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Pharmacology > Exam 2 sweep 1 > Flashcards

Exam 2 sweep 1 Flashcards

1
Q

Local anesthetics used in dental practice are ——— amines).

A

secondary or tertiary

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2
Q

Local anesthetics cross the axon membrane and interact with the ——- forms of the Na+ channel, blocking Na+ conductance.

A

open and inactivated

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3
Q

Local anesthetics are not effective ———.

A

outside the axon

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4
Q

Because local anesthetics bind to the open form of the sodium channel, they produce a more rapid nerve block on axons with a more

A

rapid firing rate.

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5
Q

Functions served by—– are more readily disrupted by local anesthetics than the motor functions served by ——–

A

B and C fibers

(larger) A fibers*

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6
Q
  1. First on, last off.
A

The faster a fiber is blocked, the longer it takes to recover.

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7
Q

Local anesthetic selectivity

Phenomenon: bupivacaine

A

produces sensory anesthesia at 1/3 the concentration required for motor blockade. Etidocaine shows no selectivity??
Although the mechanism is unclear, bupivacaine would be favored for epidural anesthesia during childbirth (maintain unterine muscle contractility).

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8
Q

Inflammed tissue
Products released by cells in inflamed tissue ——– making it more difficult to get sufficient levels of anesthetic inside the axon.

A

lower pH,

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9
Q

Anesthetic must be sufficiently ——– to diffuse to its site of action.
Once at site, the more ——— have a longer duration of action (increased protein binding, decreased clearance by local blood flow).

A

hydrophilic

lipid-soluble local anesthetics

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10
Q

Most local anesthetics are prepared as a —— (pH of the solution around 6 or 7)

A

water soluble HCl salt

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11
Q

If epinephrine is included, the pH is frequently lowered to —– to stabilize the epinephrine.

A

4 or 5

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12
Q

Local anesthetics: in CNS

A
  1. Readily pass from the periphery to the CNS

2. CNS neurons are very sensitive to local anesthetics

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13
Q

Local anesthetics Direct effects on the heart:

A

Block cardiac Na+ channels

Block cardiac Ca++ channels (much higher concentrations)

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14
Q

Local anesthetics

Effects on the autonomic nervous system:

A

(inhibition of sympathetic responses)

Depress contractility Produce hypotension

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15
Q

Bupivacaine is especially ——-

Binds tighter to Na+ channels and leaves slower

A

cardiotoxic

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16
Q

Local anesthetics bind to ——-: (5%-95%, depends on hydrophobicity of the anesthetic)

A

plasma proteins

a1 glycoprotein albumin

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17
Q

prilocaine

A

(secondary amine, dealkylation not required, extrahepatic metabolism)

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18
Q

articaine

A

(inactivated in blood by esterase)

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19
Q

Treatment of serious adverse events

Convulsions:

A

benzodiazepine, barbituate (thiopental), succinylcholine (treats symptoms only).

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20
Q

Treatment of serious adverse events

Respiratory distress:

A

Ventilation, oxygen.

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21
Q

Treatment of serious adverse events

Hypotension:

A

sympathomimetic agents (epinephrine)

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22
Q

Treatment of serious adverse events

Cardiac function disrupted:

A

cardiopulmonary resuscitation

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23
Q

2 week window in which to treat root canal after

A

root resection

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24
Q

Antimuscarinics:

A

minimize salivation, laryngospasm (block vagal stimulation), reflex bradycardia

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25
Q

Various analgesics:

A

preoperative pain relief, sedation, amnesia

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26
Q

Nitrous oxide and/or opioids:

A

reduce anesthetic requirement, provide analgesia

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27
Q

Anti-nicotinics:

A

paralyze skeletal muscle

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28
Q

Antiemetics

A

no vomiting

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29
Q

Meyer-overton correlation

A

Solubility in olive oil related to anesthetic potency

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30
Q

Membrane lipid hypo

A

Anesthesia begins when the anesthetic reaches a critical concentration in membrane lipids.

