Cns Pharm V

Front 1

What percentage of Americans are clinically depressed?

Back 1

5-6%

Front 2

What percentage of Americans will have a depressive episode in their lifetime?

Back 2

10%

Front 3

This drug, used for hypertension and scizophrenia, was found to CAUSE DEPRESSION

Back 3

Reserpine

Front 4

How does Reserpine act?

Back 4

inhibits the storage of amine neurotransmitters like serotonin and norepinephrine

Front 5

Historically, it was supposed that depression was due to decreased amine-dependent synaptic transmission, BUT

Back 5

the effects of antidepressent agents on amines in the CNS are very quick but the clinical effects take weeks to occur

Front 6

What are the two types of antidepressant agents?

Back 6

1. Tricyclic Antidepressants (TCAs)
2. Selective Serotonin Reuptake Inhibitors (SSRIs)

Front 7

What drug is a TCA?

Back 7

Amitriptyline

Front 8

What is the chemistry of a TCA?

Back 8

three-ring nucleus that resembles the phenothiazines

Front 9

Explain Absorption, Distribution, and Metabolism of a TCA

Back 9

1. Rapidly cleared by first-pass metabolism in the LIVER
2. Elimination half lives range from 12-76 hours

*Remember it takes 5 HALF-LIVES to reach steady-state levels*

Front 10

What is the Mechanism of Action (MOA) of TCAs

Back 10

1. Non-specifically target the serotonin and norepinephrine receptors in the CNS
2. TCAs also bind to alpha-adrenergic, histaminergic, and cholinergic receptors (this accounts for many of the adverse effects of these drugs)

Front 11

TCAs should be reserved for what 4 conditions?

Back 11

1. A previous responder to another TCA
2. Medically healthy patients
3. Non-suicidal patients
4. Patients refractory to newer agents such as SSRIs

Front 12

What 3 adverse effects may accompany use of TCAs?

Back 12

1. Anticholinergic effects
2. alpha-adrenergic block
3. Antihistamine effects

Front 13

Anticholinergic effects (an adverse effect associated with use of TCAs) include

Back 13

blurred vision, dry mouth, urinary retention, and constipation

Front 14

Alpha-adrenergic block (an adverse effect associated with use of TCAs) lead to

Back 14

orthostatic hypotention, male impotence, and dizziness

Front 15

Antihistamine effects (an adverse effect associated with use of TCAs) include

Back 15

sedation

Front 16

What does TCA stand for?

Back 16

Tricyclic Antidepressants

which is 1 of 2 types of antidepressant agents

Front 17

What is the only TCA drug we have to know?

Back 17

Amitriptyline

AmiTRIptyline-->TRIcyclic.....

Front 18

What does SSRI stand for?

Back 18

Selective Serotonin Reuptake Inhibitors

which is 1 of 2 types of antidepressant agents

Front 19

There are 4 specific agents that are SSRIs. What are they?

Back 19

1. Prozac-prototypical agent
2. Paxil
3. Celexa
4. Zoloft

How does CQualley remember this? There are 4 letters for SSRI...thus 4 drugs. CZPP ("see ze pee pee"). Celexa, Zoloft, Prozac, and Paxil

Front 20

What is the chemistry of SSRIs

Back 20

most are based on the structure of fluoxetine (Prozac), the prototypical SSRI

Front 21

Explain the absorption, distribution, metabolism, and excretion of SSRIs

Back 21

-Metabolized by cytochrome P450s

-May take 2-3 weeks to see any effect with these agents

Front 22

Mechanism of action of SSRIs

Back 22

SPECIFICALLY increase serotonin levels in the brain by inhibiting its reuptake

Front 23

What are the 3 adverse effects of SSRIs

Back 23

1. Nausea/Vomitting, dry mouth
2. Insomnia and drowsiness
3. Sexual dysfunction

Front 24

Bipolar Disorder is treated with what drug?

Back 24

Lithium

Front 25

What is bipolar disorder?

