N210 Cns Pharmacology Lecture Notes

Front 1

Why don't we know how CNS drugs work?

Back 1

CNS research is technically difficult

Front 2

What kinds of drugs cross the BBB?

Back 2

Lipid-rich drugs

Front 3

What kind of drugs DON'T cross the BBB?

Back 3

Protein-bound or ionized drugs

Front 4

What happens with prolonged exposure to CNS drugs?

Back 4

Increased therapeutic effects
Decreased side effects
Tolerance, physical dependence

Front 5

Normal function of dopamine CNS receptors:

Back 5

Pleasure, reward, motivation, reinforcement, wide variety of behaviors and emotions

Front 6

Diseases associated with dopamine receptors:

Back 6

Parkinson's
Schizophrenia

Front 7

Normal function of norepinephrine CNS receptors:

Back 7

Arousal, wakefulness, learning, memory, mood

Front 8

Normal function of norepinephrine PNS receptors:

Back 8

ANS "fight or flight"

Front 9

Diseases associated with norepinephrine:

Back 9

Depression

Front 10

Normal function of serotonin CNS receptors:

Back 10

Sleep, dreaming, mood, eating, pain, aggressive behavior

Front 11

Diseases associated with serotonin:

Back 11

Depression

Front 12

Normal function of serotonin PNS receptors:

Back 12

GI tract function

Front 13

Normal function of GABA CNS receptors:

Back 13

Inhibitory, with a role in sleep and eating

Front 14

Diseases associated with GABA:

Back 14

Anxiety

Front 15

Normal function of acetylcholine CNS receptors:

Back 15

Arousal, attention, memory, motivation, movement

Front 16

Normal function of acetylcholine PNS receptors:

Back 16

ANS "housekeeping"

Front 17

Disease associated with CNS acetylcholine:

Back 17

Alzheimer's

Front 18

Normal function of glutamate CNS receptors:

Back 18

Long-term memory, pain perception

Front 19

Diseases associated with glutamate:

Back 19

Alzheimer's

Front 20

Normal function of endorphin/enkephalin CNS receptors:

Back 20

Pain perception, inhibition of pain

Front 21

Diseases associated with endorphins/enkephalin:

Back 21

Addiction

Front 22

Normal function of histamine 1 CNS receptors:

Back 22

Sleep/wake cycle

Front 23

What two CNS receptors are associated with memory?

Back 23

Acetylcholine
Glutamate

Front 24

What receptors do opiates effect?

Back 24

Endorphin

Front 25

What is a seizure?

Back 25

Widespread hyperactivity of neurons in the brain

Front 26

How do seizure drugs work?

Back 26

Suppress the discharge of neurons at the focus/propagation from the focus outward

Front 27

What four ways do seizure drugs work?

Back 27

Suppress sodium influx
Suppress calcium influx
Antagonism of glutamate
Potentiation of GABA

Front 28

Which class of seizure drugs will stop a seizure fastest?

Back 28

Benzodiazepenes

Front 29

Traditional anti-seizure medications:

Back 29

phenobarbital
phenytoin
valproic acid
carbameazepine

Front 30

Pros of traditional antiseizure medications:

Back 30

Cheap! Well established

Front 31

Cons of antiseizure medications:

Back 31

Not as well tolerated, drug interactions, less safe in pregnancy

Front 32

What is gabapentin usually prescribed for?

Back 32

Peripheral neuropathy

Front 33

Cons of newer anti-seizure drugs:

Back 33

EXPENSIVE

Front 34

Common side effects of anti-seizure drugs:

Back 34

CNS (sedation, uncoordination)
GI (early)
Dermatologic (rashes -> SJS)
Hematologic (myelosuppression)
Hepatic/renal
Weight changes (may increase)
Risk of suicidal behavior

Front 35

Uses of phenobarbital:

Back 35

Epilepsy, sleep/sedation

Front 36

Action of phenobarbital:

Back 36

Binds to GABA receptors

Front 37

Half-life of phenobarbitol:

Back 37

4 days (long!)

