Pharmacology Barbiturates And Antiepileptic Drugs

Front 1

Are bentobarbital and secobarbital ultrashort-, intermediate-, or long-acting?

Back 1

Intermediate

Front 2

Where do barbituates act?

Back 2

They may act at Ci- ionophore of GABA receptor, facilitating GABAergic transmission

Front 3

What do barbituates cause?

Back 3

Widespread CNS depression ranging, with increasing dose, from mild sedation through drowsiness, anesthesia, coma, and death (due to profound depression of respiratory and vasomotor centers in medulla)

Front 4

What terminates the action of ultra-short acting barbituates?

Back 4

Action terminated by redistribution and metabolism

Front 5

Desribe short-acting barbituate metabolism

Back 5

Mainly hepatic metabolism

Front 6

Desribe intermediate-acting barbituate metabolism

Back 6

Mainly hepatic metabolism

Front 7

Describe long-acting barbituate metabolism

Back 7

Hepatic metabolism and renal excretion of unmetabolized drug.

Front 8

What are the untoward effects of barbituates?

Back 8

1. Daytime Hangover
2. Cross-tolerance
3. Taken concurrently with other depressants, such as ethanol, can cause severe CNS depression
4. Respiratory depression
5. Paradoxical excitement, especially in children and the elderly
6. Therapeutic index decreases with sustained use

Front 9

What non-clinical use are barbituates frequently used for?

Back 9

Suicide attempts

Front 10

What are the signs of barbituate intoxication?

Back 10

a. Moderate intoxication resembling inebriation
b. Depression of medulla results in respiratory depression and hypotension.
c. Death can result from respiratory or renal failure

Front 11

What is the supportive treatment for barbituate poisoning?

Back 11

Dialysis

Front 12

What are the clinical uses of barbituates?

Back 12

1. Ultrashort used as IV anesthetics
2. Phenobarbital for seizures

Front 13

What is epilepsy?

Back 13

A chronic CNS disorder involving sudden, transitory change in sensory and/or motor functioning (seizure).

Front 14

What occurs on hte cellular level during a seizure?

Back 14

Synchronous repetitive firing of brain cells, either locally (focal) or globally

Front 15

What can cause a seizure in a patient?

Back 15

May have no identifiable cause (primary/idiopathic) or may be caused by variety of insults to brain (secondary/symptomatic), such as tremors, inflammation, head injuries.

Front 16

What are the causes of seizures on a cellular level?

Back 16

Possible causes:
a. Change in balance of excitatory and inhibitory inputs; reduction in GABA-mediated feed-forward excitation, perhaps mediated by NMDA receptors.
b. Change in membrane properties of dendrites; ionic conductances contribute to tendency for bursting

Front 17

What are the characteristics of a simple partial seizure?

Back 17

Motor (clonic twitching) or sensory (tingling) abnormalities in one area of the body; spreading to adjacent areas; no impairment of consciousness.

Front 18

What are the therapeutic agents for a simple partial seizure?

Back 18

Phenytoin*
Carbamazepine*
Phenobarbital
Valproic acid
Primidone
Gabapentin
Lamotrigine
Topiramate

Front 19

What are the characteristics of a complex partial seizure?

Back 19

Confusion, impairment of consciousness, stereotyped repeated movements, e.g. chewing

Front 20

What are the therapeutic agents for a complex partial seizure?

Back 20

Phenytoin*
Carbamazepine*
Phenobarbital
Valproic acid
Primidone
Gabapentin
Tiagabine

Front 21

What are the characteristics of a generalized absence (petit mal) seizure?

Back 21

Brief loss of consciousness, often with local or widespread clonic movements

Front 22

What are the therapeutic agents for an absence (petit mal) seizure?

Back 22

Ethosuximide*
Valproic acid*
Clonazepam

Front 23

What are the characteristics of a generalized tonic-clonic (grand mal) seizure?

Back 23

Loss of consciousnes, tonic spasm of entire body, then synchronous clonic movements; followed by confusion, sleep

Front 24

What are the therapeutic agents for a generalized tonic-clonic (grand mal) seizure?

Back 24

Phenytoin*
Carbamazepine*
Valproic acid*
Phenobarbital
Primidone
Lamotrigine
Topiramate

Front 25

What are the characteristics of generalized status epilepticus?

Back 25

Series of tonic-clonic seizures so closely spaced that consciousness is not regained between seizures

Front 26

What are the therapeutic agents for generalized status epilepticus?

Back 26

Diazepam*
Lorazepam*
Phenytoin*
Phenobarbitol*

Front 27

What are the uses of phenobarbital?

Back 27

i. Tonic-clonic and cortical focal, often concurrently with phenytoin, status epilepticus (IV).
ii. Agent of first choice for young children (less than 5 years)

Front 28

What is the cellular mechanism of action for phenobarbital?

