Cu Etp Pharmacology: Lecture 2

Front 1

The ANS has 4 classes of drugs. What are they?

Back 1

1. cholinergic agonist
2. cholinergic antagonist
3. adrenergic agonist
4. adrenergic antagonist

Front 2

What is an adrenergic agonist?

Back 2

A drug that stimulates the adrenergic receptors of the sympathetic NS, either directly (reacting with receptor sites) or indirectly (by increasing NE levels)

Front 3

What are cholinergic agonists?

Back 3

chemicals that act on the same site as the NT Ach and increase the activity of the Ach receptor sites throughout the body

Found extensively in parasympathetic NS

Their stimulation produces a response similar to what is seen when the parasympathetic NS is activated (parasympathomimetic)

Front 4

Effects of the Sympathetic NS?

Back 4

1. Increase CO
2. Pulmonary ventilation
3. Routes blood to the muscles (more energy)
4. Raise blood glucose
5. Slows digestion
6. Decreases kidney filtration
7. Pupil dilation

*All of these reactions occur at the same time

Front 5

Effects of the Parasympathetic NS?

Back 5

1. Slow HR
2. Increase gastric secretion
3. Empty bladder/bowel
4. Constrict pupil (miosis)
5. Contract bronchial smooth muscle

*All reactions do not have to occur at once, can pick and choose

Front 6

Give sympathetic and parasympathetic response for:

the heart

Back 6

S: increase HR

P: decrease HR

Front 7

Give sympathetic and parasympathetic response for:

Lung bronchioles

Back 7

S: Dilation

P: constriction

Front 8

Give sympathetic and parasympathetic response for:

Stomach

Back 8

S: Decreased secretion and motility

P: Increased secretion and motility

Front 9

Give sympathetic and parasympathetic response for:

urinary bladder

Back 9

S: urination inhibited

P: urination promoted

Front 10

Give sympathetic and parasympathetic response for:

eye

Back 10

S: dilates (mydriasis)

P: constricts (miosis)

Front 11

What ganglionic NT does the sympathetic preganglionic neuron release?

Back 11

Ach

Front 12

In the sympathetic NS, what type of receptor does ganglionic Ach bind to?

Back 12

Nicotinic

Front 13

What NT does the sympathetic postganglionic neuron release?

Back 13

NE

Front 14

In the sympathetic NS, what type of receptor is located on the effector organ at the 2nd synapse?

Back 14

adrenergic

Front 15

What ganglionic NT does the parasympathetic preganglionic neuron release?

Back 15

Ach

Front 16

In the parasympathetic NS, what type of receptor does ganglionic Ach bind to?

Back 16

Nicotinic receptor

Front 17

In the parasympathetic NS, what NT is released at the 2nd synapse?

Back 17

Ach

Front 18

In the parasympathetic NS, at the 2nd synapse, what type of receptor is located on the effector organ?

Back 18

Muscarinic receptor

Front 19

Are there ganglia in the somatic nervous system?

Back 19

no

Front 20

What NT is released by the somatic NS and which receptor does the effector organ present?

Back 20

Ach

Nicotinic

Front 21

Size of sympathetic preganglionic neurons? What do these neurons do?

Back 21

short

release Ach to activate nicotinic receptors on postganglionic neurons

Front 22

Size of sympathetic postsynaptic neurons?

Where do they synapse?

What do these neurons release?

Back 22

long

on target organs

release NE to activate adrenergic receptors on target organs

Front 23

Size of parasympathetic preganglionic neurons? What do these neurons do?

Back 23

long

release Ach to activate nicotinic receptors on postganglionic neurons

Front 24

Size of parasympathetic postsynaptic neurons?

Where do they synapse?

What do these neurons release?

Back 24

short

synapse on a target organ

release Ach to activate muscarinic receptors on the target organ

Front 25

What 2 substances form Ach?

Back 25

coenzyme A and choline

Front 26

Which enzyme degrades Ach?

Back 26

acetylcholinesterase

Front 27

Receptor(s) that Ach binds to?

Back 27

muscarinic or nicotinic receptors (Ach not selective)

Front 28

How is NE created?

Back 28

conversion of:

tyrosine-->dopamine-->NE

Front 29

Which enzymes degrade NE?

Back 29

1. MAO: monoamine oxidase

2. COMT: catechol-O-methyl-transferase

Front 30

2 receptors for Ach?

Back 30

muscarinic, nicotinic

*Ach is nonselective

Front 31

What is the primary Ach receptor in parasympathetic junctions? What effector organs bear this receptor?

Back 31

Muscarinic

GI, bladder, heart, smooth muscle

Front 32

4 receptors for NE?