Front 38

Side effects of phenobarbitol:

Back 38

Respiratory depression, dependence, sedation
Abuse, fetal harm, depression, learning impairment, rash

Front 39

Interactions with phenobarbitol:

Back 39

CNS depressants, valproic acid (increases levels), OCP/warfarin (decreased levels)

Front 40

Action of phenytoin (Dilantin):

Back 40

Blocks Na entry into hyperactive neurons

Front 41

Use of phenytoin (Dilantin):

Back 41

Epilepsy/seizure prevention

Front 42

PK of phenytoin (Dilatin):

Back 42

Half-life depends on dose! (This is WEIRD.) Liver has limited capacity to metabolize.

Front 43

Side effects of phenytoin (Dilantin):

Back 43

CNS (nystagmus, sedation, diplopia, cognitive impairment)
Gingival hyperplasia
Skin rash
Teratogenic
CV effects when given IV

Front 44

Interactions with phenytoin (Dilantin):

Back 44

CNS depressants
Decreases levels of OCP, warfarin, glucocorticoids
Levels are increased by diazepam, valproic acid, cimetidine, alcohol, isoniazid
Levels are decreased by carbamazepine, phenobarbital

Front 45

IV administration of phenytoin (Dilantin):

Back 45

Give ONLY with normal saline
IV push no more than 50mg/min

Front 46

Target serum levels of phenytoin (Dilantin):

Back 46

10-20mcg/mL

Front 47

Oral adminstration of phenytoin (Dilantin):

Back 47

With meals to lower GI side effects

Front 48

Use of carbamazepine (Tegretol):

Back 48

Epilepsy, bipolar, neuralgias

Front 49

Half-life of carbamazepine (Tegretol):

Back 49

Half-life decreases as treatment progresses

Front 50

Side effects of carbamazepine (Tegretol):

Back 50

Visual sx, ataxia, vertigo, headache
Myelosuppression
Teratogenic
Skin reactions

Front 51

Use of valproic acid (Depakote):

Back 51

First line for many seizures
Bipolar disease
Migraine headaches

Front 52

Side effects of valproic acid (Depakote):

Back 52

GI effects
Hepatotoxicity
Pancreatitis
Teratogenic
Rash, weight gain, hair loss, tremor

Front 53

Interactions with valproic acid (Depakote):

Back 53

Increases levels of phenytoin and phenobarbital

Front 54

What is the goal of seizure treatment?

Back 54

Minimize seizures, eliminate entirely if possible

Front 55

How do we diagnose seizures?

Back 55

EEG

Front 56

Is possible to switch brands/generics of antiseizure drugs?

Back 56

Really not recommended

Front 57

Do patients ever come off anti-seizure drugs?

Back 57

Withdrawal trials can happen, but need to happen slowly (over 6 weeks)

Front 58

What cases Parkinson's?

Back 58

Loss of dopamine from the substantia nigra to striatum and the imbalance of dopamine/ACh

Front 59

Are dopamine and ACh inhibitory or excitatory?

Back 59

Dopamine is inhibitory
ACh is excitatory

Front 60

Goal of PD treatment drugs:

Back 60

Increase dopamine
Block ACh

Front 61

Signs and symptoms of PD:

Back 61

Resting tremor (dominant side)
Rigidity
Postural instability
Shuffling gait
Bradykinesia
Dementia
Depression
Memory impairment
Drooling

Front 62

Is PD reversible?

Back 62

No; therapy improves symptoms, does not reverse degeneration

Front 63

First line drugs for PD:

Back 63

Dopamine replacement
Dopamine agonists

Front 64

Dopamine replacement drugs:

Back 64

Levodopa, levodopa/carbidopa (Sinemet)

Front 65

Dopamine agonist drugs:

Back 65

pramipexole (Mirapex)
ropinirole (Requip)
rotigotine (Neupro)

Front 66

2nd line drug for PD:

Back 66

Dopamine releaser (amantidine/Symmetrel)

Front 67

How do COMT inhibitors work?

Back 67

Block the breakdown of levodopa in the gut

Front 68

How do MAO-B inhibitors work?

Back 68

Prevent dopamine breakdown

Front 69

MAO-B inhibitor drugs:

Back 69

selegiline (Carbex/Zelapar)
resagiline (Azilect)

Front 70

If a patient is 70 or older, how do we treat PD?

Back 70

Start with levodopa

Front 71

If a patient is younger, how do we treat PD?

Back 71

Start with dopamine agonist or MAO-B, save the levodopa

Front 72

How long is levodopa effective for?

