Exam 4 Flashcards

1
Q

Sympathetic system

A

Two neurons
Short then long ganglion
Postganglion release NE and E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The sympathetic trunk ganglia innervates what

A

Thorax, abdomen, head, neck

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

The prevertebral ganglia innervates what

A

Organ below diaphragm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the percentage release of E and NE in sympathetic system and adrenal medulla

A

Sympathetic: 80% NE, 20% E
Adrenal Medulla: 20% NE, 80% E

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens in the adrenal medulla

A

One neuron system
ACh is released by pregnaglion
Preganglion innervates chromaffin cells in medulla and release NE and E
(NE and E are hormones because they are in the circulation and not released at a synapse)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the presynaptic receptors in the sympathetic system and adrenal medulla

A

Both are nicotinic receptors (Nn)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

For the adrenergic presynaptic receptors what do the auto receptors and hetero receptors do in respect to NE release

A

Auto receptors: inhibit and activate NE release
Hetero receptors: inhibit NE release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the two subgroups of the adrenergic receptors

A

Alpha and Beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does a2 receptor do

A

autoreceptor that inhibits of NE release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does b2 receptor do

A

autoreceptor that facilitates of NE release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Heteroreceptors presynaptically

A

inhibit release of NE (M2, M4)
-DA receptor
-Histamine receptor
-Serotonin receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a1 receptor

A

Gq, PLC, increase IP3 DAG and Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a2 receptor

A

Gi, AC, decrease cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is b1, b2, and b3 receptor

A

Gs, AC, increase cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

E and NE in a1, a2, b1, b2, b3

A

a1: E > NE
a2: E = NE
b1: E = NE
b2: E > NE
b3: E < NE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Catecholamines

A

Involved in chemical transmission in the CNS and PNS
Dopamine (mesocortical neuron) -> NE (sympathetic postganglionic neurons) -> E (adrenal medulla)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Synthesis of catecholamines

A

hydroxylation -> decarboxylation -> hydroxylation -> methylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Enzyme locations of catecholamines

A

DBM in secretory vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Enzymes and primary product of dopaminergic neurons

A

Product: Dopamine
Little or no DBM and PNMT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Enzymes and primary product of adrenergic neurons

A

product: NE
Less PNMT than DBM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Enzymes and primary product of adrenal medulla

A

E (80%) NE (20%)
DBM and PNMT present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What drugs inhibit CA synthesis

A

alpha-methyltyrosine (inhibit tyrosine hydroxylase, treat pheochromocytoma)
carbidopa (increases DOPA, treatment of parkinsonism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What drugs inhibit CA storage

A

reserpine (inhibit VMAT, antihypertensive drug)
tetrabenazine (inhibit VMAT, hyperkinetic disorders)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Inhibitor effects of VMAT mechanism

A

decrease NE storage -> decrease NE release
depletion of CA at synapse
NE accumulated in cytoplasm is degraded