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31
Q

Membrane Protein Based Theories of Anesthesia

A

Direct action of the anesthetic on proteins leads to alterations in protein function
The notion that anesthetics interact with hydrophobiic sites on proteins and affect their function is the more popular one these days

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32
Q

—– receptors are an attractive general anesthetic target

A

GABA - there is no one specific receptor though

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33
Q

Studies on the sympathetic nervous system indicate ——– generally more sensitive to anesthetics than action potentials

A

synaptic transmission

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34
Q

The ———— appears to be important in consciousness

A

reticular activating formation

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35
Q

Many neuroscientists believe the ——– is essential to maintaining consciousness

A

thalamocortical loop

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36
Q

The ——– is involved in memory. Inhibition of this system is likely to be involved in anesthetic-induced amensia

A

limbic system

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37
Q

Pain pathways involve the ——–

A

spinal cord

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38
Q

The blood gas partition coefficient

A

brain brain

[blood]/[gas]

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39
Q

Lower blood gas partition coefficient

A

Faster induction and recovery

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40
Q

Higher blood gas partition coefficient

A

lower induction rate and slower recovery

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41
Q

Barbituates act as CNS depressants by potentiating the activity of the ——-. Binding of GABA to its receptor activates ———. The influx of the negatively charged chloride ——– the post synaptic membrane, thus providing an inhibitory influence on synaptic transmission.

A

GABA-A receptor

chloride channels

hyperpolarizes

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42
Q

Barbituates

A

Use of intravenous agents in anesthesia has become more popular: 1) Rapid distribution
Drug into vein
2) Reduced cardiac depression
rapidly gets to brain
3) No risk of malignant hyperthermia
4) Eliminate risk of occupational exposure to volatile anesthetics

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43
Q

Barbituates - major bad effect

A

respiratory depression

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44
Q

Barbituates used as

A

maintenance (total intravenous anesthesia).

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45
Q

Methoxhexital

A

Barbituates
Similar to thiopental but
2.5 x more potent, faster acting, shorter duration of action
Sleep time 5 -7 minutes
Cleared 3x faster than thiopental
Fast recovery renders it more favorable in dental outpatient procedures

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46
Q

Ketamine produces

A

Dissociative Anesthesia

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47
Q

Channels that let in —– will hyper- polarize

A

Cl-

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48
Q

Channels that let in —— will depolarize

A

Na+

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49
Q

Channels that let out——will hyper- polarize

A

K+

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50
Q

PREsynaptically: Hyperpolarization diminishes

A

Ca++ influx and neurotransmitter release

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51
Q

PREsynaptically: Depolarization enhances

A

Ca++ influx and neurotransmitter release

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52
Q

POSTsynaptically:

A

Hyperpolarization diminishes opening of Na+ channels and reinitiation of action potentials

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53
Q

POSTsynaptically:

A

Depolarization enhances opening of Na+ channels and reinitiation of action potentials

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54
Q

Opioid GPCRS

They activate

A

Gai

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55
Q

Formed from processing of pro-opiomelanocortin (POMC)

Made in the pituitary and hypothalamus

A

beta endorphin

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56
Q

is the natural agonist of the m-opioid receptor

A

b-endorphin

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57
Q

Dynorphin A, Dynorphin B, and a/b neo-endorphin agonists of

A

kappa opioid receptor

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58
Q

Opioid Receptors Activate

A

Gai and GbGg

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59
Q

Activation of Gi leads to an inhibition of ——-, a diminution in —— levels and a reduction in ——– activity. The reduction of —— activity results in a reduction of

A

adenylate cyclase activity

cAMP

Protein Kinase A

PKA

Ca++ entry from voltage sensitive Ca++ channels.

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60
Q

Activation of opioid receptors will also lead to activation of a particular type of

A

potassium channel (via GbGg). This will hyperpolarize the cell.

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61
Q

Postsynaptically, hyperpolarization will diminish generation of an

A

action potential.

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62
Q

Presynaptically, —— is required for transmitter release and inhibition of the voltage sensitive Ca++ channel and hyperpolarization will each diminish ——. Thus, opioids acting presynaptically will inhibit synaptic transmission by reducing

A

Ca++

Ca++ entry

transmitter release.

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63
Q

m receptors

Three forms,

A

m1, m2, m3. m1 and m2 are physiologically important.

