Background Flashcards

1
Q

Wet AMD - Progression

A

Outer seg of PR&raquo_space; Engulfed by RPE&raquo_space; Drusen (accumulation of debris) &raquo_space; Autophagy (debris-filled macrophages)&raquo_space; Inflammation&raquo_space; (Inc) VEGF&raquo_space; Neovasc&raquo_space; Leaky BVs (under RPE)

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2
Q

Type I - Hypersensitivity rxn

A

(Common) = Immediate / Anaphylactic - (Fast) - Few min / Initial exposure - B cells&raquo_space; Produ IgE / Second exposure - IgE binds to mast cells, Antigen binds IgE, IgEs cross-link&raquo_space; Mast cell degranulation, Histamine release (e.g. Hay fever, Asthma)

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3
Q

Type IV - Hypersensitivity rxn

A

(Common) = Cell-Mediated / Delayed - (Slow) 1-2 days - Antigen interacts w/ T cell&raquo_space; Cytokine release (e.g. Contact dermatitis, Vernal conj)

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4
Q

[COX], [LOX] pathway

A

Linoleic acid (Dietary PUFA, omega-6 fatty acid - Corn oil&raquo_space; livestock/ Dec by omega-3 - Fish oil) OR Cell membrane phospholipids&raquo_space; (Phospholipase A2)&raquo_space; Arachidonic acid&raquo_space; LOX - Leukotrines / COX&raquo_space; Insertion of O2&raquo_space; Eicosanoids - Prostanoids (Thromboxane - TXA2, Prostaglandin, Prostacyclin - PGI2)

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5
Q

[COX-1]

A

Constituent (In all tissues, esp GI)&raquo_space; Thromboxane (TXA2), Prostaglandins (PGD2, PGE2, PGF2), Prostacyclins (PGI2)

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6
Q

[COX-2]

A

Inducible (In kidney, GI, CNS, (vascular) endo&raquo_space; Upreg during inflammation)&raquo_space; Prostaglandins (PGE2), Prostacyclins (PGI2)

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7
Q

Why [COX-2]- inhibitors removed from market

A

(e.g. Refecoxib - Vioxx) - (Inhibit) prostacyclins (PGI2) inhibiting platelet aggregation that usually counteracts thromboxane (TXA2) that (inc) platelet aggregation&raquo_space; Clogging BVs - Inc risk of MI, CVA

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8
Q

Thromboxane (TXA2)

A

Platelet aggregation, VC (Triggered by atherosclerosis)

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9
Q

Prostaglandin (PGD2)

A

(DP receptor) - (inc) cAMP, Ca - Allergic rxn, Sleep/wake cycle

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10
Q

Prostaglandin (PGE2)

A

(EP receptor) - (inc) cAMP - Uterine contractions during labor, VD, (dec) stomach acid, Renal homeostasis

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11
Q

Prostaglandin (PGF2)

A

(FP receptor) - Uterine contractions during labor

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12
Q

Prostacyclin (PGI2)

A

(IP receptor) - (inc) cAMP - (Inhibits) platelet aggregation, VD, Renal homeostasis

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13
Q

Nociceptive pain processing

A

Stimulus&raquo_space; Factors/inflammation (PG, NO, Bradykinin, Nerve GF), Nt (Glutamate, Substance P)&raquo_space; Afferent nerve fibers (A-delta) - Myelinated (sharp somatic pain) - (C) - Unmyelinated (dull visceral pain)&raquo_space; CNS (Spinal cord) - Dorsal horn, (Brain) - Thalamus/reticular formation (sense pain), Cortex/limbic system (emo to pain)

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14
Q

Neg feedback (to nociceptive pain processing)

A

Serotonin, NE, Opioid&raquo_space; Opioid receptor (Inhibitory G-protein)&raquo_space; (dec) cAMP&raquo_space; (dec) Ca influx, dec nt release&raquo_space; (inc) K out, dec excitability

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15
Q

Opioid receptor subtypes

A

(w/ endogenous opioid affinity) - (u) - Endorphins, (k) - Dynorphins, (delta) - Enkephalins / (u) - Euphoria, (dec) respiration, (k) - Dysphoria, hallucinations, (u and k) - Sedation, Constipation, miosis, (u, k, and delta) - Analgesia

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16
Q

Empirical vs. Definitive vs. Prophylactic antibiotic use

A

Empirical - Initiate Tx prior to det Dx

Definitive - Tx after confirming Dx

Prophylactic - Preventative measure (for patients predisposed to condition)

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17
Q

Prokaryotic cell - Cell wall, Plasma (cytoplasmic) membrane, Nuclear membrane, Genome, Organelles, Ribosomes, Cell division

