathetic pre-ganglionic neuron cell bodies
|
brain stem and spinal cord segments s2-s4
|
|
Parasympathetic post-ganglionic neuron cell bodies
|
terminal ganglia in or near target organ
|
|
Chromaffin cells
|
(Sympathetic) N2 receptor (ACh) --> Epi/NE
|
|
Parasympathetic Pre/Post-ganglionic Neurotransmitters
|
Pre: ACh, (Enkephalin, Substance P, GnRH)
Post: ACh (VIP) |
|
Fast EPSP
|
Nicotinic response
|
|
Slow IPSP
|
M2 response
|
|
Slow EPSP
|
M1 response
|
|
Late slow EPSP
|
Peptide response
|
|
Muscarinic receptors in CNS
|
Predominantly M4, M5
|
|
M1, M3, M5
|
Muscarinic (Parasympathetic)
Gq -> PLC-Beta -> IP3, DAG -> Ca2+, PKC -> excitatory |
|
M2, M4
|
Muscarinic (Parasympathetic)
dec. AC -> dec. cAMP -> K+ channels -> hyperpolarization |
|
M1
|
parasympathetic:
CNS. Autonomic ganglia. Parietal cell. |
|
M2
|
parasymp:
Cardiac; SA and AV node. Autonomic ganglia. |
|
M3
|
PS:
Everywhere not covered by M1, M2. Smooth muscle contraction, GI gland secretion, bronchial secretion, vasodilation. |
|
Parasympathetic: erection
|
ACh/bradykinin --> endothelial cell M3 receptor --> Ca2+ -> activate eNOS --> NO to vascular smooth muscle receptor --> open K+ channels, activate GC --> cGMP --> relaxation.
Sildenafil (Viagra) blocks enzyme that degrades cGMP. |
|
Hemicholinium
|
Prevents choline reuptake
|
|
Vesamicol
|
Prevents vesicular storage of ACh
|
|
Botulinium Toxin
|
Degrades synaptobrevin (SNARE) and prevents exocytosis of ACh.
Clinically used with increased muscle tone, Eaton-Lambert, focal dystonia. |
|
Edrophonium
|
anti-AChE.
Short duration; alcohol. Diagnose Myasthenia gravis and Eaton Lambert. |
|
Neostigmine
Physostigmine |
Carbamic Acid derivatives: anti-AChE.
Longer acting than alcohol derivatives. reverse neuromuscular blockers. Physostigmine crosses BBB (treat atropine poisoning). Hydrolyzed by AChE - covalent bond, increases half life of inhibition. Clinical: Treat MG |
|
Parathione
|
anti-AChE
Irreversible. Pesticides. New receptors take weeks. |
|
Myasthenia Gravis
|
autoimmune disease against Nm subtype (receptor internalized).
|
|
Lambert-Eaton
|
Autoimmune disease against presynaptic Ca2+ channels. Reduces ACh release.
|
|
AChE inhibitor uses
|
Increase PS tone: decrease intraocular pressure (glaucoma), GIT motility, treat atropine poisoning.
Improve dementia (Rivastigmine). Delays development of impairment by 6 months. Reverse paralysis brought by non-depolarizing neuro-muscular blockers. |
|
Negative anti-AChE effects.
|
Excessive muscarinic stimulatio --> salivation, miosis, diarrhea, bradycardia, lacrimation.
Excessive nicotinic stimulation --> muscle weakness/paralysis Chemical warfare |
|
Carbachol
|
Muscarinic receptor agonist:
ACh derivative, resistant to ChE. affinity for both Nm and Muscarinic receptors; not useful, overall effects. |
|
Pilocarpine
|
Muscarinic receptor agonist:
alkaloid similar to muscarine. Treat dry mouth in Srogrens (autoimmune against salivary glands). |
|
Methacholine
|
Muscarinic receptor agonist.