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64
Q

M receptors found in

A

Found in periaqueductal gray region, superficial dorsal horn of the spinal cord, nucleus accumbens, amygdala, cerebral cortex. Mainly, presynaptic.
Found in GI tract (inhibit peristaltic action, cause constipation).

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65
Q

Majority of analgesic drugs act primarily at

A

m receptors

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66
Q
  1. Opioids inhibit the inhibitor, thus helping to activate the pathway that produces
A

CNS mediated inhibition of pain.

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67
Q
  1. opioids inhibit —– release
A

GABA

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68
Q

GABA activates a

A

Cl- channel, producing hyperpolarization

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69
Q

Opioids help reduce ——- system expression on pain

A

limbic (emotional)

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70
Q

All opioid analgesics produce:

A

analgesia, respiratory depression, constipation, gastrointestinal spasm, physical dependence

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71
Q

Constipation is a side effect of

A

morphine

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72
Q

Morphine is metabolized by ——- very quickly in the liver. -====== is the primary product —– is the secondary product

A

UGT2B7

Morphine-3- glucuronide (M-3-G)

Morphine-6-glucuronide (M-6-G)

Reason why morphine isn’t effective when taken orally.

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73
Q

Add methyl to —- location to make opioids

A

3’

More effective

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74
Q

The difference in strength between morphine or heroin on one hand and fentanyl on the other hand arises from differences in their chemical structures. All three bind to the m opioid receptor in the brain, but two major factors contribute to fentanyl’s enhanced therapeutic activity. These two factors are also the major contributors to fentanyl’s enhanced toxicity. The two factors are:

A

(1) Fentanyl is more lipid soluble than morphine or heroin. (2) Fentanyl binds tighter to the m opioid receptor than morphine or heroin

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75
Q

therapeutic index is not the problem for

A

fentanyl

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76
Q

Fentanyl produces more prolonged —– than other opioids

A

respiratory depression

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77
Q

m receptor antagonists. Used to treat

A

opioid toxicity. Naloxone is injected and works rapidly. Naltrexone is effective orally and lasts a long time Nalmefene is active orally and lasts even longer than naltrexone. (Could naltrexone or nalmefene be used as a treatment of opioid addiction??).

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78
Q

Since activation of all the opioid receptors produce analgesia, might it be possible to produce drugs that act on

A

k or d receptors and don’t have the major adverse effects (i.e. respiratory depression) and/or don’t produce dependence.

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79
Q

Injured cells release certain chemicals called

A

alarmins

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80
Q

The alarmin IL-33 can produce ‘——-’ of resident immune cells called mast cells

A

degranulation

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81
Q

———- is one of the more important initial mediators of the inflammatory response released by mast cells

A

Histamine

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82
Q

——— acts through a G protein coupled receptor to produce local ——— and render the capillaries ‘leaky’. This will allow more immune cells to enter the injury site and also produce edema.

A

Histamine

vasodilation

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83
Q

Histamine-H1 receptor activity on vascular endothelium increases

A

intracellular Ca++ - causes smooth muscle relaxation (endothelial cell pathway), causes MLCK mediated contraction of capillary endothelium

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84
Q

The anti-inflammatory properties and pain relief comes from attenuating the production of —–

A

prostaglandins

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85
Q

Prostaglandins are all derived from —-. The four principal ones are PGE2, PGD2, PGF2, and PGI2

A

arachidonic acid

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86
Q

The action of the enzymes —– sends the arachidonic acid down the path leading to production of the prostaglandins

A

COX1 and COX2

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87
Q

Prostaglandins (via their G protein coupled receptors) act at ———- to sensitize pain responses.

A

peripheral nerve endings

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88
Q

PGE2 mediated activation of —– leads to increased activity of PKA. PKA mediated phosphorylation of the ———— enhances its activity leading to a sensitized pain response.

A

Gas

TRP type nociceptor

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89
Q

Aspirin decreases

A

Pain
Fever
Inflammation
Thrombosis

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90
Q

ibuprofen and naproxen do the same as aspirin except

A

no decrease in thrombosis

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91
Q

acetamionphen lowers

A

pain, fever

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92
Q

Platelet aggregation is mediated in part through the ——— production of

A

autocrine

thromboxane (TXA2 in the picture).