Back 28

Possibly be reducing high-frequency firing and enhancing GABAergic inhibition

Front 29

Describe the uptake of phenobarbital

Back 29

i. Absorbed well from gut
ii. Half bound to plasma proteins

Front 30

Describe elimination of phenobarbital

Back 30

i. Up to 25% by renal excretion, remainder by hepatic (enzymatic) inactivation.
ii. Induces hepatic microsomal enzymes.
iii. Concurrently administered valproate causes phenobarbital plasma concentration to rise.
iv. t1/2 ~ 90 hrs

Front 31

What are the side effects of phenobarbital?

Back 31

Sedation
Fatigue
Tolerance to these as well as anticonvulsants effects may develop

Front 32

What are the uses of phenytoin?

Back 32

i. Primary agent in treatment of tonic-clonic, cortical focal and psychomotor seizures, especially for patients over the age of 5.
ii. Preferred for psychomotor seizures, especially if there are associated tonic-clonic seizures.
iii. Status epilepticus (IV)

Front 33

What is the cellular mechanism of action for phenytoin?

Back 33

Reduces high-frequency firing by increasing Na+ inactivation

Front 34

Explain the uptake of phenytoin

Back 34

i. Absorbed slowly from the guy
ii. 90% in plasma bound to protein, mainly albumin

Front 35

Explain the elimination of phenytoin

Back 35

i. Almost all phenytoin inactivated by hepatic enzymes.
ii. Dose-dependent elimination:
- first order at low to moderate plasma concentrations, zero order at higher concentrations.
- at higher concentrations, t1/2 increases as concentration increases, so on regular dosing regimen, plateau plasma concentration increases more than would be expected as dose increases.
iii. Elimination also affected by several drugs when administered concurrently.

Front 36

What are the side effects of phenytoin?

Back 36

Sedation (much less than phenobarbital)
Ataxia
Nystagmus
Nausea
Gingival hyperplasia (especially in children)
Hirsutism

Front 37

Describe the structure of carbamazepine

Back 37

Unrelated to barbiturates, related to tricyclic antidepressants

Front 38

What is the cellular mechanism of action for carbamazepine?

Back 38

Possibly by reducing high-frequency firing by increasing sodium inactivation.

Front 39

What are the uses of carbamazepine?

Back 39

i. For psychomotor, tonic-clonic and cortical focal seizures.
ii. Often preferred over phenytoin for children and young women because it does not cause gingival hyperplasia or hirsutism.

Front 40

What are the side effects of carbamazepine?

Back 40

i. Sedation, vertigo, etc.
ii. Possibility of serious liver and bone marrow problems

Front 41

Describe tiagabine

Back 41

i. Inhibits neuronal and glial uptake of GABA
ii. Partial seizures, especially complex

Front 42

Describe gabapentin and pregabalin

Back 42

i. They are GABA analogs, but the mechanism of action is uncertain
ii. Partial seizures

Front 43

Describe lamotrigine

Back 43

It is for partial and tonic-clonic seizures

Front 44

Describe topiramate

Back 44

i. Inhibitor of carbonic anhydrase - this may affect GABAergic transmission.
ii. Partial and tonic-clonic seizures

Front 45

Describe the use of new drugs

Back 45

New drugs currently used mainly as add-ons

Front 46

Describe the uses, cellular mechanism of action, uptake, elimination, and side effects of Ethosuximide

Back 46

a. Uses
Preferred agent for absences.
b. Cellular mechanism of action
Reduces slow frequency, pacemaker-driven repetitive firing by blocking Ca++ T channels.
c. Uptake
From gut.
d. Elimination
Most metabolized in liver to inactive compound.
e. Side effects
Nausea, lethargy, ataxia; serious side effects unlikely.

Front 47

Describe the uses, uptake, elimination and side effects of Valproate

Back 47

a. Uses
i. Absences
ii. Tonic-clonic
iii. Cortical focal
b. Uptake
Rapid from the gut.
c. Elimination
i. Short t.
1/2ii. Most metabolized by liver.
d. Side effects
Less likely than with other drugs.

Front 48

What are the benzodiazepines?

Back 48

Clonazepam
Diazepam
Lorazepam

Front 49

Describe clonazepam

Back 49

Benzodiazepine
i. Used to suppress absence seizures
ii. Substantial tolerance to anti-seizure activity often develops; also can cause hyperactivity and restlessness in children, so is not an agent of choice.

Front 50

Describe diazepam and lorzepam

Back 50

Benzodiazepines
i. Used for status epilepticus
ii. Administered intravenously

Front 51

What are the principles of treatment with barbituates and and anti-epileptic drugs?

Back 51

1. Start and stop treatment gradually
2. Monitor plasma concentration of drug when starting treatment
3. Use multi-drug therapy only when monotherapy is clearly insufficient

Front 52

Describe the use of anti-epileptic drugs (AEDs) for conditions other than epilepsy

Back 52

1. many prescriptions of AEDs are not for epilepsy
2. Most common uses are for neuropathic pain (phenytoin, carbamazepine, gabapentin, pregabalin) and migraine (valproate); may be some commonality in etiologies of these and seizures
3. Also used to treat numerous movement disorders (e.g. essential tremor) and trigeminal neuralgia (carbamazepine).
4. AEDs also effective for psychiatric disorders (e.g. bipolar disorder and schizophrenia), though reasons for effectiveness unclear