Pharmacology Exam I (Spring 2007)

Front 1

The clinical manifestation of a hyperexcitable neuronal network, in which the electrical balance underlying normal neuronal activity is pathologically altered---excitation predominates over inhibition.

Back 1

Seizure

Front 2

Epileptogenesis

Back 2

A sequence of events through which a normal neuronal network is converted to a hyperexcitable network that generates seizures.

Front 3

Most cases of epilepsy are idiopathic. How are the other cases obtained?

Back 3

Some epilepsies are acquired, for example, head trauma and ischemia induce a high risk for development of epilepsy. Other potential causes are tumor, CNS infection, metabolic imbalances, drugs, genetic predisposition, and congenital malformations. Developmental abnormalities such as in Cortical dysplasia and Fragile X Syndrome are responsible also.

Front 4

9% of these seizures are these. Occurs in infants and toddlers.

Back 4

Febrile Seizures

Front 5

Seizure which occurs in children between 5 months and 5 years. Fever of 39 degrees. Seizure occurs during rise in temp, not at peak. Generally tonic-clonic with drowsy post-ictal period. 1/3 to 1/2 of children experience recurrence of this seizure.

Back 5

Febrile Seizure

Front 6

Seizure remains focal with limited spread. During a simple seizure, normal consciousness and awareness is maintained. No impairment of consciousness.

Back 6

Simple Partial Seizures

Front 7

Abnormal firing spreads to other parts of the cortex. Consciousness is impaired. The characteristics of the seizure will depend on the site of origin and the degree of spread.

Back 7

Complex partial seizures

Front 8

The gradual spread of motor symptoms to adjacent parts of the body as the abnormal activity invades adjacent cortical areas.

Back 8

Jacksonian March

Front 9

Stereotyped movements such as lip smacking

Back 9

Automatisms

Front 10

The most common type of epilepsy characterized by complex partial seizures.

Back 10

Temporal lobe epilepsy

Front 11

Type of seizure most common in children. They have and abrupt beginning and end. They do NOT involve a loss of consciousness.

Back 11

Absence or petit mal

Front 12

Tonic rigidity of extremities followed by clonic jerking. Followed by post-ictal depression in EEG.

Back 12

Tonic-clonic or Grand Mal

Front 13

Seizure starts out focal and then spreads bilaterally throughout the cortex to become generalized.

Back 13

Secondarily Generalized Seizures

Front 14

The most common type of seizure in adults involving the temporal lobes.

Back 14

Temporal lobe epilepsy

Front 15

A medical emergency defined as at least 30 minutes of continued seizure activity, or multiple seizures during this time without full recovery between.

Back 15

Status Epilepticus

Front 16

The advantage of newer AEDs is generally less CNS sedative effects. The exception is ?????? a classic AED with little sedating action.

Back 16

Ethosuximide

Front 17

True or False?
On an ionic level, inhibition is typically mediated by inward chloride or outward potassium currents, and excitation by inward sodium or calcium currents.

Back 17

True

Front 18

The most important CNS inhibitory neurotransmitter is what?

Back 18

GABA

Front 19

The most important excitatory CNS neurotransmitter is what?

Back 19

Glutamate

Front 20

Glutamate receptors are targets for AED.
What is an important glutamate receptor?

Back 20

NMDA receptor

Front 21

These receptors have several modulatory sites: separate (allosteric) binding sites for BZDs and barbiturates, which bind directly to the receptor and increase the inhibitory synaptic action of GABA.

Back 21

GABA-A receptors

Front 22

These receptors have a G-protein that mediates slow synaptic transmission by activating K+ channels; it can also be located presynaptically where it reduces neurotransmitter release.

Back 22

GABA-B

Front 23

What channels do Phenytoin and Carbamazepine block?

Back 23

Na+ channels

Front 24

Felbamate is pleiotropic. What are the two mechanisms it follows?

Back 24

It blocks Na+ channels and also antagonizes NMDA receptors by blocking the glycine site.

