Exam 2 Questions (Part 1) Flashcards Preview

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Flashcards in Exam 2 Questions (Part 1) Deck (90):
1

Active clotting factor that catalyzes the reaction to change Fibrinogen(I) to Fibrin (Ia)

Thrombin (IIa)

2

Stimulators of platelet aggregation

- TXA2 (Thromboxane)
- 5HT (5-Hydroxytryptamine)
- ADP (From Platelets)

3

Inhibitors of platelet aggregation

- PGI2 (Prostaglandin, released from vessel walls)

4

Circulating protein that inactivates several clotting factors

Antithrombin III

5

Plasminogen activator that changes plasminogen to plasmin to cause fibrinogen and fibrin breakdown

t-PA: Tissue Plasminogen Activator

6

Hemophilia A

Factor VIII Deficiency

7

Hemophilia B

Factor IX Deficiency

8

Arterial thrombus occludes vessels, which leads to...

Ischemia

9

Venous thrombus tail becomes detached, referred to as...

Embolus... into pulmonary, cerebral or coronary embolism

10

Inhibit hepatic synthesis of clotting factors

Warfarin (Coumadin)

11

Inactivate clotting factors via Antithrombin III

Heparin (Unfractionated) and Low Molecular Weight Fractions of Heparin (LMWFH)

12

Accelerate clot dissolution

Fibrinolytic Agents

13

Inhibit platelet aggregation by preferentially and irreversibly inhibiting TXA2 formation for the lifetime of the platelet

Aspirin

14

Inhibit platelet aggregation by acting as an ADP receptor inhibitor

Clopidogrel (Plavix)

15

Inhibition of platelet aggregation by inhibiting a protein...

Glycoprotein (GP) IIb-IIIa Inhibitors

16

Oral Direct Thrombin (IIa) inhibitors

Dabigatran (Pradaxa)

17

Oral Factor Xa Inhibitors

(Class Name is Prototype)
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)

18

Heparin

GENERAL
- Normal body constituent found in mast cells
- Binds to Antithrombin III to accelerate its binding to active clotting factors to inhibit their activity
-MW: 5000-30000
- Effective in vitro and in vivo
- Rapid Onset: Administer via IV

TOXICITY
- Low Therapeutic Index: Monitor clotting time (aPTT)
- Bleeding
-Allergic Reactions (Extracted from cows and pigs)
- Thrombocytopenia

INDICATIONS
- Prevent and treat venous thrombosis and pulmonary emboli
- Treat AFib with embolism
- Prevent clotting in heart surgery, blood transfusions, and extra-corporeal circulation

19

Low Molecular Weight Heparins

- Class Name is Prototype!
- Enoxaparin (Lovenox)
- Dalteparin (Fragmin)
- Tinzaparin (Innohep)

GENERAL
- Lower Molecular Weight (2000-9000)
- Goal: Fewer side effects such as thrombocytopenia
- Given sc, longer half life than UFH
- More Predictable action (inhibits factor Xa), requires less monitoring

INDICATIONS
- Used for prophylaxis and treatment of deep vein thrombosis
- Given 1-2 hours preop and 5-10 days postop

ANTIDOTE
- Protamine

20

Antidote for LMWH

Protamine

21

Warfarin (Coumadin)

MECHANISM
- Inhibits synthesis of Factors II, VII, IX, X
- Need Vitamin K to make these proteins...
- Inhibits Vitamin K epoxide reductase and the regeneration or activation of Vitamin K

TOXICITIES
- Low TI: Monitor Clotting Time
-Bleeding
- Contraindicated during pregnancy

INDICATIONS
- Prevention and treatment of venous thrombosis and complications of Afib
- Traditionally drug of choice for long term outpatient therapy

DRUG INTERACTIONS
- Metabolism Inducers/Inhibitors
- Plasma Protein binding competition
- Vitamin K
-Concurrent aspirin or certain vitamin/dietary supplements

