S2014 Pharm - Ans

Front 1

how is nervous system classified

Back 1

1. physical location - peripheral vs. CNS
2. function - Autonomic vs Somatic

Front 2

Define neurotransmitter function

Back 2

transfer information from nerve terminals across the synaptic cleft and bind receptors

Front 3

examples of ANS functions

Back 3

visceral functions -
ex. CO, blood flow to vital organs, digestion

Front 4

Examples of Somatic functions

Back 4

movement, respiration, posture

Front 5

2 major sections of ANS

Back 5

sympathetic, parasympathetic

Front 6

thoracolumbar - what does this refer to?

Back 6

sympathetic

Front 7

craniosacral - what does this refer to?

Back 7

parasympathetic

Front 8

where do sympathetic efferent nerve fibers exit

Back 8

through thoracic and lumbar spinal nerves

Front 9

where do parasympathetic efferent nerve fibers exit

Back 9

through cranial nerves and 3rd and 4th sacral spinal routes

Front 10

define origination and connection of preganglionic neurons of the efferent ANS

Back 10

originate in CNS and connect to ganglia in peripheral nervous system

act as relay stations to pass messages on to postganlionic nerves

Front 11

define termination of postganglionic neurons of the efferent ANS

Back 11

terminate on effector organs

Front 12

describe afferent neurons

Back 12

regulate the ANS system by sensing actions and providing feedback to the CNS

bring information from effector organ to CNS

CNS can then adjust its message to efferent nerves

Front 13

acetylocholine - released from

Back 13

cholinergic nerve fibers

- ALL preganglionic efferent ANS
- Parasym post gang efferent ANS
somatic nerve fibers to skeletal muscle

Front 14

norepinephrine - released from

Back 14

adrenergic nerve fibers
- most postgang sympathetic nerve fibers

Front 15

ACh made from? where? how transported? where/how stored?

Back 15

acetyl-CoA using choline O-acetyltranferase

made in nerve fiber mitrochondria

transported by choline transporters to nerve terminals

stored in packages of 'quanta' in vesicles located on surface of nerve terminal facing synapse

Front 16

describe release of ACh

Back 16

action potential reaches terminal

influx of Ca2+ into terminal

Ca2+ interacts with vesicles fusing membrane to terminal membrane

pore opens into synapse and hundreds of quanta are released into synaptic cleft

Front 17

ACh-R

Back 17

cholinorceptor

ACh binds here

Front 18

present in synaptic cleft and breaks down any unused ACh into choline and acetate

Back 18

Acetylcholinesterase AChE

Front 19

Acetylocholinesterase breaks down what NE into what parts?

Back 19

ACh ------> choline and acetate

Front 20

adrenergic nerve fibers make up....

Back 20

postganglionic neurons of symp nervous system

Front 21

adrenergic nerve fibers release

Back 21

norepinephrine

Front 22

name termination mech of adrenergic action

Back 22

1. NE metabolized by catalytic enzymes
- monoamine oxidase (MAO)
2. Diffusion away from receptor site (then metabolized)
3. Reuptake into terminal by norepinephrine transporter (NET)

Front 23

describe - receptor

Back 23

structures made of protein that are designed to bind endogenous molecules

Front 24

cholinergic recptors

named after? name types?

Back 24

name after alkaloids that bind them

1. muscarinic receptors
2. nicotinic receptors

Front 25

adrenergic receptors

based on? name types

Back 25

based on agonist and antagonist selectivity

Alpha 1 and Alpha 2 adrenoceptors
Beta 1 and Beta 2 adrenoceptors
Dopamine receptors

Front 26

parasympathetic system - sometime referred to as...

Back 26

trophotropic - energy storing

Front 27

sympathetic system - sometimes referred to as...

Back 27

ergotrophic - energy expenditure

Front 28

why is control of autonomic function important?

done by?

Back 28

1. prevent system from overstimulation
2. maintain effector organ functions within a narrow window of tolerance

done by:
1. presynaptic regulation
2. postsynaptic regulation
3. other integrated systems

Front 29

describe presynaptic regulation of ANS

Back 29

1. alpha 2 receptors
2. Beta receptors

Front 30

presynaptic regulation of ANS - describe alpha 2 receptor function

present on ?
activated by?

Back 30

present of nonadrenergic nerve terminals

activated by binding of NE released from same nerves

- results in reduced NE release

Front 31

autoreceptors

Back 31

responds to NE released from same neuron (usually inhibitory)

Front 32

heteroreceptors

Back 32

respond to neurotransmitters from other neurons

Front 33

presynaptic regulation of ANS - describe beta receptor function

present on ?
function?

Back 33

present on some neurons

facilitate release of more NE

Front 34

postsynaptic regulation
- name 2 mech

Back 34

1. up/down regulation
2. action of one receptor is affected by action of other receptors

Front 35

up and down regulate receptors - response to what?

Back 35

to high or low activation from neurotransmitters

Front 36

effector organs
- describe

Back 36

1. multiple sites throughout body - sensitive to adrenergic or cholinergic action
2. actions of NE and ACh are oftentimes opposite to each other


blockade of either NE or ACh receptors also results in opposite action caused by actual neurotransmitter

Front 37

effectors of ANS - EYE
name symp effects

Back 37

iris radial muscle - contracts (dil pup) - Alpha 1

Iris cirular muscle - NO effect

Ciliary Muscle - Relaxes (better dist focus) - Beta

Front 38

effectors of ANS - EYE
name parasymp effects

Back 38

iris radial muscle - No effect

Iris cirular muscle - Contracts (controls lght entry - accomodation) - M3

Ciliary Muscle - Contracts (allows focus of near) - M3

Front 39

effectors of ANS - HEART
name symp effects

Back 39

Sinoatrial node - accelerates (inc HR, chronotropic) B1 B2

Ectropic pacemakers - accelerates (inc HR) - B1, B2

contractability - increases (inotropic) B1, B2

Front 40

effectors of ANS - HEART
name parasymp effects

Back 40

Sinoatrial node - Decelerates (dec HR) - M2

Ectropic pacemakers - NO effect

contractability - decreases M2

Front 41

effectors of ANS - BLOOD VESSELS AND LUNGS
name symp effects

Back 41

Blood vessels
- contract (vasocontrict incBP) - alpha
- relax (vasodil decBP) - beta

bronchiolar smooth muscle - relaxes beta 2

Front 42

effectors of ANS - BLOOD VESSELS AND LUNGS
name parasymp effects

Back 42

Blood vessels - NO effect

Bronchiolar smooth muscle - contracts - M3

Front 43

effectors of ANS - GI tract
name symp effects

Back 43

Smooth muscle - relax (slow activity) - alpha 2, B2

sphincters - contract (blocks passage)- alpha 1

secretion - NO effect

Front 44

effectors of ANS - GI tract
name parasymp effects

Back 44

Smooth muscle - contract (inc activity)- M3

sphincters - Relax (opens passage) - M3

secretion - increases - M3

Front 45

effectors of ANS - Genitourinary Smooth muscle
name symp effects

Back 45

Bladder wall - relaxes (prevents urination) - beta 2

sphincter - contracts (blocks release) - alpha 1

uterus - relaxes - Beta 2, contracts - alpha

penis - ejaculation - alpha

Front 46

effectors of ANS - Genitourinary Smooth muscle
name parasymp effects

Back 46

Bladder wall - contracts (facilitates urination) - M3

sphincter - relaxes (allows release) M3

uterus - contracts - M3

penis - erection- M3

Front 47

effectors of ANS - metabolic functions
name symp effects

Back 47

liver - gluconeogenisis - B2, alpha
- glycogenolysis - B2, apha

fat cells - lipolysis - B3

kidney - renin release - B1

Front 48

effectors of ANS - metabolic functions
name parasymp effects

Back 48

liver - No effects

fat cells - NOeffects

kidney - NO effects

Front 49

Drug effects on neurtransmitters

Back 49

Alter:
1. synthesis
2. storage
3. release

Terminate action

alter neurotransmitter receptors

Front 50

what is ACh made from

Back 50

acetlyl-CoA and choline

Front 51

name 2 key actions at muscarinic receptors

Back 51

PARAsympathetic NS

1. nerves in parasympathetic NS release ACh that ACTIVATES muscarinic receptors on target organs (alters organ function by creating a positive stimulus)

2. ACh released from nerves of parasympathetic NS bind to receptors on nerve terminals to INHIBIT release of other neurotransmitters (also alters organ function by crating a neg stim)

Front 52

do nicotinic or muscarinic receptors have inhibitory capabilities?

Back 52

muscarinic only

Nicotinic have NO inhibitory capabilities (only relay the efferent message sent form teh CNS)

Front 53

Role of ACh at Nicotinic receptors in the somatic NS

where present?
binding of ACh causes?
prolonged binding causes?