Back 32

1. alpha 1
2. alpha 2
3. beta 1
4. beta 2

Front 33

NE-alpha 1 receptor causes...

Is it excitatory or inhibitory?

Back 33

vasoconstriction .:. increase BP

excitatory

Front 34

When NE binds to an alpha 2 receptor...

Is it excitatory or inhibitory?

Back 34

inhibition of NE release occurs.:. decrease in BP since it prevents NE from acting on alpha 1

inhibitory

Front 35

NE-beta 1 receptor causes...

Is it excitatory or inhibitory?

Back 35

1. tachycardia
2. myocardial contractility

excitatory

Front 36

NE-beta 2 receptor causes...

Is it excitatory or inhibitory?

Back 36

1. vasodilation
2. bronchodilation

excitatory

Front 37

What are receptor agonists?

What do they do?

Back 37

drugs that mimic NTs

they activate receptors

Front 38

What are receptor antagonists?

What do they do?

Back 38

drugs that block NTs

they block endogenous NTs from activating the receptors

Front 39

What are 2 primary NTs of the ANS?

Back 39

1. Ach

2. NE

Front 40

3 equivalents of parasympathomimetic

Back 40

1. mimic ach
2. cholinergic
3. muscarinic agonist

Front 41

3 equivalents of parasympatholytic?

Back 41

1. block ach
2. anticholinergic
3. muscarinic antagonist

Front 42

3 equivalents for sympathomimetic?

Back 42

1. mimic NE
2. adrenergic
3. adrenergic agonist

Front 43

3 equivalents for sympatholytic?

Back 43

1. block NE
2. antiadrenergic
3. adrenergic antagonist

Front 44

3 types of Adrenergic Agonists?

Back 44

1. alpha- and beta-adrenergic agonists
2. alpha-specific adrenergic agonists
3. beta-specific adrenergic agonists

Front 45

Give an example of an alpha- and beta- adrenergic agonist

Back 45

dopamine

Front 46

Give an example of an alpha-specific adrenergic agonist

Back 46

phenylephrine

Front 47

Define adrenergic agonist

Back 47

compounds that mimic the effects of adrenergic nerve stimulation (NE)

Front 48

What are direct acting agonists?

Back 48

chemicals that directly bind and activate a given receptor

Front 49

What are indirect acting agonists?

Back 49

chemicals that stimulate a receptor by an increased concentration of NT (ex: NE)

Front 50

Name 2 uses for adrenergic agonists

Back 50

1. eye drops
2. systemic shock

Front 51

Dopamine:

What type of adrenergic agonist is it?

Indication?

MOA?

Back 51

alpha and beta adrenergic agonist

Tx: shock

MOA: (high dose) stimulates heart and blood pressure; (lower dose) renal dilation

*choice drug for shock

Front 52

Dobutamine:

What type of adrenergic agonist is it?

Receptor preference for...?

Indication?

Back 52

alpha-and beta-adrenergic agonist

beta-1

tx: heart failure

Front 53

Ephedrine:

What type of adrenergic agonist is it?

Indication?

MOA?

Back 53

alpha-and beta adrenergic agonist

tx: shock, allergies

MOA: increases the release of NE and acts on adrenergic receptors

Front 54

Is dopamine or ephedrine used more often?

Back 54

dopamine

Front 55

Alpha- and beta-adrenergic agonists (PK)

abs:
met:
exc:

Back 55

abs: rapidly after injection

met: liver

exc: urine

Front 56

Why do we give alpha- and beta- adrenergic agonists by the IV route?

Back 56

1. they have low oral bioavailibility

2. they have a short half life

Front 57

Alpha-and Beta-Adrenergic Agonists:

CI

Back 57

1. pheochromocytoma: a tumor on adrenal glands that increases the amount of NE and E in the body; giving the drug would cause systemic overload

2. tachyarrhythmias

3. hypovolemia

Front 58

Alpha-and Beta-Adrenergic Agonists:

caution

Back 58

1. peripheral vascular disease (may make atherosclerosis/ Raynaud's disease worse)

Front 59

Alpha-and Beta-Adrenergic Agonists:

adverse effects

Back 59

CV: arrhythmias, hypertension, palpitations

GI: N/V/ constipation (slows GI)

heading, sweating, tension, anxiety

extravasion:if leaked out of blood vessel, tissue may necrose and cause cell death
*why we need to monitor IV sites

Front 60

Alpha-and Beta-Adrenergic Agonists:

Drug interaction

Back 60

1. TCAs--> increases NE levels
2. MAOIs-->increases NE levels
3. Caffeine-->increases risk of hypertension

Front 61

What are alpha-specific adrenergic agonists?