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Diffusion of CA (catecholamine action) at synapse
Dilution of CA at synapse Uptake at extraneuronal sites by non-neuronal transporters
26
Reuptake of CA (catecholamine action) at synapse
(85% of CA) Into nerve terminals by neuronal transporters CA can be stored in vesicles and/or metabolized
27
Metabolism of CA (catecholamine action) at synapse
Following uptake and reuptake, CA undergoes enzymatic catabolism
28
Reuptake of CA: Neuronal and Non-Neuronal transporters
Neuronal: -Norepinephrine transporter (NET) --neurons, adrenal medulla, liver, placenta -Dopamine transporter (DAT) --neurons, kidney, stomach, pancreas Non-neuronal: -OCT1, OCT2, ENT --liver, kidney, intestine
29
NET affinity and DAT affinity
NET: NE > E and DA DAT: DA > NE and E
30
DAT and NET transporters
block antidepressants and substance of abuse increase NT levels at synapse NET - Cocaine, Desipramine DAT - Cocaine, Mazindol
31
NET transporter movement of molecules
Co-transporter (symport) Na+, Cl-, NE Na+ and energy dependent, Na/K ATPase creates Na+ gradient Binding of K+ returns the transporter to outward position
32
What are MAO (monoamine oxidase)
MAO-A -Periphery: placenta and liver -Brain: region containing catecholamines -NE, E, DA, serotonin MAO-B -Periphery: platelets, lymphocytes, liver -Brain -DA, amines
33
What are COMT (catechol-O-methyl-transferase)
Largely cytoplasmic enzyme Exception in adrenal medulla is membrane bound Less COMT than MAO in sympathetic neurons
34
Catabolism of NE and E: MAO mechanism
MAO forms aldehyde (DOPGAL) then turns into an alcohol (DOPEG)
35
Catabolism of NE and E: COMT mechanism
COMT methylates DOPEG to form MOPEG converted to VMA
36
What is the final end product of DA metabolism
HVA (homovanillic acid)
37
What is another route to form VMA other than COMT main pathway
minor pathway in neurons methylation of NE and E by COMT then deamination by MAO, MOPGAL formed then VMA
38
Classification of adrenergic agonists
Adrenergic agonists: Directing acting -> Selective and nonselective: act directly on one or more of the adrenergic receptors Mixed-acting: indirectly release NE and activate receptors Indirect acting -> Releasing agents, uptake inhibitor, MOA inhibitor, COMT inhibitors: increase NE or E levels to stimulate adrenergic receptors
39
Adrenergic Effects in the eye
Dilation of pupils (mydriasis) Far vision: muscle relaxation, increase ligament tension, flat lens
40
Adrenergic receptors: Iris dilator
radial muscle only sympathetic innervation pupil dilation
41
Adrenergic receptors: Ciliary muscle
also parasympathetic innervation M3R far vision (flat lens)
42
a1 adrenergic receptors in the eye
Gq increase Ca2+ Muscle contraction
43
B2 receptors in the eye
Gs Increase cAMP myosin light chain kinase-P (inactive) Muscle relaxation
44
Difference between radial muscle and circular muscle
radial muscle: pull out, dilation circular muscle: muscle relaxation, decrease pupil size
45
Adrenergic effects on the respiratory tract
Bronchodilation: relax bronchial smooth muscle, decrease airway resistance Decrease bronchial secretion
46
What kind of receptors do bronchi have
B2 receptors -> E has a better effect than NE
47
Short-acting beta 2 adrenergic agonists
Albuterol (salbutamol) Levalbuterol (xopenex) sulfation metabolism
48
Systemic SABA beta 2 adrenergic agonists
Terbutaline (brethine) Epinephrine sulfation metabolism
49
Long Acting beta 2 adrenergic agonists
Formoterol (foradil) Salmeterol (serevent) COMT and MAO metabolism
50
Very long acting beta 2 adrenergic agonists
Indacaterol (arcapta neohaler) Arformoterol (brovana) Olodaterol (striverdi, resoimat) Vilanterol only in combination inhalers Glucuronidation and O-demethylation
51
Mechanism of action of smooth muscle contraction
Increase intracellular Ca2+ bind to calmodulin (CaM) activates myosin light chain kinase (MLCK) Increase myosin ATPase activity cross bridges slide along actin and create muscle tension
52
Combination inhalors
Contain long-acting inhaled B2 agonist & corticosteroid Advair: Salmeterol and fluticasone Symbicort: Formoterol and budesonide Dulera: Formoterol and nometasone Brea Ellipta: Vilanterol and fluticasone
53
Adverse effect die to excessive activation of B2 receptors
Muscle tremor (skeletal muscle) Tachycardia: due to reflex effect, vasodilation, stimulation of heart Hypokalemia Metabolic effects
54
Adrenergic effects in the heart