Front 25

What are the MOA of Lamotrigine?

Back 25

It blocks Na+ channels, decreases excessive glutamate release, and also may block Ca++ channels.

Front 26

What the MOA of Topiramate?

Back 26

It blocks Na+ channels, enhances GABA currents by increasing the frequency at which the channel opens, and may also inhibit AMPA/kainate glutamate receptors.

Front 27

Usefulness as antiepileptic was accidentally discovered. MOA is similiar to BZDs, by binding on GABA receptor. Prolongs openings of Cl- channels. Blocks sustained high-freq repetitive neuronal firing. Used for generalized tonic-clonic and partial seizures.

Back 27

Phenobarbital

Front 28

True or False?
Blood levels must be monitored while on phenobarbital.

Back 28

True

Front 29

Mephobarbitol and Primidone

Back 29

Other Barbiturates

Front 30

At therapeutic levels, Phenytoin blocks Na channels and inhibits regeneration of repetitive action potentials. What specific actions to these effects cause?

Back 30

Phenytoin has great ability preventing the "spread" of the seizure from the seizure focus to normal neurons.

Front 31

What are the adverse effects of Phenytoin?

Back 31

Dose-related: neurological-ataxia, nystamus, diplopia, cognitive impairment.
Immunologic: can vary from mild rash to rare, severe exfolliative dermatitis.
hematologic: thrombocytopenia, megaloblastic anemia

Front 32

What is a new water soluble prodrug form of phenytoin for parental use?

Back 32

Fosphenytoin

Front 33

What is the DOC for generalized tonic-clonic seizures and partial seizures (TLE)
It is also used for bipolar disorder and neuralgic pain.

Back 33

Carbamazepine

Front 34

What is the MOA for carbamazepine?

Back 34

Similiar to phenytoin-blocks Na+ channels in nerve cell membrane at therapeutic dose and inhibits high-frequency repetive firing in neurons.

Front 35

What are the adverse effects of Carbamazepine?

Back 35

Common-diplopia, ataxia, GI, visual disturbances, rash.
Rare-aplastic anemia or agranulocytosis

Front 36

Which drugs are NOT anesthetics?

Back 36

Narcotics, Sedatives, and Muscle Relaxants

Front 37

What are the four properties of Anesthetics?

Back 37

1. Unconsciousness and amnesia during sugery.
2. Analgesia
3. Blunting of protective reflexes. (makes intibation easier)
4. Reduced Muscle Tone

Front 38

What are the five different IV anesthetics?

Back 38

1. Thiopental
2. Methohexital
3. Etomidate
4. Propofol
5. Ketamine

Front 39

What are the four stages of anesthesia?

Back 39

Stage I - Analgesia - Patient is conscious with Increased pain tolerance
Stage II - Excitement - Disinhibition, unresponsive, thrashing, irregular respirations (try to pass quickly).
Stage III - Surgical Anesthesia - Begins with respirations becoming regular, patient still not responsive to command.
Stage IV - Medullary depression - Too far, life threatening respiratory and CV depression.

Front 40

True or False?
The higher the B:G, the faster the induction and recovery.

Back 40

False!

Front 41

What is the concentration of an inhaled anesthetic requiring at least 50% of patients not to move in response to a stimuli?

Back 41

Minimum alveolar concentration

Front 42

What are the physiological effects of Inhaled Anesthetics?

Back 42

1. CV - sympathetic tone decreases, arteries dilate, veins dilate, HR and contractility decrease.
2. Cellular metabolism decreased
3. Respiratory effects - RR increases, Title volume decreases?
4. Brain - all functions decrease. Cerebral blood flow increases (exception being NO2)
5. Renal - GFR decreases with oliguria

Front 43

What kinds of toxicities are seen with Inhaled Anesthetics?

Back 43

1. Hepatotoxicity (Halothane
2. Malignant Hyperthermia (Halothane and Isoflurane)
3. Nephrotoxicity (Sevoflurane)

Front 44

Malignant Hyperthermia is a very serious toxic effect of inhaled anesthetics. If this occurs, what drug is given IV?

