Pharmacology Ii Test 1

Front 1

What is sedative anesthesia?

Back 1

for patients who do not need to be anesthetized completely during a procedure

Front 2

What is local or regional anesthesia?

Back 2

allows patients to be awake during a surgical procedure

Front 3

What is general anesthesia?

Back 3

- drugs that act reversibly on the CNS to produce immobility despite noxious stimulation and amnesia
- Surgery requires immobility, and most patients desire amnesia for the surgical experience.

- Other clinically effects of general anesthetic agents include unconsciousness, analgesia, suppression of autonomic reflexes (e.g., the increases in blood pressure and heart rate that can occur during surgery), and muscle relaxation.

Front 4

What is stage 1 of anesthesia?

Back 4

-Analgesia without amnesia, impaired judgement, vertigo/ataxia, increased respiration, blood pressure, heart rate

Front 5

What is stage 2 of anesthesia?

Back 5

-excitement
-Delirious, excited, amnesic. Irregular respirations, struggling, retching and vomiting

Front 6

What is stage 3 of anesthesia?

Back 6

-surgical
-Recurrence of regular respiration --> cessation, Loss of corneal, swallowing, eyelid reflexes, Skeletal muscle relaxation, Decreased blood pressure

Front 7

What is stage 4 of anesthesia?

Back 7

-medullary depression
-Begins at cessation of spontaneous respiration --> severe depression of vasomotor and respiratory centers-->without support = Death

Front 8

What are the 4 A's of anesthesia?

Back 8

-Amnesia (with loss of consciousness)
-Analgesia
-Akinesia (skeletal muscle relaxation)
-Autonomic and sensory reflex blockade

Front 9

What are mechanisms of anesthesic action? Administration?

Back 9

-all about excitable membranes
-effect dependent on membrane depolarization
-anesthesia designed around deecreasing membrane reactivity
-to createa reversbile state characterized by loss of consciousness and pain sensation
-administered by inhalation or intravenously

Front 10

What are inhaled anesthetics? Examples?

Back 10

Inhaled anesthetic substances are either volatile liquids or gases and are usually delivered using an anesthesia machine.
-includes nitrous oxide, desflurane,halothane, isoflurane, sevoflurane
-halothane is a prototype

Front 11

What is minimal alveolar concentration? How is it affected?

Back 11

-the concentration of anesthetic agent that renders 50% of patients immobile during surgery.
-a direct measure of the potency of a drug
-MAC is influenced by the age and physiologic state of the patient and by the presence of other pharmacologic agents. In fact, although nitrous oxide produces only weak anesthetic effects, it is widely used adjunctively for its "second
gas" effect to enhance coadministered anesthetic agents.
-MAC decreases with age and peaks with infants
-Increases in MAC result from hyperthermia and hypernatremia.
-Decreases in MAC can result from hypothermia, hyponatremia, pregnancy, hypotension, and drugs such as lithium, lidocaine, opioids, and a2 agonists.

Front 12

What is the blood:gas coefficient?

Back 12

-describes an anesthetic’s relative affinity for the blood compared to air
-#molecules in blood/# molecules in gas at SS
Agents with low solubility require relatively few molecules to dissolve into the blood to raise partial pressure to equilibrium (opposite for highly soluble agents)

Front 13

What is nitrous oxide as a general anesthetic?

Back 13

- high MAC (i.e., low potency) limits the usefulness

Front 14

What is sevoflurane as a general anesthetic?

Back 14

intermediate solubility in blood and tissues, does not cause respiratory irritation, circulatory stimulation, or hepatotoxicity. It is particularly useful for the induction of anesthesia, and it is environmentally friendly. Associated with nephrotoxicity from physical degradation, seizures, and postoperative agitation.

Front 15

What is isoflurane as a general anesthetic?

Back 15

relatively high solubility in blood and tissues, associated with an intermediate risk for respiratory irritation (between that of sevoflurane and desflurane), circulatory stimulation, and hepatotoxicity. It does not cause seizures. Isoflurane has a minimal effect on the ozone layer

Front 16

What is desflurane as a general anesthetic?

Back 16

has a lower solubility in blood and tissues (i.e., it allows the most rapid recovery). It is associated with essentially no risk for hepatotoxicity. Desflurane is not associated with seizures, and it is environmentally friendly. However, desflurane is associated with a higher risk of respiratory irritation and circulatory stimulation than the other agents.

Front 17

What are intravenous anesthetics? Mechanism of action?

Back 17

-Include etomidate, midazolam, propofol, thiopental, methohexital, ketamine, and opioid agonists.
-etomidate, midazolam, propofol, thiopental act by enhancing the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the CNS.
-ketamine antagonizes the effect of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) on NMDA receptors
-opioid agonists stimulate opioid receptors

Front 18

What is thiopental as an intravenous anesthetic?

Back 18

-ultra-short acting barbiturate
most commonly used in the induction phase of general anesthesia
-Following intravenous injection the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds.
-At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. -Thereafter, the drug distributes to the rest of the body and in about 5–10 minutes the concentration is low enough in the brain such that consciousness returns.

Front 19

What is methohexital as an intravenous anesthetic?

Back 19

-a barbiturate derivative
primarily used to induce anesthesia, and is generally provided as a sodium salt (i.e. methohexital sodium).
-It is only used in hospital or ambulatory care settings, under strict supervision.
-short-acting, and has a rapid onset of action
-similar in its effects to sodium thiopental
-Metabolism is primarily hepatic via demethylation and oxidation. -Side-chain oxidation is the primary means of metabolism involved in the termination of the drug's biological activity.
-Protein binding is approximately 73% for methohexital.

Front 20

What is propofol as an intravenous anesthetic?

Back 20

-Phenol derivative
-precise mechanism of action is currently unknown, is thought to work through GABA receptors
has a fast onset of action and a fast recovery time with less of a "hangover" effect than that of barbiturates. (**advantage for outpatient surgeries because it allows patients to be discharged rapidly)
-is highly lipophilic and distributes rapidly into the CNS and other tissues, which accounts for its rapid onset of action
amnesic and antiemetic (**advantage for patients at risk of postoperative nausea and vomiting) properties
-least residual sedation
-produces unconsciousness within the time it takes for the drug to travel from the injection site to the brain
-onset of anesthesia is smooth, although the drug can cause pain at the injection site
Effects similar to barbiturates
rapidly and extensively metabolized in the liver and at extrahepatic sites, which means it has a high rate of total body clearance.
-euphorigenic, but does not have residual psychotic effects as does ketamine
-propofol emulsion contains egg phospholipids and is contraindicated in patients with known hypersensitivity This white emulsion is facetiously termed "milk of amnesia

Front 21

What is ketamine as an intravenous anesthetic?

Back 21

-Unlike the parenteral agents that stimulate GABA receptors,
ketamine is a dissociative anesthetic that binds to the "PCP“
binding site on the N-methyl-D aspartate (NMDA-type)
glutamate receptor.
-Ketamine blocks (antagonizes) this stimulatory ion channel
receptor. Ketamine is a version of Phencyclidine (PCP;
"angel dust") and can elicit delirium (hallucinations) and vivid
dreams during recovery.
-It also has a strong amnesic effect.
-Ketamine causes less respiratory depression than do other
general anesthetics and stimulates heart rate, blood pressure,
and cardiac output by sympathomimetic actions. These
properties are useful inpatients at risk for hypotension but not
for the patient at risk of myocardial infarction.
-Ketamine also is advantageous because of its inherent
analgesic properties.
-NMDA receptor antagonist, and at high, fully anesthetic
level doses, ketamine has also been found to bind to opioid
mu receptors and sigma receptors
like other pharmaceuticals of this type, ketamine is used
illicitly as a recreational drug. -Ketamine has significant abuse
Liability and is sometimes abused at "rave“ clubs.
-Ketamine is frequently used for its anesthetic and analgesic
effects on dogs, cats, rabbits, and other small animals.

Front 22

What is etomidate as an intravenous anesthetic?

Back 22

-etomidate, like propofol, has a rapid onset and
short duration; however, it increases blood pressure,
making it useful for patients at risk for hypotension.
-In the operating room with a stable patient, anesthesiologists may choose an alternative
induction agent, such as propofol, thiopental or methohexital.
-At the typical dose, anesthesia is induced for about 5–10 minutes even though the half-life of drug
metabolism is approximately 75 minutes. This is because etomidate is redistributed from the plasma to other tissues.

Front 23

What are benzodiazepines (midazolam) as an intravenous anesthetic?

Back 23

-Primarily for anxiolytic/amnestic effects
-Preop/intraop sedation
-Uncommonly used as induction agents
-Midazolam = most popular (short t1/2 and water soluble)
-Specific antagonist = Flumazenil

Front 24

What are opioids (Fentanyl, Remifentanil) as intravenous anesthetics?

Back 24

-Main analgesic agents
CV stability allows high dose techniques
-Dose dependent respiratory depression i.e. decreased RR, decreased minute ventilation
-Chest wall rigidity

Front 25

What are muscle relaxants as anesthetics?

Back 25

-Tubocurarine, Atracurium, Vecuronium, Succinylcholine, Pancuronium, and Mivacurium
-Surgical paralysis can be achieved through two approaches: competitive inhibition with NMJ nicotinic receptor antagonists (tubocurarine, atracurium, and vecuronium) or depolarization blockade with succinylcholine. The first approach uses curare derivatives. These paralytic drugs work by competitive antagonism of the NMJ nicotinic receptor. Because of the side effects associated with first-generation drugs, they have largely been replaced by short-acting versions (atracurium and vecuronium).
-The second approach to adjuvant paralysis makes use of succinylcholine. This agent is actually an agonist that leads to depolarization blockade and paralysis. This counterintuitive concept is worthy of brief discussion. Like acetylcholine, succinylcholine binds to the NMJ nicotinic receptor and stimulates muscle contraction. However, unlike acetylcholine, it is not degraded as rapidly and so remains in the synapse and overstimulates the receptor. The NMJ nicotinic receptor is unique in that it is exquisitely sensitive to overstimulation and responds by desensitizing-essentially shutting down as the receptors desensitize. Therefore, the succinylcholine agonist provides a short-term phase I activation of the NMJ that can lead to muscle fasciculations. This is rapidly followed by a phase II desensitization that is characterized by flaccid paralysis. The advantage of this approach is that it is short-acting and readily reversed. This is another example of the importance of receptor theory (receptor desensitzation) having direct clinical relevance.

Front 26

How are spasmolytics uses as anesthetics?

Back 26

-Dantrolene, Diazepam, and Baclofen
-An important aspect of anesthesia involves the need
for spasmolytics-agents to block muscle contraction
directly-in the case of malignant hyperthermia.

Front 27

What is malignant hyperthermia?

Back 27

-Rare, inherited, potentially lethal syndrome
-Characterized by hypermetabolic activity, marked CO2 production, altered skeletal muscle tone and metabolic acidosis
-Triggers = potent inhaled agents and succinylcholine
-Probably altered Calcium metabolism
-Treatment = Dantrolene (Ca++ blocker)

Front 28

What are local anesthetics? Examples?