Increase heart rate (chronotropy) Increase rate of conduction (dromotropy) Increase force of contraction (inotropy) Disturb cardiac rhythm and cause arrhythmias
55
What does the AV and SA node do
AV increase conduction velocity SA increase heart rate
56
Cardiac therapeutic uses of beta agonists
Rapid on set short duration E: cardiac arrest Dobutamine: increase contractility -> used for cardiac surgery, heart failure, acute myocardial infarction
57
Blood vessels are only activated by what system
Sympathetic (increase system, increases vasoconstriction)
58
What are the receptors in the sympathetic vessels and what do they do
Alpha 1: contraction caused by baroreceptors Beta 2: relaxation, increases blood flow
59
Alpha 1 adrenergic agonist drugs to treat hypotension
Metadaminol Midodrine (prodrug) Side effects are urine retention, goose bumps, bradycardia
60
Condone alpha 2 adrenergic agonist
Treats hypertension and opiate withdrawal Diagnose hypertension and pheochromocytoma
61
Postsynaptic a2 agonist Brimonidine
Treat glaucoma (reduce eye pressure) Side effects: drowsiness, eye itching Treat eye redness Decrease fluid pressure and construction
62
Difference between direct and indirect effect on glands
Direct: increase secretion (Refresh-eye, Glaucon-eye) Indirect: decrease secretion (decongestant, afrain)
63
Sympathetic effects in the urinary tract
Detrusor muscle - B2 activation, muscle relaxation Urethral Sphincter - a1 activation, contract sphincter Urinary retention
64
Adrenergic effects in the GI tract
Decrease motility and GI tone Constrict sphincters Decrease movement B2 receptors in smooth muscle a1 in sphincter
65
Adrenergic effects on uterine contraction
uterine relaxation B2 uterine contraction a1
66
Ritodrine and Terbutaline receptor selectivity (uterine contraction)
Beta 2
67
E in emergency treatment for anaphylaxis
Release histamine a1 - increase vasoconstriction, increase BP, decrease mucosal edema B2 - increase bronchodilation, decrease mediator release
68
NE effects
Increase contractility and heart rate and vasoconstriction Used for maintain BL in cardiogenic and septic shock Adverse reaction: arrhythmia, anxiety, headache
69
Adrenergic agonists releasing agents and uptake inhibitors
releasing: amphetamine, tyramine uptake: cocaine (increase E and NE to stimulate adrenergic receptors)
70
What are indirect adrenergic agonists drugs that decrease and increase NE and E
Drugs that decrease NE and E re-uptake -Cocaine -Desipramine Drugs that increase NE and E release -Amphetamine -Ephedrine -Tyramine
71
Does indirect adrenergic agonists have the same mechanism as NT release
no
72
Mechanism of action of indirect agonists
-Amphetamine is transported into nerve terminal by NET -> competitively inhibit reuptake -Drug taken in by VMAT -> exchange drug for NE -NE increase in cytosol
73
Amphetamine effects in CNS stimulant
wakefulness good mood increased motor physical improvement need to keep increasing dosage
74
Amphetamine effects in peripheral alpha and beta actions
Increase BP Increase HR -> cardiac arrhythmias Pupil Dilation Urinary incontinence
75
Ephedrine effects
Mixed-acting sympathomimetic -a and B receptors -Increase release of NE from sympathetic neurons Effects -Increase HR -Increase peripheral resistance -Broncodilation -Urinary retention -CNS stimulant
76
Tyramine effects (not a drug)
Product of tyrosine metabolism Produced in high concentration in rich-protein foods by decarboxylation of tyrosine during fermentation Indirect sympathomimetic action (caused by catecholamines)
77
Tyramine increase NE release causing severe hypertensive response. If patient is taking MAO inhibitors, patient should avoid eating what
Cured meats, pickled food, cheese, wine
78
Inhibitors of NE uptake: Cocaine
causes tachycardia and increase BP CNS causes euphoria and excitement
79
Inhibitors of NE uptake: Desipramine
Tricyclic antidepressent
80
Inhibitors of NE uptake: Atomxetine
selective inhibitor with clonidine-like effect in CNS
81
What do adrenergic antagonist do
Block the effects of NE, E and other sympathomimetic drugs by preventing their binding to adrenergic receptors
82
alpha 1 receptor antagonists
block contraction of arterial and venous smooth muscle -> vasodilation -> decrease BP (block contraction of visceral smooth muscle
83
alpha 2 receptor antagonists
block regulation of sympathetic output
84
beta 1 receptor antagonists
block cardiac receptors
85
Non-selective alpha 1 antagonists