THERAPY CONSIDERATIONS
- Complete Oral Absorption
- 1-3 day lag time between initial administration and maximum anticoagulant effect

22

Thrombolytic Agents

MECHANISM
- Plasminogen Activators
- Stimulate conversion of plasminogen to plasmin (enzyme that dissolves clots)
- May reopen clogged vessels

FIRST GENERATION DRUG
- Urokinase (abbokinase)

SECOND GENERATION DRUGS
- More clot specific, less effect on circulating plasminogen
- Tissue Plasminogen Activators (t-PA): Class prototype. ex. Alteplase (Activase)

INDICATIONS
- IV Administration ONLY
- Pulmonary Emboli
-Central DVT
- Acute MI and Ischemic Stroke

ADVERSE EFFECTS
- Hemorrhage (Low TI)

23

Lipoproteins

Transport forms of cholesterol and triglycerides
- HDL
-Chylomicrons
-VLDL
-LDL

24

High Density Lipoproteins (HDL)

- GOOD!
- Remove cholesterol from arterial wall and transports to liver
- Antioxidant properties

25

Chylomicrons

- Carry fats (primarily triglycerides) absorbed in diet

26

Very Low Density Lipoproteins (VLDL)

- HARMFUL
- High triglyceride content
- Carry fats from liver
- Precursor to LDL

27

Low Density Lipoproteins (LDL)

- HARMFUL
- High Cholesterol
- Deposit cholesterol onto arterial walls

28

HMG-CoA Reductase

- Enzyme that is responsible for increasing cholesterol synthesis in the liver
- Inhibited by Atorvastatin (Lipitor)

29

STATINS: Atorvastatin (Lipitor)

MECHANISM
- Inhibit HMG-CoA Reductase, which results in decreased cholesterol synthesis in liver
-- Increases breakdown of LDLs by increasing LDL receptors
-- Decrease synthesis of VLDL
- Pleiotropic effects, including improved function of vascular wall

ADVERSE EFFECTS
- Liver dysfunction (rare, but serious)
- Muscle pain, inflammation
- Rhabdomyolysis (monitor creatine kinase)
- Reversible memory loss
- Hyperglycemia

TOXICITY
- Pregnancy Category X (Absolute NO!)

OTHER
- CYP450 inhibitors INCREASE toxicity by DECREASING elimination... lovastatin and simvastatin most problematic

30

Fibric Acids (Fibrates)

PROTOTYPE
- Gemfibrozil (Lopid)

MECHANISM
- Increase lipoprotein lipase activity
- Decrease triglycerides
- Increase VLDL breakdown

ADVERSE EFFECTS
- GI Distress
-Gallstones

31

Resins: Cholestyramine (Questran)

MECHANISM
- Bind Bile Acids in GI
- Increase bile acid excretion
- Increase liver cholesterol breakdown to replace lost bile acids
- Increase LDL receptors in liver
- Decrease LDL- C
- Mild Effect alone: Effective in combination

ADVERSE EFFECTS
- Constipation
- Impaired drug absorption

32

Niacin (Niotinic Acid, Vitamin B3, Niaspan)

MECHANISM
- Decrease fatty acid mobilization from tissue
- Decreases formation and secretion of VLDL by liver
a. Effect 2' to decreased FA mobilization
b. Decreases FA in plasma and liver
c. Decreases FA available for TG and VLDL synthesis
- Decreases LDL
- Increases HDL

ADVERSE EFFECTS
- Cutaneous flush most common
- Effective in combination

33

Ezetimibe (Zetia)

- INHIBITOR of intestinal cholesterol absorption

MECHANISM
- Inhibits transport protein that delivers dietary cholesterol across small intestine walls
- Decreases LDL-C
- Effective alone or in combination with statins

34

Vytorin (Simvastatin plus Ezetimibe)

- Combo effectively decreases LDL-C, but may alter the consequences...
- Controversial potential for increase in cancer risk