Back 25

alternating depressive episodes and mania

Front 26

Lithium is an ion that:

Back 26

competes with K+, MG2+, Ca2+, and Na+ in the body

Front 27

What does Lithium cause in the CNS?

Back 27

1. overactivity of neurotransmitters thought to contribute to mania
2. increases catecholamine destruction
3. decreases neurotransmitter release at the synapse
4. decreases sensitivity of postsynaptic receptors to neurotransmitters

Front 28

Lithium has adverse effects in what areas of the body?

Back 28

CNS, GI, Muscular, Blood

Front 29

What adverse effects does Lithium have in the CNS?

Back 29

dizziness, lethargy, HA (?), memory loss

Front 30

What adverse effects does Lithium have in the GI system?

Back 30

nausea, vomitting, diarrhea

dry mouth

Front 31

What adverse effects does Lithium have on the muscles?

Back 31

hand tremors, muscle weakness

Front 32

What adverse effect does Lithium have on blood?

Back 32

reversible leukocytosis

Front 33

What percentage of the US is schizophrenic?

Back 33

1%

Front 34

Are many homeless people schizophrenic?

Back 34

yes :(

Front 35

Symptoms of Schizophrenia can be positive or negative. What are the positive symptoms?

Back 35

hallucinations, delusion, though disorders, insomnia, bizarre behavior

Front 36

What are the negative symptoms?

Back 36

apathy, amotivation, anhedonia (lack of pleasure from normal pleasurable experiences), asocial behavior

Front 37

What are the 5 goals of treatment of schizophrenia?

Back 37

1. Alleviate perception abnormalities such as delusions and hallucinations
2. help the patient get control of their thoughts and actions
3. prevent self-inflicted harm
4. restore social and occupational function to the greatest degree possible
5. prevent relapse

Front 38

Antipsychotic agents can be _____________ or _______________

Back 38

traditional or nontraditional

Front 39

The prototyphical traditional antipsychotic agent is

Back 39

Chlorpromazine (Thorazine)

Front 40

What is the chemistry of the traditional antipsychotic agent?

Back 40

most are based on the structure of phenothiazines (PTZs)

Front 41

What is the MOA of a traditional antipsychotic agent?

Back 41

non-specifically inhibit dopamine

Front 42

When would you use a traditional antipsychotic agent?

Back 42

when a patient is not responding to other agents

Front 43

List the 4 adverse affects of traditional antipsychotic agents

Back 43

1. Extrapyramidal side-effects
2. Parkinsonism
3. Tardive dyskinesia
4. Neuroleptic malignant syndrome

Front 44

What happens when you have extrapyramidal side effects (1 of 4 adverse side effects of traditional antipsychotic agents)?

Back 44

sudden muscle spasms, grimaced face, restlessness

Front 45

what happens when you have parkinsonism effects?

1 of 4 types of adverse side effects of antipsychotic agents

Back 45

shuffling gait, rigidity, etc

Front 46

What happens when you have Tardive Dyskinesia?

1 of 4 adverse side effects of traditional antipsychotic agents

Back 46

abnormal body movements occurring late (months to years) after beginning drugs

Front 47

What happens when you have neuroleptic malignant syndrome?

1 of 4 adverse side effects of traditional antipsychotic agents

Back 47

serious (can be life-threatening) syndrome due to dopamine

Front 48

Extrapyramidal side-effects (EPS) can have early or late onsets. Early onset is __________ and late onset is _________

Back 48

Early is SOMETIMES REVERSIBLE

Late is SELDOM REVERSIBLE

Front 49

Early-onset EPS involves what conditions?

Back 49

-pseudoparkinsonism (brasykinesia, rigidity, tremor)
-acute dystonia (sudden muscle spasms)
-akathisia

These occur hours to days after drug administration

Front 50

Late-onset EPS involves what conditions?