Back 53

present primarily at neuromuscular junction of skeletal muscle

binding of ACh (or agonist) causes depolarization of the membrane (creating a positive stimulus - skel muscl contraction)

prolonged binding causes postganglionic neuron to stop firing
- causes skel muscle to relax
- prevents further stimulation (muscl paralysis)
- creates NEGATIVE stimulus

Front 54

define cholinomimetic agents

Back 54

nonacetylcholine compounds that mimic actions oof acetylcholine

- as stimulents - direct agonist
---direct binding to ACh receptors

-as cholinesterase inhibitors - indirect agonist
---prevents breakdown of ACh

Front 55

name examples of cholinergic compounds

aka

Back 55

alkaloids (derived from plants)
1. produce actions that mimic those seen when ACh binds to muscarinic receptors of teh parasympathetic nervous system

parasympathomimetics

2. produce actions that mimic those seen when ACh binds to nicotinic receptors of autonomic ganglia and skeletal muscle receptors

Front 56

name types of muscarinic receptors
and basic functions

where mostly found?

Back 56

M1, 3, 5 - cellular excitation

M2, 4 - inhibit cellular excitability

mostly found on autonomic effector organs (heart, smooth muscle, brain, exocrine glands)

Front 57

name types of nicotinic receptors

- where found?

Back 57

Nm - located at neuromuscular junction

Nn - in any other locations (CNS, adrenal medulla, autonomic ganglia)

Front 58

name direct acting cholinomimetics

Back 58

1. esters of choline
- ex. acetylcholine
2. alkaloids
-ex. muscarine and nicotine

Front 59

describe choline esters

Back 59

quarternary ammoniums

insoluble in lipids

cannot pass BBB

ex. methacholine, acetylcholine, carbachol, bethanechol

Front 60

describe charc of quarternary ammoniums

Back 60

1. hydrophilic
- poorly penetrate CNS
2. hydrolyzed by acetylcholinesterase (AChE)
- vary in rate of hydrolysis - affect half life
3. variations in chem structure alter charc.
- potency (binding affinity)
- susceptibility to hydrolysis by AChE

Front 61

describe cholinomimetic alkaloids

Back 61

typically teriary amines

ex - muscarine, pilocarpine, nicotine
lobeline

Front 62

methacholine - what type

Back 62

choline ester
- quarternary ammoniums

Front 63

acetylcholine - what type

Back 63

choline ester
- quarternary ammoniums

Front 64

carbachol - what type

Back 64

choline ester
- quarternary ammoniums

Front 65

bethanechol - what type

Back 65

choline ester
- quarternary ammoniums

Front 66

muscarine - what type

Back 66

cholinomimetic - tertiary amine

Front 67

pilocarpine - what type

Back 67

cholinomimetic - tertiary amine

Front 68

nicotine - what type

Back 68

cholinomimetic - tertiary amine

Front 69

lobeline - what type

Back 69

cholinomimetic - tertiary amine

Front 70

characteristics of cholinomimetic alkaloids

Back 70

- well absorbed after oral administration

lipid soluable - large volume of distribution
- cross BBB (musc only effects in super high doses)

not susceptible to acetylcholinesterase!!!

Front 71

what type of Neurotransmitter is not susceptible to acetylcholinesterase

Back 71

cholinomimetic alkaloids

Front 72

mech of indirect acting cholinomimetics

Back 72

inhibit AChE

Front 73

name types of AChE inhibitors

Back 73

1. simple alcohols - w/ quarternary ammonium
- ex. edrophonium

2. carbomate esters of alcohols w/ quarternary or teriary ammonium
- ex. neostigmine, physostigmine, pyridostigmine

3. organophosphates
- ex. echothiophate, isofluorophate

Front 74

edrophonium - what type

Back 74

AChE inhibitor
- simple alcohol w/quarternary ammonium

Front 75

neostigmine - what type

Back 75

AChE inhibitor
carbamate esters of alcohol w/ quarternary or teriary ammonium

Front 76

physostigmine

Back 76

AChE inhibitor
carbamate esters of alcohol w/ quarternary or teriary ammonium

overcome the anticholinergic action

Front 77

pyridostigmine

Back 77

AChE inhibitor
carbamate esters of alcohol w/ quarternary or teriary ammonium

Front 78

echothiophate

Back 78

organophosphate

Front 79

isofluorophate

Back 79

organophosphate

Front 80

binding difference between AChE inhibitors

Back 80

1. simple alcohols bind weakly and reversibly to AChE
- shorter half life of <10 min

2. Carbamate esters bind reversibly but tighter to AChE
- prolongs half-life - 30 min to 6 hours

3. organophosphates covalently bond
- extremely stable (nearly irreversible)
- very long half life of hundreds of hours

Front 81

what organ systems are similarly affected by direct and indirect cholimimetics

Back 81

eye
respiratory system
GI tract
GU tract

Front 82

what organ systems see different responses to direct and indirect cholimimetics

Back 82

CV system
secretory glands
CNS
peripheral NS
Neuromuscular junction

Front 83

cholinomimetic effects on the eye

eye is sensitive to what types?
cause eye to?

Back 83

sensitive to muscarinic agonists and AChE inhibitors

causes:
1. iris phrincter smooth muscle resulting in miosis
2. ciliary muscle resulting in accomodation
3. facilitate flow of aqueous humor out of anterior chamber
4. alter amount of foucs of light reaching retina

Front 84

clinical use of cholinomimetics

Back 84

glaucoma

muscarinic agonists and AChE inhibitors reduce intr-ocular pressure in narrow and wide angle glaucoma by allowing for the outflow of aqueous humor

Front 85

piocarpine

Back 85

cholinomimetic

reduce aqueous humor production - reduce pressure
allow for outflow

Front 86

physostigmine

Back 86

cholinomimetic - indirect

reduce aqueous humor production - reduce pressure
allow for outflow

Front 87

cholinomimetic effects on respiratory system

Back 87

1. cause contraction of smooth muscle in bronchial tree (restricts outflow)
2. stimulates secretions from tracheobronchial mucosa

ACh agonists aren't used much in respiratory medicine

Anticholinergics help increase airflow in pts with respiatory diseases like asthma

Front 88

Cholinomimetic effects on GI tract

Back 88

increase secretory and motor activity in teh gut

1. stimulates salivary and gastric glands, pancreas, and small intestine
2. increases peristalsis
3. relaxes most GI sphincters allowing GI contents to pass along tract

Front 89

use of cholinomimetics in GI disorders

Back 89

use agents to correct depressed smooth muscle activity and increase motility
- post-operative ileus (neostigmine)
- congenital megacolon

Front 90

use of cholinomimetics in respiratory disorders

Back 90

ACh agonists aren't used much in respiratory medicine

Anticholinergics help increase airflow in pts with respiatory diseases like asthma

Front 91

cholinomimetic effects on GU tract

Back 91

trigger voiding of bladder

- stimulate detrusor muscle (contraction) and relax the trigone and sphincter muscles of bladder

Front 92

use of cholinomimetics in GU disorders

Back 92

use agents to correct depressed smooth muscle activity

- treat urinary retention
- post-op, post partum, spinal cord injury, neurogenic bladder

ex. bethanecol, neostigmine

Front 93

bethanecol - clinical use

Back 93

urinary retention

Front 94

neostigmine

Back 94

urinary retention
increase gut motility
Myasthenia Gravis
reversal of neuromuscular paralysis (folwing surgery)

Front 95

effects on cardiovascular system
(direct cholinomimetics)

Back 95

two effects of muscarinic agonists
1. reduce peripheral vascular resistance
- vasodialation, dec BP
***dec BP can cause indirect reflex incr in HR***

2. decrease HR
- decrease rate of firing at sinoatrial node
- results in bradycardia
- reduces CO

DIFFICULT TO PREDICT OUTCOME

Front 96

use of cholinomimetics in CV disorders

Back 96

DIFFICULT TO PREDICT OUTCOME

arnet used much because better drugs and more predictable drug

Front 97

effects on cardiovascular system
(indirect cholinomimetics)

Back 97

increase cholinergic activity
1. sym and parasym nerves in heart
---neg chronotropic - bradycardia
---neg iontropic - drop in CO

2. observations result from greater impact of AChE inhibitors on parasym system

3. cholinergic receptors in cardiac and vascular smooth muscle

MODEST drop in BP

Front 98

Cholinomimetic effects on misc secretory glands

Back 98

ACh mediates
1. sweat glands - diaphoresis to help reg temp
2. lacrimal glands
3. nasopharyngeal glands

Cholinomimetics can trigger all these as well!

sweating, tearing, runny nose

Front 99

effects on CNS (direct cholinomimetics)

Back 99

nicotinic receptors:
1. induce tremor
2. stimulate emesis
3. stimulate respiratory center

muscarinic receptors:
1. induce tremor
2. cause hypothermia
3. interfere w/ nociception

