Pharmacology - Cns

Front 1

Drugs used in Alzheimer's disease - organization and members

Back 1

1. Cholinesterase inhibitors
I. Donepezil (Drug of choice)
II. Galantamine
(Agonist activity at nicotinic receptors to enhance release of Ach)
III. Rivastigmine
(Cholinergic GI side effects)
IV. Tacrine
(Oldest, hepatotoxicity, 4x\day)

(These are selected for their selectivity to the brain enzyme. Used in mild-to-moderate disease)

2. NMDA antagonist (subset of Glu receptor)
I. Nemantine

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Front 2

NMDA receptor
a. Full name
b. What, involved in
c. Implicated in
d. Name a antagonist and describe its mechanism of action

Back 2

a. N-methyl-D-aspartate.

b. A type of glutamate receptor that participates in excitatory neurotransmission and also allows Ca influx. Learning and memory.

c. Excitotoxicity in the presence of excess glutamate. Associated with Alzheimer's and Huntington's disease.

d. Memantine
Low affinity blocker -> block excess Ca influx, but cannot block the physiologic actions of Glu involved in learning.
(Used for Alzheimer's in combination with cholinesterase inhibitors.)

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Front 3

CNS
a. Tolerance
b. Dependence

Back 3

a. Tolerance
A physiologic state characterized by a reduced drug effect with repeated use of the drug.
(Higher doses are needed to produce the same effect.)

b. Dependence
Characterized by signs and symptoms of withdrawal when drug levels fall. Can by physical or psychologic.

(Can have cross-tolerance and cross-dependence to different related drugs.)

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Front 4

Anxiolytics\Hypnotics\Sedative-Hypnotics
a. Organization of classes
b. Which of the drugs have cross-tolerance and cross-dependence, what other agent do they also have cross- tolerance and dependence with

Back 4

a.
1. Barbiturates
(Phenobarbital, Thiopental)
(No longer used to treat anxiety)
2. Benzodiazepines
(Alprazolam, chlordiazepoxide)
3. Others
I. Buspirone
II. Chloral hydrate
III. Eszopiclone
IV. Zaleplon
V. Zolpidem

(All reduce anxiety at low doses and produce sedation at slightly higher doses, most also induce sleep (hypnosis) (-> 'sedative-hypnotics'. Barbiturates continue to cause anesthesia, medullary depression, and death.)

b. Cross-tolerance and cross-dependence occur between all of the CNS sedatives - the barbiturates, benzodiazepines (BZDs). Ethanol.

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Front 5

Barbiturates
a. Common ending
b. Members (6)
c. Mechanism
d. Effect according to increasing dosage (6)

Back 5

a. Most end in -barbital, all end in -tal.

b.
1. Phenobarbital
2. Thiopental
3. Amobarbital
4. Methohexital
5. Pentobarbital
6. Secobarbital

c. Enhance GABAergic transmission.
(Enhance GABA response and act as agonist)

d.
1. Anxolytic
2. Sedative
3. Hypnotic
4. Anesthetic
5. Suppress respiration
(Inhibit the hypoxic and hypercapnic responses of the chemoreceptors)
6. Death

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Front 6

Benzodiazepines (BZDs)
a. Common ending
b. Members

Back 6

a. Most end in -pam\-lam
(Except chlordiazepoxide).

b.
1. Alprazolam
2. Chlordiazepoxide
3. Diazepam
4. Lorazepam
5. Clonazepam

Front 7

Barbiturates
a. Effect on the cytochrome P-450 system
b. Which is used for anesthesia, why
c. Which is used for epilepsy, why
d. What are the withdrawal symptoms (4)

Back 7

a. Induce.

b. Thiopental and methohexital. Due to their very low half life.
(High lipid solubility -> rapidly enters the brain due to its high perfusion rate and exerts its effect -> 'eliminated'\half-life from redistribution into peripheral fatty tissue)

c. Phenobarbital, long half-life.
(Low lipid solubility)

d.
1. Nausea and vomiting
2. Anxiety and psychosis
3. Seizures
4. Hypotension and cardiovascular collapse

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Front 8

Anesthesia
a. General definition
b. Describe the three types

Back 8

a. Loss of awareness or feeling.