3x more resistant to hydrolysis by AChE. Little affinity for Nicotinic receptor. Used to diagnose asthma. |
|
Bethanecol
|
Muscarinic receptor Agonist.
selective for muscarinic receptor. promote GIT/urinary motility following surgery, etc. can cross BBB --> treat cerebral palsy. |
|
Atropine
|
Muscarinic receptor ANTAGONIST.
competitive antagonist. pupil dilation, tachycardia, dec. secretions. (mimics symp.) |
|
Clinical uses of Atropine
|
Muscarinic antagonist
1. Mydriasis 2. Reverse sinus bradycardia caused by excessive vagal tone. 3. inhibit excessive salivation and mucus secretion. 3. counteract muscarinic/anti-AChE poisoning. |
|
Scopolamine
|
Muscarinic antagonist
treatment of nausea, motion sickness. truth drug. general depressant! Significant CNS effect. |
|
Pirenzepine
|
Muscarinic antagonist.
treat peptic ulcers, histamine receptor antagonist. |
|
Ipratropium
|
Muscarinic antagonist
Selective for M3. Reduce bronchial secretions --> treat COPD/asthma. |
|
Succhinylcholine
|
Nicotonic receptor depolarizing blocker.
excessive activation of Nm receptor. use: short term paralysis (intubation). Short duration: BuChE (genetic defects will be noticed.) Side effects: prolonged paralysis (faulty BuChE). K+ release, malignant hyperthermia. |
|
Nicotinic receptor non depolarizing blockers
|
Occupy Nm receptors, competetive. Reversal with anti-AChE.
Flaccid paralysis. |
|
D-tubocurarine
Pancuronium Vecuronium Mivacurium |
Non-depolarizing Blockers:
Plant alkaloid ("arrow poison") Useful during surgery for flaccid muscles. Long acting Intermediate Short acting **More selective on Nm than Nn. Side effects: Hypertension, apna, bronchospasm, salivation, flushing, respiratory failure. |
|
NE/Epi synthesis
|
Tyrosine (tyrosine hydroxylase)
DOPA (DOPA decarboxylase) Dopamine (Dopamine B-hydroxylase) Norepinephrine **In chromaffin cells: (Phenylethanolamine-N-methyl transferse) Epinephrine Notes: Dopamine -> VMAT -> vesicle, NE synthesis. Ca2+ dependent release -> post: a1, a2, b1, b2. Pre: a2. |
|
Mechanism for terminating catecholamine
|
1. reuptake
2. metabolism to inactive metabolite 3. diffusion |
|
Catecholamine metabolism
|
MAO A: Sero > NE > Dopamine, Tyramine
MAO B: Dopamine > sero > NE Catechol-O-methyl transferase: cytosolic enzyme in liver |
|
A1 receptor
|
Adrenergic receptor (sympathetic)
Gq -> IP3/DAG -> Ca2+, PKC -> MLCK activity -> contraction Peripheral vessels vasoconstriction. GENERALLY CAUSES CONSTRITICTION |
|
A2 receptor
|
Adrenergic receptor (sympathetic)
Gi -> AC, cAMP -> K+, (hyper) dec. Ca2+ (dec. NE release) Neural feedback, inhibition. Inhibit insulin. |
|
B1 receptor
|
Adrenergic receptor (sympathetic)
HEART Gs -> CA -> cAMP -> PKA Heart, Juxtaglomerular cells. Inc. contractility, HR. Kidney -> renin -> angiotensin -> vasoconstriction -> TPR angiotensin -> inc. blood volume, aldosterone (bld volume) |
|
B2 receptor
|
Adrenergic receptor (sympathetic)
AC -> cAMP -> PKA -> phosphorylate MCLK (dec. activity) Gs -> open K+ channels -> hyper. RELAXATION. Smooth muscle, liver, skeletal muscle (Epi > NE) GENERALLY CAUSES RELAXATION. Also: Lipolysis, Glucagon (alpha pancreas) liver glucose production, glycogenolysis, gluconeogenesis. |
|
B3 receptor
|
Adrenergic receptor (sympathetic)
cAMP -> PKA Adipose tissue |
|
Adrenergic regulation of vascular smooth muscle
|
A receptors -> contraction
B receptors -> relaxation. arteries, constrict/dilate = (a1a2/b1/b2) veins, constrict/dilate = a1/a2/b2) Predominant effect of NE, Epi = vasoconstriction, increasing BP. exception: exercise -> B2 -> dilate. |
|
GI smooth muscle, adrenergic regulation.