---- note muscerine can't get into CNS, but muscerinic like drugs can

Front 100

effects on CNS (inderect cholinomimetics)

Back 100

1. low conc cause little effects
2. higher conc - convulsions, coma, respiratory arrect

Front 101

use of cholinomimetics for CNS conditions

Back 101

alzheimer's disease
- AD is related to def. of cholinergic neurons in CNS
- cannot be cured, but progression of cognitive dysfunction can be slowed with ***AChE inhibitors
ex - tacrine, donepezil, galantamine, rivastigmine

2. smoking cessation
- varenicline is a direct nicotinic agonist helpful for pts lookign to stop smoking
- reduce cravings and pleasurable effect of cigarets

Front 102

Tacrine

Back 102

cholinomimetic - AChE inhibitor

used in alzheimers

allow ACh to hang around longer

Front 103

donepezil

Back 103

cholinomimetic - AChE inhibitor

used in alzheimers

allow ACh to hang around longer

Front 104

galantamine

Back 104

cholinomimetic - AChE inhibitor

used in alzheimers

allow ACh to hang around longer

Front 105

rivastigmine

Back 105

cholinomimetic - AChE inhibitor

used in alzheimers

allow ACh to hang around longer

Front 106

varenicline

Back 106

direct nicotinic agonist - smoking cessation

reduce cravings, red pleasurable effects of ciggaretts

Front 107

actions of cholinomimetics on
- peripheral nervous system

Back 107

causes discharge of both sympathetic and parasympathetic nervous systems

- increase BP
- sympathetic tachycardia or vagal induced bradycardia
- parasympathetic effects on GI tract such as nausea, vomiting, diarrhea, and urinary voiding

Front 108

acetylcholine at neuromuscular junction

Back 108

ACh is released from pre-synaptic neurons

ACh binds to nicotinic cholinergic receptors on muscle fiber

results in depolarization of muscle fiber that leads to contractoin of skeletal muscle

Front 109

indirect cholinomimetic effects on neuromuscular junction

Back 109

low doses: AChE inhibitors prolong effects of ACh
- increases strength of muscle contraction

Medium doses: may cause muscle to fibrilate making the muscles less effective

high doses: block muscle depolarization leading to paralysis

Front 110

use of cholinomimetics in disorders at the neuromuscular junction

Back 110

Myasthenia Gravis
- autoimmune process of antibodies targeting nicotinic receptors
- these antibodies block binding of AC to the receptors
- symptoms include ptosis, difficulty speaking and weakness
- AChE inhibitors are very effective (pyridostigmine adn neostigmine)

reversal of neuromuscular paralysis
- following surgery (neostigmine)

Front 111

cholinomimetic use in the treatment of anticholinergic intoxication

Back 111

1. excessive anticholinergic action can be lethal in children
- can cause arrythmias in adults
- atropine, tricyclic antidepressants (TCAs)

2. increasing amount of ACh at receptor sites can overcome the anticholinergic action
- AChE inhibitors (physostigmine)

Front 112

pyridostigmine

Back 112

AChE inhibitor

treatment for neuromuscular junction disorders
- myasthenia gravis (autoimmune)

Front 113

toxicity of cholinomimetics

differ by?
mech of action?

Back 113

differ by receptor site
- muscarinic vs nicotinic

mechanism of action:
- direct cholinomimetic vs AChE inhibitor

Front 114

toxicity of direct muscarinic agonists

signs?
treat with?

Back 114

signs:
1. nausea
2. vomiting
3. diarrhea
4. urinary urgency
5. salivation
6. sweating
7. cutaneous vasodilation
8. bronchial constriction

treat with Atropine, anticholinergic

Front 115

what is used to treat toxicity of direct muscarinic agonist

Back 115

atropine

Front 116

atropine - describe
aka

Back 116

anticholinergic - muscarinic anticholinergic

aka - hyoscyamine
come from plant - Atropa belladonna

lots of synthesized forms

used to treat toxicity of direct muscarinic agonist

drugs with similar structures - produce similar effects
-- antihistamines, phenothiazine antipsychotics, tricyclic-antidepressants
- results in side effects from the intended benefits of these medications

used to dry upper and lower respiratory secretions prior to surgery or in mech vented pts

- reduce GI secretions - treating diarrhea (combined with diphenoxylate to mkae lomotil)

Front 117

acute toxicity of direct nicotinic agonists

symptoms
what level is toxic
treatment

Back 117

acute nicotine toxicity
- fatal at doses >40mg (i drop of pure nicotine liquid)
- 2 cigarettes contain lethal dose (if eaten)
---ingestion by children = vomiting

large doses:
1. CNS stimulation (seizure coma death)
2. skeltal muscle dpolarization - blockade and respiratory paralysis
3. hypertension adn cardiac arrythmias

treatment is supportive care until drug is metabolized - few hours as long as brain damage or death has not occurred

NO real treatment

Front 118

chronic nicotine toxicity

Back 118

chronic use risk is unclear

very addictive

Front 119

toxicity of cholinesterase inhibitors

related to?
symptoms?
used as?
treatment?

Back 119

pesticide exposure

organophosphates adn carbamates cholinesterase inhibitors

nerve agents

symptoms: show muscarinic excess (miosis, salivation, sweating, bronchial constriction, diaphragm paralysis, vomiting, diarrhea, convulsions)

treatment:
1. monitor VS
2. decontaminate if possible (throw up)
3. antidote w/ parenteral atropine or pralidoxime (2-PAM)
----2-PAM reactivates inhibited AChE before the full covalent bind forms through aging

COMMON on FARMS

Front 120

name two groups/types of cholinergic antagonists
(anticholinergic)

Back 120

1. muscarinic
- parasympatholytic or antimuscarinic
- block effects of parasympathetic autonomic discharge
- ex. atropine, scopolamine

2. nicotinic
- ganglionic blockers (ANS)
- neuromuscular blockers (NMJ)
- ex. tetraethylammonium, tubocurarine, succinylcholine

Front 121

tubocurarine

Back 121

Neuromuscular blocker - NON DEPOLARIZING antagonist

nicotinic anticholinergic

Front 122

tetraethylammonium

Back 122

ganglion blocker - nicotinic anticholinergic

nondepolarizing competitive antagonist

block all autonomic outflow

mixed sym and para effects

CNS - sedation, tremor, choreiform movements, mental aberrations

eye - cycloplegia, loss occommodation, mod dilation of pupil

CV system - tachycardia

GI tract - dec sec, dec motility

NOT a lot of therapeutic use - results difficult to predict

Front 123

succinylcholine

Back 123

depolarizing Neuromuscular blocker

nicotinic anticholinergic - POLARIZING neuromuscular blocker - agonist


contracts then causes paralysis by preventing further depolarization

Front 124

actions of atropine

Back 124

reverisbly blocks muscarinic receptors
- prevents ACh from binding to those sites

blocks actions of exogenously administered cholinergics > endogenous acetylocholine

actions vary with tissue type

tissue most sensitive are salivary, bronchial, and sweat glands

Front 125

tissues affected by atropine

Back 125

1. eye
2. CV system
3. respiratory system
4. GI tract
5. GU tract
6. sweat glands
7. CNS

Front 126

CNS effects of anticholinergics

Back 126

Atropine minimal affect or use (due to hydrophylic)

scopolamine can produce drowsiness and amnesia

scopolamine toxicity can cause CNS excitement, agitation, hallucinations, and coma

Front 127

scopolamine

Back 127

anticholinergic
- used for sea sickness or prevent motion system
- dry upper/lower respiratory secretions prior to surgery, or in mech vented pts

if toxic levels - cause CNS excitement, agitation, hallucinations, coma

Front 128

antimuscarinics - therapeutic uses in CNS disorders

Back 128

antimuscarinic agents may be used as adjuncts to treat tremor seen in parkison's disease
- ex. benztropine

scopolamine used to treat or prevent motion sickness
- injection, oral, transdermal patch

Front 129

benztropine

Back 129

anticholinergic - antimuscarinic

used in treating tremor in parkinsons

Front 130

effects of antimuscarinics on the eye

Back 130

antimuscarinic drugs (atropine) block cholinergic stimulation of pupillary constrictor muscle
- mydriasis

prevents contraction of ciliary muscle, resulting in cycoplegia, which is loss of accommodation
- prevents focusing of the eye for near vision (blurred vision)

reduces lacrimal secretion (dry eyes)

antimuscarinics can dangerously worsen narrow angle glaucoma due to lack of outflow of aqueous humor