Back 28

-Local anesthesia is accomplished through the use of such agents as lidocaine, bupivacaine, and cocaine by administration directly to the site where their action is needed.
-They act via direct interactions with voltage-gated Na+ channels that are responsible for action potentials.
-One of their key characteristics is that they are readily ionizable compounds (weak bases) that cross cell membranes in the uncharged state, become protonated (and stuck) inside the cells, and interact with an intracellular component of sodium channels.
-Thus, local anesthetics reversibly block action potentials responsible for nerve conduction.
-While lidocaine and bupivacaine are the two most widely used clinical agents, there are a variety of other local anesthetics with unique characteristics.
-Cocaine remains a commonly used drug for nasal surgery because of its anesthetic and vasoconstrictive effects. -Benzocaine is a protypical over-the-counter local anesthetic that is used for such varied applications as hemorrhoidal itching and oral pain (toothache or teething).

Front 29

What is the mechanism of action of local anesthetics?

Back 29

-reversibly inhibit the propagation of signals along nerves. When it is used on specific nerve pathways, effects such as analgesia (loss of pain sensation) and paralysis (loss of muscle power) can be achieved.

Front 30

What are examples of esters as local anestetics?

Back 30

-benzocaine
-chloroprocaine
-cocaine
-procaine
-tetracaine
-Esters are prone to producing allergic reactions, which may necessitate the use of an Amide. The names of Amides contain an "i" somewhere before the -aine. Esters do not.

Front 31

What are examples of amides as local anestetics?

Back 31

-bupivacaine
-dibucaine
-lidocaine
-mepivacaine
-prilocaine
-ropivacaine

Front 32

What is the chemistry of local anestetics?

Back 32

All local anesthetics are weak bases, classified as tertiary amines. 

Front 33

What is the pathway for the mechanism of action of local anesthetics?

Back 33

-LAs gain access to the receptors from the cytoplasm or membrane. Because the drug molecule must cross the lipid membrane to reach the cytoplasm, the more lipid-soluble (nonionized, uncharged) form reaches effective intracellular
concentrations more rapidly than the ionized form.
-Once inside the axon, the ionized (charged) form of the drug is the more effective blocking entity.

Front 34

What is state dependent blockade of local anesthetics?

Back 34

-Local anesthetic drugs bind more readily to "open" sodium channels, thus onset of neuronal blockade is faster in neurons that are rapidly firing.

Front 35

How does pH affect local anesthetics?

Back 35

-charged (cationic) form binds to receptor site and the uncharged form penetrates membrane, efficacy of drug can be changed by altering extracellular or intracellular pH

Front 36

What is ion trapping of local anesthetics?

Back 36

-Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble.
-At the chemical's pKa the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in an equilibrium but only the unprotonated molecule diffuses readily across cell membranes.
-Once inside the cell the local anesthetic will be in equilibrium, with the formation of the protonated (ionized form), which does not readily pass back out of the cell.
-In the protonated form, the molecule binds to the local anesthetic binding site on the inside of the ion channel near the cytoplasmic end.

Front 37

What is use-dependent blockade eof local anesthetics?

Back 37

-action of local anesthetics is dependent upon Na+ channel activity
-via high affinity binding to inactivated state of channel (very important for antiarrhythmic activity of some LAs)

Front 38

How does the ionized form of local anesthetics block sodium channels?

Back 38

-by binding to an internal sequence to gain access to intracellular face of the Na+ channel, local anesthetics must penetrate the nerve in the un-ionized, or neutral, form; hence, action is strongly dependent upon local pH (alkaline – good; acidic – bad)

Front 39

How do nerve fiber type affect local anesthetics?

Back 39

-small, unmyelinated fibers, such the type C fibers that carry nociceptive signals (pain), are more susceptible to local anesthetic block than are larger fibers.
-Nerves that are of small diameter and very active (having high frequency impulses), such as pain fibers carrying signals from damaged tissue, will be preferentially blocked.

Front 40

How does lipophilicity accect local anesthetic potency?

Back 40

-Lipid solubility appears to be the primary determinant of intrinsic anesthetic potency. Chemical compounds which are highly lipophilic tend to penetrate the nerve membrane more easily, such that less molecules are required for conduction blockade resulting in enhanced potency.

Front 41

What is the affect of protein bindign to local anesthetics?

Back 41

increased binding increases duration of action

Front 42

What is th effect of diffusibility of local anesthetics?

Back 42

increased diffusibility = decreased time of onset

Front 43

What is the effect of vasodilator activity on local aneshtetics?

Back 43

-greater vasodilator activity = decreased potency and decreased duration of action

Front 44

What is local anesthetic toxicity?

Back 44

-While generally safe, local anesthetic agents can be toxic if used in excessive doses or administered improperly. Even when administered properly, patients may still experience unintended reactions to local anesthetics.

Front 45

What are local symptoms and causes of local anesthetic toxicity?

Back 45

-include neurovascular manifestations such as prolonged anesthesia (numbness) and paresthesia (tingling, feeling of "pins and needles", or strange sensations). These are symptoms of localized nerve damage.
-causes include neurotoxicity due to allergenic reaction, damage to the nerve due to excessive fluid pressure, or severing of nerve fibers and support tissue with the needle.
-A cause of local toxicity is allergic reaction to para- aminobenzoic acid (PABA). These reactions range from urticaria to anaphylaxis.

Front 46

What are systemic symptoms and causes of local anesthetic toxicity?

Back 46

-Systemic toxicity of anesthetics involves the central nervous system (CNS), the cardiovascular system, and the immune system. It can be described by the direct effects on the immune system, blood (hematologic), and cardiovascular system.
-Allergic reaction to metabolic break-down of anesthetic agents and preservatives (PABA) can cause anaphylaxis.
-Methemoglobinemia is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis and symptoms of hypoxia. Benzocaine, Lidocaine, and Prilocaine all produce this effect, especially Benzocaine.
-Cardiovascular effects are primarily those of direct myocardial depression and bradycardia, which may lead to cardiovascular collapse.

Front 47

What are topical uses of local anesthetics?

Back 47

-skin and mucosa

Front 48

What are infiltration uss of local anesthetics?

Back 48

-direct injection

Front 49

What are periphreal nerve block uses of local anesthetics?

Back 49

-injected close to nerve trunks (eg. brachial)

Front 50

What are spinal uses of local anesthetics?

Back 50

-injection into subarachnoid space near spinal cord

Front 51

What are epidural uses of local anesthetics?

Back 51

-injection just above dura surrounding spinal

Front 52

What is cocaine as a locla anesthetic?

Back 52

-the first local anesthetic was -Cocaine which was isolated from cocoa leaves
-Treatment for nosebleeds

Front 53

What is lidocaine as a local anesthetic?

Back 53

-along with all other injectable anesthetics used in modern dentistry) is in a broad class of chemicals called amides, and unlike ester based anesthetics, amides are hypoallergenic. It sets quickly and when combined with a small amount of epinephrine (adrenalin), it produces profound anesthesia for several hours. -Lidocaine is still the most widely used local anesthetic in the US.
-Lidocaine-epinephrine-tetracaine (LET) gel is an effective alternative to LET solution to anesthetize a child's face or scalp before suturing an uncomplicated laceration. (COMPOUNDED MEDICATION)

Front 54

What is mepivacaine as a local anesthetic?

Back 54

-much less vasodilative qualities and hence can be used without the epinephrine vasoconstrictor
-advantage is that it can be used more safely in patients who are taking medications which may interact negatively with a vasoconstrictor.  These drugs include certain blood pressure medications (most notably non selective beta blockers) and tricyclic antidepressants. 

Front 55

What is buviacaine as a local anesthetic?

Back 55

-Bupivacaine is used in dental anesthesia mostly by surgeons who want to produce very long acting anesthetic effects in order to delay the post operative pain from their surgery for as long as possible.
-Bupivicaine comes in 0.5% solution with a vasoconstrictor. It is the most toxic of all the anesthetic agents.
- it has a very alkaline (basic) pKa which means that a relatively low percentage of the uncharged base radical is available for immediate diffusion through the cell membrane.
-Thus it takes a fairly long time to set.
-However, once inside the cell membrane, over 80% of the radicals that do diffuse become available for binding to the sodium channel proteins. This high protein binding ability causes the drug to remain active for a long time once it has diffused through the cell membrane.

Front 56

What is procaine as a local anesthetic?

Back 56

-trade name, "Novocain“
-used less frequently today
-Procaine (like cocaine) has the advantage of constricting blood vessels, which reduces bleeding, unlike other local anesthetics like lidocaine, and without the euphoric and addictive qualities of cocaine.
-Procaine, an ester anesthetic, is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-amino benzoic acid (PABA), which is then excreted by the kidneys into the urine.
-Allergic reactions to procaine are usually not in response to procaine itself, but to PABA.

Front 57

What is prilocaine as a local anesthetic?

Back 57

-low systemic toxicity of prilocaine is comparatively low
-its metabolite, o-toluidine, is known to cause methemoglobinemia. As methemoglobinemia reduces the amount of hemoglobin that is available for oxygen transport, this side effect is potentially life-threatening. Therefore dose limits for prilocaine should be strictly observed. Prilocaine is not recommended for use in infants.

Front 58

How are vasoconstrictors used with local anesthetics?

Back 58

-No matter how quickly an anesthetic agent can enter a nerve, the local blood vessels begin to absorb the unused anesthetic as soon as it is injected.
-To slow this process down, a substance is added that in low concentrations acts to cause the local blood vessels to constrict, or narrow down.
-This restricts the amount of blood and plasma entering and leaving the site of the injection which has the net effect of slowing the vascular absorption of the anesthetic solution. This keeps the unused anesthetic solution in place longer and prolongs the action of the drug.
-The vasoconstrictor used is the naturally occurring hormone epinephrine or one of its analogs called levonordefrin.
-Most anesthetic solutions are sold with added vasoconstrictor. Only two, mepivicaine and prilocaine are sold with or without vasoconstrictor.
-Mepivicaine and prilocaine have the advantage of producing only minor vasodilation and, though both are short acting without their vasoconstrictor added, they still produce adequate anesthesia for short procedures.
-The major advantage of using an anesthetic without a vasoconstrictor is that there are virtually no interactions with other drugs the patient may be taking. -Vasoconstrictors may not be used with certain types of blood pressure medications or tricyclic antidepressants.
-These naturally occurring hormones are not very stable, and must be stabilized by the addition of an acidic preservative.
-The presence of the preservative can lower the pH of the anesthetic solution to the range of 3.8 to 5.0, thus reducing the amount of the neutral basic radical and slowing the onset of action of the anesthetic.

Front 59

What is alcohol as a drug?

Back 59

-Alcohol is one of the oldest and most widely used drugs.
-As a psychoactive drug, alcohol-induced changes brain chemistry to produce a wide range of behaviors.
-The modern use of the term “alcohol” describes various compounds composed of carbon, hydrogen and oxygen.
-The three most commonly encountered alcohols are:
-methyl alcohol (methanol)
-isopropyl alcohol (isopropanol)
-ethyl alcohol (ethanol)

Front 60

What is the chemistry of alcohol?

Back 60

-always contain a hydroxyl group, "OH", attached to a carbon molecule, which itself is connected to various combinations of carbon and hydrogen molecules.

Front 61

What is alcohol intoxication?

Back 61

-Two specific neurochemical systems in the brain have been strongly implicated in mediating alcohol intoxication:
-gamma aminobutyric acid (GABA) and its receptor; and
g-lutamate, and one of its receptors, N methyl- D-aspartic acid (NMDA).

Front 62

How is GABA a major inhibiotory neurotransmitter for mediating alcohol intoxication?