Back 50

-tardive dyskinesia (muscles of lips and buccal cavity
-tardive dystonia
-tardive akathisia

These occur months to years after beginning drugs

Front 51

Neuroleptic Malignant syndrome (NMS) is due to dompamine blockade. What is it characterized by?

Back 51

-Hyperthermia (can die from dehydration)
-Muscular rigidity
-Autonomic instability (can lead to syncope, respiratory failure)
-altered consciousness

Front 52

How is neuroleptic malignant syndrome treated?

Back 52

involves dantrolene (muscle relaxant) and dopamine agonist

Front 53

What are the two NON-TRADITIONAL antipsychotic agents we have to know?

Back 53

1. Haloperidol (Haldol)

2. Risperdone (Risperdal)

Front 54

Tell me about Haloperidol (Haldol)

Back 54

-Greatest chance of EPS
-Less likely to cause sedation and hypotension compared with the PTZs
-This drug is most associated with MNS

Front 55

Tell me about Risperdone (Reisperdal)

Back 55

-Inhibits serotonin rather specifically
-is a first line agent for treatment of psychosis
-has adverse effects similar to the typical antipsychotics but much less severe and occurring with much less incidence

Front 56

What are some etiologic factors associated with epilepsy?

Back 56

neurological diseases, infections, cancer, head injury, drugs, heredity, hypocalcemia

Front 57

What invention in the 1920s was a breakthrough in the study of epilepsy?

Back 57

EEG (graphical representation of the electrical activity of the neurons as recorded by the scalp surface)

Front 58

Primarily because of drug therapy, what percentage of epileptics in the US are fairly well controlled?

Back 58

80%

Front 59

About ___________- people in the US still have uncontrolled seizures

Back 59

500,000

Front 60

Phenobarbital/Primidone (1912)

-What is its chemistry?

Back 60

barbituate

Front 61

Phenobarbital/Primidone (1912)

Explain its ADME (absorption/distribution/metabolism/excretion)

Back 61

-well absorbed PO
-Primidone is a prodrug--converted to phenobarbital
-Half life of 24 hr (primidone) and 100 hr (phenobarbital)

Front 62

What are the uses of Phenobarbital/Primidone (1912)?

Back 62

-many consider these only for infants (fast absorption for quick effects)
-BUT: cognitive effects with long-term use in children

Front 63

What is Phenobarbital/Primidone's MOA?

Back 63

-GABA potentiation

Front 64

What are Phenobarbital/Primidone ADRs?

Back 64

Most common: sedation, dependence, tolerance, unduction of many P450 enzymes, cognitive and learning problems in children

-Primidone has more N&V associated with it vs. phenobarbital

Front 65

What are the interactions of Phenobarbital/Primidone?

Back 65

inducer of P450s

Front 66

Phenytoin (1938) is yet another anti-epiletic agent

Back 66

that is all

Front 67

Explain the ADME of Phenytoin (1938)?

Back 67

-can be given PO and IV
-crummy and extremely variable PO absorption
-Dilantin: actually an EXTENDED RELEASE form of phenytoin
-Highly PP bound-primarily to albumin
-Non-linear metabolism of phenytoin

Front 68

What are the uses of Phenytoin (1938)?

Back 68

one of the most effective AEDs against Tonic-Clonic and Partial Seizures

Front 69

What is Phenytoin (1938)'s MOA?

Back 69

-alters multiple channels-in particular Na+ and to a lesser extent Ca++
-has antiarrhythmic activity

Front 70

What ADRs are associated with Phenytoin (1938)?

Back 70

-drowsiness
-gingival hyperplasia
-nystagmus (changes in eye muscle movements)
-hirsuitism (hair growth)
-skin rash and fever may indicate hypersensitivity
-lympadenopathy can be fatal and may look like leukemia

Front 71

What are the interactions of Phenytoin?

Back 71

potent inducer of many liver enzymes (P450s, MFOs)

Front 72

Ethosuximide started being used in what decade?

Back 72

1960s

Front 73

What is the chemistry of Ethosuximide (1960s)?