Front 131

therapeurtic uses in eye disorders

Back 131

mydriasis and cycloplegia - both useful to ophthamologists to view retina

gtts or ointment

other drugs usually used first line

Front 132

effects of antimuscarinics on CV system

Back 132

low doses: (0.5 fm) of atropine block M1 receptors only
- observe bradycardia
- ACh still binding to M3 receptors on sinus node - dec HR

mod to high doses: (1-5 mg): block M2 in SA and AV nodes -
- tachycardia, blockade of vagal slowing
- ( inhibiting brakes on HR)

toxic doses: (>10mg) - intraventricular conduction block (death - severe bradychardia)
- inhibits elecrical pulse generation in pacemaker nodes


little effect on BP due to minimal innervation from parasympathetic system

Front 133

antimuscarinics - therapeutic uses in CV disorders

Back 133

in unwanted bradycardia and impaired cardiac output (abnormally depressed function)

moderate doses: atropine or other - may correct this by blocking M2 receptors
- triggers increased HR and CO

could SAVE pts life

Front 134

effects of anticholinergics on respiratory system

Back 134

bronchodilation and reduce/dry up secretions

good good good

Front 135

antimuscarinics - therapeutic uses in respiratory disorders

Back 135

ipratropium or tiotropium
-used in inhaler or nebulizer
- asthma, COPD - bronchodialation

atropine, scopolamine - dry upper and lower respiratory secretions prior to surgery or in mech vented pts

Front 136

iprtropium

Back 136

anticholinergic - use in asthma, COPD

Front 137

tiotropium

Back 137

anticholinergic - use in asthma, COPD

Front 138

effects of antimuscarinics on GI tract

Back 138

slow activity, emptying time, reduce secretions

reduce salivary secretion
- xerostomia

Front 139

atropine used for GI disorders

Back 139

atropine combined with diphenoxylate to make lomotil

treat diarrhea - esp when irinotecan (chemo drug) is cause

Front 140

how do antimuscarinics affect stomach acid

Back 140

DO NOT AFFECT acid secretion in dtomach

Front 141

effects of antimuscarinics on GU tract

Back 141

relaxation of smooth muscle in ureter and bladder wall (detrusor muscle)
- reduces vomiting

worsen urinary retention (MEN _ BPH)

Front 142

antimuscarinics - therapeutic uses in urinary disorders

Back 142

useful to treat overactive bladder or urinary tract spasm associated w/imflammation, surgery, neurologic cond

oxybutinin
- selective M3 - rec antagonist
- provides targetd relief for bladder spasm

other anticholinergics:
1. trospium
2. darifenacin
3. solifenacin
4. tolterodine

Front 143

oxybutinin

Back 143

selective M3 receptor antagonist

provides targeted relief for bladder spasms

Front 144

trospium

Back 144

anticholinergic

provides targeted relief for bladder spasms

Front 145

darifenacin

Back 145

anticholinergic

provides targeted relief for bladder spasms

Front 146

solifenacin

Back 146

anticholinergic

provides targeted relief for bladder spasms

Front 147

tolterodine

Back 147

anticholinergic

provides targeted relief for bladder spasms

Front 148

therapy for muscarininc toxicity

Back 148

usually pesticide exposure - organophosphates

atropine - CNS PNS symptoms
- doses may need to be repeated overal several days - for agents like parathion and nerve gas

use in addition to 2-PAM - recycles AChE
- reduces ACh to reduce cholinergic activity

Front 149

treatment of mushroom poisoning

mushrooms contain:?
two types of poisoning?
treatments?

Back 149

mushrooms contain natural cholinergic agents

two types of poisoning:
1. rapid onset
- within 15-30 min after ingestion
- treat with atropine
2. delayed onset
- 6-12 hrs after ingestion
- muscarinic side effects as well as renal and hepatic toxicity
- ATROPINE ineffective - use supportive care

Front 150

effects of anticholinergics on sweat glands

Back 150

treats hyperhidrosis
- not always effective - different types of sweat glands

glycopyrrolate

Front 151

glycopyrrolate

Back 151

anticholinergic

- works for hyperhidrosis

Front 152

anticholinergic adverse effects

Back 152

dry mouth (dry as a bone)
mydriasis (blind as a bat)
tachycardia
hot, flushed skin (red as a beet)
agitation (mad as a hatter)

plus...
urinary retention (can't pee)
visual changes (can't see)
constipation (can't sh*t)

Front 153

when are anticholinergics contraindicated?

Back 153

glaucoma (esp narrow ang)
men wit BPH
Gastric ulcers (may have issues due to slow gastric emptying)

Front 154

presynaptic inhibition of cholinergic action

Back 154

toxins from clostridium botulinum

target presynatpic proteins that block release of ACh

- paralysis of sk muscle
- dec activity at parasympathetic and sym synapses
- inhibition lasts several weeks to months

treat blepharospasm, focal muscle spasms, hperhirosis of palms and axillae, rid wrinkles

onabotulinum toxin
abobotulinum toxin
rimabotulinum toxin

Front 155

onabotulinum toxin

Back 155

toxins from clostridium botulinum

target presynatpic proteins that block release of ACh

- paralysis of sk muscle
- dec activity at parasympathetic and sym synapses
- inhibition lasts several weeks to months

treat blepharospasm, focal muscle spasms, hperhirosis of palms and axillae, rid wrinkles

Front 156

abobotulinum toxin

Back 156

toxins from clostridium botulinum

target presynatpic proteins that block release of ACh

- paralysis of sk muscle
- dec activity at parasympathetic and sym synapses
- inhibition lasts several weeks to months

treat blepharospasm, focal muscle spasms, hperhirosis of palms and axillae, rid wrinkles

Front 157

rimabotulinum toxin

Back 157

toxins from clostridium botulinum

target presynatpic proteins that block release of ACh

- paralysis of sk muscle
- dec activity at parasympathetic and sym synapses
- inhibition lasts several weeks to months

treat blepharospasm, focal muscle spasms, hperhirosis of palms and axillae, rid wrinkles

Front 158

ganglionic blocking agents

describe
AKA
block what?

Back 158

block ACh (and agonists) at nicotinic receptors of parasympathetic and sym ganglia

AKA - nondepolarizing competitive antagonists

block ALL autonomic outflow

tetraethylammonium (TEA)
hexamethonium (C6)
mecamylamine
trimethaphan

Front 159

hexamethonium (C6)

Back 159

GANGLIONIC BLOCKERS
- MIXED RESULTS (SYM/PARA)

NOT A LOT OF THERAPEUTIC USES - RESEARCH USES

Front 160

mecamylamine

Back 160

GANGLIONIC BLOCKERS
- MIXED RESULTS (SYM/PARA)

NOT A LOT OF THERAPEUTIC USES - RESEARCH USES

Front 161

trimethaphan

Back 161

GANGLIONIC BLOCKERS
- MIXED RESULTS (SYM/PARA)

NOT A LOT OF THERAPEUTIC USES - RESEARCH USES

Front 162

NEUROMUSCULAR BLOCKERS
where do they affect
name two groups

Back 162

block neuromuscular transmission betwen motor end plate and nicotinic receptors on skeletal muscle

two groups -
1. nondepolorizing (antagonists)
2. depolarizing (agonists)

Front 163

nondepolarizing meurmuscular blockers

Back 163

block ACh from binding to rec recp.
bind in competitive fashion

prevent dpolarization of muscle fibers - inhibit contraction

results - paralyzed muscle

effect can be terminated with AChE inhibitors (neostigmine) to increase ACh 0 overcome competition for blockaded receptors

Front 164

uses of nondepolarizing neurmuscular blockers

Back 164

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

drugs differ - half-life, means of elim
- tubocurarine
- mivacurium
- atracurium
- doxacurium
- pancuronium
- cisatracurium
- vecurolum
- rocuronium

Front 165

- tubocurarine

Back 165

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 166

- mivacurium
-

Back 166

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 167

atracurium
-

Back 167

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 168

doxacurium

Back 168

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 169

- pancuronium

Back 169

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 170

- cisatracurium

Back 170

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 171

- vecurolum

Back 171

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 172

- rocuronium

Back 172

nondepolarizing neurmuscular blockers

used in surgery as adjucts to anesthesia to produce muscle paralysis (relaxation)

Front 173

depolarizing neuromuscular blockers

Back 173

succinylcholine

binds to nicotinic receptors on skel muscle and acts like ACh
- constant stim of receptor
- initially causes depolarization of muscle by binding
- then prevents further impulses
- causes resistance to further depolarization and paralysis results

Front 174

name types of receptors that bind acetylcholine

Back 174

NIC, MUSC

Front 175

where are cholinergic receptors found int eh ANS?