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93
Q

COX enzymes inhibit ——– production

A

Thromboxane A2

94
Q

Prostaglandins (made primarily from COX-1 activity) stimulate ——— that help comprise the ‘——-’ that protects the stomach from digesting itself

A

mucus and bicarbonate secretion

mucus gel

95
Q

Adverse effects of NSAIDS

A 
Increases in bleeding time (acetylsalicylic acid) Kidney problems (water, Na+ retention) Increased BP
Heart failure (rare)
96
Q

Reye’s Syndrome

A

Fatty change in liver and edematous encephalopy after aspirin use 3-5 days later. Preceded by upper respiratory tract infection.

97
Q

Ulcer

Acetylsicylic acid contraindication

A

Internal bleeding

98
Q

Diabetes

Acetylsicylic acid contraindication

A

Hyper or Hypo glycemia

99
Q

Gout

Acetylsicylic acid contraindication

A

Complex effects on plasma Urate levels

100
Q

Hypocoagulation conditions

Acetylsicylic acid contraindication

A

Bleeding

101
Q

Anti-inflammatory - best

A

Ibuprofen or naproxen (not acetaminophen)

102
Q

Risk of heart attack or stroke greater with

A

Greater with ibuprofen or naproxen

103
Q

Liver toxicity most serious with

A

Most serious with high doses of acetaminophen

104
Q

Lupus erythematosus is a name given to a collection of

A

autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues, including, but not limited to, the joints.

105
Q

Psoriatic arthritis is a long- term inflammatory arthritis that occurs in people affected by the autoimmune disease

A

psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage- like appearance. Skin changes consistent with psoriasis (e.g., red, scaly, and itchy plaques) frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals.

106
Q

Septic arthritis, also known as

A

joint infection or infectious arthritis, results from the invasion of a joint by an infectious agent, resulting in joint inflammation.

107
Q

Osteoarthritis also involves the entire joint, including

A

subchondral bone and synovium

108
Q

Chondrocytes of healthy cartilage:

A

Anabolic and catabolic activities are balanced. The extracellular matrix is maintained in a healthy state

109
Q

Chondrocytes of inflammed cartilage:

A

Anabolic and catabolic activities are not balanced, the catabolic activities dominate. The extracellular matrix is not maintained in a healthy state.
One sees decreased production of collagen. Increased production of proteolytic enzymes such as matrix metalloproteases.

110
Q

——- produce change in chondrocytes that shifts to osteoarthritis. ——- are particularly important

A

Inflammatory mediators

IL-1b and TNFa

111
Q 
Proinflammatory cytokines (e.g. IL- 1b, TNFa)
Reduced -----, increased ---------, increased expression of other proteases, increased --------
A

collagen expression

MMP expression

iNOS, COX-2, PEG-2

112
Q

Then a pharmacological hierarchy for treating arthritis

A

If no inflammation: acetaminophen

Acetaminophen fails or signs of inflammation NSAIDS Direct injection of corticosteroids into articular cartilage

113
Q

Hyaline cartilage matrix is mostly made up of ———, and ———, both of which are also found in elastic cartilage. It also includes ———

A

type II collagen

chondroitin sulphate

keratin sulphate

114
Q

The ——– is the site of initial inflammatory process

A

synovium

115
Q

Synovitis is characterized by proliferation of cells of the ——–, increased vascularization, and infiltration by inflammatory cells (especially lymphocytes and macrophages).

A

synovial lining

116
Q

Eventually, synovitis leads to extension of the inflammatory tissue mass to the articular cartilage. This overgrowth is called the ——-.

A

pannus

117
Q

Pannus is an abnormal layer of —— or ——– tissue. Common sites for pannus formation include over the ——-, over a ——– (as seen in rheumatoid arthritis), or on a ———

A

fibrovascular tissue

granulation

cornea

joint surface

prosthetic heart valve.

118
Q

The immune cells,

A

osteoclasts (cells responsible for bone resorption), and chondrocytes (cells involved in making and breaking down cartilage) make things and have activities that lead to the destruction of bone and cartilage.
MMP = matrix metaloproteases
Cathepsins = cysteine proteases
ROS = reactive oxygen species

119
Q

What do we know about what causes Rheumatoid Arthritis?
Triggered by a———– to an immunological trigger, such as an infectious agent.
People with certain alleles of —— genes are predisposed

A

T cell-mediated response

MHC

120
Q

The major histocompatibility complex (MHC) is a set of cell surface proteins essential for the

A

acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility.