Back 62

-GABA receptors form ion-selective channels, or ligand-gated ion channels. When these receptors are activated, cellular activity changes.
-Drugs that mimic the effects of GABA enhance and prolong the behavioral effects of alcohol. Those drugs that block the effects of -GABA have the opposite effects.
-Ethanol activates the GABA-mediated increase in chloride ion flows causing neuronal inhibition
-Behavioral results include sedation, muscle relaxation, and inhibition of cognitive & motor skills
-Increased levels of GABA have positive effects of reward center in brain

Front 63

How is glutamate a major excitatory neurotransmitter for mediating alcohol intoxication?

Back 63

-Ethanol is a potent inhibitor of the function of glutamate receptors
-It disrupts by depressing the responsiveness of NMDA receptors to release glutamate
-Chronic alcohol intake and glutaminergic suppression causes up regulation of NMDA receptors
-Removal of ethanol’s inhibitory effects results in withdrawal signs like seizures

Front 64

What is the absorption of alcohol?

Back 64

– Soluble in both water & fat
– Can be called a food because it contains calories
– Diffuses easily across all biological membranes
– Rapidly & completely absorbed from entire GI tract
– Presence of food in stomach slows the speed of absorption
– Most absorbed from upper intestine due to large surface area
» A person with an empty stomach, 20% of a single dose absorbed directly from stomach & remaining 80% absorbed rapidly & completely from upper intestine

Front 65

What is the distribution of alcohol?

Back 65

• After absorption, alcohol evenly distributed throughout all body fluids & tissues
• Once it reaches the brain, it crosses blood brain barrier almost immediately
• Freely distributed across placenta & will easily enter the brain of fetus

Front 66

What is fetal alcohol syndrome?

Back 66

Developmental disorder that occurs in children of mothers who drank during pregnancy
– Mother does not need to be an alcoholic
• No safe level of alcohol intake
during pregnancy
• Damage is irreversible

Front 67

What is the metabolism of alcohol?

Back 67

• About 95% of alcohol ingested is enzymatically metabolized by enzyme alcohol dehydrogenase
• 5% is excreted mainly through lungs, sweat, & urine
• 85% of metabolism occurs in the liver
• Up to 15% of the metabolism is done by gastric alcohol dehydrogenase enzyme located in the lining of the stomach

Front 68

What is the three step metabolic process involved in the breakdown of alcohol?

Back 68

1. Alcohol dehyrogenase functions to convert alcohol to acetaldehyde
2. Enzyme aldehyde dehydrogenase converts acetaldehyde to acetic acid
3. Acetic acid is broken down into carbon dioxide & water
-alcohol--> acetaldehyde-->acetic acid--> carbon dioxide and water

Front 69

What is blood/alcohol content dependent on?

Back 69

– Presence of food
– Rate of consumption
– Concentration of
alcohol
– Drinker’s body
composition

Front 70

How does alcohol affect serotonin?

Back 70

• Chronic alcohol consumption results in augmentations in serotoninergic activity
• Serotonin dysfunction may play role in pathogenesis of alcoholism

Front 71

What are pharmacological affects of alcohol?

Back 71

• Effects of alcohol are graded, reversible depression of CNS function

• Respiration becomes progressively depressed & at very high blood concentrations, causes death

Front 72

What are acute effects of alcohol?

Back 72

• Irritant & promotes flow of gastric juices
• Effects pituitary gland which tells kidneys to produce more
than normal amounts of dilute urine (diuretic)
• Moderate doses (2 drinks per day):
– Reduces incidence of ischemic strokes
• Brain released from normal inhibitory restraints
• Liver can accumulate fat in liver cells
• Increases dopamine activity
• Hypoglycemia

Front 73

What are chronic effects of alcohol?

Back 73

1.Visible symptoms:
-Thin, bloated appearance -Hyperpigmented or jaundiced skin, Multiple bruise, Enlarged bulbous
2. Irritation, Bleeding, & Malabsorption:
-Alcohol irritates stomach lining
-Irritates esophagus resulting in mild chest pain
-Causes ulcers and stomach bleeding
3. Liver Disease:
– Fatty liver
– Alcoholic hepatitis
(jaundice)
– Cirrhosis of the liver
(non reversible)
4. Hematological System:
– Anemia
– Effects white blood cells (increases susceptibility to infection)
– Bruising easily & clotting problems
5. Cardiovascular System:
– AHMD (alcoholic heart muscle disease)
– Shortness of breath & dramatic enlargement of heart
– Arrhythmias
– Increase risk of stroke
6. Psychological Effects:
– Behavioral reaction is determined by person, mental expectations, & environment
• Relaxation & euphoria
• Withdrawn & violent
– Mental expectations & setting become less important at increased doses due to sedative effects
– Low doses:
• Memory, concentration, & insight are dulled
• Confident, social ability, & courage increased

Front 74

What are long-term effects of alcohol?

Back 74

Involves many different organs & depends on the drinkers intake amount
• Can promote cancers & tumors
• Alcohol is high in calories but have little nutritional value
• Larger amounts over time can lead to:
– Serious neurological, mental, & physical disorders
– Vitamin deficiencies
– Nutritional disease
– May result in physical deterioration

Front 75

What is metabolic tolerance of alcohol?

Back 75

-Liver increases its amount of drug-metabolizing enzyme

Front 76

What is tissue or function tolerance of alcohol?

Back 76

• Neurons in brain adapt to amount of drug present
• Display blood alcohol levels about twice those of non-tolerant people at similar level of intoxication

Front 77

What is homeostatic tolerance of alcohol?

Back 77

-Environmental manipulations can counter effects of ethanol

Front 78

What is alcohol dependency?

Back 78

• Physical dependence is defined by presence of tolerance
• After physical dependence established, withdrawal symptoms can occur
• Cravings are also associated with addiction & results from changes in the CNS

Front 79

What are withdrawal symptoms of alcohol dependency?

Back 79

• severity of symptoms widely depends on alcohol abuse
• Hangover is a mini-withdrawal
• Tremors
• Seizures
• Rapid pulse
• Sweating
• Increased body temperature
• Depression
• Insomnia
• Vomiting
• Illusions/hallucinations

Front 80

What are the 3 signs of alcohol withdrawal?

Back 80

-Tremulous syndrome - shakes, cramps and nausea
-Seizures - contraindicated in epilepsy
-Delirium Tremens - Confusion, hyperthermia and tremors

Front 81

How do you treat excessive CNS depression from alcohol use?

Back 81

-Maintain vital signs and prevention of aspiration after vomiting.
-IV Dextrose
-IV Thiamine to prevent against the -Wernicke-Korsakoff syndrome (ataxia, confusion, and paralysis of extraocular muscles)
-Correction of electrolyte imbalances (Banana bag)

Front 82

How do you treat alcohol withdrawal syndrome?

Back 82

-Correct electrolyte imbalance
-IV Thiamine
-Sedative-hypnotic
-long acting benzodiazepine (diazepam or chlordiazepoxide is preferred)
-UNLESS patient has compromised liver function then a short acting benzodiazepine w/less complex metabolism is used like lorazepam

Front 83

What drugs are used to treat alcoholism?

Back 83

-Naltrexone : stops the rush; opioid receptor antagonist; decrease effects of opioid peptides in the brain; Blocks ETOH induced release of dopamine which results in decreased euphoria; side effects are nausea, headache and hepatotoxicity
-Acamprosate: used for someone going cold turkey; NMDA glutamate receptor antagonist, and agonist of GABA receptors; side effects include Diarrhea and headache. It is renally cleared. 
It is used for withdrawal and abstinence.
-Disulfiram: used as adjunct, associates drinking with something bad; Inhibits Acetaldehyde dehydrogenase à results in -Acetaldehyde poisoning; Inhibits metabolism of warfarin, phenytoin, isoniazide, toxic to liver and teratogenic.
-Ondansetron – 5-HT3 serotonin receptor antagonist
-Topiramate

Front 84

What is methanol as an alcohol?

Back 84

-Methanol is in many industrial solvents, and causes similar effects as Ethanol.
-It causes less CNS depression than ethanol, however it can cause toxic effects of metabolic acidosis, and blindness. The acidosis is the result of the production of formic acid by ADH (alcohol dehydrogenase - note that antidiuretic hormone is also abbreviated ADH) and acetaldehyde dehydrogenase. The blindness is the result of formaldehyde’s toxic effects on the retina.

Front 85

What is ethylene glycol as an alcohol?

Back 85

-used as an automotive antifreeze. -In its pure form, it is an odorless, colorless, syrupy liquid with a sweet taste.
-produces CNS depression similar to that of ethanol. Symptoms of ethylene glycol toxicity include confusion, ataxia, hallucinations, slurred speech, and coma. -Symptoms are most severe six to 12 hours after ingestion, when the acidic metabolites of ethylene glycol are at their maximal concentration. The presentation may be similar to ethanol intoxication, if the patient presents early or has consumed small amounts of ethylene glycol. -However, an ethanol odor will be absent, and serum or respiratory ethanol levels will be too low to account for the degree of CNS depression.
-The absence of a strong odor of alcohol in a patient who appears intoxicated should raise the suspicion of ethylene glycol ingestion.

Front 86

How do you treat methanol and ethylene glycol toxicity?

Back 86

1.      Sodium bicarbonate is given to offset the metabolic acidosis.
2.      Ethanol and fomepizole are given to prevent the formation of formaldehyde.

Front 87

What is huntington's chorea?

Back 87

-Huntington's Chorea is a genetic disorder that is characterized by choreiform movements-abnormal voluntary movements (jerky motor incoordination). It is caused by the inheritance, in non-Mendelian fashion, of trinucleotide repeats in the protein Huntingtin. This trinucleotide expansion (long tracts of glutamine residues) leads to selective loss of medium spiny neurons that project from the striatum to the globus pallidum.
- This leads to a loss of inhibitory activity and increased excitatory drive that promotes uncontrolled movements. Unfortunately, there are no drugs to slow progression of the disease (death occurs within 15 to 20 years). In addition, there are no effective drugs to treat the movement symptoms, because the loss of neurons is so selective that global treatments produce too many side effects.
-Huntington disease is invariably accompanied by depression with occasional paranoia and psychosis. These symptoms are treated with standard antidepressants or antipsychotics.

Front 88

What is parkinson's disease? symptoms?

Back 88

-Parkinson's disease is characterized by loss of dopaminergic neurons in the basal ganglia. The mainline treatments are based on:
-Replacing the lost dopamine with an excess of precursor (levodopa).
-Directly stimulating dopamine receptors with an agonist (bromocriptine, pergolide, ropinirole, and pramipexole).
-Inhibiting dopamine breakdown (selegiline, tolcapone, and entacapone).
-Blocking muscarinic activity (trihexyphenidyl, benztropine). basal ganglia produce less dopamine
-tremor, or trembling in hands, arms, legs, jaw, and face
-rigidity, or stiffness of limbs and trunk
-bradykinesia, or slowness of movement
-postural instability or impaired balance and coordination.
-Dopaminergic degeneration in the substantia nigra
-in the deep gray matter of the brain
basal ganglia produce less dopamine

Front 89

What is levodopa as a drug used for parkinson's treatment?

Back 89

-dopamine precursor
-Still the preferred medication to control motor symptoms
-Used in combination with carbidopa to prevent premature decarboxylation
-Downsides include:
-Continual use can lead to motor complications (dyskinesia), which must be treated
-This can be somewhat offset by lowering the dosage

Front 90

What is late stage parkinson's? Treatment?

Back 90

-Seen in 40% of Patients having received Levadopa treatment for 5+ years
-Motor complications usually arise
-Patients experience a “wearing off” effect
-Each dose of levadopa has a shorter duration of effect
-Motor Complications treated with:
Dopamine Agonists, MAO-B Inhibitors, COMT Inhibitors

Front 91

What are dopamine agonists as treatment for parkinson's? Mechanism of action?