Back 175

gang - both sym/para
para - effector

plus - muscles

Front 176

what type of neurons release norephinephrine

Back 176

adregernic

effector sym (post gang)

Front 177

muscarinic agonist causes what effects on eye

Back 177

accommadation, facilitate draining of aqueous humor, miosis

Front 178

muscarinic agonist causes what effects on respiratory system

Back 178

restriction, mucus prod

Front 179

muscarinic agonist causes what effects on cardiovascular system

Back 179

dec HR, dec squeeze

not too much effect on BB - may be slight dec

Front 180

muscarinic agonist causes what effects on Gu system

Back 180

voiding, relax sphincter, contracts muscle

Front 181

muscarinic agonist causes what effects on GI tract

Back 181

speed up, increase secretions

Front 182

what effect would a muscarinic agonist have on sympathetic portion of the autonomic nervous system

Back 182

NONE

Front 183

what is the name of the enzyme that metabolizes acetylcholine

Back 183

AChE

Front 184

why do organophosphates inhibit acetylcholinesterase for so long compared to other types of aceylcholinesterase inhibitors

Back 184

covalent bonds

Front 185

what effect does nicotine have inn toxic conc in humans

Back 185

CNS

acute nicotine toxicity
- fatal at doses >40mg (i drop of pure nicotine liquid)
- 2 cigarettes contain lethal dose (if eaten)
---ingestion by children = vomiting

large doses:
1. CNS stimulation (seizure coma death)
2. skeltal muscle dpolarization - blockade and respiratory paralysis
3. hypertension adn cardiac arrythmias

treatment is supportive care until drug is metabolized - few hours as long as brain damage or death has not occurred

NO real treatment

Front 186

what effects do anticholinergic agents have on the eye?

Back 186

mydrosis

Front 187

what effects do anticholinergic agents have on the respiratory tract

Back 187

open, dec secretion

Front 188

what effects do anticholinergic agents have on the GI tract

Back 188

slow down , dec mot, dec secretions

Front 189

what effects do anticholinergic agents have on the GU tract

Back 189

retention

Front 190

what effects do anticholinergic agents have on the CV system

Back 190

low - bradycardia (atropine blocks M1 only)
- occurs because M3 still have ACh

mod to high: tachycardia - blockade of vagal slowing

very high - death - stop pulse

Front 191

what types of patients might use an anticholinergic agent be contraindicated

Back 191

BPH, ulcers, glaucoma

Front 192

explain mech of action of a ganglionic blocking agent

Back 192

antagonists
block both sides(para/sym) - at ganglion

no clinical applicatoins

Front 193

what is difference between a nondepolarizing neuromuscular blocker and a depolarizing neuromuscular blocking agent/

Back 193

nondepolarizing - antagonist

polarizing - agonist (super agonist)

Front 194

classify the following as either a nondepolarizing neruomuscular blocker or depolarizing neurmuscular blocker
1. Tubocurarine
2. atracurium
3. succinylcholine
4. rocuronium
5. doxacurium
6. vecuronium

Back 194

1. Tubocurarine - NON DEPOL - antagonists
2. atracurium - NON DEPOL - antagonists
3. succinylcholine - DEPOL - agonist
4. rocuronium- NON DEPOL - antagonists
5. doxacurium- NON DEPOL - antagonists
6. vecuronium - NON DEPOL - antagonists

Front 195

when would someone use a neuromuscular blocking agent

Back 195

surgery
intebation
ICU - to keep still

Front 196

provide some theurapeutic uses of anticholinergics

Back 196

urinary tract spasm associated with inflammation, surgery, neurologic cond
- oxybutinin (selective M3 antagonist)
- Tropsium, darifenacin, solifenacin, tolterodine

used to treat rapid onset mushroom poisoning - atropine

used to treat blepharospasm - clostridum botulinum toxins

sweat glands overactive - glycopyrrolate

Front 197

catecholoamines

Back 197

general term for neurotransmitters/hormones in sympathetic nervous NS

Front 198

name major catecholamines

Back 198

1. dopamine
2. norepinephrine
3. epinephrine

Front 199

name 4 basic catagories of adrenergic receptors

Back 199

alpha1 (A1A, A1B, A1D)
alpha2 (A2A, A2B, A2C)
beta type (B1, B2, B3)
dopamine (D1, D2, D3, D4, D5)

all of g-protein coupled

Front 200

Alpha 1 receptors
coupled to what?
what happens?

Back 200

coupled with Gq proteins to phospholipase C

- when activated, results ACTIVATION of protein kinases - activate other enzymes that result in physiologic actions

Front 201

Alpha 2 receptors
coupled to what?
what happens?

Back 201

coupled with Gi proteins to adenylyl cyclase

- when activated, results in INHIBITORY activity that dec cAMP - reduces transduction of activting types of enzymatic messages

Front 202

beta receptors
coupled to?
what happens?

Back 202

coupled to Gs proteins to adenyly cyclase (some to Gq)
inc conversion of ATP to cAMP

activates multiple kinases that activate additional enzymes leading to physiologic actions

Front 203

dopamine receptors
couple to what?
what happens

Back 203

D1 receptors STIMULATE adenylyl cyclase (inc cAMP)
D2 receptors INHIBIT adenylyl cyclase (dec cAMP)

Front 204

what are the factors that alter the degree to which any adrenergic receptors respond to a stimulus

Back 204

1. selectivity
2. regulation
3. polymorphisms
4. catecholamine metabolism

Front 205

describe receptor selectivity

low doses vs high doses?

Back 205

allows sympathomimetic drugs to bind to one subgroup of receptors without binding to others

degree of binding is drug conc dependent
-low doses - selective binding
- high doses - nonselective binding

Front 206

describe receptor regulation

- give example

Back 206

receptor response up or down over time
- ex desensitization

Front 207

desensitizatoin - describe, aka

Back 207

aka - tolerance, refractoriness, tachyphylaxis

occurs after long term exposure to catecholamines or drugs

results in dec responsiveness of that cell/tissue to additional stimulation

Front 208

mech of desensitization

Back 208

1. altered transcription or translation of DNA and/or RNA
2. modifications of receptors
- by interactions with enzymes or other proteins
3. long term exposure to an agonist
4. interactions or messages from other receptors

Front 209

using desensitization for therapeutic benefit

Back 209

- sometimes desensitization of receptors is the desired effect of a drug
- results in an inc response followed by the desired dec physiologic action

****takes time to get to dec.

Front 210

describe receptor polymorphisms

Back 210

varying amino acid sequences in different people

- can alter receptor response - inc/dec risk to develop certain dz
-alter degree of susceptibility to desensitization
- alter degree or responsiveness to drugs

Front 211

termination of neurotransmitter action

Back 211

1. norepinephrine transmporter (NET)
2. movement of NE out of synaptic cleft and into the bloodstream
3. metabolism by catecholamine-O-methyltransferase (COMT)
4. metabolism by monoamine oxidase

Front 212

Norephinephrine Transporter (NET)

Back 212

most common
- removes up to 90% of released NE

acts as a pre-synaptic pump to move nE out of synapse and back into the neuron
- NE can now be recycled or metabolized by monoamine oxidase

Front 213

NET as a therapeutic target

Back 213

some drugs can bind and inhibit NET action
- atomozetine (ADHD), cocaine

NET inhib allows NE to stay around longer
- stim of adrenergic receptors

other drugs can reverse NET action and release NE that was originally taken up

Front 214

Catechol-O-Methyl Transferase (COMT)

Back 214

- metabolizes all catacholamines
- assists in terminating actions of NE, E, DA

Drugs can inhibit COMT and allow for prolonged action of catacholamines
- ex. entacopone
- Parkinson's disease inhibit metabolism of levodopa

Front 215

- atomozetine (ADHD), cocaine

Back 215

bind and inhibit NET action

Front 216

ex. entacopone

Back 216

- used in Parkinson's disease to inhibit metabolism of levodopa

Front 217

monoamine oxidase
what do?
how many forms? name

Back 217

metabolizes endogenous monoamines
- NE, E, DA, serotonin

two forms (A and B)

Front 218

sympathomimetics

Back 218

drugs that mimic actions of NE,E,DA

direct agonists
- bind to receptors- result in activation

indirect agonists
- cause release of stored catacholomines
- inhibit reuptake of already released catacholamines

Front 219

direct agonists - sympathomimetics

Back 219

structure allows for binding to adrenergic receptors resulting in activation

Front 220

indirect agonists - sympathomimetics

Back 220

2 mech
1. cause release of stored catecholamines
2. inhibit reuptake of catacholamines already released

Front 221

describe benzene ring substitutions in sympathomimetic drugs

Back 221

1. add OH group to C3 and C4
- max alpha and beta activity
- creates catacholamine cmpnds - susceptible to COMT

2. adding -OH to C3 OR C4
- reduce adrenergic potency
- inc drug duration - less susceptible to COMT

3. absence of -OH group on benzine ring
- hydrophobic
- entry into CNS

Front 222

describe amino group substitutions sympathomimetic drugs

Back 222

increase size of alkyl substitutions on the amino group
- increase Beta activity
- larger the group, lower the alpha infinity

isopropyl group on amino nitrogen
- inc Beta activity even more

Front 223

describe alpha carbon substitutions in sympathomimetic drugs

Back 223

- block oxidation by monoamine oxidase (MAO)
- prolonged duration

adding CH3
- increase ability to act as indirect sympathomimetic as well as direct agontists

Front 224

describe beta carbon substitutions in sympathomimetic drugs

Back 224

less significant impact on activity

add -OH group enables direct agonist activity
- but not necessary

Front 225

what is major target of sympathomimetics

Back 225

cardiovascular

Front 226

outcome of giving a drug is dependent upon ....what?