a.
1. General - hypnotic
2. Local - causes loss of feeling in a part of the body such as a tooth or an area of skin without affecting consciousness.
3. Regional - --||-- for a region (lower extremities)

(medterms.com)

Front 9

Benzodiazepines
a. Mechanism
b. Effect - which (4), how do they vary from barbiturates
c. Withdrawal symptoms (3)
d. What is used in benzodiazepine overdoses
e. Which agent is used in the treatment of status epilepticus
f. Which agent is used in the treatment of alcohol withdrawal
G. Most commonly used benzodiazepine for anxiety

Back 9

a. Potentiate GABA A receptors by binding to a regulatory site.

b. Effects
1. Anxiolytic
2. Sedative
3. Anticonvulsant
4. Induce general anesthesia\Hypnotic

In contrast to barbiturates, they are anxiolytic in a concentration that don't produce sedation.

c. Psychological
1. Confusion
2. Agitation
3. Restlessness & anxiety

d. Flumazenil
(A competitive inhibitor)

e. Diazepam and lorazepam.

f. Chlordiazepoxide
(Alcohol also potentiate GABA)

g. Alprazolam.

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Front 10

Other anxiolytics - list the mechanism and functions of buspirone eszopiclone, zaleplon, and zolpidem

Back 10

I. Buspirone - non-BZD, agonist at 5-HT1A, 5-HT2A, and D2 receptors, treat generalized anxiety disorder

II. Zolpidem, zaleplon, eszopiclone
Structurally not BZDs
Act on GABA complex
Short-term treatment of insomnia

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Front 11

Antidepressants
a. All of the drugs in this group ....
b. What is the four groups, and what are the reason for their names
c. Which group are most widely prescribed

Back 11

a. Increase the concentration of norepinephrine or serotonin in the synaptic cleft.

b.
1. Selective serotonin reuptake inhibitors
(fluoxetine, citalopram, fluvoxamine, paroxetine, sertraline, escitalopram, reboxetine)

2. MAO inhibitors
(isocarboxazid, phenelzine, tranylcypromine)

3. Heterocyclics - tricyclic compounds, similar structure
(Also have similar actions and side effects)
(Desipramine, imipramine, amitriptyline, doxepin, maprotiline, nortriptyline)

4. Others
(Bupropion, mirtazapine, nefazodone, trazodone, venlafaxine, duloxetine)

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Front 12

SSRIs
a. Efficient for (4)
b. Effect on cholinergic or adrenergic receptors
c. Members (7)

Back 12

a.
1. Depression
2. Eating disorders
3. Panic disorderrs
3. OCD
4. Borderline personality disorder

b. None

(Atomoxetine, a selective norepinephrine reuptake inhibitor is used to treat ADHD)

c.
1. Fluoxetine
2. Citalopram
3. Fluvoxamine
4. Paroxetine
5. Sertraline
6. Escitalopram
7. Reboxetine

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Front 13

Heterocyclics
a. Members (6)
b. Mechanism
c. General side effect profile - which receptors do they work on (3)
d. Dangerous side effects at overdoses

Back 13

a.
1. Desipramine
2. Imipramine
3. Amitriptyline
4. Doxepin
5. Maprotiline
6. Nortriptyline
(Most are tricyclics)

c.
1. Potent muscarinic cholinergic antagonists
(Xerostomia, constipation, urinary retention, blurred vision)
2. Weak alpha-1 antagonists
3. Weak H1 antagonists
(Intestinal and bronchial smooth muscle, sedation)

d. Psychosis, delirium, and fatal arrhythmias

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b. Block the reuptake of biogenic amines - norepinephrine, serotonin

c.

Front 14

MAO inhibitors
a. Members (3)
b. Mechanism
c. Side effects

Back 14

a.
1. Isocarboxazid
2. Phenelzine
3. Tranycypromine
(This group is rarely used anymore)

b. Increase levels of NE, serotonin, and dopamine by inhibiting their degradation via irreversible inhibition of both MAO A and B.
(It appears that the antidepressant effect is due to inhibition of MAO-A)

c.
1. Fatal hypertensive crisis
2. Cardiac arrhythmias
(Should not eat food rich in tyramine (cheese, beer, red wine). The degradation in the stomach by MAO is inhibited -> absorbed tyramine cause release of NE -> #1,2)