A

(Wall) - Proteins, peptidoglycan, lipids / NO sterols / NO nuclear membrane / Single, circular DNA in nucleoid / NO organelles / 70 S (50 S + 30 S subunits) / Binary fission

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18
Q

Human Eukaryotic cell - Cell wall, Plasma (cytoplasmic) membrane, Nuclear membrane, Genome, Organelles, Ribosomes, Cell division

A

NO wall / Sterols / nuclear membrane / Multiple DNA molecules / 80 S (60 S + 40 S subunits) / Mitosis, Meiosis

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19
Q

Design of antibacterial combo drugs

A

Diff MOA (One bacteriostatic, One bacteriocidal), Diff spectrum coverage (One for Gram +, One for Gram -)

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20
Q

Antibiotic resistance in US vs Europe

A

In US antibiotics are not filtered from water supply (but in Europe they are)

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21
Q

Bacteria’s diff mech to antibiotic resistance

A

(Inactivate) - via Enzyme modification of drug, (Dec uptake) - Porin prevents drug entry, (Alt target) - Drug can NOT bind to target, (Inc elim) - Pump ejects drug that entered / (VRSA) - Swap genetic material w/ another bacteria, (Staph) Beta-lacatamse - Penicillinase - Change beta-lactam structure

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22
Q

(e.g. Antibiotic/Methicillin/Vancomycin/Multidrug-resistant)

A

(Mycobacterium TB, Staph aureus (MRSA) - Leading cause of hospital-acquired infections (VRSA), Enterococci (VRE), Neisseria gonorrhoeae/Gram neg bacteria - K pneumoniae, E coli)

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23
Q

Gram (+) vs Gram (-)

A

(+) w/ THICK peptidoglycan cell wall (above cytoplasmic membrane w/ penicillin-binding protein / below outer membrane w/ beta-lactamase) (Purple stain) / (-) w/ outer membrane w/ porin channel, lipopolysaccharides (evade ID by human immune system / major component of bacterial endotoxin released upon bacterial death&raquo_space; fever, dec BP) (Pink stain)

24
Q

MIC

A

(Minimum Inhibitory Conc) - Lowest conc of antibiotic that completely inhibits bactieral growth

25
Q

Cmax

A

(Max - Peak Conc) of antibiotic

26
Q

Cmax / MIC

A

(Conc-dep) = (Time-indep) - Rate/Extent of bacterial killing dep on conc of antibactieral

27
Q

AUC / MIC

A

(Time-dep) AND (Conc-dep)

28
Q

T > MIC

A

(Time-dep) = (Conc-indep) - Rate/Extent of bacterial killing does NOT dep on conc of antibactieral

29
Q

Folate synthesis pathway

A

PABA&raquo_space; (Dihydropteroate synthetase)&raquo_space; Folate&raquo_space; (Dihydrofolate reductase)&raquo_space; Tetrahydrofolate&raquo_space; Synthesis of thymidylate, etc.&raquo_space; DNA

30
Q

Narrow spectrum vs. Broad spectrum Anti-bacterial

A

(Narrow) - If ID bacterial type&raquo_space; Have killing power / (Broad) - Unsure of bacterial type

31
Q

Bacteriostatic vs. Bacteriocidal

A

INHIBITS bacterial multiplication&raquo_space; Allow immune system to take over w/ killing power (vs.) KILLS bacteria

32
Q

Ocular DNA viruses

A

Herpes simplex virus (HSV) / Varicella zoster virus (VZV) / Adeno virus&raquo_space; Keratitis, Conjunctivitis / Cytomegalo virus (CMV) - Opportunistic in immunocompromised patients&raquo_space; Necrosis, Hemorrhage, Retinitis

33
Q

Category B vs. Category C drugs

A

(B) - NO animal data, NO human data suggesting fetal abnormalities vs. (C) - ANIMAL data, but NO human data suggesting fetal abnormalities

34
Q

Drug depots

A

DEP on type of condition Tx (e.g. Pigmented area = Target site = Good = NOT depot) (e.g. Lipid membranes, fat deposits, plasma proteins, pigment in iris/RPE (site of toxicity) /ciliary body/PE/choroid) &raquo_space; (dec) onset (b/c longer time bound to non-target site)&raquo_space; (inc) duration (b/c longer time drug in existance)

35
Q

Intra/Extraocular injections - Reason

A

b/c topical drugs can NOT pass through lens/vitreous (though inc space if IOL)/compete (backwards) against nat fluid flow (forward)