Back 226

1. selectivity for alpha/beta receptors
2. pharmacologic action at receptors (ag/atag)
3. action of body's compensatory mech (desensitization)

Front 227

key sympathomimetic effects in cardiovascular system include... (4)

Back 227

1. HR
2. CO
3. peripheral vascular resistance (BP)
4. venous return

Front 228

where are Alpha 1 receptors present in cardiovascular system?

Back 228

vascular bed

Front 229

activation by an alpha 1 agonist in cardiovascular system results in ....what?

Back 229

arterial and venous vasoconstriction
- inc BP
reflex slowing of HR...should dec CO ...but
venous return inc, inc stroke volume, maintain CO

CO=HR x SV

Front 230

phenylephrine

Back 230

alpha 1 agonist

maintain BP in pt with poor organ perfusion (vascular shock)

treat stuffy nose
- constricts blood vessels in nasal passage

Front 231

where are alpha 2 receptors in cardiovascular system?

Back 231

vascular beds and CNS

Front 232

activation by an alpha 2 agonist in cardiovascular system results in ....what?

Back 232

activation of peripheral receptors - vasoconstriction
----only locally, IV push, very high oral doses

systemic admin results in activation of central alpha 2 receptors - inhibits sympathetic vascular tone
----dec sympathetic activity
---- dec BP

Front 233

dec in sympathetic activity ----aka

Back 233

sympatholytics

Front 234

what do B1 receptors in heart do?

Back 234

inc contractility
inc HR
inc CO

Front 235

what do B2 receptors in vasculature do?

Back 235

dec peripheral resistance (vasodilation)
dec BP

Front 236

stim of D1 receptors cause what in cardiovascular system

Back 236

vasodilation in renal, splanchnic, coronary, cerebral

Front 237

stimulation of alpha, beta receptors by dopamine
- describe affects

Back 237

low dose - activates B2 - vasodilation, dec BP

med dose - activates B1 - inc contractility, HR, CO

high dose - activates A1 - vasoconstriction

Front 238

effects of sympathomimetics on LUNGS

Back 238

B2 receptors - brochodilation


no alpha, no B1

Front 239

effects of sympathomimetics on EYE

Back 239

alpha receptors in radial muscle
- mydriasis
- inc outflow of aqueous humor and can reduce intraocular pressure in glaucoma

Front 240

effects of sympathomimetics on Genitournary

Back 240

alpha receptors in bladder, urethral sphincter, prostate

promote urine retention, mediate ejaculation
contracts uterus

Front 241

effects of sympathomimetics on Salivary glands

Back 241

beta receptors - increase salilvation

Front 242

effects of sympathomimetics on apocrine sweat glands

Back 242

increase production in response to stress (NOT TEMP)

Front 243

effects of sympathomimetics on Metabolism

Back 243

inc glycogenolysis in liver (beta receptors)
---inc serum glucose

lipolysis: Beta inc alpha 2 dec
insulin: Beta 2 inc (islet cells) alpha 2 dec
K+ uptake: Beta 2 inc (can cause hypokalemia)
renin: Beta 1 inc alpha 2 dec
(mediates renal perfusion)

Front 244

parathyroid - mediated by what ANS

Back 244

adrenergic receptors

Front 245

calcitonin - mediated by what part of ANS

Back 245

adrenergic receptors

Front 246

thyroxine - mediated by what part of ANS

Back 246

adrenergic receptors

Front 247

gastrin - mediated by what part of ANs

Back 247

adrenergic receptors

Front 248

epinephrine - aka
describe where acts
what effects?

Back 248

adrenaline
agonsits at alpha and beta

potent vasoconstrictor , cardiac stimulant
--- inc systolic BP (alpha 1)
--- inc HR, CO (Beta 1)

vasodilation (Beta 2)
----skeletal muscle blood vessels during exercise
--- drop diastolic BP

Front 249

Norepinephrine - aka

where acts?
what effects?

Back 249

aka - noradrenaline, levophed

A1,A2, B1 - minimal B2

potent vasoconstrictor, cardiac stim
----inc systolic and diastolic BP (A1 recept)
----inc HR and CO (B1 rec)

Front 250

dopamine - action in CNS?

Back 250

significant actions in CNS
- contributes to development of addiction based on reward stimuli

- deficiency - parkinsons (entacapone)

Front 251

phenylephrine

Back 251

direct A1 agonist

not inactivated by COMT which prolongs duration of action

DECONGESTANT
RAISE BP

Front 252

Midodrine

Back 252

direct A1 agonist

RAISE BP
Treat orthostatic hypotension

Front 253

what is used to treat orthostatic hypotension

Back 253

Midodrine - direct A1 agonist

Front 254

Clonidine

Back 254

Direct A2 agonist

REDUCE BP, Treat HTN

Front 255

Methylodopa

Back 255

Direct A2 agonist

REDUCE BP, Treat HTN

Front 256

Guanfacine

Back 256

Direct A2 agonist

REDUCE BP, Treat HTN

Front 257

Guanabenz

Back 257

Direct A2 agonist

REDUCE BP, Treat HTN

Front 258

Dexmedetomidine

Back 258

Direct A2 agonist

acts in CNS - sedation of patients in ICU setting

Front 259

Oxymetazoline

Back 259

Direct A1 and A2 agonist

A1 - vasoconstriction - DECONGESTANT

A2 - decrease BP

Front 260

Isoproterenol

Back 260

Nonselective B agonist

B2 - vasodilation - Dec BP, mean arterial pressure

B1 - Pos chronotropic and inotropic on heart
---inc. HR, CO

Front 261

Beta selective agonists - effects on heart

Back 261

Inc. CO without a reflexive increase in HR

Front 262

dobutamine

Back 262

B1 selective agonist
- racemic mixture of 2 isomers (diff activity)

+ isomer: potent B1 action, A1 antagonism
---allows for an increase in CO without increasing BP

-isomer - gives potent A1 action, inc BP

GIVE TOGETHER:
pos inotropic action, little BP change

Front 263

B2 selective agonists - therapeutic uses

Back 263

provide bronchodilation - tx asthma, COPD

Front 264

Albuterol

Back 264

B2 selective agonist

tx asthma COPD

Front 265

Terbutaline

Back 265

B2 selective agonist

tx asthma COPD
relax uterine smooth muscle during labor

Front 266

Metaproterenol

Back 266

B2 selective agonist

tx asthma COPD

Front 267

Pirbuterol

Back 267

B2 selective agonist

tx asthma COPD

Front 268

Salmeterol

Back 268

B2 selective agonist

tx asthma COPD

Front 269

Formoterol

Back 269

B2 selective agonist

tx asthma COPD

Front 270

Ritodrine

Back 270

B2 selective agonist

relax uterine smooth muscle during labor

Front 271

Mixed A and B sympathomimetics - effects?

Back 271

provide A and B effects
- vasocontriction, decongestion, bronchodilation, CNS effects: appetite supp, stimulation

potency varies from drug to drug

Front 272

Ephedrine

Back 272

Mixed acting sympathomimetic

from plant
- bronchodilation in asthma (better drugs out there)

Front 273

Pseudoephedrine

Back 273

Mixed acting sympathomimetic

Front 274

two mech of indirect acting sympathomimetics

Back 274

1. displace stored catecholamines
2. inhibit reuptake of released neurotransmitter by interfering with NET

Front 275

Amphetamines

Back 275

indirect acting sympathomimetics

causes release of stored NA and DE

CNS stimulant - inc mood, alertness, dec appetite

Front 276

doluxetine

Back 276

indirect acting sympathomimetics

catecholamine reuptake inhibitor

Front 277

Methamphetamine

Back 277

indirect acting sympathomimetics

similar to amphetamine

made from pseudoephedrine
potent CNS actions

Front 278

Phenmetrazine

Back 278

indirect acting sympathomimetics

similar to amphetamine

Front 279

Methylphenidate

Back 279

indirect acting sympathomimetics
amphetamine derivative

ADHD
- reduces uptake of NE, function in the brain

Front 280

Modafinil

Back 280

indirect sympathomimetic

inhibits NE, DA transporters in CNS

inc wakefulness in pts, narcolepsy, obstructive sleep apnea, shift work disorder

Front 281

Armodafinil

Back 281

indirect sympathomimetic

R-enantiomer or modafinil
- similar actions to modafinil

Front 282

Tyramine products
- how work?