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Front 15

Function of the other antidepressants - bupropion, mirtazapine, nefazodone, trazodone, venlafaxine, and duloxetine

Back 15

I. Venlafaxine, Sibutramine
Block reuptake of serotonin, NE, and dopamine.
(Venlafaxine - can cause hypertension (acts on NE and dopamine)
(Sibutramine is used as a weight-loss agent. 5-HT enhance satiety, NE reuptake inhibition increase metabolic rate)

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II. Duloxetine, Nefazodone
Serotonin and NE reuptake inhibitor
(Nefazodone also antagonizes 5-HT2 and alpha-1 receptors)

III. Trazodone is a sdeative

IV. Bupropion
Uncertain mechanism, structurally unrelated to the others
(Effective, used for smoking cessation programs, few side effects)

V. Mirtazapine
Antagonize central presynaptic alpha-2 receptors -> increased release of NE and serotonin
(Also 5-HT1A agonistic effect)

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Front 16

Bipolar disorder
a. What is the main goal in pharmacological treatment
b. Members
c. Adverse effects of lithium

Back 16

a. To reduce the frequency and severity of fluctuations in mood.

b.
1. Lithium
(Standard treatment)
2. Carbamazepine
3. Valproate
(2 and 3 is anticonvulsants)

c.
1. Low therapeutic index
2. Hypothyroidism
3. Nephrogenic diabetes insipidus

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Front 17

Antipsychotics
a. Synonyms (3)
b. Effects common to all the members (3)
c. Groups and the most common members

Back 17

a. Neuroleptics, antischizophrenics, major tranquilizers.

b.
1. Alpha-blockade
2. Muscarinic antagonists
3. Histamine H1 antagonists

c.
Typical\First generation neuroleptics
1. Chlorpromazine
2. Haloperidol
3. Acetophenazine
4. Fluphenazine
(Most end in -azine)

Atypical\Second generation\5-HT-DA antagonists
1. Clozapine
2. Loxapine
3. Olanzapine
4. Quetiapine
(Also block 5-HT2A receptors)

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Front 18

Typical\First generation antipsychotics
a. Mechanism, what part in particular is supposed to cause the antipsychotic effect
b. Effects (2)
c. Side effects (3)

Back 18

a. Antagonize
1. Dopamine - most linked to antipsychotic effect
2. Muscarinic cholinergic
3. Alpha-adrenergic
4. H1-histaminergic

b.
1. Antipsychotic - most linked to dopamine antagonism
2. antiemetic - block D2 receptors of the chemoreceptor trigger zone in the medulla

c.
1. Galactorrhea <- ↑PRL <- ↓Dopamine
2. Extrapyramidal effects
I. Parkinsonism
(Rigidity, tremor, shuffling gait)
II. Akathisia (a-, kathisis - sitting)
(Motor restlessness)
III. Tardive dyskinesia
(Stereotyped involuntary movements - lip smacking, jaw movements, darting of the tongue)
IV. Acute dystonia
(Spasm of the muscles of the face, tongue, neck, and back)
(From dopamine blockade in the mesostriatal pathway)
(All these are irreversible and can arise during or after therapy)
(Drugs with anticholinergic actions cause fewer extrapyramidal effects because the dopamine-acetylcholine balance in the motor system is less affected. Remember Parkinson's is treated with cholinergics)
3. Anticholinergic side effects
(Tend to be inversely related to the potency of the drug
4. Neuroleptic malignant syndrome
(Potentially fatal. Resemble a very severe form of parkinsonism with catatonia, autonomic instability, and sutopr. 10-20% mortality, can persist for more than a week after suspension of the drug. Most common with high doses of the more potent agents)

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Front 19

Second generation\Atypical neuroleptics
a. Members
b. Characteristic mechanism for this class, effect
c. Side effect
d. What is the drug of choice for new onset schizophrenia

Back 19

a. Members
1. Clozapine
2. Risperidone
3. Loxapine

b. Antagonist at dopamine and 5-HT 2A receptors -> reduce both positive (hallucinations, delusions, disordered thought, agitation) and negative (withdrawal, flat affect, anhedonia, catatonia) symptoms of schizophrenia

c. As with typical antipsychotics, in addition clozapine can cause fatal agranulocytosis.

d. Risperidone.