Back 91

-The direct dopamine agonists offer an alternative to levodopa therapy for maintaining dopaminergic "tone."
-Because partial agonists do not elicit a full biological response (they have reduced efficacy), they antagonize the full agonist potential of the endogenous dopamine. -Bromocriptine (partial D1 & D2-receptor) and pergolide(D1 and D2) are prototypical agents.
-The later generation, ropinirole and pramipexole, are more selective for D2 receptor subtypes.
-Because their duration of action is longer than that of levodopa, dopamine agonists may be beneficial for patients experiencing the "on-off" symptoms of levodopa.

Front 92

What are the side effects for dopamine agonists?

Back 92

-All the dopamine receptor agonists have troubling psychotic side effects, nausea, and fatigue, as well as orthostatic hypertension. -Recall that the antipsychotic agents work by blocking excess dopaminergic activity.
-So it is not surprising that dopamine agonists can lead to psychotic side effects. The newer drugs (pramipexole and ropinirole) exhibit more rapid onset kinetics and less gastrointestinal disturbance.
-They are limited by the risk of producing sleep disorders (sudden sleep attacks).
-Pergolide may also cause damage to cardiac valves related to its cumulative dosage and duration of use.

Front 93

What is apomorphine as a treatment for parkinson's?

Back 93

-morphine derivative but does not actually contain morphine, or bind to opioid receptors
-relatively non-selective dopamine receptor agonist considered to be a "rescue" drug to treat "off" periods in patients who have been using standard dopamine agonist therapy for 3 to 5 years.
-administered as a subcutaneous injection and works quickly-within 5 to 10 minutes.
-causes substantial nausea and vomiting and hypotension.

Front 94

What are MAO-B inhibitors as treatment for parkinson's? Mechanisms of action? side effects?

Back 94

MAO = monoamine oxidase
-Reduce disability and delay need for Levodopa
-Believed to be somewhat neuroprotective
-Just as carbidopa inhibits levodopa metabolism
-tolcapone and entacapone (inhibitors of catechol-O-methyltransferase; COMT) -selegiline (an MAO-B inhibitor) block the degradative metabolism of dopamine.
-These drugs increase the half-life of the neurotransmitter in synapses.
-The side effects for tolcapone are similar to the levodopa/carbidopa combination: nausea, orthostatic hypertension, and psychotic episodes.
-Tolcapone is noteworthy for causing hepatotoxicity, an adverse event that is much less problematic with entacapone.
-Selegiline targets the dopamine-selective MAO-B and may have neuroprotective antioxidant effects.
-selegiline lacks the peripheral side effects of the MAO-A inhibitors. -Taken together, all the drugs that prevent dopamine breakdown are used to extend the actions of levodopa to prevent the end-of-dose "wearing-off" effect and to lower the levodopa dose.

Front 95

What are anticholinergic agents as treatment for parkinson's? mechanisms of action?

Back 95

-Some therapies target this cholinergic activity with anticholinergics such as trihexyphenidyl or benztropine.
-These compounds have modest clinical utility and are limited by considerable antimuscarinic side effects (sedation, urinary retention, blurred vision, and confusion).
Anticholinergic therapies are effective for treating parkinsonian tremor, especially early in therapy when symptoms are mild.
-Although numerous drugs possess anticholinergic properties, only those that cross the blood-brain barrier will be effective treatments for Parkinson's disease.

Front 96

What are Antimuscarinic Drugs as treatment for parkinson's?

Back 96

-Benztropine (Cogentin)
-centrally acting antimuscarinic agent with antihistaminic properties resulting from the combination of the tropine portion of the atropine molecule and the benzohydryl portion of diphenhydramine

Front 97

What are NMDA receptor antangonists as treatment for parkinson's?

Back 97

-Shown to reduce motor complications from L-DOPA therapy
-Amantadine :
-Coenzyme Q10

Front 98

What are drugs that elicit parkinson-like symptoms? How?

Back 98

-haloperidol and fluphenazine.
-The typical antipsychotics work by blocking dopamine receptors (predominantly D2).
- At sufficient concentrations, dopaminergic blockade begins to resemble the loss of neurons typical of Parkinson's disease.
-Care, then, must be taken to monitor doses and side effects for patients receiving antipsychotic therapy.

Front 99

What are acetylcholiesterase inhibitors as treatment for parkinson's?

Back 99

-based on their mechanism (cholinesterase inhibition) they can elicit effects similar to the Salivation, Lacrimation, Urination, Defecation (SLUD) syndrome [overstimulation of the cholinergic systems (muscarinic)].
-tacrine is associated with hepatotoxicity and is rarely used. -Memantine is unique among the drugs used to manage Alzheimer's disease in that it is an NMDA receptor antagonist. Since it has been postulated that overexcitation of glutamate may play a role in Alzheimer's disease, memantine may prevent adverse effects associated with abnormal glutamate transmission. It has been beneficial for even advanced forms of Alzheimer's disease and is better tolerated than cholinesterase inhibitors.
includes:
-Donepezil
-Rivastigmine
-Galantamine
-Tacrine

Front 100

What is epilepsy? Possible causes?

Back 100

-There are 2.5 million Americans with epilepsy in the US alone.
-More than 40 forms of epilepsy have been identified.
-Therapy is symptomatic in that the majority of drugs prevent seizures, but neither an effective prophylaxis or cure is available.
-The etiology of epilepsy is unknown in 60-70% of cases, but heredity is an important factor.
-Damage to the brain-for example, by tumors, head injury, infections, or cerebrovascular accident-may subsequently cause epilepsy.
-The neurochemical basis of the abnormal discharges in epilepsy is not known, but it may involve altered GABA metabolism.

Front 101

What are causes of acute seizures?

Back 101

-Trauma
-Encephalitis
-Drugs
-Birth trauma
-Withdrawal from depressants
-Tumor
-High fever
-Hypoglycemia
-Extreme acidosis
-Extreme alkalosis
-Hyponatremia
-Hypocalcemia
-Idiopathic

Front 102

What are common types of epilepsy?

Back 102

-Absence Epilepsy
-Temporal Lobe Epilepsy
-Frontal Lobe Epilepsy
-Occipital Lobe Epilepsy
-Parietal Lobe Epilepsy

Front 103

What is absence epilepsy?

Back 103

-one of the most common types of epilepsy
-once diagnosed, these patients often have repeated absence seizures
tends to run in families

Front 104

What is temporal epilepsy?

Back 104

-most frequent cause of partial seizures and aura
-the temporal lobe is located close to the ear. It is the part of the brain where smell is processed and where the choice is made to express a thought or remain silent to treat TLE as early as possible.

Front 105

What is frontal lobe epilepsy?

Back 105

-The frontal lobes of the brain lie behind the forehead. They are the largest of the five lobes and are thought to be the centers that control personality and higher thought processes, including language and speech.
-causes a cluster of short seizures that start and stop suddenly. The symptoms depend upon the part of the frontal lobe affected

Front 106

What is occipital lobe epilepsy?

Back 106

-The occipital lobe lies at the back of the skull.
-Occipital lobe epilepsy is like frontal and temporal lobe epilepsies, except that the seizures usually begin with visual hallucinations, rapid blinking, and other symptoms related to the eyes

Front 107

What is parietal lobe epilepsy?

Back 107

-The parietal lobe lies between the frontal and temporal lobes. Parietal lobe epilepsy is similar to other types in part because parietal lobe seizures tend to spread to other areas of the brain.

Front 108

What are seizures?

Back 108

-A seizure is a sudden, transitory, and uncontrolled episodes of brain dysfunction produced by an abnormal high-frequency discharge of a group of neurons, starting focally and spreading to a varying extent to affect other parts of the brain.
-Seizures are associated motor, sensory or behavioral changes.
-According to the focus and spread of discharges, seizures may be classified as:
-Partial (focal), which originate at a specific focus and do not spread to involve other cortical areas.
-Generalized, which usually have a focus (often in the temporal lobe) and then spread to other areas.

Front 109

What is the classification of partial seizures?

Back 109

-Simple Partial Seizures
-Complex Partial Seizures
-Partial Seizures Secondarily Generalized

Front 110

What is the classification of generalized seizures?

Back 110

-Generalized Tonic-Clonic Seizures
-Absence Seizures
-Tonic Seizures
-Atonic Seizures
-Clonic and Myoclonic Seizures

Front 111

What are simple partial seizures? EEG?

Back 111

-Involves one side of the brain at onset.
-Focal w/motor, sensory or speech disturbances.
-Confined to a single limb or muscle group.
-Seizure-symptoms don’t change during seizure.
-No alteration of consciousness.
-EEG: Excessive synchronized discharge by a small group of neurons. Contralateral discharge.

Front 112

Wat are complex partial seizures?

Back 112

-Produces confusion and inappropriate or dazed behavior.
-Motor activity appears as non-reflex actions.
- Automatisms (repetitive coordinated movements).
-Wide variety of clinical manifestations.
-Consciousness is impaired or lost.
-EEG: Bizarre generalized EEG activity with evidence of anterior temporal lobe focal abnormalities. Bilateral.

Front 113

Wat are partial seizures secondarily generalized?

Back 113

-Seizures of this kind start as a partial seizure in one limited area of the brain.
-The forms they take vary as much as other partial seizures. But then (sometimes so quickly that the partial seizure is hardly noticed) the seizure spreads throughout the brain, becoming generalized.
-Symptoms that are initially associated with a preservation of consciousness that then evolves into a loss of consciousness and convulsions.

Front 114

What are generalized tonic-clonic seizures?

Back 114

-Major convulsions, usually with two phases:
1) Tonic phase-general body stiffening
2) Clonic phase-violent jerking after which the patient goes into a deep sleep (the postictalor after-seizure phase).
-Convulsions: motor manifestations, may or may not be present during seizures, excessive neuronal discharge.
-Convulsions appear in Simple Partial and Complex Partial Seizures if the focal neuronal discharge includes motor centers; they occur in all Generalized Tonic-Clonic Seizures regardless of the site of origin. Atonic, Akinetic, Absence Seizures are non-convulsive

Front 115

What is the tonic phase of generalized tonic-clonic seizures?

Back 115

- Sustained powerful muscle contraction (involving all body musculature) which arrests ventilation.
-EEG: Rhythmic high frequency, high voltage discharges with cortical neurons undergoing sustained depolarization, with protracted trains of action potentials.

Front 116

What is the clonic phase of generalized tonic-clonic seizures? EEG?

Back 116

- Alternating contraction and relaxation, causing a reciprocating movement which could be bilaterally symmetrical or “running” movements.
-EEG: Characterized by groups of spikes on the EEG and periodic neuronal depolarizations with clusters of action potentials.

Front 117

What are absence seizures (petite mal)? EEG? spike phase?

Back 117

-Brief and abrupt loss of consciousness.
-Sometimes with no motor manifestations.
-Usually symmetrical clonic motor activity varying from occasional eyelid flutter to jerking of the entire body.
-Typical 2.5 – 3.5 Hz spike-and-wave discharge.
-Usually of short duration (5-10 sec), but may occur dozens of times a day.
-Often begin during childhood (daydreaming attitude, no participation, lack of concentration).
-A low threshold Ca2+ current has been found to govern oscillatory responses in thalamic neurons (pacemaker) and it is probably involve in the generation of these types of seizures.
-EEG: Bilaterally synchronous, high voltage 3-per-second spike-and-wave discharge pattern.
-Spike Phase: Neurons generate short duration depolarization and a burst of action potentials. No sustained depolarization or repetitive firing.