35

PCSK9 Inhibitors

- New class
- Proprotein convertase subtilisin/kexin type 9
- Imrpove LDL receptor efficiency

36

An ICU sedative; Alpha-2 Receptor Agonist

Dexmedetomidine (Precedex)

37

Barbiturates

GENERAL
- Inactive Metabolites
- Carried across placental barrier; potential respiratory problems in newborns
- Degree of CNS depression DOSE RELATED
- Directly opens Cl channels at high doses
- Interacts with more than GABA in CNS
TOLERANCE
-CNS Adaptation
-Drug Disposition Tolerance: the longer you give, the faster drug is eliminated
DEPENDENCE
-Psychologic
-Physiologic
-Abuse Potential
WITHDRAWAL
- More severe with chronic, high does
-More severe with short acting versions
- Symptoms: Disturbed sleep patterns, tremor, anxiety, agitation, confusion, hallucinations, convulsions
- May be life threatening, especially if short acting agents are abruptly withdrawn

38

Ultra Short duration BAR, used as IV anesthetic

Thiopental (Pentothal)

39

Intermediate half life BAR (18-48 hours); Hypnotic (rare)

Pentobarbital (Nembutal)

40

Long half life BAR (4-5 days); Used as a sedative and anti-epileptic

Phenobarbital (Luminal)

41

Benzodiazepines

INDICATIONS
-Anxiety: GAD, Panic, OCD, PTSD
- Preanesthetic Medication and surgical adjunct
- Insomnia
-Skeletal Muscle Spasm
-Alcohol Withdrawal
-Epilepsy

CLINICAL CONSIDERATIONS
- Dose requirements VARY GREATLY
- Has a shallower dose response curve compared to BAR

ADVANTAGES
-Higher TI (little respiratory depression)
-Little effect on CYP450 enzymes in liver

SIDE EFFECTS
-Dose Related drowsiness and Ataxia
-Anterograde Amnesia
-Respiratory Depression (Polypharm dangerous!)

TOLERANCE/DENDENCE/WITHRAWAL
- Lower risk of physiological dependence
-Elderly patients sensitive to actions: Decrease dose by half
- Cross placental barrier: Greater risk of teratogenic effects and neonatal withdrawal

METABOLISM
- All are metabolized by liver, most by P450 family
- Some metabolites are active (Desmethyldiazepam)

42

BZD Discontinuation Syndrome

- Symptoms: Rebound anxiety, agitation, restlessness, sweating, irritability (delusions, seizures)
- Appear in 1-2 days (Type II-III) or 5-10 days (Type I)
- Gradually taper down dose

43

Long Half Life BZD

- Diazepam (Valium)
- 200-100 hours
- Converted to desmethyldiazepam (>40 hours)
- Accumulation of drug and/or metabolite will occur with multiple doses
- Benefit: Smooth effect
- Drawback: Residual drowsiness, hangover

44

Intermediate Half Life BZD

- Oxazepam (Serax)
- 5-15 hours
- NOT metabolized by CYP450... Glucuronidation (Phase II) less sensitive to liver function changes with age
- Preferred type for elderly and patients with impaired hepatic function

45

Short Half Life BZD

- Triazolam (Halcion)
- 1.5-5 hours
- Less daytime sedation (when used as hypnotic)
- Serious CNS side effects include aggression and violence

46

Benzodiazepine Antagonist

- Flumazenil (Romazicon)

GENERAL
- High affinity for CNS BZD receptors, but lack efficacy (pure competitive antagonist)
- Used to reverse BZD anesthesia or treat overdose
- Ultra short half life; repeated administration required
- Does NOT affect CNS action of barbiturates, opiates, or other CNS depressants

ADVERSE EFFECTS
- Agitation
- Confusion
- Dizziness

47

Buspirone (BuSpar)