36
Q

Extraocular injections - Types

A

Subconjunctival, Sub-Tenon’s capsule, Retrobulbar, Peribulbar, Intramuscular

37
Q

Intraocular injections

A

Intravitreal (Anti-VEGF), Subretinal (btwn ret and RPE - Gene therapy), Intracameral (into ant chamber - Cataract surgery)

38
Q

Purite preservative

A

(in Brimonidine) - (inc) oc penetration - less cytotoxic effects

39
Q

BAK preservative

A

(in Timolol) - (anti-fungal) - (inc) corneal penetration BUT (erode) corneal epi (bad for dry eye)

40
Q

EDTA preservative

A

(in Levobunolol) - Ca chelating agents - Binds to Ca - (inc) drug movement

41
Q

Purpose of nasolacrimal occlusion

A

INCREASES ABSORPTION - b/c Decrease tear drainage (Lacrimal turnover limits contact time btwn cornea and drug mixed with tears = Less corneal absorption of drug), PREVENTS UNDESIRABLE SIDE EFFECTS - Occlude puncta&raquo_space; Prevent drainage of drug mixed w/ tears into systemic circulation = Prevent systemic side effects

42
Q

Prodrug vs. Soft drug

A

(NOT inclusive OR mutually exclusive - Drug can be both, or only one) - (Pro) - Admin inactive / less active precursor of more active metabolite (but NOT gen more potent than drugs admin active form) - Activated after admin (w/ Phase I biotransformation) vs. (Soft) (e.g. Steroids) - Deactivated locally - Less prone to causing long-term/sig syst SE

43
Q

Effect of long-term/cont exposure of receptor to AGONIST

A

Desensitize receptors, Alter coupling btwn receptors and its downstream 2nd messenger (but enzymes do NOT interact w/ receptors)

44
Q

First-pass effect - Type of drug admin influenced

A

Orally-admin drugs (NOT rectal/inhaled/topical - mucosa of nose/mouth&raquo_space; BVs, bypassing liver)

45
Q

Therapeutic index

A

TI = LD50/ED50

LD50 - Lethal dose (conc causing 50% death)

ED50 - Effective dose (conc causing 50% therapeutic outcome)

Higher = Better (req > conc to cause 50% death) - “Curves are further apart”

Provides info on safety of drug BUT does NOT indicate closeness of toxic effect (which is shown w/ safety margin)

46
Q

Diff in 1 drop of 1% vs. 2 drops of 0.5%

A

(2 drops) - Over max capacity of eye to hold drops - Rapid drainage - First drop wash out second drop Twice as much preservative

47
Q

Sig of seq of dilating drops - Proparacaine&raquo_space; Phenylephrine&raquo_space; Tropicamide

A

PROPARACAINE - Disrupts corneal epi&raquo_space; (inc) corneal penetration&raquo_space; PHENYLEPHRINE (alpha1-agonist) - VC (prevents nonproductive absorption) - Induces dilator - Mydriasis&raquo_space; TROPICAMIDE (anti-M3) - Blocks sphincter constriction and causes dilation by working on the dilator

48
Q

Plasma conc of oral drug dep on…

A

Dose, Rate of absorption, Bioavailability, Rate of elim

49
Q

Effects of binding of drug to plasma protein

A

(dec) tissue levels of drug/apparent vol of distrib/metabolism of drug, (inc) half life (depot effect) / excretion of drug

50
Q

Drug affinity for albumin vs. globulin

A

Acidic (affinty for albumin) vs. Basic (affinity for globulin)

51
Q

Effects that may result from repeated drug admin

A

(inc) drug metabolism / metabolism of another drug taken concurrently / metabolism of endogenous component, (dec) response to drug

52
Q

Phase I biotransformation - Effects

A

Always inducible upon repeated drug admin - For drug elim&raquo_space; Biotransformation (via Catabolic - Breakdown) - Usually, but does NOT always yield water-soluble molecules / BUT important to activate prodrugs, may intro active center for further conjugation

53
Q

(Inc) IOP in glaucoma

A

(inc) IOP&raquo_space; Change BVs&raquo_space; (dec) BP, (dec) Blood flow&raquo_space; Ischemia / Mech&raquo_space; ONH damage / Shift in peak of diurnal fluctuation - (inc) IOP - (dec) Diastolic BP, (dec) Diastolic oc perfusion P

54
Q

Conventional outflow

A

via TM, Schlemm’s canal

55
Q

Unconventional outflow

A

via Choroid, Sclera

56
Q

Glutamate pathway

A

Glutamate (in higher levels of vitreous in glaucoma patients)&raquo_space; NMDA receptor&raquo_space; (inc) Ca&raquo_space; Cell membrane failure&raquo_space; Free radicals