Front 118

What are tonic seizures?

Back 118

-Opisthotonus, loss of consciousness.
-Marked autonomic manifestations

Front 119

What are atonic seizures?

Back 119

-Loss of postural tone, with sagging of the head or falling.
-May lose consciousness.

Front 120

What are clonic seizures?

Back 120

Rhythmic clonic contractions of all muscles, loss of consciousness, and marked autonomic manifestations.

Front 121

What are myoclonic seizures?

Back 121

-Isolated clonic jerks associated with brief bursts of multiple spikes in the EEG.

Front 122

What are infantile spasms?

Back 122

-An epileptic syndrome.
-Attacks, although fragmentary, are often bilateral.
-Characterized by brief recurrent myoclonic jerks of the body with sudden flexion or extension of the body and limbs.

Front 123

What is status epilepticus?

Back 123

-Describes a state of recurring seizures between which consciousness does not return in between the seizure events.
-If a seizure does not stop within 5 minutes, the individual may be in danger of going into status
epilepticus.
-This is a potentially life-threatening
event.

Front 124

What are febrile seizures?

Back 124

-convulsions brought on by a fever in infants or small children.
-During a febrile seizure, a child often loses consciousness and shakes, moving limbs on
both sides of the body.
-Most febrile seizures last a minute or two, although some can be as brief as a few seconds while others last for more than 15 minutes.
-The majority of children with febrile seizures have rectal temperatures greater than 102 degrees F.

Front 125

What are cellular and synpatic mechanisms of epileptic seizures?

Back 125

-Cellular and synaptic mechanisms generating epileptic seizures. A seizure can be divided into three phases:
-focal epileptogenesis (initiation);
-synchronization of the surrounding neurons; and
-propagation of the seizure discharge to other areas of the brain

Front 126

What are the goals for treating seizures?

Back 126

-Block repetitive neuronal firing
-Block synchronization of neuronal discharges
-Block propagation of seizure
-Prevent reoccurrence of seizures
Minimize side effects with the simplest drug regimen.
-MONOTHERAPY IS RECOMMENDED IN MOST CASES

Front 127

How do you treat seizures?

Back 127

-Effective antiseizure drugs have, to varying degrees, selective depressant actions on such abnormal neuronal activity. -However, they vary in terms of their mechanisms of action and in their & effectiveness in specific seizure disorders.
-The antiseizure drugs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action.
-The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action.

Front 128

What is the mechanism of action of antiseizure drugs for sodium channels?

Back 128

(phenytoin, carbamazepine and oxcarbazepine)
-Sodium channel blockade is the most common and the most well-characterized mechanism of currently available antiepilieptic drugs (AEDs).
-AEDs that target these sodium channels prevent the return of the channels to the active state by stabilizing the inactive form. In doing so, repetitive firing of the axons is prevented.
-The presynaptic and postsynaptic blockade of sodium channels causes stabilization of the neuronal membranes, blocks and prevents post-tetanic potentiation, limits the development of maximal seizure activity, and reduces the spread of seizures.

Front 129

What is the mechanism of action of antiseizure drugs for calcium channels?

Back 129

-Calcium channels exist in 3 known forms in the human brain L, N, and T.
-These channels are small and are inactivated quickly.
- The influx of calcium currents in the resting state produces a partial depolarization of the membrane, facilitating the development of an action potential after rapid depolarization of the cell.
-AEDs that inhibit these T-calcium channels are particularly useful for controlling absence seizures. -Ethosuximide and valproate inhibits low threshold (T type) Ca 2+ currents, especially in thalamic neurons that act as pacemeakers to generate rhythmic cortical discharge.
-Lamotrigine, topiramate, zonisamide, valproate are N- and L-calcium channel blockers.

Front 130

What is the mechanism of action of antiseizure drugs on GABA receptors/channels?

Back 130

-The most important inhibitory neurotransmitter in the brain is GABA.
-GABA has 2 types of receptors, GABA-A and GABA-B. Some AEDs function as an agonist to this mode of chloride conductance by
blocking the reuptake of GABA (ie, tiagabine) or by inhibiting its
metabolism mediated by GABA transaminase (ie, vigabatrin), resulting in increased of GABA at the postsynaptic receptors.
-Benzodiazepines interact with specific receptors on the GABAA
receptor chloride ion channel macromolecular complex.
-In the presence of benzodiazepines, the frequency of chloride ion channel
opening is increased: these drugs facilitate the inhibitory effects of
GABA.
-Phenobarbital and other barbiturates also enhance the inhibitory actions of GABA but interact with a different receptor site on chloride ion channels that results in an increased duration of chloride ion channel opening.

Front 131

What is the mechanism of action of antiseizure drugs for glutamate receptors?

Back 131

-topiramate, lamotrigine, felbamate
-Glutamate receptors bind glutamate, an excitatory amino acid neurotransmitter.
-Upon binding glutamate, the receptors facilitate the flow of both sodium and calcium ions into the cell, while potassium ions flow out of the cell, resulting in excitation. -The glutamate receptor has 5 potential binding sites and causes different responses depending on the stimulated or blocked site. -These sites are the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) site, the kainate site, the N-methyl-D-aspartate (NMDA) site, the glycine site, and the metabotropic site that has 7 subunits (GluR 1-7). -AEDs that modify these receptors are antagonistic to glutamate. The primary D glutamate receptor is specifically sensitive to N-Methyl-D-Aspartate, which causes direct action of the central pore of the receptor, an ion channel, to drive the neuron to depolarize. -Depolarization will trigger the firing, or action potential of the neuron, therefore NMDA is excitatory.

Front 132

What is the mechanism of action of antiseizure drugs for carbomate anhydrase inhibition

Back 132

-Acetazolamide, topiramate, zonisamide
-Inhibition of the enzyme carbonic anhydrase increases the concentration of hydrogen ions intracellularly and decreases the pH.
-The potassium ions shift to the extracellular compartment to buffer the acid-base status.
-This event results in hyperpolarization and an increase in seizure threshold of the cells. -Acetazolamide has been used as an adjunctive therapy in refractory seizures with catamenial pattern (ie, seizure clustering around menstrual period).
-Topiramate and zonisamide also are weak inhibitors of this enzyme.

Front 133

What is phenytoin as an antiseizure drug? mechanism of action? toxicity?

Back 133

-Oldest nonsedative antiepileptic drug.
-“Fetal hydantoin syndrome”.
-It alters Na+, Ca2+ and K+ conductances.
-Inhibits high frequency repetitive firing.
-Alters membrane potentials.
-Ataxia and nystagmus
-Cognitive impairment
-Gingival hyperplasia
-Coarsening of facial features
-Exhibits nonlinear pharmacokinetics
-Life threatening rash “Stevens-Johnson”

Front 134

What is fosphenytoin as an antiseizure drug? Toxicity?

Back 134

-Fosphenytoin sodium injection is a prodrug intended for parenteral administration.
-Its active metabolite is PHT.
-It is safer and better tolerated than PHT and can be infused 3 times faster than intravenous (IV) PHT. -Fosphenytoin is a better IV preparation than PHT, mainly because of tolerability and safety.
-However, fosphenytoin is much more expensive than PHT.
-Cardiovascular depression and hypotension may occur
-Slower infusion is recommended. -Severe burning, itching, and/or paresthesia have been associated with rapid infusion.

Front 135

What is carbamazepine as an anti-epiletic drug? Mechanism of action? Toxicity?

Back 135

-Tricyclic, antidepressant (bipolar)
-3-D conformation similar to phenytoin.
-Mechanism of action, similar to phenytoin. Inhibits high frequency repetitive firing.
-Decreases synaptic activity presynaptically.
-Potentiates postsynaptic effects of GABA.
-Metabolite is active.
-Can induce its own metabolism
-Nausea and visual disturbances.
-Aplastic anemia.
-Exacerbates absence seizures.
-Life threatening rash

Front 136

What is oxcarbazepine as an anti-epiletic drug? mechanism of action? toxicity?

Back 136

-Closely related to carbamazepine
-Improved toxicity profile.
-Less potent than carbamazepine
-Active metabolite
-Use in partial and generalized seizures as adjunct therapy
-May aggravate myoclonic and absence seizures
-Mechanism of action, similar to carbamazepine.
- It alters Na+ conductance and inhibits high frequency repetitive firing
-Hyponatremia
-Less hypersensitivity and induction of hepatic
enzymes than with carbamazepine

Front 137

What is lamotrigine as an anti-epiletic drug? Toxicity?

Back 137

-Add-on therapy with valproic acid
-Almost completely absorbed
-Effective in myoclonic and generalized seizures in childhood and absence attacks.
-Involves blockade of repetitive firing involving Na channels, like phenytoin.
-Also effective in myoclonic and generalized seizures in childhood and absence attacks.
-Dizziness
-Headache
-Nausea
-Life threatening rash “Stevens-Johnson

Front 138

What is ethosuximide as an anti-epiletic drug? mechanism of action? toxicity?

Back 138

-Drug of choice for absence seizures
-High efficacy and safety
-Mechanism of action involves reducing low-threshold Ca2+ channel current (T-type channel) in thalamus.
-At high concentrations:
Inhibits GABA aminotransferase
-Gastric distress
-Lethargy and fatigue
-Headache
-Hiccups
-Euphoria
-Skin rashes - Life threatening rash “Stevens-Johnson”

Front 139

What is zonisamide as an anti-epiletic drug? mechanism of action? toxicity?

Back 139

-Sulfonamide derivative.
-Effective against partial and generalized tonic-clonic seizures.
-Approved by FDA as adjunctive therapy in adults.
-Mechanism of action involves voltage and use-dependent inactivation of sodium channels.
-Inhibition of Ca2+ T-channels.
-Binds GABA receptors
-Drowsiness
-Cognitive impairment
-Anorexia
-Nausea

Front 140

What is phenobarbital as an anti-epiletic drug? mechanism of action? toxicity?

Back 140

-One of the oldest antiepileptic drug.
-Although considered one of the safest drugs, it has sedative effects.
-Many consider them the drugs of choice for seizures only in infants.
-Useful for partial, generalized tonic-clonic seizures, and febrile seizures
-Prolongs opening of Cl- channels.
-Blocks excitatory GLU (AMPA) responses. Blocks Ca2+ currents (L,N).
-Inhibits high frequency, repetitive firing of neurons only at high concentrations.

Front 141

What is primidone as an anti-epiletic drug? mechanism of action? toxicity?

Back 141

-Metabolized to phenobarbital and phenylethylmalonamide (PEMA), both active metabolites.
-Effective against partial and generalized tonic-clonic seizures.
-Should be started slowly to avoid sedation and GI problems.
-Its mechanism of action may be similar phenytoin and/or barbiturates.
- toxicity same as phenobarbital
-Sedation occurs early
-Gastrointestinal complaints

Front 142

What is gabapentin as an anti-epiletic drug? mechanism of action? toxicity?

Back 142

-Used as an adjunct in partial and generalized tonic-clonic seizures
-not bound to plasma proteins.
-drug-drug interactions are negligible
-Low potency
-Analog of GABA that does not act on GABA receptors, it may however alter its metabolism, non-synaptic release and transport.
-Somnolence
-Dizziness
-Ataxia
-Headache
-Tremor

Front 143

What is clonazepam as an antiepiletic drug? mechanism of action? toxicity?