reversible antagonist -> Phentolamine irreversible antagonist -> Phenoxibenzamine
86
selective alpha 1 antagonists
"-osin" ending drugs
87
Phentolamine
can dissociate from receptor competitive inhibitor -> can be reversed with sufficiently high concentration of agonists used in short-term control of hypertension decreases BP
88
Phenoxybenzamine
blocks alpha 1 and alpha receptors alkylating agent persistent effects anti-hypertensive decreases vasoconstriction produced by NE and E decreases BP
89
What do prazosin, terazosin, and doxazosin do (alpha 1 adrenergic antagonists)
used for hypertension
90
What do tamsulosin, silodosin do (alpha 1 adrenergic antagonists)
selective for alpha 1 A mainly for benign phosphate hyperthrophy
91
Effects of alpha 1-antagonists
Block alpha 1 receptors in blood vessels Block vasoconstriction produced by endogenous CA Decrease venous return Decrease BP
92
How do alpha 1 antagonists completely reverse effects of phenylephrine but only partially reverse the effects of NE
NE has an extra methyl group
93
Therapeutic uses of alpha 1 adrenergic antagonists
-Treatment of essential hypertension -Benign prostatic hyperplasia - Tamsulosin and Silodosin ---Enlargement of prostate increased smooth muscle mass and tone in prostate ---Decrease flow of urine
94
Adverse effects of alpha 1 antagonists
Orthostatic hypotenstion Dizziness and headache Syncope Tachycardia Miosis Nasal stuffiness
95
alpha 2 receptor antagonists
Block CNS receptors Increase NE release Increase HR and BP (Yohimbine, Indoramin)
96
Beta adrenergic antagonists
Antagonize effects of catecholamines Treatment of hypertension, heart failure
97
Traditional beta blockers: nonselective and selective
nonselective: block beta 1 and 2, propanolol selective: block beta 1, esmolol, metoprolol
98
Third generation beta blockers: nonselective and selective
nonselective: carvededilol, vasodilation (alpha 1) selective: betaxolol, vasodilation
99
Beta blockers with ISA activity
B1 > B2 selective not used because of partial agonist activity
100
Effects of beta antagonists in the heart
Decrease HR, rate of conduction, force of contraction, cardiac output
101
Therapeutic uses of beta blockers
Hypertension Angina Cardiac arrhythmias Glaucoma
102
Adverse effects of Beta 1 adrenergic antagonists
hypotension bradycardia dizziness fatigue heart block
103
Histamine
biologically active amine that functions as a NT -mediator for allergic rxns
104
Histamine metabolism
rapidly inactivated excreted in urine N-methyltransferase in most tissues (MAO)
105
Histamine release: Immunologic
Allergic reactions Degranulation of sensitized mast cells or basophils (needs Ca2+)
106
Histamine release: Chemical release
Caused by therapeutic agents released from mast cells directly and without sensitization
107
Allergin-induced histamine release
evokes IgE production cell sensitization allergen (antigen) binds to IgE degranulation of sensitized cells
108
Localized responses of histamine
Allergic Rhinitis (hay fever) -rxn in conjunctivae and nasal mucosa Asthma -rxn in mucous membranes of bronchi Food Allergy -rxn in upper or lower GI can induce smooth muscle contraction and vasodilation -> vomiting and diarrhea
109
Systemic Type 1 responses
Systemic Anaphylaxis (shock-like reaction) -onset w/in minutes of type I reaction -decreased BP, urination, defecation Wide range of antigens E used to counteract effects of mediators
110
H1 Histamine Receptors
Gq Phospholipase C IP3, DAG In Smooth muscles, heart, CNS Increases vascular permeability at sites of inflammation Allergies
111
H2 Histamine receptors
Gs Adenylyl cyclase Increase cAMP In gastric parietal cells, cardiac muscle, mast cells, CNS Increase gastric acids release, cardiac stiimulation Acid reflex
112
Histamine effects in cardiac system
Increase HR, AV conduction, force and rate of contraction
113
Histamine effects in vascular system
vasodilation -> smooth muscle relaxation -decreases BP Edema In blood vessels
114
Histamine effects at H1 receptors
Higher affinity for histamine activation at low histamine concentration vasodilation is mediated by NO production rapid onset short duration
115
Histamine effects at H2 receptors
Produces vasodilation mediated by cAMP and PKA pathway Slow onset long duration
116
Histamine effects on capillaries
Dilation of blood vessels increased capillary permeability in small vessels -> activation of H2 receptors Induction of endothelial cell contraction -> capillaries become leaky Fluid and proteins move into ECM tissue -> edema formation