Back 282

causes release of stored catecholamines
- similar actions to NE (A1, A2, B1)

metabolized by MAO
- so careful with pts taking MAO inhibitors
- dangerous HTN

Front 283

Atomozetine

Back 283

selective inhibitor of NE reuptake with mostly CNS effects
- may cause inc BP
- ADHD

Front 284

Subutramine

Back 284

Serotonin and NE reuptake inhibitor
- appetite suppressant

Front 285

doluxetine

Back 285

serotonin and NE reuptake inhibitor
- antidepressent

Front 286

Cocaine

Back 286

inhibits peripheral reuptake of NE by NET

- enters CNS and produces amphetamine-like actions, more intense

- inhibition of DA reuptake in pleasure center of brain
- very rapid addiction

Front 287

Sympathomimetic - therapeutic application
Cardiovascular - Hypotension

Back 287

inc BP, CO

used to maintain perfusion of vital organs

A1 agonists to raise BP
- NE, phenylephrine

inotropic agents in shock syndromes inc CO
- Dopamine, dobutamine

Front 288

Sympathomimetic - therapeutic application
Cardiovascular - Hypertension

Back 288

Central acting A2 agonist - dec HTN
- Clonidine

oral tablets, topical patch

Front 289

Sympathomimetic - therapeutic application
Cardiovascular - Orthostatic Hypotension

Back 289

normla sympathetic reflex action (inc HR, peripheral vasoconstriction) revents this
- can be inhibited by antihypertensives

TX with A1 agonist - midodrine

Front 290

Sympathomimetic - therapeutic application
Cardiovascular - emergency

Back 290

used in complete heart block or cardiac arrest

Epinephrine - part of resuscitation measures
- redistributes blood flow from less important areas to more important areas
--------A1, B2

Front 291

Sympathomimetic - therapeutic application
sugical applications

Back 291

A1 activity
reduce blood loss at site of sugical manipulations
- Epinephrine or cocaine

slow diffusion of anesthetics away from site of admin
- Epi, NE, phenylephrine

Front 292

Sympathomimetic - therapeutic application
Sinus Decongestant

Back 292

A1 agonist
decrease nasal stuffiness
- nasal sprays to cause vasoconstriction
----phenylephrine, oxymetazoline

REBOUND effect (3day limit) - ischemic changes followed by hyperemia when agents discontinued (changed receptors)

Front 293

Sympathomimetic - therapeutic application
pulmonary uses

Back 293

B2 selective agents

improve pulmonary air flow

asthma , COPD

Albuterol,
metaproterenol,
pirbuterol,
salmeterol,
formoterol

Front 294

Sympathomimetic - therapeutic application
Anaphylactic reactions

Back 294

reverse vascular complications of immune hypersensitivity

epinephrine activates A1, B1, B2 receptors to reverse all symptoms

used in comb w/ steroid (pregnesone) or antihistamine (benedryl)

Front 295

Sympathomimetic - therapeutic application
ophthalmic applications

Back 295

mydriasis - eye exams

decongestion - reduce eye redness w/ allergies (A1 agonist)

red intraocular pressure (A2 agonist)
- apraclonidine, brimonidine

Front 296

Sympathomimetic - therapeutic application
Genitourinary applications

Back 296

B2 selective - relax uterus in premature labor

ritodrine
terbutaline

Front 297

Sympathomimetic - therapeutic application
CNS applications

Back 297

tx narcolepsy - increase alertness, defer sleep
- amphetamine, modafinil

appetite suppression

ADHD - improve attention, reduce hperkinetic behavior, elim behav barriers to learning
- Methylphenidate,
- Dextroamphetamine/amphetamine
- Lisdexamfetamine

Front 298

Sympathomimetic - therapeutic application
ICU sedation

Back 298

improve pt comfort in ICU
Pts under severe physiologic stress (mech vent, post-operative) - need sedation

A2 agonist w/ other drugs
- helps lower req of other drugs
- dexmedetomidine

Front 299

adrenergic actions - cardiovascular

Back 299

A1 - vasoconstriction
B1 - increase HR, CO
B2 - vasodilation
A2 - central vasodilation

Front 300

adrenergic actions - respiratory

Back 300

A1 - decongestion
B2 - bronchodilation

Front 301

adrenergic actions - ophthalmic

Back 301

A1 - mydriasis, dec redness
A2 - dec intraocular pressure

Front 302

adrenergic actions - genitourinary

Back 302

B2 - delay fetal delivery

Front 303

adrenergic actions - Secretory glands

Back 303

B increase appocrine sweat glands adn salivary glands

Front 304

adrenergic actions - metabolism

Back 304

B - inc glycogenolysis and lipolysis
A2 - dec lipolysis
B2 - inc insulin release
A2 - dec insulin release

Front 305

adrenergic actions - CNS

Back 305

feelings - wakefulness, nervousness, anorexia, euphoria

Front 306

reversible antagonists vs irreversible antagonists

Back 306

reversible - compete with agonists, endogenous catecholamines
- block receptors, conc dependent
- duration based on affinity, half life

irreversible - covalent bonds
- duration dependent on synthesis of new receptors (may take several days)

Front 307

how do Alpha antagonists work w/ the cardiovascular system

Back 307

block A1 mediated vasoconstriction
---lead to vasodilation
--- dec peripheral vascular resistance and dec BP

may cause othostatic hypotension and reflex tachycardia
(CO=SVxHR)

Front 308

effects of A1 antagonists

Back 308

vasodilation
tachycardia (reflex)
miosis
sinus congestion
facilitates urination

Front 309

Phenoxybenzamine

Back 309

irreversible A1 (>A2) antagonist

1. blockade of vasoconstriction - causes vasodilation
2. blocks presynatpic A2 - blocks reuptake of NE (not very potent)

Used to Tx excessive catecholamine release (pheochromocytoma - adrenal medulla tumor)

Front 310

phentolamine

Back 310

reversible A1 and presynaptic A2 antagonists

A1 blockade: dec peripheral vascular resistance (D BP)

A2 blockade: inc cardiac stim (inc HR, cardiac workload0
= potential for arrhythmias
---due to enhanced NE activity from blocking NE reuptake

managment of pheochromocytoma

Front 311

Prazosin

Back 311

A1 antagonist

HTN Tx drug

Front 312

Terazosin

Back 312

A1 antagonist

HTN Tx drug

Front 313

Doxazosin

Back 313

A1 antagonist

HTN Tx drug

Front 314

Tamsulosin

Back 314

A1 antagonist

HTN Tx drug
highly A1 selective

relaxation of arterial venous smooth muscle
relax smooth muscle in prostate
------ TX BPH------

Front 315

name several drugs that have A1 antagonism side effect and what these lead to

Back 315

lead to hypotension

Haloperidol (antipsychotic)
Chlorpromazine (antipsychotic)
Trazodone (sleep aid, antidepressent)
Erotamine and dihydroergotamine (migraine HA)

Front 316

describe B receptor antagonists

Back 316

bind reversibly


most are pure antagonists, some have partial B agonist activity
(low conc of endogenous catecholamines)

drugs are selective for B1 or B2 - dec at high doses

some have local anesthetic properties

Front 317

describe B - antagonists in cardiovascular system
aka

Back 317

beta blockers
- first line in:
1. CHF
2. Angina
3. MI

- reduce cardiac workload (neg inotropic, neg chronotropic)
- slow AV node conduction - dec HR
- suppresses renin release
- reduce peripheral vascular resistance and BP

DEC heart workload

- also used to control BP -debatable!

Front 318

B-blockers and blood pressure

Back 318

block peripheral B2 receptors
- but instead of vasocontriction (inhib vasodilation)
vasodilation occurs over time - think due to receptor changes

effect enhanced with agents that block both A and B receptors (labetolol) - block vasoconstriction

Front 319

B-blockers in angina

Back 319

help pts by improving oxygen supply and demand
- block adrenergic effects that would occur under sym conditions
- reduction in cardiac workload - reduces demand for O2
- improves exercise tolerance

Front 320

b-blockers contraindicated in which pts

Back 320

pts with asthma and COPD

No pure selective B1 blockers - B blockers could worsen cond of asthma/COPD - dirty actions

HOWEVER - some pts just fine - best with informed consent

Front 321

B blocker -ophthalmic effects

Back 321

tx open angle glaucoma
- also cholinergic agents, A2 agonists (increase flow), prostaglandin analogs, diuretics

B-blockers common - gives as gtts
- reduce prod of aqueous humor

betaxolol, timolol, carteolol

Front 322

betaxolol

Back 322

beta blocker
gtts - reduce prod of aqueous humor
tx open angle glaucoma

Front 323

timolol

Back 323

beta blocker
gtts - reduce prod of aqueous humor
tx open angle glaucoma

Front 324

carteolol

Back 324

beta blocker
gtts - reduce prod of aqueous humor
tx open angle glaucoma

Front 325

unexpected effects of beta blockers

Back 325

block glucose mobilization
worsen high cholesterol
intrinsic sympathomimetic activity (act as agonists)
local anesthetic activity