121
Q

The main function of MHC molecules is to bind to

A

antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.

122
Q

T helper 17 cells (Th17) are heavily implicated in

A

autoimmune disorders such as RA

123
Q

—— produce IL-17

A

Th17

124
Q

Th17 cells play an important role in maintaining —— and contributing to ———–, but they have also been implicated in ————

A

mucosal barriers

pathogen clearance at mucosal surfaces

autoimmune and inflammatory disorders.

125
Q

——-is a really, really, really important therapeutic target in auto immune disorders. - secreted by

A

(TNFa)

Th17

126
Q

Some antibodies associated with RA

A

Anti-collagen antibodies
Anti-cardiolipin antibodies
Anti-keratin antibodies Anti-calpastatin antibodies

Antiperinuclear factor antibodies

127
Q

Cardiolipin is a ——- that is an important component of the inner ——–, where it constitutes about 20% of the total lipid composition.

A

phospholipid

mitochondrial membrane

128
Q

Antiperinuclear factor antibodies

——- around nucleus of neutrophils

A

Stain

129
Q

Calpastatin is an

A

endogenous calpain (calcium- dependent cysteine protease) inhibitor.

130
Q

———– is an antibody that is an important diagnostic marker of RA

A

Rheumatoid Factor (RF)

131
Q

RF: antibody against the ———.

A

Fc portion of IgG

132
Q

RF and —— join to form immune complexes that are likely to contribute to the disease process. Although predominantly encountered as —–, rheumatoid factor can be of any isotype of immunoglobulins, i.e. IgA, IgG, IgM, IgE, IgD.

A

IgG

IgM

133
Q

Antibodies against ——— are frequent in patients with RA

A

citrullinated proteins

134
Q

Citrullination of peptides catalyzed by

A

peptidyl arginine deaminase

135
Q

Identification of antibodies directed against ———-** represent an important diagnostic test for RA and are liable to be causative factors in the disease

A

cyclic citrullinated peptide

136
Q

———- recognize a diverse set of proteins and are highly cross reactive

A

Anti-citrullinated Protein Antibodies (ACPA)

137
Q

ACPAs bind and induce ——– by osteoclasts

A

bone resorption

138
Q

Citrullinated fibrinogen and collagen are ——– in mouse models of arthritis

A

arthrogenic (impairment due to ongoing reflex)

139
Q

Citrullinated fibrinogen activates ——–

A

macrophages

140
Q

DMARDS

A

2) Disease-Modifying Anti-Rheumatic Drugs (DMARDS)

141
Q

DMARDS are

A

A category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is used to distinguish these drugs from nonsteroidal anti-inflammatory drugs (which refers to agents that treat the inflammation but not the underlying cause) and glucocorticoids (SAIDS?) (which blunt the immune response but do not slow down the progression of the disease).

142
Q

Methotrexate:

A

Enzyme inhibitor of dihydrofolate reductase

This interference with folate metabolism is the mechanism by which methotrexate acts as a chemotherapeutic agent

143
Q

Potential mechanisms of action of low-dose methotrexate in rheumatoid arthritis

A

Possible (most likely?) bottom line, potentiation of adenosine signaling as an immune modulator

144
Q
  1. Reduction of cell proliferation
  2. Enhanced apoptosis of T cells
  3. Increased adenosine release
  4. Altered expression of cellular adhesion molecules 5. Influences cytokine production
A

Some biological effects resulting from lower dose methotrexate

145
Q

Bottom line: lower dose methotrexate treatment produces

A

immuno-suppressive and anti-inflammatory effects

146
Q

leflunomide Inhibits

A

dihydroorotate dehydrogenase, thereby inhibiting pyrimidine biosynthesis

147
Q

4) Cyclosporin (inhibitor of cytokine gene expression more frequently used to treat organ and graft rejection)
Cyclosporine forms a
complex with cyclophilin
The cyclosporin-cyclophilin complex inhibits a phosphatase called ——— that is activated by cell signaling. ——— of NF-AT (a transcription factor) by calcineurin results in activation of transcription of ———– and boosting of the immune response. Thus, cyclosporin ——– the immune response

A

calcineurin

Dephosphorylation

cytokine gene expression

attenuates

148
Q

Azathioprine

a drug that inhibits

A

DNA replication

149
Q

Tofacitinib – a

A

JAK
kinase inhibitor
It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), i.e. it interferes with the JAK-STAT signaling pathway.