Back 143

-A benzodiazepine
-Long acting drug with efficacy for absence seizures
-One of the most potent antiepileptic agents known.
-Also effective in some cases of myoclonic seizures
-Has been tried in infantile spasms
-Doses should start small.
-Increases the frequency of Cl- channel opening.
-Sedation is prominent
-Ataxia

Front 144

What is vigabatrin as an anti-epiletic drug? mechanism of action? toxicity?

Back 144

-Use for partial seizures
-Contraindicated if preexisting mental illness is present.
-Irreversible inhibitor of GABA-aminotransferase (enzyme responsible for metabolism of GABA) => Increases inhibitory effects of GABA.
- (+) enantiomer is active.
-Drowsiness
-Dizziness
-Weight gain
-Agitation
-Confusion
-Psychosis

Front 145

What is tiagabine as an anti-epiletic drug? mechanism of action? toxicity?

Back 145

-Derivative of nipecotic acid
-Effective against partial seizures in pts at least 12 years old
-Approved as adjunctive therapy
GABA reuptake inhibitor by binding to y- aminobutyric acid transporter (GAT) by neurons and glial cells
-Abdominal pain and nausea
-Dizziness
-Nervousness
-Tremor
-Skin rash

Front 146

What is topiramate as an antiepiletic drug? mechanism of action? toxicity?

Back 146

-Blocks repetitive firing of neurons, thus its mechanism may involve blocking of voltage-dependent sodium channels
-Potentiates inhibitory effects of GABA (acting at a site different from BDZs and BARBs)
-Depresses excitatory action of kainate on AMPA receptors.
-Teratogenic in animal models
-Somnolence
-Fatigue
-Dizziness
-Cognitive slowing
-Nervousness
-Confusion

Front 147

What is felbamate as ananti-epiletic drug? toxicity?

Back 147

-Effective against partial seizures but has severe side effects.
-Because of its severe side effects, it has been relegated to a third-line drug used only for refractory cases.
-Aplastic anemia
-Severe hepatitis

Front 148

Wat is levetiracetam as an anti-epiletic drug? toxicity?

Back 148

-Piracetam (S-enantiomer pyrrolidone) derivative
-March 2007 it was approved by the FDA for primary generalized tonic-clonic seizures in adults and children aged 6 years and older.
-No significant drug interactions have been identified.
-Mechanism unknown
-Well tolerated
-Somnolence
-Dizziness

Front 149

What anti-epiletic drugs cna be used during pregnanacy?

Back 149

-Phenytoin -Phenobarbital
-Carbamazepine -Primidone
-They may all cause hemorrhage in the infant due to vitamin K -deficiency, requiring treatment of mother and newborn.
-They all have risks of congenital anomalies (oral cleft, cardiac and neural tube defects).

Front 150

What anti-seizure drugs have known teratogenic effects?

Back 150

-Valproic acid causes spina bifida.
-Topiramate causes limb agenesis in rodents and hypospadias in male infants.
-Zonisamide is teratogenic in animals.

Front 151

What are anti-seizure drug interactions?

Back 151

-Drug interactions: barbiturates (e.g. phenobarbital, primidone)
Alcohol increases CNS depression barbiturates.
-Drug interactions: clonazepam
-Alcohol or other CNS depressants will be additive in effect.
-Clonazepam increase phenytoin levels.
-Drug interactions: phenytoin
-Alcohol decreases phenytoin efficacy.
-Other anticonvulsants may alter phenytoin serum levels
-Drug interactions: carbamazepine
-Verapamil may increase carbamazepine levels
-Serum levels of other anticonvulsants may decreased due to increased from metabolism activity.
 -Drug interactions: ethosuximide
-Carbamazepine decreases ethosuximide levels
-Ethosuximide may alter phenobarbital and ethosuximide's levels
-Drug interactions: valproic acid
-Valproic acid can cause serum phenobarbital to increase by as much as 40%.
-Alcohol can potentiates CNS depression caused by antiepileptic agents

Front 152

What is pain?

Back 152

-Pain is a subjective symptom, an unpleasant sensory or emotional experience that is associated typically with actual or potential tissue damage and is the most common reason for seeking medical care.

Front 153

What is analgesia?

Back 153

-Analgesia is a state in which no pain is felt despite the presence of normally painful stimuli.

Front 154

What are the specialized receptors of the pain pathway? stimulation? types of neurons? distinct processes?

Back 154

-Specialized receptors = free nerve endings
Stimulation:
-Mechanical damage
-Extreme temperature
-Chemical irritation
Two types of neurons:
-A-delta: first pain, sharp
-C: second pain, dull
Four distinct processes:
-Transduction, transmission, modulation, perception

Front 155

What is the pathway mechanism of pain?

Back 155

-A thermal, chemical, or mechanical sensory event activates a specific peripheral receptor, leading to ion influx and depolarization of the peripheral terminal.
-Activation of the peripheral terminal by a noxious stimulus leads to the generation of action potentials, which are conducted to the dorsal horn of the spinal cord.
-Norepinephrine, GABA, and opioids, released by descending and/or local-circuit inhibitory neurons, act both presynaptically and postsynaptically to inhibit neurotransmission.

Front 156

What are the opioid receptors?

Back 156

-CNS distribution is not uniform
-they are located at areas concerned with pain
-bind to specific opioid receptors in the central nervous system and in other tissues
-are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta).
-In addition, there are two subtypes of μ receptor: μ1 and μ2.
-opioid-receptor-like receptor 1 (ORL1), which is involved in pain responses as well as having a major role in the development of tolerance to μ-opioid agonists used as analgesics.
-These are all G-protein coupled receptors acting on GABAergic neurotransmission.
-The pharmacodynamic response to an opioid depends on which receptor it binds, its affinity for that receptor, whether the opioid is an agonist or an antagonist.

Front 157

What is the mu receptor of the opioid receptors?

Back 157

-appears to be the major opioid target
-Activation causes analgesia, sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils) and decreased bowel motility often leading to constipation.
-Some of these effects, such as sedation, euphoria and decreased respiration, tend to disappear with continued use as tolerance develops.
-Analgesia, miosis and reduced bowel motility tend to persist; little tolerance develops to these effects.
-Tolerance develops to different effects at different rates largely because these effects are caused by activation of different μ-receptor subtypes.
-Stimulation of μ1-receptors blocks pain while stimulation of μ2-receptor causes respiratory depression and constipation

Front 158

What is the delta receptor of the opiod receptors?

Back 158

-activation produces analgesia. -related to seizures.
-The endogenous ligands for the δ receptor are the enkephalin.
-analgesia (spinal & supraspinal)
-release of growth hormone   

Front 159

What is the kappa receptor of the opioid receptors?

Back 159

-are also involved with analgesia, but activation also produces marked nausea nauseasea and dysphoria (sadness, irritability, anxiety)

Front 160

What is the deriviation and structure of opium?

Back 160

-from exudate of the incised unripe seed capsules of the poppy plant
-Opium Alkaloids (25% by weight of opium) - morphine, codeine, and papaverine are among the alkaloids found in opium
-Semisynthetic Derivatives: many new molecules have been made by simple modifications of morphine or thebaine.
-Completely synthetic

Front 161

What structural elements of opium is necessary for activity?

Back 161

-aromatic ring
-spacer
-quarternary carbon center
-basic nitrogen

Front 162

What is acute temporal pain?

Back 162

-Identifiable injury, usually < 1-3 months

Front 163

What is chronic temporal pain?

Back 163

-May lack clear pathology, usually > 1-3 months

Front 164

What are nonopioids that reduce pain?

Back 164

-Tramadol (“atypical opioid”)
-Acetaminophen
-Acetylsalicylic acid
-Nonsteroidal anti-inflammatory drugs (NSAIDs)

Front 165

What are routes of administration of opioids?

Back 165

-Oral
-Intravenous
-Subcutaneous
-Intramuscular
-Oral
-Transmucosal and Buccal
-Rectal
-Transdermal

Front 166

What is morphine as an opiate? metabolites? issues? side effects?

Back 166

-prototype
-pure mu-receptor agonist
-has two biologically active metabolites:
-morphine-3-glucuronide (M3G)
-morphine-6-glucuronide (M6G)
-M3G does not bind to opioid receptors
-M6G exhibits opioid activity; it is at least two to four times more potent than morphine and may significantly contribute to analgesia with chronic use.
-Both metabolites are renally eliminated
-known to induce histamine release causing hypotension and pruritus.
-hydrophilic opioid:
-has a slower onset and longer duration compared with more lipophilic opioids (e.g., fentanyl, meperidine).
-significant first-pass metabolism reduces the amount of orally administered drug that reaches the circulation, giving a parenteral-to-oral dose ratio of 1:3.
-side effects include respiratory depression, nausea and vomiting, cough suppression, sedation, and dependence leading to addiction
-effect on the muscle of the bowel and urinary tract, causing the sphincter to contract and reduce the peristalsis
-results in a delayed emptying of the stomach, constipation, and may also lead to urinary retention.

Front 167

What is fentanyl as an opiate? mechanism of action? issues? side effects?

Back 167

-100 times more potent than morphine when administered intravenously and is dosed in micrograms.
-acts selectively at the mu receptor, leading to an improved side effect profile:
-negligible histamine release
-less sedation
-less constipation.
-extremely lipophilic
-almost immediate onset when administered intravenously
-duration is relatively short compared to other opioids, usually lasting only 30 to 60 minutes.
-Analgesic effects may be prolonged after continuous infusion or repeated administration due to the redistribution of the drug into fat stores
-the elimination half-life may be extended to 13 to 24 hours.
-no pharmacologically active metabolites and is one of the safest options for patients with renal failure.

Front 168

What are the fentanyl analogs as opiates?

Back 168

-alfentanil
-remifentanil
-sulfentanil
-carfentanil

Front 169

What is meperidine as ab opiate? metabolite? issues? side effects?

Back 169

-not recommended as a first-line opioid analgesic
-is lipophilic
-has a rapid onset
-shorter duration of analgesia (usually 2-3 hours) than other short-acting opioids
-causes euphoric effects, which may be related to its lipophilicity and rapid transport into the central nervous system (CNS).
limited by its active metabolite, normeperidine
-metabolite is neurotoxic and can cause irritability, delirium, agitation, tremors, and seizures. -Normeperidine toxicity is not reversed by administration of the opioid antagonist naloxone
-Accumulation of normeperidine often occurs after repeated dosing due to its extended half-life, which is five to 10 times longer than the parent drug
-eliminated renally, the risk of accumulation and serious adverse effects is higher in patients with renal insufficiency
-inhibits the reuptake of norepinephrine and serotonin
-not recommended for PCA administration
-may be appropriate for patients who have allergic reactions to other opioids such as morphine or hydromorphone
-treatment or prevention of drug- or blood product–induced rigors; or treatment of postanesthesia shivering.

Front 170

What is hydromorphine as an opiate?

Back 170

-five to seven times more potent than morphine
-has an improved side effect profile over morphine
-less histamine release
-no opioid-active metabolite.
-preferable option to morphine for patients with renal impairment
-The use for chronic pain has been limited by the lack of a sustained-release product.
-is currently available in parenteral, oral, and rectal immediate-release formulations.
-The intravenous and oral formulations are not dose equivalent, as hydromorphone also undergoes first-pass metabolism; the parenteral-to-oral dose ratio is 1:5.

Front 171

What is methadone as an opiate for heroine addiction?