Back 61

Drugs that bind primarily to alpha receptors

Front 62

Alpha-Specific Adrenergic Agonists:

uses

Back 62

Vary, depending on the specific drug

Front 63

Phenylephrine

type of adrenergic agonist?

specific receptor?

use?

route?

Back 63

Alpha-Specific Adrenergic Agonists

alpha 1

tx: potent vasoconstrictor

routes:
1. parenterally (shock)
2. topically (allergic rhinitis)
3. ophthalmically (pupil dilation)

Front 64

Midodrine

type of adrenergic agonist?

specific receptor?

use?

route?

Back 64

alpha-specific adrenergic agonist

alpha 1

tx: orthostatic hypotension (causes vasoconstriction to increase BP; monitor BPs on patient lying down, sitting up, and standing)

route: oral

Front 65

Clonidine

type of adrenergic agonist?

specific receptor?

use?

route?

Back 65

Alpha-specific adrenergic agonist

alpha 2 agonist

tx: hypertension (reduces sympathetic outflow to decrease BP; watch for extreme hypotension!)

route: oral or transdermal

Front 66

Alpha-Specific Adrenergic Agonists (PK)

abs:
dist:
met:
ex:

Back 66

abs: well absorbed
dist: wide
met: liver
ex: urine

Front 67

How often should you change the Clonidine Transdermal Patch?

Back 67

every 7 days

Front 68

Alpha-Specific Adrenergic Agonists

CI

Back 68

1. allergy
2. severe hypertension or tachycardia
3. narrow angle glaucoma

*may exacerbate these conditions

Front 69

Alpha-Specific Adrenergic Agonists

Caution

Back 69

1. CVD
2. thyrotoxicosis (increased level of thyroid hormone)
3. diabetes
4. renal or hepatic impairment

Front 70

Alpha-Specific Adrenergic Agonists

Adverse Effects

Back 70

CNS: anxiety, restlessness, depression, fatigue

Blurred vision, light sensitivity

CV: arrhythmias, BP changes, peripheral vascular system

GI: N/V/anorexia

GU: decreased urine output, difficult urinating

Front 71

Alpha-Specific Adrenergic Agonists

Why shouldn't you stop these suddenly?

Back 71

May cause symptoms of withdrawal. Taper down 2-4 days to prevent causing tachycardia or hypotension

Front 72

Alpha-Specific Adrenergic Agonists

Drug-Drug Interactions:
Never mix Phenylephrine with...

Back 72

MAOIs: severe hypotension/headache

Front 73

Alpha-Specific Adrenergic Agonists

Drug-Drug Interactions:
Never mix Clonidine and...

Back 73

TCAs: can decrease anti hypertensive effect of clonidine

Front 74

Alpha-Specific Adrenergic Agonists

Drug-Drug Interactions:
Never mix midodrine with...

Back 74

digoxin,
beta blockers,
antipsychotics

Front 75

Name 2 types of adrenergic blocking antagonists:

Back 75

1. alpha-blockers

2. beta-blockers

Front 76

What effect to adrenergic alpha blockers have?

Back 76

Vasodilation, leading to decreased BP

Front 77

What effect to adrenergic beta blockers have?

Back 77

decrease in the vasoconstrictive effects of NE, causing vasodilation and a decrease in BP

Front 78

2 types of cholinergic agonists?

Back 78

1. direct-acting cholinergic agonists

2. indirect-acting cholinergic agonists

Front 79

What is the prototype drug for direct-acting cholinergic agonists?

Back 79

Bethanechol

Front 80

What is the prototype drug for indirect-acting cholinergic agonists?

Back 80

1. agents for Myasthenia Gravis:

Pyridostigmine

2. Agents for Alzheimer Disease

Donepezil

Front 81

What 2 dieases are indirect-acting cholinergic agonists targeted toward?

Back 81

1. myasthenia gravis

2. alzheimer's disease

Front 82

Direct cholinergic agonists:

use:

can these drugs be nonspecific?

Tx?

Back 82

use: systemic or ophthalmic agents

yes, because our own Ach is nonspecific

tx:
1. urinary retention; relaxes sphincter
2. relieve IOP from glaucoma
3. increase secretions in mouth and GI

Front 83

Which direct cholinergic agonist would you prescribe to treat urinary retention?

Back 83

Bethanechol

Front 84

Which direct cholinergic agonists would you prescribe to treat glaucoma?

Back 84

Carbachol

Pilocarpine

Front 85

Which direct cholinergic agonist would you prescribe to increase secretions in the mouth and GI?

Back 85

Cevimeline

Pilocarpine

Front 86

Direct cholinergic agonists PK:

abs: oral, topical

is the half life short or long in oral administration?