150
Q
  1. Biologics that interfere with —— signaling can be used to treat RA
A

TNFa

151
Q

TNFa is a “————-” that plays a major role in the immune/inflammatory response

A

pleotropic cytokine

152
Q

Antibodies/biologicals directed against TNFa act as ——- in rheumatoid arthritis and have positive effects on a slew of autoimmune disorders

A

DMARDS

153
Q

The —– region recognizes antigens

A

Fab

154
Q

Glutamate

Sometimes glutamate acts as an —— and sometimes it acts as ——- (activates a G protein coupled receptor)

A

excitatory neurotransmitter (opens a channel to let in Na+)

neuromodulator

155
Q

GABA (g amino butyric acid) receptors activate —- channels and produce ——

A

Cl-

hyperpolarization

156
Q

Glycine receptors also activate ——- and

produce hyperpolarization

A

Cl- channels

157
Q

Schizophrenia positive symptoms

A

linked to excess dopamine

delusions, auditory hallucinations, disturbances in thought

158
Q

Schizophrenia negative symptoms

A

linked to prefrontal pathology

Loss of affect, catatonia, immobility

159
Q

-azine:

A

phenothiazine-like antipsychotics

160
Q

Dopamine paths relevant to schizophrenia

A

mesolimbic path overactivity, mesocortical path disfunction.

161
Q

Glutamate hypothesis

A

hypofunction of NMDA receptors

162
Q

Schizophrenia drugs

A

Antagonism of D2 and D4 dopamine receptors,
5HT2A serotonin receptors,
H1 histamine receptors,
M1 muscarinic receptors
and a1 adrenergic receptors (Gq)
is thought to be important in producing the therapeutic and adverse effects of anti-pyschotics.

163
Q

All G protein coupled receptors

A

Schizo drugs

164
Q

Class of anti-psychotic drugs =

A

neuroleptic drugs

165
Q

Atypical

A

5HT2, D4, weak D2 blockade.

166
Q

Anti-psychotic drugs are known to be ———— They are classified as typical (older, first generation) or atypical (newer second generation).

A

receptor antagonists (they might also be doing other things).

167
Q

The —— anti- pyschotics affect only the positive symptoms. The ——– anti-psychotics affect both the positive and negative symptoms

A

typical

atypical

168
Q

Some atypical antipsychotics end in -

A

idone

169
Q

Typical anti-psychotics generally are strong antagonists of the ——-, have little activity on ——–, and varying activities on ———- receptors.

A

D2 dopamine receptor

D4 dopamine receptors

5-HT2 (serotonin), H1 (histamine), M1 (muscarinic AcCh), and a1 (adrenergic)

170
Q

Atypical anti-psychotics generally have ——-, are stronger on the—— receptor relative to the ——-, and varying activities on

A

antagonistic activity on D4 dopamine receptors

5-HT2

D2 dopamine receptor

on H1 (histamine), M1 (muscarinic AcCh), and a1 (adrenergic) receptors.

171
Q

Monoamine hypothesis

A

Depression due to lack of NE, serotonin, dopa

172
Q

Most drugs that are used as anti-depressants act in one of three ways:

A
  1. Block transmitter reuptake
  2. Inhibit MAO
  3. Inhibit presynaptic autoreceptors
173
Q

Block transmitter reuptake
There are two types of drugs working here. The ——) are rather non-specific blockers of transmitter reuptake that are generally also muscarinic receptor antagonists. Both of these properties make for significant side effects.
The ——— are more specific for serotonergic systems and also have less anti-muscarinic activity.

A

tricyclic antidepressants (TCAs

Selective Serotonin Reuptake Inhibitors (SSRIs)

174
Q

Normally, activation of ——– in the striatum affects acetylcholine and GABA release

A

dopamine D2 receptors(Gai) in

175
Q

Difference between L dopa and dopa

A

L dopa crosses BBB

176
Q

L-dopa treatment okay for

A

3-4 years - degenerate or too many adverse effects.