Front 326

metabolic effects of B blockers

Back 326

block glucose mobilization
- reduce energy availability
- inhibit sympatetic stim of lipolysis
- partial inhibition of glycogenolysis
-----could block the body's ability to make glucose available when needed

USE WITH CAUTION in PTS at risk of complicatoins associated with HYPOGLYCEMIA
- insulin dependent diabetics

Front 327

in what patients are beta blockers contraindicated

Back 327

insulin dependent diabetics - can complicate hypoglycemia

Front 328

cholesterol issues with B blockers

Back 328

alter levels of some types of stored cholesterol and inc cardiovascular risk and CAD
- inc VLDL
- dec HDL

- occurs with both selective and nonselective B blockers

may be less with partial agonists like labetolol

Front 329

Intrinsic sympathomimetic activity

Back 329

B blocker has partial B agonist activity
- based on structure

dec likelihood of neg features of B blocker (bronchoconstriction, bradycarida)

reduce therapeutic effects of B blockers, especially cardioprotective benefits
(labetolol, pindolol, Acebutolol)

Front 330

labetolol

Back 330

Beta Blocker with Intrinsic Sympathomimetic Activity

Front 331

Pindolol

Back 331

Beta Blocker with Intrinsic Sympathomimetic Activity

treat HTN w pts w/ compelling indications

Front 332

Acebutolol

Back 332

Beta Blocker with Intrinsic Sympathomimetic Activity

Front 333

Local Anesthetic Action of B blockers

describe, AKA

Back 333

aka - membrane stabilization

results from blockade of sodium channels in axons of nerves (similar to lidocaine)

prevents electrolytic excitation of the nerves - preventing depolarization and subsequent transfer of sensation information

ex. acebutolol
labetolol
pindolol
propanolol

typically not used since better agents available

Front 334

uses of B blockers

Back 334

hypertension
ischemic heart disease
arrhythmias
heart failure
glaucoma
migraine headaches
perf anxiety

Front 335

B blockers and hypertension

describe, give ex

Back 335

considered 1st line for pts with compelling indications
(heart failure, post-MI, diabetes)

not 1st line - in pts without compelling indications

ex
atenolol - most common
metoprolol - most common
bisoprolol
nadolol
pindolol

Front 336

atenolol

Back 336

b blocker
tx hypertension in pts with compelling indications

Front 337

bisoprolol

Back 337

b blocker
tx hypertension in pts with compelling indications

heart failure

Front 338

nadolol

Back 338

b blocker
tx hypertension in pts with compelling indications
hepatic Dz

Front 339

B blockers - ischemic heart disease

describe
give examples

Back 339

IHD
occurs when cholesterol plaques line cardiac arteries, dec blood flow, oxygen delivery
- leads to angina, poor exercise tolerance

B blockers dec cardiac workload (slow HR, dec strength of heart squeeze)

results in less demand for oxygen - so limited supply meets less demand

1st line for pts at risk or after MI or angina, left ventricular dysfunction

ex. propranolol, metoprolol

Front 340

propranolol

Back 340

B blocker - IHD

hyperthyroidism

migraine HA

Hepatic dz

Front 341

metoprolol

Back 341

B blocker - IHD

Arrhythmias

heart failure

HTN in pts w/ compelling indications

Migrain HA

Front 342

B blockers -arrhythmias

Back 342

suppress supraventricular and ventricular arrhythmias
- extend the resting periord of AV nodal cells
- slows ventricular response to electrical stimulation

tx - atrial fibrillation, atrial flutter
tx - life-threatening ventricular arrhythmias

ex. metoprolol, sotalol

Front 343

sotalol

Back 343

B blocker

suppress supraventricular and ventricular arrhythmias
- extend the resting periord of AV nodal cells
- slows ventricular response to electrical stimulation

tx - atrial fibrillation, atrial flutter
tx - life-threatening ventricular arrhythmias

Front 344

B blockers and heart failure

Back 344

chrinic heart failure (not acute)

ex. metoprolol, bisoprolol, carvedilol

Front 345

carvedilol

Back 345

chronic heart failure (not acute)

Front 346

B blocker in glaucoma

Back 346

reduce interocular pressure
- dec prod of aqueous humor

ex.
Timolol
Betaxolol
Carteolol
Levobunolol

can slow heart rate

Front 347

Levobunolol

Back 347

B blocker - tx glaucoma

Front 348

B Blocker in hyperthyroidism

Back 348

hyperthyroidism - can lead to excessive catecholamine action (ex. tachycardia)

B blockers
- dec symptoms - block adrenergic rec
- dec conversion of thyroxine (T4) to T3

exp useful in thyroid storm (when first diagnosed)

ex. propranolol

Front 349

B blocker use for migraine headaches

Back 349

metoprolol, propranolol

reduce freq and intensity

better drugs exist (triptan class)

Front 350

B blocker - perf anxiety

Back 350

eliminate many symptoms induced by stress, anxiety

slow heart rate
reduce palmar sweating

Front 351

B blocker in hepatic disease

Back 351

reduce elevated BP (LV dz - portal vein hypertension)

ex. nadolol
Propranolol

Front 352

what unwanted side effects can occur with B blockers

Back 352

1. bradycardia
2. worsening of asthma
3. may worsen CO in pts w/ heart failure
4. exacerbation of hypoglycemia in DM

others minor:
mild sedation
vivid dreams
depression

Front 353

what are key neurotransmitters/hormones of the parasympathetic and sympathetic nervous system?

Back 353

ACh - nic/musc rec (pregang sym/para), post gang (para) - sk muscle junction

NE, E, DA - adrenergic post gang

Front 354

name the types of receptors that bind acetylcholine and where they are located?

Back 354

Nic, Musc , MS junctions

Front 355

muscarinic agonist causes what effects on the eye?

Back 355

miosis

Front 356

muscarinic agonist causes what effects on the respiratory system?

Back 356

constrict

Front 357

muscarinic agonist causes what effects on the cardiovascular system?

Back 357

dec HR - may dec BP

Front 358

muscarinic agonist causes what effects on the Genitourinary system

Back 358

empty bladder

Front 359

muscarinic agonist causes what effects on the gastrointestingal tract

Back 359

inc secretion, inc motility

Front 360

name types of adrenergic receptors

Back 360

A1, A2, B1, B2, D

Front 361

what effect would a muscarinic agonist have on the sympathetic portion of hte autonomic nervous system?

Back 361

NONE

Front 362

what is the name of the enzyme that metabolizes acetylcholine

Back 362

AChE

Front 363

What are the names of 2 enzymes that metabolize norepinephrine, epi, DA

Back 363

Monamine oxidase (MAO)

COMT

Front 364

what is NET and what does it do?

Back 364

takes back in and reuses

Front 365

what effect occurs when the following receptors are stimulated by an agonist in the cardiovascular system?

what med cond these agents be used?

A1, A2, B1, B2

Back 365

A1 - vasocontriction (non in heart) - inc BP

A2 - vasoconstriction (locally)
A2 - vasodilation (brain)

B1 - inc HR, inc contractility (heart - not in vasculature)

B2 - vasodilation (vasculature) - Dec BP

Front 366

what effects do anticholinergic agents have on teh eye?

Back 366

mydrosis

Front 367

what effects do anticholinergic agents have on the respiratory tract?

Back 367

dilation

Front 368

what effects do anticholinergic agents have on the gastrointestinal tract?

Back 368

dec motility, dec secretion

Front 369

what effects do anticholinergic agents have on the genitourinary tract?

Back 369

retention of urine

Front 370

what actions occur with use of adrenergic antagonists in cardio system?

Back 370

dec HR
Dec BP (vasodilation)_
Dec contractibility

Front 371

what actions occur with use of adrenergic antagonists in pulmonary system

Back 371

bronchoconstriction

Front 372

what actions occur with use of adrenergic antagonists in ocular?

Back 372

dec interocular pres - constriction

Front 373

what actions occur with use of adrenergic antagonists - glucose

Back 373

prevent lipolysis, glycolysis

Front 374

what actions occur with use of adrenergic antagonists - lipids

Back 374

inc VLDL, dec HDL

Front 375

explain the mechanism of action of a ganglionic blocking agent?

Back 375

block nic receptors - both P/S system

block all autonomic outflow

Front 376

What is ISA? How does it change the effect of a beta blocker

Back 376

intrinsic sympathetic activity

acts as an agonist instead of an antagonist

Front 377

what are some limitations of B blocker use

Back 377

- worsen sysm in asthma /COPD
- bradycardia
- blocks mech of body to compensate for hypoglycemia
-worsen cond w high cholesterol - but usually pts already on chol medications