Back 171

-safe and efficacious for the treatment of narcotic withdrawal and dependence.
-Heroin releases an excess of dopamine in the body and causes users to need an opiate continuously occupying the opioid receptor in the brain
-Methadone occupies this receptor and is the stabilizing factor that permits addicts on methadone to change their behavior and to discontinue heroin use.
-Taken orally once a day, methadone suppresses narcotic withdrawal for between 24 and 36 hours.
-only effective in cases of addiction to heroin, morphine, and other opioid drugs, and it is not an effective treatment for other drugs of abuse.
-reduces the cravings associated with heroin use and blocks the high from heroin, but it does not provide the euphoric rush
methadone patients do not experience the extreme highs and lows that result from the waxing and waning of heroin in blood levels.

Front 172

What is codeine as an opiate?

Back 172

-naturally occurring opiate
-weak analgesic
-should be used only for mild-to-moderate pain
-not recommended for patients with impaired renal function
-Approved indications for codeine include:
-Cough
-Diarrhea
-Moderate to severe pain - irritable bowel syndrome
-combination preparations with acetaminophen
-prodrug since it is metabolized in vivo to morphine
-less potent than morphine since only about 10% of the codeine is converted
-lower dependence-liability than morphine.
-The conversion of codeine to morphine occurs in the liver and is catalyzed by the cytochrome P450 enzyme CYP2D6.
-Approximately 6 to10% of the Caucasian population have poorly functional CYP2D6 and codeine is virtually ineffective for analgesia in these patients.

Front 173

What is hydrocodone as an opiate?

Back 173

-a semi-synthetic opioid derived from codeine and thebaine
-orally active narcotic analgesic and antitussive
-compared with codeine, it provides significantly more pain relief and a longer duration of action
-prodrug metabolized by CYP2D6, with analgesic effects dependent on its active metabolite hydromorphone
-drug interactions with CYP2D6 inhibitors and genetic enzyme deficiencies may affect the analgesic benefit
-hydrocodone combination products contain acetaminophen

Front 174

What is oxycodone as an opiate?

Back 174

-more potent than morphine
-causes fewer severe adverse effects than morphine.
-metabolized by CYP2D6 to an active metabolite, oxymorphone
unlike codeine and hydrocodone, oxycodone is itself a potent analgesic
-unknown whether oxymorphone significantly contributes to the analgesic activity of oxycodone.
-Patients with CYP2D6 deficiencies who do not respond well to codeine or hydrocodone may achieve more pain relief from using oxycodone

Front 175

What is propoxyphene as an opiate?

Back 175

-structurally different from codeine and hydrocodone and more closely resembles the phenylheptylamine opioid methadone
-weak analgesic
-propoxyphene may cause adverse effects, such as dizziness and euphoria
-metabolized to norpropoxyphene, which may cause irreversible cardiac toxicity and arrhythmias
-norpropoxyphene has a half-life of 30 to 34 hours and accumulates with repeated dosing

Front 176

What is tramadol as an opiate?

Back 176

-weak opioid analgesic
-unique dual mechanism includes weak binding to mu receptors and inhibition of norepinephrine and serotonin reuptake.
-high incidence of nausea and vomiting
-Dosages should be reduced for patients older than 75 years or for patients with renal or hepatic dysfunction

Front 177

What is buprenorphine as an opiate?

Back 177

-Potent (25 to 40 times as potent as morphine)
-long-acting phenanthrene derivative that is a partial mu receptor agonist
-Long duration of action
-κ-opioid receptor antagonist, and partial/full agonist at the recombinant human ORL1 nociceptin receptor
-management of opioid dependence
-not administered orally, due to very high first-pass metabolism

Front 178

What is pentazocine as an opiate?

Back 178

-synthetically-prepared opioid used to treat mild to moderately severe pain
-may exist as one of two enantiomers, named (+)-pentazocine and (-)-pentazocine.
-(-)-pentazocine is a kappa-opioid receptor agonist
-(+)-pentazocine is not, and displays selectivity to the related sigma receptor.

Front 179

What is butorphanol as an opiate?

Back 179

-morphinan-type synthetic opioid analgesic
-most closely structurally related to dextromethorphan
-exhibits partial agonist and antagonist activity at the μ opioid receptor and agonist activity at the κ opioid receptor
-Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work.
can cause dysphoria at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.

Front 180

What is nalbuphine as an opiate?

Back 180

-synthetic narcotic agonist-antagonist analgesic of the phenanthrene class
-chemically related to both the widely used narcotic antagonist, naloxone, and the potent narcotic analgesic, oxymorphone
-potent analgesic and is essentially equivalent to that of morphine
-strong kappa receptor agonist and mu receptor antagonist
-narcotic antagonist activity of nalbuphine is one-fourth as potent as nalorphine and 10 times that of pentazocine

Front 181

What is toxicity of morphine? treatment?

Back 181

-acute overdose:
-respiratory depression
-pinpoint pupils (miosis)
-coma
-Treatment:
1. establish adequate ventilation
1a. 4 point restraints needed
2. give OPIOID antagonist (naloxone)

Front 182

How do you antagonize morphine?

Back 182

-Two drugs: naloxone and naltrexone (pure antagonists)

Front 183

What is naloxone for the treatment of opiate toxicity?

Back 183

-used to counter the effects of opioid overdose, for example heroin or morphine overdose
-specifically used to counteract life-threatening depression of the central nervous system and respiratory system.
-no analgesic activity at all
-competitive antagonist at mu, kappa, and sigma receptor
-displaces morphine and other OPIOID from receptor site
-reverses all actions of the OPIOID and does it rather quickly

Front 184

What is naltrexone for the treatment of opiate toxicity?

Back 184

-same effect of naloxone except it is used orally so can't use it if for person with acute toxicity
-long duration of activity
-single dose block action of heroin effects for 24 hours
-also used for treatment of alcoholism 

Front 185

What is nalmefene for the treatment of opiate toxicity?

Back 185

-opioid receptor antagonist
-opiate derivative similar in both structure and activity to the opiate antagonist naltrexone.
-Advantages of nalmefene relative to naltrexone include:
-longer half-life
-greater oral bioavailability
-no observed dose-dependent liver toxicity.
-also has high affinity for the other opioid receptors, and is known as a "universal antagonist" for its ability to block all three.

Front 186

What is nalorphine for the treatment of opiate toxicity?

Back 186

-acts to reverse the effects of morphine and other narcotics
-counteracts narcotic-induced nervous system and respiratory system depression but is not effective against depression induced by other sedatives such as barbiturates
-useful in reversing the effects of narcotic overdoses

Front 187

What is diphenoxylate as an opiate?

Back 187

-therapeutic use is as an antidiarrheal
-has very little analgesic properties at therapeutic dose
-no antitussive effect
-at high doses it has analgesic problems
-causes respiratory depression and euphoria at high doses
opioid agonist used for the treatment of diarrhea that acts by slowing intestinal contractions
-congener to the narcotic meperidine
is potentially habit-forming, particularly in high doses or when long-time usage is involved.
-Because of this, diphenoxylate is manufactured and marketed as a combination drug with atropine
designed to discourage abuse, because the anticholinergic effect of atropine will produce severe weakness and nausea if standard dosage is exceeded

Front 188

What is loperamide as an opiate?

Back 188

-opioid receptor agonist
-acts on the μ-opioid receptors in the myenteric plexus large intestines
-decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall
-increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. -Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex.
-Does not affect the central nervous system like other opioids
does not cross the blood-brain barrier and has no analgesic properties.
-Tolerance in response to long-term use has not been reported.
-can cause physical dependence. -Symptoms of opiate withdrawal have been observed in patients abruptly discontinuing long-term therapy with loperamide.
-OTC

Front 189

What are the drug interactions of opiates with sedative-hypnotics? antipsychotic seizures? MAO inhibitors? phenothiazines? tricyclkic antidepressants

Back 189

Sedative-hypnotics:
-Increased CNS depression (esp. respiratory)
Antipsychotic tranquilizers:
-Increased sedation
MAO Inhibitors:
-High incidence of hyperpyrexic coma
OPIOID and phenothiazines:
-produces an additive CNS depression as well as enhancement of the actions of OPIOID (respiratory depression)
-this combination may also produce a greater incidence of orthostatic hypotension
OPIOID and tricyclics antidepressants:
-can produce increased hypotension
-meperidine and MOA inhibitors
-results in severe and immediate reactions that include excitation, rigidity, hypertension, and severe respiratory depression

Front 190

What cautions should be made with opiates?

Back 190

-Use of pure agonists with weak partial agonists
-Use in patients with head injuries
-Use in pregnancy
-Use in patients with impaired pulmonary function
-Use in patients with impaired renal and hepatic function
-Use in patients with endocrine disease

Front 191

What allergies cna occur with opiates?

Back 191

-Some opioids can cause histamine release as a part of their pharmacologic action.
-When a patient is an allergic to an opioid in one chemical class, an opioid from a different class may be less likely to cause an allergic reaction and possibly used safely

Front 192

What is opioid therapy?

Back 192

-Give opioid scheduled around-the-clock instead of "prn."
-Order different opioid doses for mild, moderate, and severe pain.
-Hold for excessive sedation or respiratory depression.
-Observe response to initial regimen, and titrate accordingly.
-For moderate and severe pain, keep opioid separate from NSAID or acetaminophen dosing. (Avoid combination drugs.)

Front 193

What is dextromethorphan in use for inflammation?

Back 193

-Suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. 
Mechanism of Action:
-sigma agonist
-alpha3/beta4 nicotinic receptor antagonist
-targets the serotonin reuptake pump
binds to and acts as antagonist to the NMDA glutamatergic receptor

Front 194

How is prostaglandin involved in inflammation?

Back 194

-Inflammatory states are often associated with the production of prostaglandin (mediators of both peripheral and central pain sensitization).
-In the periphery, prostaglandins produced by inflammatory cells sensitize peripheral nerve terminal prostaglandin receptors
-more responsive to a painful stimulus.
-In central pain pathways, cytokines released in response to inflammation induce prostaglandin production in the dorsal horn of the spinal cord.
-sensitize secondary nociceptive neurons, thereby increasing the perception of pain.

Front 195

What are NSAIDs in inflammation?

Back 195

-block peripheral and central sensitization mediated by prostanoids that are released in inflammation
-reduce the extent of inflammation.

Front 196

What is the inflammation pathway of someone with severe burns?

Back 196

-Intense heat stimulated thermosensitive TRPV receptors
-tissue burn injury stimulated the production of chemical activators, including protons and kinins
-voltage-gated sodium channels in Aδ and C fibers were activated and transmitted signals to the dorsal horn of the spinal cord, where N-type voltage-gated calcium channels controlled release of neurotransmitters at the secondary projection neurons

Front 197

How is cyclooxygenase (COX) involved in inflammation?

Back 197

-the key enzyme for the production of prostaglandins in inflammation
-exists in at least two forms, so that inhibitors of the inducible COX-2 have similar efficacy to other NSAIDs but have reduced gastrointestinal side effects, although there is an increased risk of cardiovascular and renal side effects.

Front 198

what is the mechanism of action of NSAIDs?

Back 198

-The mechanism of action of NSAIDs is to inhibit prostaglandin production by blocking its precursor, cyclooxygenase.
-2 isoforms of cyclooxygenase exist: COX-1 and COX-2. Both isoforms act to convert arachidonic acid into prostaglandins, prostacyclins, and thromboxanes.
-Prostaglandins are mediators of pain and inflammation.
-Additionally, prostaglandins contribute to the maintenance of GI mucosal lining, regulate renal blood flow, and mediate normal platelet function.
-Traditional NSAIDs such as aspirin, ibuprofen, and naproxen block both COX-1 and COX-2 isoforms. -Blocking prostaglandin production provides an anti-inflammatory effect, but other effects of traditional (nonselective) NSAIDs lead to GI complications and renal impairment.