GENERAL
- May interact with dopamine or serotonin (5HT) pathways
- 5HT1A receptor partial agonist
- Lack of GABA interaction means lack of muscle relaxation, anti-epileptic and hypnotic activity
- Lower incidence of sedation, abuse potential, and withdrawal syndrome (not scheduled)
- Selective anti-anxiety action delayed 1-2 weeks

ADVERSE EFFECTS
- Tachycardia
- Miosis
- Paresthesia
- Tinnitus
- Chest Pain

48

Treatment of Insomnia with Barbiturates

- Effectiveness limited to only a few days
- Rapid Eye Movement (REM) Rebound upon discontinuance

49

Treatment of Insomnia with Benzodiazepines

- Effective for a longer term than barbiturates
- Less REM suppression and rebound (if low doses used for short periods)
- Drugs with long half lives may causes hangovers

50

Zolpidem (Ambien)

- Selective BZ1 Agonist
- Less anxiolytic, muscle relaxant or anti- epileptic activity than other BZDs
- Short half lives
- No active metabolites
- Less daytime sedation
- At low doses, produces very little REM suppression, tolerance or dependence
- Higher risk of next morning impairment for patients taking extended release of the drug
- Women eliminate more slowly then men... lower dose

51

Ramelteon (Rozerem)

- Melatonin agonist
- Not scheduled

52

Suvorexant (Belsomra)

- Orexin Receptor antagonist
- Orexins are endogenous chemicals that regulate sleep-wake cycles (stimulatory)

53

Generalized Antidepressant Function

- Increase interaction between biogenic amines and their receptors... increase "synaptic residence time"
- Relives depression via receptor downregulation/desensitization or increased nerve growth factors (increase neurogenesis)
- For most drugs, maximum therapeutic effects delayed 2-3 weeks

54

Tricyclic Antidepressants (TCA)

PROTOTYPES
- Amitriptyline (Elavil) = Parent Drug (Tertiary Amine)
- Nortriptyline (Aventyl) = Active Metabolite (Secondary Amine)

GENERAL
- Inhibit reuptake of NE and 5HT
- Delay in antidepressant activity... side effects occur immediately

SIDE EFFECTS
- Anticholinergic
-Sedation
- Cardiovascular: Tachycardia, dysrhythmias (anticholinergic action and direct cardiotoxicity), postural hypotension (alpha 1 blockade)
- Sedation, Seizures
- Fine tremor, weight gain, sexual disturbances

55

Bupropion (Wellbutrin)

- 2nd/3rd generation drug
- Little effect on NE or 5HT reuptake
- Mechanism may be inhibition of DA reuptake (structural similarity to amphetamine)
- Anxiety, restlessness, insomnia, seizures may occur
- No classic tricyclic side effects
- Aids in smoking cessation (Zyban)

56

Venlafaxine (Effexor)/Desmethyl Metabolite

- Prototype SNRI: selectively inhibits NE and 5HT reuptake
- Has little anticholinergic action, sedation, or orthostatic hypotension
- Effective for anxiety and depression
- Several SNRI's used to treat chronic pain syndromes

57

SSRI's

PROTOTYPE
- Fluoxetine (Prozac)/Desmethyl Fluoxetine
GENERAL
- Selective for Serotonin
- No effect on NE reuptake

CLINICAL CONSIDERATIONS
- Most have higher TI (compared to classic tricyclics)
- Most have a better side effect pattern... less anticholinergic and cardiotoxicity, little or no weight gain or sedation
- Pregnancy warnings (heart defects)
- Many of CYP450 inhibitors... drug interactions
- Longer half lives than TCAs

INDICATIONS
- Several chronic anxiety disorders
-Depression

SIDE EFFECTS
- Sexual dysfunction, nausea, nervousness, anxiety, headache, GI episodes (especially upper GI bleed), movement disorders, withdrawal syndromes
- Suicidal behavior (controversy.. for patients 18-24 years old during first two months of treatment)
- Serotonin Syndrome possible