177
Q

carbidopa, a

A

peripheral dopa decarboxylase inhibitor.

Helps with vomiting, gets more to cross BBB

178
Q

Dopamine receptor agonists benefits

A
  1. Not as toxic as L-DOPA

2. Don’t require neuron from substantia nigra for delivery (function during more advanced stages of disease ???)

179
Q

Phenytoin and other anti-seizure drugs block

A

high frequency firing of action potentials

180
Q

anti-convulsants potentiate the effects of GABA to

A

dampen synaptic nerve impulses
GABA produces hyperpolarization by activating Cl- influx
This renders post- synaptic generation of an action potential more difficult

181
Q

GABA transaminase is involved in metabolism of —–. Inhibition of the enzyme will potentiate the effects of GABA.

A

GABA

182
Q

convulsing pts use

A

benzodiazepine

183
Q

muscle spasm is the result of faulty coordination of the —— mediating control of movement. There are different reasons why nerves might fire inappropriately (Electrolyte imbalance, faulty vertebrae, others).

A

spinal cord mediated reflex arc

184
Q

The two major classes of drugs of the sedative-hypnotic and anti-anxiety type are

A

barbiturates and benzodiazapines.

185
Q

barbiturates and benzodiazapines.

Both of these types of drugs increase —- conductance via action at —– receptors but they do it slightly differently

A

Cl-

GABA-A

186
Q

The GABA A receptor is a —–. The GABA B receptor is a —-. GABA is the ligand for both types of receptor. Activation of either receptor results in hyperpolarization

A

ligand gated ion channel

G protein coupled receptor

187
Q

GABA B hyperpolarize by activating ——–. They also diminish —– entry into cells

A

K channels via GbGg

Ca++

188
Q

Barbiturates increase the

A

duration and frequency of GABA -mediated channel opening

189
Q

Benzodiazapines Anti-anxiety effects at doses that don’t produce

A

ataxia or somnolence. Barbiturates tend to knock-out everything.

190
Q

Sedative-hypnotic drugs

A

Barbiturates

191
Q

Drugs to treat anxiety/retrograde amnesia

A

Benzodiazepines in conjunction with local anesthetics

192
Q

Drugs to treat anesthetic-induced seizures

A

Benzodiazepines

193
Q

COPD:

A

chronic bronchitis and emphysema, a pair of two commonly co-existing diseases of the lungs in which the airways become narrowed. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath.

194
Q

T effector cells are critical mediators of

A

asthma

195
Q

—– determine the course of an inflammatory asthma response

A

Th cells

196
Q

Th2 cells mediate an inflammatory response in (eosinophilic) asthma leading to eosinophil infiltration of the lung by

A

cytokines

197
Q

Cytokines also regulate the balance between

A

Th1 and Th2

198
Q

Th1

A

Cell mediated immunity
Intracellular pathogens
Yeast, viruses, intracellular bacteria, cancer

199
Q

Th2

A

Humoral or antibody mediated immunity
Extracellular pathogens
Parasites, normal bacteria, toxins, allergens

200
Q

Atopy: Predisposition to

A

Th2 responses (frequently linked to asthma

201
Q

Eosinophilic Asthma

A

Eosinophils, basement membrane thickening
ICS* first line of defense
*Inhalational Corticosteroids

202
Q

Non-eosinophilic Asthma

A

No eosinophils, no basement membrane thickening

New treatment regimens needed - usually refractory to tx with ICS

203
Q

Eosinophilic asthma is glucocorticoid

A

responsive Th2

204
Q

Neutrophilic asthma is glucocorticoid

A

resistant - Th17

205
Q

——– (1000x more potent than histamine in the airway)

A

Leukotrienes

206
Q

Goals of asthma treatment

A

1) Relieve or prevent bronchoconstriction

2) Inhibit airway inflammation (reduce mucus production) 3) Prevent airway remodeling

207
Q

Goals of COPD treatment

A

Relieve bronchoconstriction
Improve exercise tolerance (keep patient active) Prevent and treat complications
Slow progress of the disease