Front 199

How do COX-2 inhibitors cause cardiovascular issues?

Back 199

-Selective COX-2 inhibitors decrease vascular dilatory prostacyclin (PGI2) without decreasing the prothrombotic thromboxane production that occurs with traditional NSAIDs

Front 200

What is the mechanism of action of NSAIDs as an analgesic?

Back 200

-The analgesic effect is largely a peripheral effect due to the inhibition of prostaglandin synthesis at the site of inflammation and pain.
-Prostaglandins do not produce pain directly but sensitize nocioceptive fiber nerve endings to other inflammatory mediators amplifying the basic pain message.
-So NSAIDs are most effective against pain with an inflammatory component
-A small component of the analgesic component is a consequence of the central effect in reducing the prostaglandin synthesis in the CNS (APAP works in this way)

Front 201

What is the mechanism of action of NSAIDs as anti-inflammatory?

Back 201

-Prostaglandins produce increased vasodilatation, vascular permeability, and edema in an inflammatory reaction
-Inhibition of prostaglandin synthesis reduces this part of the inflammatory reaction
-NSAIDs do not inhibit the other inflammatory mediators so inflammatory cell accumulation is not inhibited.

Front 202

what is the anti-pyretic mechanism of action of NSAIDs?

Back 202

-During a fever, leukocytes release inflammatory pyrogens (eg interleukin-1) as part of the immune response.
-These act on the thermoregulatory center in the hypothalamus.
-This effect is believed to from an increase in hypothalamic prostaglandins, of which their generation is inhibited by NSAIDs
-NSAIDs do not affect temperature under normal conditions or in heat stroke.

Front 203

What is the molecular properties of NSAIDs?

Back 203

-generally hydrophobic molecules, most of which have a carboxylic acid group
-categorized by classes depending on one or more of the key moieties in the structure.
-The moiety that is common to members of each class is highlighted by a box
-acetaminophen is not actually an NSAID, because it has only weak anti-inflammatory properties; this drug is included here because, as with NSAIDs, acetaminophen is commonly used for its analgesic and antipyretic effects.

Front 204

What are COX-2 selective inhibitors for anti-inflammation?

Back 204

-hydrophobic sulfonic acid derivatives
-block the hydrophobic channel leading to the active site of cyclooxygenase and thus inhibit the enzyme.
-Note that the COX-2 selective inhibitors are generally larger molecules than NSAIDs.
-preferentially inhibit COX-2 compared to COX-1, because the hydrophobic channel of COX-2 is larger than that of COX-1.
(That is, COX-2 selective inhibitors are too bulky to access the smaller hydrophobic channel of the COX-1 enzyme.)
-The COX-2 selective inhibitors display approximately 100-fold greater selectivity for COX-2 compared to COX-1.

Front 205

What is celcoxib for anti- inflammation?

Back 205

-Highly selective COX-2 inhibitor -Minimized GI ADR

Front 206

What is aspirin for anti-inflammation?

Back 206

-Irreversible Nonselective COX –1 and 2 Inhibitor
-use linked to Reye's syndrome
-avoid use with viral illness in children

Front 207

Whatb is ibuprofin for anti-inflammation?

Back 207

-Reversible Nonselective COX –1 and 2 Inhibitor
-OTC

Front 208

What is naproxin for anti-inflammation/

Back 208

-Reversible Nonselective COX –1 and 2 Inhibitor
-OTC

Front 209

What is sulindac for anti-inflammation?

Back 209

-Reversible Nonselective COX –1 and 2 Inhibitor
-much more likely than other NSAIDs to cause damage to the liver or pancreas

Front 210

What is duflunisal for anti-inflammation?

Back 210

-Reversible Nonselective COX –1 and 2 Inhibitor
-Not metabolized to salicylate, no salicylate intox, no antipyretic act, does not enter CNS

Front 211

What is diclofenac for anti-inflammation?

Back 211

-Reversible Nonselective COX –1 and 2 Inhibitor
-FIRST topical NSAIDs, comb prod with misoprostil

Front 212

what is etodolac/ nabumetone for anti-inflammation?

Back 212

-Reversible Nonselective COX –1 and 2 Inhibitor
-Less potent COX-1

Front 213

What is ketorolac for anti-inflammation?

Back 213

-Reversible Nonselective COX –1 and 2 Inhibitor
-PO and IV forms, better analgesic action short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level

Front 214

What is indomethacin for anti-inflammation?

Back 214

-Reversible Nonselective COX –1 and 2 Inhibitor
-Better anti-inflammatory action

Front 215

What is the adverse effects and causes of the GI tract from NSAID use?

Back 215

-Dyspepsia, Nausea and Vomiting
-Ulcer formation and potential hemorrhage risk in chronic users -Inhibition of the normal protective actions of prostaglandins on the gastric mucosa
-PGE2 and PGI2 normally inhibit gastric acid secretion, increase mucosal blood flow, and have a cytoprotective action.

Front 216

What are renal adverse effects and causes from NSAID use?

Back 216

-Renal damage/nephrotoxicity
-Renal failure can occur after years of abuse
-Inhibition of PGE2 and PGI2 mediated vasodilatation in the renal medulla and glomeruli

Front 217

What are other adverse effects and causes from NSAID use other than the GI tract and kidneys?

Back 217

-Bronchospams, skin rashes and other allergic-type reactions -Hypersensitivity reaction/allergy to drug

Front 218

How do NSAID's like aspirin inhibit clotting?

Back 218

-They do this by interfering with the synthesis of thromboxane A2 in platelets.

Front 219

Why can’t you use Aspirin and NSAIDs together?

Back 219

-Increased risk (additive effects) of bleeding and GI side effects

Front 220

What is the molecular mechanism of aspirin?

Back 220

-Irreversible covalent bond via acetylation of a serine hydroxyl group near the active site of COX enzymes.

Front 221

What is the antiplatelet aggregation property of aspirin?

Back 221

-Even a low dose (81-mg baby aspirin vs 325-mg full dose) exerts irreversible inhibition of TXA2 synthesis; an elevation in prothrombin time is noted at high doses.
-antiplatelet effect is used to prevent the platelets from initiating the formation of blood clots inside arteries, particularly in individuals who have atherosclerosis or are otherwise prone to develop blood clots in their arteries.

Front 222

What are platelets? blood clots?

Back 222

-Platelets are particles (actually remnants of cells) circulating in the blood that are necessary in order for blood clots to form.
-initiate the formation of blood clots by clumping together, a process called platelet aggregation.
-Clumps of platelets then are further bound together by a protein (fibrin) formed from clotting factors present in the blood.
-the clumps of platelets and fibrin make up the blood clot.
-Blood clots are important because they stop bleeding when we get cut.
-However, if a blood clot forms inside an artery , it blocks the flow of blood to the tissue that the artery supplies, and that can damage the tissue.
-For example, a blood clot that forms in a coronary artery supplying blood to heart muscle causes a heart attack, and a blood clot that forms in an artery supplying blood to the brain causes a stroke.

Front 223

What is the analgesic property of aspirin?

Back 223

-Moderate doses inhibit formation of prostaglandins, which in turn blunts peripheral pain receptor responses to pain mediators such as bradykinin and histamine.

Front 224

What is the antipyresis property of aspirin?

Back 224

-Pyrogens typically release IL-1, leading to increased PGE2 in the hypothalamus and increasing the body's "set-point" temperature.
-At moderate doses, aspirin causes sufficient inhibition of PGE2 and lowers the "set-point" to normal.

Front 225

What is the anti-inflammatory property of aspirin?

Back 225

-At moderate-to-high doses, strong inhibition of COX-2 is noted.
-Aspirin also interferes with cell surface selectins and integrins, thereby inhibiting leukocyte adhesion.

Front 226

What is the uric acid excretion property of aspirin?

Back 226

-At low-to-moderate doses, a decrease in renal tubular secretion is noted that leads to hyperuricemia
-however, at high doses, a reduction of tubular reabsorption is noted, which leads to uricosuria

Front 227

What is the acid-base balance property of aspirin?

Back 227

-At high therapeutic doses, a mild uncoupling of the oxidative phosphorylation chain leads to respiratory alkalosis and a compensatory metabolic acidosis.
-At toxic doses, inhibition of the respiratory center leads to respiratory acidosis, and severe uncoupling of the oxidative phosphorylation chain leads to metabolic acidosis, hyperthermia, and hypokalemia.

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What is the gastrointestinal irritation property of aspirin?

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-Inhibition of PGE2 leads to gastritis, ulcers, and bleeding.

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What is the salicylism property of aspirin?

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-First signs of toxicity are often tinnitus (ringing in ears), vertigo, and decreased hearing.

Front 230

What is the hypersensitivity property of aspirin?

Back 230

-Seen most often among those with the triad of asthma, nasal polyps, and rhinitis.

Front 231

What is reye's syndrome as a property of aspirin?

Back 231

-Potentially lethal condition in children that results in hepatotoxicity and/or encephalopathy

Front 232

What is toxicity by acetaminophen?

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-Salicylates can cause uncoupling of the oxidative phosphorylation chain
-maximum daily dose of APAP is 4 g in adults and 90 mg/kg in children
-acute overdose or when the maximum daily dose is exceeded over a prolonged period, the normal conjugative pathways of metabolism become saturated.
-Under conditions of excessive NAPQI formation or reduced glutathione stores, NAPQI binds to, and interacts with vital cellular proteins and the lipid bilayer of hepatocyte membranes. 
-An cascade of oxidative and inflammatory damage can result is hepatocellular death and centrilobular (zone III) liver necrosis

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What is the mechanism of action of acetaminophen?

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-relieves pain by elevating the pain threshold by requiring a greater amount of pain to develop before a person feels it
-reduces fever through its action on the heat-regulating center of the brain by telling the center to lower the body's temperature when the temperature is elevated

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What is acetaminophen?

Back 234

-also known as paracetamol and N -acetyl-p-aminophenol (APAP)
-rapidly absorbed from the stomach and small intestine
-metabolized by conjugation in the liver to nontoxic compounds. These water-soluble conjugates are then eliminated in the urine.

Front 235

What is the antidote for acetaminophen toxicity?

Back 235

-N -acetylcysteine (NAC)
precursor of glutathione and increases the available glutathione to conjugate NAPQI
may also enhance sulfate conjugation of any unmetabolized APAP also functions as an anti-inflammatory and antioxidant and has positive inotropic effects.

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What is gout?

Back 236

-overload of crystals of uric acid depositing in tissues of the body and features recurring attacks of joint inflammation (arthritis).
-Chronic gout can lead to deposits of hard lumps of uric acid in and around the joints, decreased kidney function, and kidney stones.
-often related to an inherited abnormality in the body's ability to process uric acid. Uric acid is a breakdown product of purines that are part of many foods we eat.

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How do you treat gout?

Back 237

-First, pain relievers such as acetaminophen (Tylenol) or other more potent analgesics are used to manage pain.
-antiinflammatory agents NSAIDS and colchicine colchicine
-treating the elevated levels of uric acid in the blood with medications that reduce these levels.

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What drugs are used in the treatment of gout?

Back 238

-Indomethacin
-Colchicine
-Allopurinol
-Sulfinpyrazone
-Probenecid