58

Serotonin Syndrome

- Too much 5HT in body
- Hyperthermia, muscle rigidity, movement disorders, confusion, coma...
- Caution with MAOI, TCA, certain drugs for migraines

59

Escitalopram (Lexapro)

- Active S-enantiomer contained in Citalopram (Celexa), a racemic mixture

60

SSRI approved for hot flashes

Paroxetine

61

MAO Inhibitors

PROTOTYPE (Class Name)
- Phenelzine (Nardil)
- Tranylcypromine (Parnate)

MECHANISM
- Inhibit MAO-A (NE, 5HT and tyramine metabolizing enzyme), which allows them to accumulate
- Inhibition essentially irreversible
- MAO-B and thus DA metabolism also inhibited
- Prolonged duration of action... effects persist 2-3 weeks after discontinuation of therapy

INTERFERING INTERACTIONS
- Tyramine containing foods... more NE released, could cause HTN episode
- Sympathomimetic drugs... Phenylephrine normally metabolized by MAO... Ephedrine and amphetamine effects potentiated

INDICATIONS
- Atypical depression
- Depressions unresponsive to other drugs

62

Dopamine Pathways in the CNS

-Project to Limbic Forebrain: closely related to behavior and emotion
- Nigrostriatal Pathway: Coordination of voluntary movement and posture (extrapyramidal tract)
- Project to hypothalamus and anterior pituitary: inhibit prolactin secretion
- Other pathways may be involved in eating behaviors and stimulation of nausea/vomiting reflexes (chemoreceptor trigger zone)

63

NMDA Receptor Antagonist

- Phencyclidine
- Produces classic schizophrenia like symptoms
- Implicates glutamate pathways

64

5HT2 Receptor Agonist

- LSD
- Produces hallucinations
- Implicates 5HT pathways
- Improve negative symptoms and cognitive impairments

65

Extra Pyramidal Syndrome (EPS)

- Side effect due to DA receptor antagonism
- Due to D2 blockade in extrapyramidal tract

- Akithisia: uncontrollable restlessness
- Acute Dystonias: facial grimacing
- Parkinson Symptoms: rigidity and tremor at rest
- Tardive Dyskinesia: stereotypic facial movements, sucking, smacking lips, fly-catching darting of tongue, dysphasia

66

Neuroleptic Malignant Syndrome

- Side effect due to DA receptor antagonism

- Muscle Rigidity
- Fever
-Hypertension
-Can be fatal

67

DA Blockade in hypothalamus may lead to...

-Weight Gain
-Hyperprolactinemia: delayed ovulation, amenorrhea, gynecomastia, loss of libido

68

Phenothiazines: D2 Receptor Antagonist Prototype

- Chlorpromazine (Thorazine)
- Advantages: Generic, inexpensive, familiar
- Disadvantages: significant autonomic and sedative actions

69

Phenothiazine: Most Potent in Group

- Fluphenazine (Prolixin)
- Advantages: Low incidence of sedation and autonomic effects; long acting form used im or sc for non-compliant patients
- Disadvantages: High incidence extrapyramidal

70

Atypical Antipsychotics

PROTOTYPES
- Olanzapine (Zyprexa)
- Risperidone (Risperdal)

GENERAL
- Less D2, more 5HT blocking
- Lower incidence of extrapyramidal effects
- Sedation/autonomic effects still present
- Equally efficacious versus "positive symptoms"
- May be better at reducing "negative symptoms"

NEW CONCERNS
- Hyperglycemia
-Weight Gain
- Hypercholesterolemia
-Skin reactions (Olanzapine)

71

Third Generation Atypical

- Aripiprazole (Abilify)

MECHANISM
- Partial D2 receptor agonist: stabilizes hyper and hypo activity
- 5HT2 receptor antagonist

SIDE EFFECTS
- Fewer D2 blockade associated effects
- Common: Headache, nausea, insomnia
- Impulse control problems

72

Levodopa (Sinemet, Sinemet CR)