Back 44

Dantrolene

Front 45

How are the pharmacokinetics different for IV anesthetics compared to Inhaled anesthetics?

Back 45

Most effects are the same; Decreased O2 consumption, decreased cardiac output and arterial pressure, decreased ventilation. However the only difference is that IV anesthetics create decreased cerebral blood flow.

Front 46

Barbiturates such as Thiopental and Methohexital are used for induction. They are also short acting. What is a very dangerous side effect from high doses?

Back 46

Myocardial depression

Front 47

Used for conscious sedation to cause amnesia. Flumazenil is used for reversal and OD.

Back 47

Benzodiazepines

Front 48

Morphine/Fentanyl
Can cause respiratory depression
Naloxone is used for reversal.

Back 48

Opiods

Front 49

Used often for outpatient surgery - conscious sedation.
Patients feel well post-op
Used for induction and maintainence.

Back 49

Propofol

Front 50

Minimal CV and respiratory depression.
No analgesic effect - opioids often used.
High incidence of N/V, involuntary muscle movements (myoclonus).
Can cause adrenal suppression

Back 50

Etomidate

Front 51

Produces "dissociative anesthesia"
Related to PCP - special K

Back 51

Ketamine

Front 52

Used for unstable pts.
Blocks effects of glutamate at NMDA receptor.
Stimulates CV system
Airway reflexes preserved
Markedly increases cerebral blood flow and ICP.

Back 52

Ketamine

Front 53

DOC for grand mal seizures, also very effective for absence seizures.
MOA: blocks sustained high-freq repetitive neuronal firing. Also affects Na+ and GABA.
Adverse effects: rare, but potentially severe/fatal hepatotoxicity. Monitor LFTs.

Back 53

Valproic Acid

Front 54

This AED should be avoided during pregnancy as it might cause Spina bifida.

Back 54

Teratogenic is the term for this??
Valproic acid should be avoided??? (check book)

Front 55

DOC for absence seizures. Often used as first-line drug due to valproic acid's hepatotoxicity.

Back 55

Ethosuximide

Front 56

What is this AED?
MOA: reduces low threshold Ca++ currents through T-type Ca++ channels in the thalamus at therapeutic concentrations.
Adverse effects - GI distress.

Back 56

Ethosuximide

Front 57

Used to treat status epilepticus.
However, tolerance can develop and seizures recur.

Back 57

BZDs
Clonazepam, Diazepam

Front 58

Newer AED
MOA: Blocks Na+ channels, stabilizing presynaptic neuronal membranes (similiar to phenytoin and carbamazepine). Often used in multi-drug regimens.

Back 58

Lamotrigine

Front 59

Analog of GABA
Does not interact with GABA receptors, but may alter GABA metabolism, release, or transport. Increases brain GABA and affects Ca+2 channels.
Used as an adjunt against partial and generalized tonic-clonic seizures. Also used for neuropathic pain, neuralgias.

Back 59

Gabapentin

Front 60

Newer AED
MOA: likely blockade of voltage-dependent Na+ channels. Also enhances GABA inhibitory synaptic activity.
Effective against partial and generalized tonic-clonic seizures.
Adverse effects: Somnolence, fatigue, dizziness, confusion. Probably teratogen.

Back 60

Topirimate

Front 61

Newer AED
Inhibitor of GABA uptake - prolongs inhibitory action of GABA.
Usually given as adjunct treatment of partial seizures.

Back 61

Tiagabine

Front 62

What are some adverse effects of Tiagabine?

Back 62

Nervousness, dizziness, confusion, tremor...

Front 63

For refractory partial seizures - causes aplastic anemia and severe hepatitis.
Likely NMDA receptor blockade.
Last line drug.

Back 63

Felbamate

Front 64

What is the main way of treating Parkinsons Disease?