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Front 20

Parkinson's disease
a. General pathological mechanism
b. General strategies for pharmacological therapy for Parkinson's disease
c. Why is not dopamine used, how do we overcome this

Back 20

a. Loss of Doapminergic neurons in substantia nigra.
These normally project to the striatum (caudate, putamen) where DA inhibits firing of its cholinergic neurons.
These cholinergic neurons form excitatory synpases onto other neurons that project out of the basal ganglia.
(= LOSS of inhibition -> increased cholinergic excitation.)

b. General strategies for pharmacological therapy of Parkinson's disease
1. DA replacement therapy
2. DA agonist therapy ('mimics')
3. Anticholinergic therapy

c. It don't cross the BBB.
-> Give levodopa\L-Dopa which is a metabolic precursor that can cross the BBB.
Levodopa is activated by dopamine decarboxylase. To prevent excess buildup of DA in the periphery, we give levodopa with carbidopa, a DA decarboxylase inhibitor that don't cross the BBB.

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Front 21

Drugs used in Parkinson's disease
a. DA replacement therapy - list the drugs used that inhibit DA breakdown and their characteristics
b. Amantadine - effect, also used for
c. Dopamine agonists - list the members according to ergotamine derivates and non-ergotamines
d. Anticholinergic therapy - drugs used

Back 21

a.
1. COMT inhibitors
I. entecapone, Tolcapone
II. Prolong the half-life of l-dopa

2. MAO-B inhibitor
I. Selegiline\Deprenyl
II. The enzyme that metabolize DA in the CNS

b. Amantadine
I. Appear to enhance the synthesis, release, or reuptake of DA from the surviving nigral neurons.
II. Antiviral for influenza.

c. Dopamine agonists
Ergotamine derivatives
1. Bromocriptine
2. Pergolide

Non-ergotamines
1. pramipexole
2. Ropinirole
(The main role of these drugs is in combination with L-dopa and carbidopa in early Parkinson's disease)

d. Anticholinergics
Muscarinic antagonist which only differ in potency
1. Trihexyphenidyl
2. Benztropine
3. Biperiden
(-> Anticholinergics - dry mouth, constipation, urinary retention, confusion..)

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Front 22

Epilepsy
a. Partial (Focal\Local) simple seizures - clinical manifestations, drugs of choice
b. Partial complex seizures - clinical manifestations, drugs of choice
c. Partial seizures with secondary generalizations - drugs of choice
d. Generalized convulsive seizures - synonyms, clinical manifestations, drugs of choice

e. Generalized nonconvulsive seizures - synonyms, clinical manifestations, drugs of choice

Back 22

a. Partial simple seizures
I. Focal motor\sensory\speech disturbance without impairment in consciousness.
II. Carbamazepine, Phenytoin

b. Partial complex
I. Dreamy state with automatisms and impaired consciousness
(Automatisms - stereotyped psychic, sensory, or motor phenomena carried out in a state of impaired consciousness of which the individual usually has no knowledge)
II. Carbamazepine, Phenytoin

c. Partial seizures with secondary generalizations - carbamazepine, phenytoin

d. Generalized convulsive\Tonic-Clonic\Grand mal seizures
I. LOC, Falling, rigid extension of trunk and limbs, clonus
II. Valproate, Carbamazepine

e. Generalized nonconvulsive\Absence\Petit mal seizures
I. Impaired consciousness with staring and eye blinksk.
II. Ethosuximide, Valproate
(Clonazepam is an alternative, benzodiazepine, develop tolerance)

(All the drugs are metabolized by the liver (<- need to be lipid soluble to cross CNS), and all except ethosuximide are highly protein bound)

(Phenobarbital is an alternative for generalized convulsive and partial seizures. Barbiturate -> sedative, induce liver enzymes. Primidone is metabolized to phenobarbital and PEMA (phenylethylmalonamide)

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Front 23

Antiepileptic drugs
a. Carbamazepine - indications, characteristics
b. Phenytoin - indications, characteristics

Back 23

a. Carbamazepine
I. Partial - simple, complex, secondarily generalized and generalized convulsive seizures.
II. Cause autoinduction of its own metabolism.
III. Associated with granulocyte suppression and aplastic anemia.