MECHANISM
- crosses BBB
- Converted to DA by DDC in brain
- Restores DA/ACH Balance
- Best of available agents!
- Given with peripheral DDC inhibitor (Carbidopa) to prevent conversion of levodopa to DA in periphery

POSITIVE EFFECTS ON MOVEMENT TASKS
- Improves movement velocity
- Reduces tremor and rigidity

ADVERSE EFFECTS
- Formation of DA in periphery: nausea/vomiting, cardiac problems, orthostatic hypotension
- Dyskinesias
- Behavioral changes: psychotic symptoms, depression
- Diminished response after 3-4 years of therapy
- On-off and wearing off phenomenon

73

Peripheral DDC Inhibitors

- Carbidopa, given in combination with Levodopa
- Prevents conversion of Levodopa to DA in periphery
- Preserves more levodopa for conversion to DA in CNS
- Decreases peripheral side effects
- Decreases levodopa dose by 75-80%

74

Dopamine Receptor Agonists

PROTOTYPE
- Ropinirole (Requip)

MECHANISM
- Stimulate DA receptors; restore DA/ACH
- Often used in combination

ADVERSE EFFECTS
- Peripheral and behavioral changes similar to levodopa
- Nausea/vomiting, cardiac problems, orthostatic hypotension
- Psychotic symptoms, depression

75

Anticholinergic Drugs (M Receptor Antagonists)

PROTOTYPE
- Benztropine (Cogentin)

MECHANISM
- Inhibits cholinergic activity in corpus striatum
- Restores DA/ACh balance

GENERAL
- Often used in combination
- Effective for antipsychotic drug induced parkinsons

ADVERSE EFFECTS
- Anticholinergic side effects

76

Amantadine (Symmetrel)

MECHANISM
- Inhibits NMDA glutamate receptor: may restrict neuronal damage
- Older mechanism: release DA

ADVERSE EFFECTS
- Patches of skin discoloration

77

MAOB Inhibitors

PROTOTYPE
- Selegiline (Deprenyl, Eldepryl, Zelapar)

MECHANISM
- Inhbiits MAOB and thus DA breakdown
- Increases DA at synapse, restores DA/ACh balance
- Enhances and prolongs levodopa effects (via prolonged DA action)
- Neuroprotective

INDICATIONS
- Early Stages: Slow disease progression
- Late Stages: with Levodopa, may reduce on-off and wearing-off phenomena

ADVERSE EFFECTS
- Does not share all the adverse effects of antidepressant MAO inhibitors (the also inhibit MAOA)
- At higher doses, loses specificity
- Somnolence
- Compulsive behaviors

78

COMT Inhibitors

PRODUCTS
- Tolcapone (Tasmar): Hepatotoxin
- Entacapone (Comtan): Prototype (only in periphery)

MECHANISM
- Inhibits COMT (Tolcapone)
- Enhance and prolong levodopa effects (both)
a. Inhibit peripheral levodopa breakdown to 3OMD
b. Decreased 3OMD may enhance levodopa active transport from GI and across BBB

GENERAL
- Used in combination
- May reduce levodopa on-off phenonemon
- Side effects similar to levodopa... difficult to assess

79

Prototype Barbiturate for Antiepileptics

Phenobarbital

MECHANISM
- Opens Cl channels (via GABA or directly) and hyperpolarizes neuronal membranes
- May also decrease excitatory effects of glutamate
- Abolishes seizures at subanesthetic doses

ADVANTAGES
- Least toxic, least expensive, and oldest anti-epileptic
- Very effective, broad spectrum

DISADVANGAGES
- Sedation, dizziness, respiratory depression limit usefulness
- Drug interactions with CYP450: induces action

80

Prototype Hydantoin (For Antiepileptics)

Phenytoin (Dilantin)
PRODUCT
- Fosphenytoin (Cerebyx)