|
sympathetic inhibition (reduce motility).
via: a1, b2, b3. (unusual; a1 causes relaxation) |
|
Eye - adrenergic
|
dilate pupil. (contraction in radially arranged smooth muscle).
Ciliary muscles relax. |
|
Kidneys: adrenergic effect.
|
B1 -> JG cells -> renin -> ANGI ->
ANG-II -> ADH -> blood volume ANG-II -> Aldosterone -> kidney -> salt/water -> blood volume ANG-II -> vasoconstriction -> TPR **INCREASE BP |
|
SLUDGE
|
Atropine (muscarinic antagonist) reduces all of the following:
Salivation Lacrimation Urination Diaphoresis (sweating) GIT motility Emesis |
|
Atropine poisoning
|
reduced sweating
block of accomodation, dilated pupils, photophobia Reduces salivation CNS effects Flushing (cutaneous vasodilation); atropine releases histamine *Antidote: Physostigmine (crosses BBB) |
|
Reserpine
Guanethidine |
Indirect acting agonist:
Inhibitor of Catecholamine storage. net release of NE; depletion. Sympathomimetic effect, followed by sympatholytic effect. Prevents sympathetically-mediated vasoconstriction; replaced by drugs with fewer side effects. |
|
Tyramine
|
Indirect acting agonist:
Inhibitor of Catecholamine storage. Significant component of food: red wine, cheese, beans, "marmite." Causes release of NE from nerve terminal, sympathomimetic. No significance in most individuals. **May cause serious cerebrovascular accidents in individuals taking MAOIs. |
|
Amphetamine
Derivatives: Meth-amphetamine, MDMA (Ecstacy) |
Indirect acting agonist:
Inhibitor of Catecholamine storage. Release NE (and DA) from nerve terminals. Block reuptake of NE (by blocking NET) Weak inhibitors of MAO. Clinical use: treatment of narcolepsy, ADHD. Increase in NE in cleft leads to increased alertness and reduced fatigue, insomnia. Major drugs of abuse, cause dependence and tolerance. Increased DA leads to paranoid hallucinations, schizophrenic-like behavior. |
|
Methylphenidate (Ritalin)
|
Indirect acting agonist:
Inhibitor of Catecholamine storage. Structural analogue of amphetamine. Clinical use: ADHD |
|
Cocaine
|
Inhibitor of Cathecolamine reuptake.
Inhibitor of NET (CNS and periphery) sympathomimetic effect: tachycardia, hypertension, pupillary dilation, peripheral vasoconstriction, hyperthermia (sweating impairment). Chronic use leads to DA depletion. |
|
Imipramine
|
Inhibitor of Cathecolamine reuptake.
Tricyclic Antidepressant Not specific; blocks 5HT reuptake and post-synaptic receptors in periphery (muscarinic, a1, 5HT, and histamine). Use: increases NE levels in CNS, treatment of depression. Promiscuous actions, adverse effects profile. |
|
Iproniazid
|
Inhibitor of cathecholamine metabolism.
Monoamine oxidase inhibitor. Raises NE in synaptic cleft. Use: depression treatment. **Individuals taking MAOIs must not eat food with Tyramine. Increased release of NE with MAO inhibited can cause a massive vasoconstriction, leading to "hypertensive crisis," which can result in a fatal stroke. |
|
Pseudoephedrine
|
Indirect Acting Sympathomimetics with Direct Agonist Effect.
Releases stored NE from nerve terminals. Also has a and b agonist activity. uses: nasal and sinus congestion (vasoconstriction) *adverse CNS stimulation. |