Back 64

Restoring Dopamine Levels

Front 65

Why are dopamine precursors almost always administered with a dopa decarboxylase inhibitor?

Back 65

L-dopa is taken up by the neuron and is released. However, only about 1% of an oral dose gets into the brain because DOPA decarboxylase.

Front 66

What is Sinimet, Atamet made up of?

Back 66

L-dopa and Carbidopa (a dopa decarboxylase inhibitor)

Front 67

What are some adverse effects of L-dopa/carbidopa?

Back 67

Anorexia, N/V (give with food to decrease), orthostatic hypotension, tachycardia, dyskinesias, and psychiatric effects

Front 68

What are drug holidays, and how do they help PD patients?

Back 68

L-dopa is withdrawn gradually for a period of 3-21 days and a lower dose can be used. This helps patients that develop a tolerance to drugs and minimizes side effects.

Front 69

What are some drug interactions and contraindications for Dopamine precursors?

Back 69

Pyridoxine (Vit B6) is a cofactor for Dopa decarboxylase. Also they are not used in combo with MAOIs which can cause hypertension.
Also, these drugs are not used in patients with psychosis or closed angle glaucoma.

Front 70

What are some Dopamine Agonists?

Back 70

Bromocriptine, Ropinirole, Pergolide, and Pramiperole.

Front 71

How do dopamine agonists work?

Back 71

MOA: Bind to dopamine receptors and activate them. (Dopamine D2 receptors)

Front 72

What is an ergot derivative that is a first line drug for dopamine agonists?

Back 72

Bromocriptine

Front 73

What is a dopamine agonist similiar to bromocriptine, but more powerful with increased half-life?

Back 73

Pergolide

Front 74

These drugs are dopamine agonists, but not ergot derivatives. They are monotherapy for mild PD.

Back 74

Pramipexole and Ropimirole

Front 75

What are some adverse effects of Dopamine Agonists?

Back 75

Cardio-Postural hypotension, digital vasospasm
Dyskinesias
Erythromyalgia-(see book)
GI-anorexia, N/V, constipation
Psych- confusion, dilusions (more common than with l-dopa)

Front 76

What is an example of an MAOI?

Back 76

Selegiline

Front 77

MOA: selective inhibitor of MAO-B, retards breakdown of dopamine.
Allows L-dopa to be reduced.
Adverse effects: avoid in patients taking TCA, SSRIs, and don't give non-specific MAOIs to patients taking L-dopa.

Back 77

Selegiline

Front 78

How does Amantadine work?

Back 78

It is an antiviral drug that has anti-PD properties because it causes neurons to release dopamine.
However, the benefit may be transient and disapper in a few weeks.

Front 79

What are some adverse effects of Amantadine?

Back 79

CNS-restlessness, agitation, hallucinations
Peripheral edema
Livedo Reticularis - peripheral vascular condition, causes reddish-blue skin.
Avoid in CHF patients and seizure patients.

Front 80

What are some examples of anticholinergics used to treat PD?

Back 80

Benztropine and Trihexyphenidyl

Front 81

What aspects of PD do anticholinergics treat?

Back 81

They have a major effect on rigidity/tremor, but only a minor effect on bradykinesia.
These drugs have atropine-like adverse effects.

Front 82

What are some examples of COMT inhibitors?

Back 82

Tolcapone, Entacapone

Front 83

How to COMTs work?

Back 83

COMT converts L-dopa to 3-O-methyldopa. Therefore, they prolong the action of l-dopa by diminishing its metabolism.

Front 84

What are some adverse effects of COMTs?

Back 84

First, they are never used alone. Adverse effects often due to increased levodopa.
Tolcapone requires LFTs

Front 85

What are two other Movement disorders?

Back 85

Huntington's Disease and Amyotrophic Lateral Sclerosis

Front 86

What is a derivative of GABA that can be used for ALS spasticity?

Back 86

Baclofen

Front 87

What drugs can treat essential tremors?

Back 87

B-blockers such as propanolol have been effective. AEDs can be tried.