b. Phenytoin
I. Partial seizures - simple, complex, with secondary generalization
II. Zero-order kinetics
(Ie metabolize 5 mg\hour, not 0.05 fraction per hour)
(In therapeutic range)
III. Cause ataxia and nystagmus at high doses
IV. Associated with masculinization - hirsutism, coarsening of facial features, gingival hyperplasia
V. Thought to act by blocking the sodium channel in the inactivated state
(Fosphenytoin is a soluble prodrug for phenytoin)

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Front 24

Antiepileptics
a. Ethosuximide - indications, characteristics
b. Valproate - indications, characteristics

Back 24

a. Ethosuximide
I. Generalized nonconvulsive seizures.
II. Associated with stomachaches, vomiting, and hiccups.
III. Thought to act by calcium channels in thalamus.

b. Valproate
I. Generalized seizures - convulsive and nonconvulsive
II. Can produce tremor
III. Elevated liver enzymes, N&V
(Can progress to fatal hepatic failure, most common when < 2 years and taking more than one antiepileptic drug)
IV. Can cause weight gain

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Front 25

Narcotics\Opiates
a. Effect of opiates on pain
b. Which receptors do they add on
c. The 3 group division

Back 25

a. Don't eliminate pain, but the patient is not as bothered by it - change perception of it.

b. Opioid receptors
1. Mu - most of the actions of the narcotic analgesics are mediated by this
2. Kappa
3. Delta

c. 3 groups
1. Agonists
(Morphine as prototype)
(Codeine, Fentanyl, Heroin, Meperidine, methadone, Hydrocodone, Oxycodone)

2. Mixed agonist-antagonists
(Pentazocine, buprenorphine, butorphanol)

3. Antagonists
(Naloxone, naltrexone, nalmefene)

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Front 26

Narcotics\Opiates - actions
a. CNS
b. Eye
c. Respiratory
d. Cardiovascular
e. GI
f. GU (Genitourinary)

Back 26

a. CNS
1. Analgesia
2. Drowsiness and sedation
3. Nausea
(More often in ambulatory patients, direct stimulation of the chemoreceptor trigger zone in the medulla oblongata and an increase in vestibular sensitivity)
4. Cough suppression
(Codeine as drug-of-choice)

b. Eye
1. Pinpoint pupils
(Direct action on Edinger-Westphal nucleus)

c. Respiratory
1. Respiratory depression
I. Rate
II. Minute volume
III. The hypoxic drive for breathing
(Through a direct actionon the CNS)

d. Cardiovascular - essentially no effects

e. GI
1. Increase the resting tone of the smooth muscle of the entire GI tract ->
I. Spasm (pain)
II. Constipation
(Also spasm of the smooth muscle in the biliary tract)

f. GU (Genitourinary)
--||-- -> Urinary retention.

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Front 27

Narcotics\Opiates
a. Withdrawal symptoms in a dependent person
b. Codeine - indications, characteristics
c. Heroin - indications, characteristics
d. Meperidine - indications, characteristics

Back 27

a. Withdrawal symptoms
1. Autonomic hyperactivity ->
I. Diarrhea
II. Vomiting
III. Chills, fever
IV. Tearing
V. Runny nose
VI. Abdominal cramps

2. Tremor
3. Pain

b. Codeine
I. Cough suppression, analgesia
II. Much less potent than morphine

c. Heroin
I. None
II. Hydrolyzed to morphine. More lipid-soluble -> rapidly cross BBB.

d. Meperidine
I. Analgesia, obstetrics
(Unlike morphine, meperidine produce no more respiratory depression in the fetus than in the mother)
II. Less potent and less spasmogenic than morphine
III. No cough suppression

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Front 28

Narcotics\Opiates
a. Diphenoxylate, Loperamide - indications, characteristics
b. Fentanyl - indications, characteristics
c. Methadone - indications, characteristics

Back 28

a. Diphenoxylate, Loperamide
I. Vs diarrhea
II. Very poor absorption -> work locally in the GIT

b. Fentanyl
I. Used by anesthesiologists for analgesia
II. 80 x as potent as morphine

c. Methadone
I. Opiate withdrawal
II. High oral absorption
III. Longer duration of action than morphine