117
Histamine effects on bronchial smooth muscle
Bronchoconstriction Increased broncho secretion (important for asthma patients)
117
Histamine effects on exocrine glands
Increase lacrimation, mucus secretion, salivation
117
Effect of histamine on GI tract
H1 receptors: contraction of intestinal smooth muscle, increase motility and GI tone, increase GI movement H2 receptors: activation of parietal cells, increase gastric acid secretion
118
Flush, flare and wheal
Flush: red line or spot due to capillary dilation Flare: red zone redness in the surrounding area due to arteriolar dilation Wheals: localized edema due to education of fluid from capillaries and venules
119
Clinical uses of histamine
Bronchial hyper-reactivity in asthmatics Allergy skin testing
120
Histamine toxicity
Hypotension Headache Tachycardia Bronchoconstriction Upset GI
121
Histamine effects
Increase secretion from glands, mucus secretion, heart rate, HCl secretion, motility of GI, bronco constriction
122
Histamine release inhibitors mechanism of action
Reduce or inhibit degranulation of mast cells -> mast cell stabilizers Prophylactic Drugs (nasalcrone, opticrome, gastrocom, nedocromil sodium) Poor absorption though GI
123
Therapeutic uses of histamine release
Decrease histamine effects Asthma - reduce level of bronchial reactivity Allergic reactions - rhinoconjunctivatis
124
Histamine receptor antagonist
H1 receptor antagonist Antihistamines H2 receptor antagonists Treatment of gastric acid secretion
125
First generation H1 blockers
Sedating drugs Not for children
126
Second gen H1 blockers
Reduce distributions into the CNS -> no sedating effect
127
First gen H1 antagonist drugs
Diphenhydramine Pyrilamine Chlorpheniramine Cyclizine Well absorbed Muscarinjc cholinergic responses
128
Second gen H1 antagonists drugs
Cetirizine Fexofenadine Loratadine Non sedating Anti inflammatory effects
129
Main effects of H1 antagonists
Decrease secretion of glands, broncoconstriction, mucus secretion, hypotension, edema, vasodilation
130
H1 antagonist effects on nerve endings
Suppress the action of histamine on nerve endings Suppress itching, pain, flare
131
H1 antagonist effects in the CNS
Depression: Slow alertness, reaction times, and somnolence Don’t use at bedtime Stimulation: Uncommon Restlessness, nervous, unable to sleep
132
Adverse effects of H1 antagonists
Sedation Dry mouth Loss of appetite Allergic response
133
H1 antagonist drug interactions
Antibiotics Grapefruit juice Additive effects with CNS depression drugs
134
Clinical uses of H1 antagonists
Allergic reactions Motion sickness (vertigo) Local anesthesia
135
Organization of components for gastric acid secretion
Parietal cells secrete H+ and Cl- separately into the gastric lumen of the stomach HCl is formed in the gastric lumen
136
Acid secretion of parietal cells
H+ from H2CO3 Exchanged for K+ Cl- into cells for HCO3 Excess K+ removed
137
Regulation of gastric acid secretion
ACh Histamine Gastrin They activate specific receptors on the parietal cells
138
Direct regulation of gastric acid
Bind ACh, gastrin, and histamine to receptors in surface of parietal cells Increase cAMP and Ca2+ activate PKA PKA phosphorylates and activates H+, K+ ATP-ase producing gastric acid
139
Indirect regulation of gastric acid secretion
ECL cells produce and release histamine Histamine activates H2 receptors on parietal cells producing gastric acid
140
Defense mechanism of gastric acid
Esophageal sphincter: prevent reflex of Garrick content into esophageal Stomach: traps bicarbonate at cell surface increase pH Mucus production: PGs stimulate this by decreasing acid secretions, NSAIDs inhibit PG synthesis -> decreasing production
141
antacids react with hydrochloric acid to form what two things
salt water
141
Therapeutic uses of antiacids
intermittent heartburn dyspepsia
141
What are the 4 gastric acid drugs
alka seltzer gaviscon maalox tums
141
H2 antagonists
inhibit gastric acid secretion from parietal cells
142
H2 antagonist drugs
cimetidine famotidine nizatidine
143
H2 antagonists: mechanism of action
-reduce gastric acid secretion -competitively inhibit histamine by binding to H2R -inhibit acid secretion stimulated by gastrin and ACh through activation of ECL cells
144
PPIs
-most potent inhibitors of gastric acid secretion -new pump molecules need to be synthesized to resume secretion
145
What are the 4 proton pump inhibitors
Omeprazole Zegrid Esomeprazole Lansoprazole