MECHANISM
- Major: Prolongs Na channel inactivation
- Other: Alters K and Ca channels and interacts with several neurotransmitters

ADVANTAGES
- Very effective, broad spectrum
- Sedation less pronounced than with phenobarbital

DISADVANTAGES
- Chronic Side effects associated with chronic use: ataxia, slurred speech, diplopia, nystagmus, gingival hyperplasia, hirsutism, acne
- Difficult to adjust dose: Zero order elimination at therapeutic doses... small dose increases may lead to large blood level changes
- Drug interactions are CYP450 related
a. induces DECREASE effect
b. Inhibitors INCREASE effect

81

Prototype Succinimide (Antiepileptics)

Ethosuximide (Zarontin)

MECHANISM
- Blocks T Calcium currents
- Has action directly opposed to convulsant agent pentylenetetrazol (Metrazol)
- Specifically blocks characteristic EEG pattern seen with absence seizures (3-Hz Wave Discharges) drug of choice

ADVERSE EFFECTS
- GI distress
- CNS effects

82

Prototype Iminostilbene (Antiepileptics)

Carbamazepine (Tegretol)

MECHANISM
- Prolongs Na channel inactivation
- Used as an adjunct for depression/mania; structurally similar to tricyclic antidepressants
- Also indicated for trigeminal neuralgia

ADVANTAGES
- Broad spectrum, little sedation

OTHER
- Drug interactions CYP450 related: Carbamazepine induces its own metabolism and that of other drugs
- Has active 10-11 epoxide metabolite (active and potentially toxic)
- Adverse dermatology reactions associated with genetic mutation

83

Valproic Acid (Depakene, Depakote)

GENERAL
- Discovered to have antiseizure activities when used as a solvent for other drugs... unique fatty acid structure
- Exhibits saturable protein binding and metabolism (small increases in dose may lead to large changes in free levels)

MECHANISM
- Elevates GABA levels in CNS
- Prolongs Na channel inactivation

SIDE EFFECTS
- Hepatotoxicity, teratogenicity (later cognitive impairment, neural tube defects), pancreatitis
- Limited therapeutic use

DRUG INTERACTIONS
- Inhibits metabolism of several drugs

84

Benzodiazepines (Antiseizure)-- 2 drugs

MECHANISM
- enhance GANA binding to its receptor

1. Diazepam (Valium) iv: highly effective for stopping continuous seizure activity (status epilepticus)

2. Clonazepam (Klonopin): Different spectrum of activity from diazepam (may act at different site on GABA-BZD complex)... disadvantages: sedation, tolerance

85

Lamotrigine (Lamictal): Second generation antiepileptic

MECHANISM
- Prolong Na channel inactivation
- May alter Ca channels: may explain effectiveness against absence seizures
- Inhibits Glutamate release
- Used as adjunct or alone as alternative for both partial and generalized seizures

SIDE EFFECT: Skin rash

NEWEST INDICATION: Bipolar I Disorder

86

Gabapentin (Neurontin IR); Gralise (SR): Second Generation Antiepileptic

- Structural Analog of Gaba
a. NOT a receptor agonist
b. May alter GABA release, uptake, or metabolism
c. May also inhibit glutamate release
- Drug excreted unchanged in urine
a. no significant drug interactions
b. elimination affected by renal function
- Other indications: Post herpetic neuralgia, diabetic neuropathy, migraines, restless leg syndrome (Horizant)

87

Pregabalin (Lyrica): Second Generation Antiepileptic

- Related to gabapentins
- Used to treat neuropathic pain and fibromyalgia

88

Levetiracetam (Keppra): Second Generation Antiepileptic

- Blocks glutamate release by inhibiting SV2A receptors on presynaptic vesicles
- Primarily excreted unchanged in the urine
- Generally well tolerated, but more psychiatric reactions being recognized

89

GABA Reuptake Inhibitor

Tiagabine (Gabitril)

90

GABA- T Inhibitor

Vigabatrin (Sabril)