Back 73

succinamide (wtf?)

Front 74

Let's go back to Phenobarbital and Primidone. In the notes it put those two together in 1912.....HOWEVER

Back 74

Phenobarbital was in 1912

Primidone was in 1954

according to a chart on the previous page. Oops

Front 75

Explain the ADME of Ethosuximide

Back 75

-well absorbed PO
-metabolized thru liver to hydroxylated metabolites

Front 76

What is Ethosuximide used for?

Back 76

drug of choice in ABSENCE seizures (?)

Front 77

What is Ethosuximide's MOA?

Back 77

reduces the low-threshold calcium current in neurons and reduces dicharge from thalamic neurons

Front 78

What are the ADRs of Ethosuximide?

Back 78

-Most common: GI distress, weight loss, lethargy

-Rare: blood dyscrasias (life-threatening)

Front 79

What groovy decade did Carbamazepine come around?

Back 79

1970s

Front 80

What is the chemistry of Carbamezepine (1970s)?

Back 80

closely related to tricyclic antidepressants

Front 81

Explain the ADME of Carbamazepine

Back 81

-PO only!
-crummy absorption and dissolution characteristics of tablets
-Metabolized thru P450s, at least one active metabolite
-strong inducer of a number of liver enzymes (P450s especially)

Front 82

What is Carbamazepine used for?

Back 82

-drug of choice for Tonic-Clonic and Partial seizures
-userful in trigeminal neuralgia

Front 83

What is the MOA of Carbamazepine?

Back 83

-alters conductance through several channels (Na channels of neurons in particular)

Front 84

What are the ADRs associated with Carbamazepine?

Back 84

-Most common: diplopia (double vision), ataxia
-Also memory loss with long-term use (as many as 50% of patients have some degree of memory loss)

Front 85

-What are the interactions of Carbamazepine?

Back 85

-induces metabolism of valproic acid, TCAs, haloperidol, lamotrigine
-Verapamil, ketoconazole, fluoxetine, nefazadone, erythromycin inhibit P450s...decrease activity of carbamazepine (because of active metabolites)

Front 86

Valproate and Divalproex also came around in what groovy decade?

Back 86

1970s

Front 87

What is the difference between Valproate and Divalproex?

Back 87

Divalproex is the coated form for less GI upset

Front 88

What are Valproate/Divalproex used for?

Back 88

-Broadest spectrum AED
-Drug of choice in Absence or Atypical Absence seizures
-Also used in migraine, bipolar disorder

Front 89

What is the MOA of Valproate/Divalproex?

Back 89

affects Na channels and increases GABA availability to synapse

Front 90

What are the ADRs of Valproate/Divalproex?

Back 90

-Most common: GI upset (though Divalproex decreases chance)
-Rare but potentially fatal: hepatoxicity and thrombocytopenia (due to hypersensitivity most likely)

Front 91

What are the interactions of Valproate/Divalproex?

Back 91

displaces phenytoin from PP binding, especially at high doses

Front 92

What decade did Gabapentin come around?

Back 92

1990s

Front 93

What is the chemistry of Gabapentin?

Back 93

amino acid analog of GABA

Front 94

Explain the ADME of Gabapentin

Back 94

although peak blood levels are achieved in 1-3 hr, takes weeks to see full effects

Front 95

What are the uses of Gabapentin?

Back 95

-back-up in partial seizures
-also useful for treating chronic pain, bipolar disorder, etc

Front 96

What is the MOA of Gabapentin?

Back 96

-Does NOT act on GABA receptor

-may alter GABA metabolism, transport or re-uptake (pretty unclear)

Front 97

What are the ADRs associated with Gabapentin?

Back 97

-Most common: ataxia, drowsiness, dizziness, fatigue

-Overall: less incidence of ADRs vs. most AEDs

Front 98

What are the interactions of Gabapentin?

Back 98

-may increase phenytoin blood levels at higher doses (probably not P450-mediated)