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Front 29

Pentacozine
a. Pharmacodynamic

Back 29

a. Agonist at Kappa receptor (->Analgesic effect) and antagonist at mu receptor (-> acute withdrawal in patients who have received regular doses of morphine or other agonists)

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Front 30

General anesthetics
a. General anesthesia
b. Structural characteristics of most of the inhaled drugs
c. Inhalational drugs (7)
d. How is the solubility expressed
e. For a inhalational gas with high solubility, how is the rate at which the brain partial pressure approaches the arterial partial pressure

Back 30

a. Absence of perception of all sensations associated with LOC, produced by inhalational or IV anesthetic agents
(Induction of anesthesia - The administration of a drug or combination of drugs at the beginning of an anesthetic that results in a state of general anesthesia.)

b. Structural characteristics of most of the inhaled drugs
I. Very simple
II. Presence of halide ions (F, Cl, Br)

c. Inhalational drugs - anes (except NO)
1. Enflurane
2. Desflurane
3. Isoflurane
4. Nitrous oxide
5. Methoxyflurane
6. Sevoflurane
7. Desflurane

d. By the blood:gas partition coefficient
(Repsents the ratio of anesthetic concentration in blood to the concentration in the gas phase, NO is quite insoluble)

e. Slow
(The potential reservoir in the blood for relatively soluble gases is large and will be filled more slowly. Therefore, for soluble gases the rate at which the tension\partail pressure in the arterial blood approaches the inspired partial pressure is slow.)
(-> The speed of onset of anesthesia is inversely related to the solubility of the gas in blood)

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Front 31

Inhalational anesthetics
a. Metabolism
b. Minimum alveolar concentration (MAC)

Back 31

a. Most are not metabolized and are eliminated unchanged in the exhaled gas.
(Of those who are metabolized, ie methoxyflurane, it has been suggested that the production of a toxic metabolites (ie fluoride ions) is responsible for most of the hepatic and renal toxicities observed with these agents)

b. MAC
I. The alveolar concentration at 1 ATM that produces immobility in 50% of patients exposed to a painful stimulus.
(Its usually expressed as the percentage of gas in the mixture required to achieve immobility in 50% of patients exposed to a painful stimulus)

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Front 32

General anesthetics
a. IV drugs (4)

Back 32

a. IV drugs
1. Propofol
(A hypnotic with rapid onset and short duration of action; used intravenously for induction and maintenance of general anesthesia.)

2. Thiopental
(An ultra–short-acting barbiturate administered intravenously or rectally for induction of anesthesia.)
(Other barbiturates such as methohexital can also be used)

3. Etomidate
(IV hypnotic)

4. Ketamine
(A parenterally administered anesthetic that produces catatonia, profound analgesia, increased sympathetic activity, and little relaxation of skeletal muscles; side effects include sialorrhea and occasional pronounced dysphoria, especially in adults; chemically related to phencyclidine (PCP), it can produce hallucinations.)

Front 33

Local anesthetics
a. In which order are the nerve fibers effected
b. General structure
c. Main difference of ester and amide local anesthetics
d. Common ending
e. Esters
f. Amides

Back 33

a.
1. Sympathetic function
2. Loss of pinprick sensation and temperature
3. Motor function
(Inverse correlation with degree of myelinization)

b. Hydrophilic amino group - connecting group of variable length which is amide or ester - lipophilic aromatic portion (benzene ring)

c. The amide local anesthetics are chemically stable in vivo, whereas the esters are rapidly hydrolyzed by plasma cholinesterase.
(Metabolism of the esters lead to formation of paraaminobenzoic acid (PABA) which is thought to be allergenic)

d. -caine

e. Esters
1. Cocaine
2. Procaine
3. Benzocaine
4. Tetracaine

f. Amides
1. Lidocaine
2. Bupivacaine
3. Etidocaine
4. Mepivacaine

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Front 34

Local anesthetics
a. Adverse effects
b. Mechanism

Back 34

a. Absorption of toxic amounts can cause medullary depression ->
I. Respiratory failure
II. Hypotension
III. Cardiovascular collapse
(-->-->Death)

b. Block the sodium channel in the nerve membrane ->
I. Elevation of the threshold for electrical excitation
II. Reduction in the rate of rise of the action potential
III. Slowing the propagation of the impulse

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