Back 72

About 5 years

Front 73

Action of levodopa:

Back 73

Converted to dopamine in the striatum

Front 74

Time until effect of levodopa:

Back 74

Over months

Front 75

Describe fluctuation in levodopa effectiveness:

Back 75

"On-off" phenomenon

Front 76

Side effects of levodopa:

Back 76

N/V (early)
DYSKINESIAS (tics, head bobbing)
Postural hypotension
Somnolence
Psychosis

Front 77

Interactions with levodopa:

Back 77

Traditional antipsychotics
MAO-Is
Pyridozine (vitamin B6)
High-protein meals

Front 78

How does adding carbidopa affect levodopa?

Back 78

Allows more dopamine to get to the brain

Front 79

Action of dopamine agonists:

Back 79

Binds to D2, D3 receptors

Front 80

Side effects of dopamine agonists:

Back 80

Less dyskinesia than levodopa
Nausea, dizziness, daytime sleepiness, insomnia, constipation, weakness, hallucinations
When combined w/ levodopa, orthostatic hypotension, dyskinesias

Front 81

Examples of anticholinergic agents:

Back 81

benztropine (Cogentin)
trihexyphenidyl (Artane)

Front 82

Action of anticholinergic agents:

Back 82

Blocks activation of muscarinic (cholinergic) receptors in brain/periphery, restores DA/Ach balance

Front 83

Side effects of anticholinergic agents:

Back 83

Can't see, can't pee, can't spit, etc...

Front 84

Who should not take anticholinergic agents?

Back 84

The elderly

Front 85

Pathophysiology of schizophrenia:

Back 85

Excessive dopamine, insufficient glutamate

Front 86

Three types of schizophrenia symptoms:

Back 86

Positive, negative, cognitive

Front 87

Two major groups of antipsychotics:

Back 87

Conventional
Atypical

Front 88

How do conventional antipsychotics work?

Back 88

Block dopamine receptors

Front 89

How do atypical antipsychotics work?

Back 89

Block serotonin (and to a low degree, dopamine)

Front 90

What are positive schizophrenia symptoms?

Back 90

Hallucinations, delusions, paranoia

Front 91

Negative symptoms of schizophrenia:

Back 91

Withdrawal, lack of insight, blunted affect, poor self-care, etc

Front 92

What's the major difference in antipsychotic classes?

Back 92

Side effects

Front 93

Uses for conventional antipsychotics:

Back 93

Schizophrenia
Bipolar disorder
Tourette's
Emesis
Dementia
Organic syndromes

Front 94

What's the danger in using antipsychotics in the elderly?

Back 94

Doubles the rate of death from CV event or infection

Front 95

Action of conventional antipsychotics:

Back 95

Blocks dopamine, ACh, histamine, NE

Front 96

Relationship between potency and SE in conventional antipsychotics:

Back 96

High potency produces lower SE

Front 97

Classification of conventional antipsychotics:

Back 97

Low potency: chlorpromazine (Thorazine), thioridazine (Mellaril)
Medium potency: loxatine (Loxitane)
High potency: haloperidol (Haldol)

Front 98

Side effects of conventional antipsychotics, by transmitter:

Back 98

Dopamine: EPS, prolactin release
Histamine: sedation, weight gain
Norepinephrine: ortho hypotension, tachycardia
Serotonin: weight gain, insulin resistance
Acetylcholine: dry mouth, constipation

Front 99

Extrapyramidal symptoms:

Back 99

Acute dystonia
Parkinsonism
Akathisia
Tardive dyskinesia

Front 100

Difference between drug-induced parkinsonism and PD:

Back 100

PD tends to affect dominant side first
Drug-induced tends to be bilateral

Front 101

Symptoms of neuroleptic malignant syndrome:

Back 101

Lead-pipe rigidity
Very high fever
ANS instability (BP up and down, arrhythmias)

Front 102

Endocrine side effects of antipsychotics:

Back 102

Gynecomastia
Galactorrhea
Mentrual irregularity

Front 103

Side effects of atypical antipsychotics:

Back 103

Metabolic effects: weight gain, diabetes, dyslipidemia
Seizures, myocarditis
Agranulocytosis

Front 104

Dangerous adverse effect of atypical antipsychotics:

Back 104

Agranulocytosis

Front 105

Examples of atypical antipsychotics:

Back 105

Zyprexa (weight gain!!)
Risperdal (for bipolar, autism)
Seroquel (for bipolar mania)
Geodon (low metabolic SE risk)
Abilify (major depression - no metabolic SE)