208
Q

In asthma Brochoconstriction part of —— response, while in COPD Broconconstriction results from change in —–

A

allergic

vagal tone

209
Q

In COPD, ——– are involved while in Asthma ——– are involved

A

Neutrophils

Eosinophils

210
Q

Tools currently in the toolbox to treat Asthma/COPD

A

b2 adrenergic receptor agonists

corticosteroids leukotriene modifiers anticholinergics anti-IgE

211
Q

Agents stimulating —- will act as bronchodilators

A

PKA (activates K+ channels)

  • blocks MLCK
212
Q

Agents increasing ———— will act as bronchoconstrictors

A

Ca++ in the smooth muscle cell

213
Q

Activation of b2AR leads to —– activation

A

PKA

214
Q

SABAs have a

A

rapid onset of action and are used as rescue

medication - Short acting B2 agonists

215
Q

LABAs have a

A

long duration of action and are used as a component of maintenance therapy

Long acting beta 2 agonists

216
Q

Short-acting b agonists (SABA)
Administered by ———
Provide acute relief, or used as prophylactic for exercise induced asthma, rescue mediation
Effective within —–

A

inhalation

minutes, effects last 4-6 hrs

217
Q

Long acting b agonists (LABA)

Control ———–

A

persistent asthma, maintenance therapy COPD

218
Q

Long acting b agonists (LABA)

Not for —– treatment

A

acute

219
Q

Long acting b agonists (LABA)
Sometimes combined with ———–
Sometimes combined with ———-

A

corticosteroids

anticholinergics

220
Q

Long acting b agonists (LABA)

Relatively ———

A

hydrophobic

221
Q 
LABA
Lipophilic (Salmeterol > Formoterol)
• Initial accumulation in -------
• Membrane translocation to aqueous layer
• Bind to the receptor
A

lipid bilayer

222
Q

Hypothalamic-pituitary axis (HPA)

A 
• Cortisol is produced on demand
• Cortisol levels follow ACTH levels
• Production is regulated by:
1) Negative Feedback 2) Stress response
3) Diurnal rhythm:
223
Q

Cortisol

A 
Carbohydrate & protein metabolism:
• Support glucose-dependent organs
• Stimulate gluconeogenesis (liver)
• Stimulate protein and fat catabolismgglucose
• Decrease glucose utilization by cells
• Increase blood glucose levels
224
Q

-In mast cells, ———— produces tonic inhibitory influence on reactivity (i.e. mast cell degranulation)
-Annexin-A1 attenuates the ————-
decrease leukocyte adhesion
decrease leukocyte transmigration (crossing endothelial barrier) increase leukocyte apoptosis
-Annexin-A1 attenuates ————-

A

annexin-A1

innate immune response

eicosanoid production

225
Q

-In mast cells, ———— produces tonic inhibitory influence on reactivity (i.e. mast cell degranulation)
-Annexin-A1 attenuates the ————-
decrease leukocyte adhesion
decrease leukocyte transmigration (crossing endothelial barrier) increase leukocyte apoptosis
-Annexin-A1 attenuates ————-

A

annexin-A1

innate immune response

eicosanoid production

226
Q

The transcription factor ——- regulates genes responsible for both the innate and acquired immune responses

A

NF kB

227
Q

Gluccorticoids induce transcription of —-

A

IkB

228
Q

Gluccorticoids block NFkB mediated transcription by ———

A

chromatin remodeling

229
Q

Corticosteroids (glucocorticoids) 1)Acute treatment (——–)
2)Long-term management (————)

A

systemic

inhaled

230
Q

Adverse effects of inhaled corticosteroids

A

• Dysphonia
• Oropharyngeal candidiasis
• Adrenal suppression (usually at high doses, systemic absorption)
• Others
-osteoporosis -growth suppression -thinning of skin -easy bruising -cataracts
• Systemic absorption in asthma patients normal?
• Rinse mouth after inhalation
• Benefits normally outweigh risks, particularly in children

231
Q

ICS treatment not effective for

A

non eosinophilic asthma, pts with Glucocorticoid resistance

232
Q

An increase in ——- contributes mightily to broncho-constriction in COPD

A

vagal tone

Pharmacology (19 decks)

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