Back 86

abs: well absorbed after oral administration

usually not absorbed after topical administration

short

Front 87

Direct Cholinergic Agonists:

CI/ Caution

Back 87

1. Allergies
2. Any medical condition that would be exacerbated by parasympathetic effects
(bradycardia, hypotension, coronary artery disease)
3. peptic ulcer, GI obstruction
4. ASTHMA (Ach will cause constriction to lungs)
5. bladder obstruction/surgery

Front 88

Direct Cholinergic Agonists:

Adverse effects

Back 88

Related to the parasympathetic NS stimulation
1. CV: bradycardia, hypotension
2. GI: N/V/D, cramps, increased salivation, involuntary defecation
3. Urinary: sense of urgency

Front 89

Indirect Cholinergic Agonists:

MOA:

Back 89

MOA: inhibit acetylcholinesterase (increase the amount of Ach)

Front 90

What is myasthenia gravis?

Back 90

a chronic, autoimmune muscle disease; antibodies form against receptors in skeletal muscles, especially in the face, throat, and neck.

may cause severe fatigue

Front 91

Indirect Cholinergic Agonists and myasthenia gravis:

MOA

Back 91

Moa: increase smuscle strength by allowing Ach to accumulate in the synaptic cleft

Front 92

What is alzheimer's disease?

Back 92

the progressive loss of Ach-producing neurons and target neurons in the brain

these neurons are linked to memory

Front 93

Indirect Cholinergic Agonists and alzheimer's disease:

MOA

Back 93

MOA: increase Ach concentration in the brain where Ach-producing cells are dying

Front 94

Indirect Cholinergic Agonists and alzheimer's disease: PK

abs:
dist:
met:
ex:

Back 94

abs: well
dist: well
met: liver (CYP450)
ex: urine

*caution with heptaic impariment

Front 95

Indirect Cholinergic Agonists and myasthenia gravis: PK

ab:
dis:

Back 95

abs: well via oral
dist: well

Front 96

Indirect Cholinergic Agonists:

CI/Caution

Back 96

any condition that could be exacerbated by cholinergic stimulation (ie asthma, coronary disease, arrhythmias)

Front 97

Indirect Cholinergic Agonists::

Adverse Effects

Back 97

*related to parasympathetic nerve stimulation

1. eye: miosis, blurred vision
2. CNS: headache, dizziness, drowsiness
3. CV: bradycardia, hypotension
4. N/V/D, increased salivation, involuntary defecation
Urinary: sense of urgency

Front 98

Indirect Cholinergic Agonists:

Drug-drug interactions

Back 98

1. + NSAIDS (motrin): cause GI bleeding
2. Tacrine
3. Theophylline (may increase the level of theophylline to 2x the concentration when given with tacrine; narrow therapeutic level)

Front 99

Cholinergic Antagonists:

prototype drug

Back 99

Atropine

*blocks Ach at the receptor

Front 100

Cholinergic Antagonists:

MOA

Back 100

MOA: blocks the Ach receptors that are responsible for the effects of the parasympathetic postganglionic impulses

*when the parasympathetic system is blocked, the effects of the sympathetic system are more prominently seen

Front 101

Cholinergic Antagonists:

Atropine

What does it do?

Back 101

Atropine:

1. inhibits GI secretions
2. bronchial dilation
3. pupillary dilation
4. increased HR

*Blocks Ach at muscarinic cholinergic sites

Front 102

Cholinergic Antagonists:

Scopolamine

What does it do?

Back 102

1. decreased N/V associated with motion sickness; decrease GI secretions
*patches behind ear on cruise

Front 103

Cholinergic Antagonists:

CI/Cautions

Back 103

Known conditions that may become exacerbated:

1. glaucoma: increase IOP
2. GI obstruction/peptic ulcer
3. bladder obstruction
4. cardiac arrythmias, tachycardia
5. myasthenia gravis
6. hypertension

Front 104

Cholinergic Antagonists:

Adverse effects

Back 104

Caused by systemic blockade of cholinergic receptors

eyes: blurred vision, pupil dilation, photophobia, increased IOP
cns: weakness, dizziness
gi: dry mouth, altered taste perception, constipation, bloated feelings
cv: tachycardia, palpitations
gu: urinary hesitancy and retention
decreased sweating

Front 105

Cholinergic Antagonists:

drug-drug interactions with...

Back 105

Drugs with anticholinergic activities:
1. antihistamines
2. MAOIs
3. TCAs

*the anticholinergic effect will worsen

Front 106

A cholinergic agonist would cause constriction of the pupil by...

Back 106

Activating the muscarinic receptors