Front 106

Examples of tricyclic antidepressants:

Back 106

imipramine (Tofranil)
amitriptyline
nortriptyline (Pamelor)
doxepin (Sinequan)

Front 107

Action of tricyclic antidepressants:

Back 107

Block reuptake of NE and serotonin

Front 108

Use of tricyclic antidepressants:

Back 108

Depression, bipolar, neuropathic pain, insomnia, ADHD, panic, OCD

Front 109

Onset of action of tricyclic antidepressants:

Back 109

1-3 weeks initial
1-2 months max

Front 110

Side effects of tricyclic antidepressants:

Back 110

CARDIAC TOXICITY
Lethal dose is 8x daily dose
Sedation, hypotension, anticholinergic

Front 111

Interactions with tricyclic antidepressants:

Back 111

MAOI, anticholinergics, CNS depressants

Front 112

Examples of SSRIs:

Back 112

fluoxetine (Prozac)
paroxetine (Paxil)
sertraline (Zoloft)
fluvoxamine (Luvox)
citalopram (Celexa)
escitalopram (Lexapro)

Front 113

Uses for SSRIs:

Back 113

Major depression
Anxiety, PTSD, panic disorders

Front 114

Time to effect of SSRIs:

Back 114

1-3 weeks

Front 115

Action of SSRIs:

Back 115

Inhibits reuptake of serotonin at synapse

Front 116

Symptoms of serotonin syndrome:

Back 116

MS changes, neuromuscular findings (tremor, hyperreflexia, myoclonus, autonomic instability), fever, mydriasis, BP fluctuations, tachycardia

Front 117

Most common SE of SSRIs:

Back 117

Sexual dysfunction

Front 118

Side effects of SSRIs:

Back 118

Sexual dysfunction
Weight-gain
Nausea
Nervousness, insomnia, anxiety
Withdrawal syndrome

Front 119

Examples of SNRIs:

Back 119

venlafaxine (Effexor)
desvenlafaxine (Pristiq)
duloxetine (Cymbalta)

Front 120

Uses of SNRIs:

Back 120

Major depression, GAD, social anxiety

Front 121

SEs of SNRIs:

Back 121

Very similar to SSRIs, but need to monitor BP

Front 122

Action of SNRIs:

Back 122

Block reuptake of both serotonin and NE

Front 123

Examples of MAOIs:

Back 123

isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)

Front 124

Danger of MAOIs:

Back 124

Hypertensive crisis if tyramine is consumed

Front 125

Action of MAOIs:

Back 125

Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A

Front 126

Interactions with MAOIs:

Back 126

Foods containing tyramines
Cold medicines and many others

Front 127

Side effects of MAOIs:

Back 127

CNS stimulation
Orthostatic hypotension
Hypertensive crisis

Front 128

Drug interactions with MAOIs:

Back 128

Epinephrine
Cold meds
Asthma meds
SSRIs
TCAs
Antihypertensives
Demerol
levodopa

Front 129

Tyramine-rich foods:

Back 129

Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas

Front 130

The structure of buproprion is similar to:

Back 130

Amphetamines

Front 131

Time to effect of buproprion:

Back 131

1-3 weeks

Front 132

Noticably lacking side effects of buproprion:

Back 132

Sexual SE, weight loss

Front 133

Most serious SE of buproprion:

Back 133

Seizures

Front 134

Side effects of bupriprion:

Back 134

Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia

Front 135

Examples of MAOIs:

Back 135

isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)

Front 136

Danger of MAOIs:

Back 136

Hypertensive crisis if tyramine is consumed

Front 137

Action of MAOIs:

Back 137

Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A

Front 138

Interactions with MAOIs:

Back 138

Foods containing tyramines
Cold medicines and many others

Front 139

Side effects of MAOIs:

Back 139

CNS stimulation
Orthostatic hypotension
Hypertensive crisis

Front 140

Drug interactions with MAOIs:

Back 140

Epinephrine
Cold meds
Asthma meds
SSRIs
TCAs
Antihypertensives
Demerol
levodopa

Front 141

Tyramine-rich foods:

Back 141

Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas

Front 142

The structure of buproprion is similar to:

Back 142

Amphetamines

Front 143

Time to effect of buproprion:

Back 143

1-3 weeks

Front 144

Noticably lacking side effects of buproprion:

Back 144

Sexual SE, weight loss

Front 145

Most serious SE of buproprion:

Back 145

Seizures

Front 146

Side effects of bupriprion:

Back 146

Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia

Front 147

Examples of MAOIs:

Back 147

isocarboxazid (Marplan)
phenelzine (Nardil)
tranylcypromine (Parnate)

Front 148

Danger of MAOIs:

Back 148

Hypertensive crisis if tyramine is consumed

Front 149

Action of MAOIs:

Back 149

Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A

Front 150

Interactions with MAOIs:

Back 150

Foods containing tyramines
Cold medicines and many others

Front 151

Side effects of MAOIs:

Back 151

CNS stimulation
Orthostatic hypotension
Hypertensive crisis

Front 152

Drug interactions with MAOIs:

Back 152

Epinephrine
Cold meds
Asthma meds
SSRIs
TCAs
Antihypertensives
Demerol
levodopa

Front 153

Tyramine-rich foods:

Back 153

Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas

Front 154

The structure of buproprion is similar to:

Back 154

Amphetamines

Front 155

Time to effect of buproprion:

Back 155

1-3 weeks

Front 156

Noticably lacking side effects of buproprion:

Back 156

Sexual SE, weight loss

Front 157

Treatment of bipolar disorder:

Back 157

Mood stabilizers (lithium, valproic acid, carbamazepine)
Antipsychotics (olanzapine, risperidone)
Antidepressants (SSRIs, Wellbutrin, Effexor) combined with mood stabilizer

Front 158

Time to effect of lithium:

Back 158

Effects in 5-7 days
Full in 2-3 weeks

Front 159

Most serious SE of buproprion:

Back 159

Seizures

Front 160

Side effects of bupriprion:

Back 160

Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia

Front 161

Uses of buproprion:

Back 161

Depression, smoking cessation

Front 162

Drug of choice for mania:

Back 162

Lithium

Front 163

Half-life of lithium:

Back 163

Very short, needs multiple daily doses

Front 164

Therapeutic serum lithium levels:

Back 164

0.8 - 1.4 mEq/L

Front 165

When taking lithium, what intake is critical to maintain?

Back 165

SODIUM - low Na increases lithium levels

Front 166

Signs of low lithium levels:

Back 166

GI upset, polyuria, lethargy, slurred speech, muscle weakness, hand tremor, hypothyroid

Front 167

Signs of lithium toxicity:

Back 167

Muscle hyperirritability, sedation, clumsy, confusion, giddiness, ataxia, polyuria, tinnitus, blurred vision, fasciculations, seizures, clonic movements

Front 168

Interactions with lithium:

Back 168

Loop and thiazide diuretics
NSAIDs
Anticholinergic agents (antihistamines, pheothiazines, antipsychotics, TCAs)

Front 169

Uses of sedative-hypnotic agents:

Back 169

Antianxiety
Anxiolytic
Tranquilizers

Front 170

Class of sedative-hypnotic agents that directly mimics GABA:

Back 170

Barbiturates

Front 171

Big three benzodiazepines:

Back 171

diazepam (Valium)
lorazepam (Ativan)
misazolam (Versed)

Front 172

Uses of benzodiazepines:

Back 172

Anesthesia
Anxiety
Seizure
Insomnia
Also muscle spasm, panic disorder, alcohol withdrawal

Front 173

Action of benzodiazepines:

Back 173

Enhances inhibitory action of GABA by binding to GABA receptors

Front 174

Side effects of benzodiazepines:

Back 174

CNS depression, respiratory depression
Amnesia, abuse, "opposite" effects

Front 175

Interactions with benzodiazepines:

Back 175

Alcohol, opioids, barbiturates

Front 176

Competitive antagonist to benzodiazepines:

Back 176

flumazenil (Romazison)

Front 177

Drugs used for insomnia:

Back 177

zolpidem (Ambien)
zaleplon (Sonata)
eszopiclon (Lunesta)

Front 178

Action of anti-insomnia drugs:

Back 178

Agonist at benzodiazepine site on GABA receptor

Front 179

Drugs used for ADHD:

Back 179

Amphetamines (CNS stimulants)

Front 180

Action of amphetamines:

Back 180

Promote release of NE, DA

Front 181

Side effects of amphetamines:

Back 181

Weight loss, CV effects