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FINAL. OPT 226A. Pharm > Background > Flashcards

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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 (-)

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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

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A

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

25
Cmax
(Max - Peak Conc) of antibiotic
26
Cmax / MIC
(Conc-dep) = (Time-indep) - Rate/Extent of bacterial killing dep on conc of antibactieral
27
AUC / MIC
(Time-dep) AND (Conc-dep)
28
T > MIC
(Time-dep) = (Conc-indep) - Rate/Extent of bacterial killing does NOT dep on conc of antibactieral
29
Folate synthesis pathway
PABA >> (Dihydropteroate synthetase) >> Folate >> (Dihydrofolate reductase) >> Tetrahydrofolate >> Synthesis of thymidylate, etc. >> DNA
30
Narrow spectrum vs. Broad spectrum Anti-bacterial
(Narrow) - If ID bacterial type >> Have killing power / (Broad) - Unsure of bacterial type
31
Bacteriostatic vs. Bacteriocidal
INHIBITS bacterial multiplication >> Allow immune system to take over w/ killing power (vs.) KILLS bacteria
32
Ocular DNA viruses
Herpes simplex virus (HSV) / Varicella zoster virus (VZV) / Adeno virus >> Keratitis, Conjunctivitis / Cytomegalo virus (CMV) - Opportunistic in immunocompromised patients >> Necrosis, Hemorrhage, Retinitis
33
Category B vs. Category C drugs
(B) - NO animal data, NO human data suggesting fetal abnormalities vs. (C) - ANIMAL data, but NO human data suggesting fetal abnormalities
34
Drug depots
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) >> (dec) onset (b/c longer time bound to non-target site) >> (inc) duration (b/c longer time drug in existance)
35
Intra/Extraocular injections - Reason
b/c topical drugs can NOT pass through lens/vitreous (though inc space if IOL)/compete (backwards) against nat fluid flow (forward)
36
Extraocular injections - Types
Subconjunctival, Sub-Tenon's capsule, Retrobulbar, Peribulbar, Intramuscular
37
Intraocular injections
Intravitreal (Anti-VEGF), Subretinal (btwn ret and RPE - Gene therapy), Intracameral (into ant chamber - Cataract surgery)
38
Purite preservative
(in Brimonidine) - (inc) oc penetration - less cytotoxic effects
39
BAK preservative
(in Timolol) - (anti-fungal) - (inc) corneal penetration BUT (erode) corneal epi (bad for dry eye)
40
EDTA preservative
(in Levobunolol) - Ca chelating agents - Binds to Ca - (inc) drug movement
41
Purpose of nasolacrimal occlusion
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 >> Prevent drainage of drug mixed w/ tears into systemic circulation = Prevent systemic side effects
42
Prodrug vs. Soft drug
(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
Effect of long-term/cont exposure of receptor to AGONIST
Desensitize receptors, Alter coupling btwn receptors and its downstream 2nd messenger (but enzymes do NOT interact w/ receptors)
44
First-pass effect - Type of drug admin influenced
Orally-admin drugs (NOT rectal/inhaled/topical - mucosa of nose/mouth >> BVs, bypassing liver)
45
Therapeutic index
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
Diff in 1 drop of 1% vs. 2 drops of 0.5%
(2 drops) - Over max capacity of eye to hold drops - Rapid drainage - First drop wash out second drop Twice as much preservative
47
Sig of seq of dilating drops - Proparacaine >> Phenylephrine >> Tropicamide
PROPARACAINE - Disrupts corneal epi >> (inc) corneal penetration >> PHENYLEPHRINE (alpha1-agonist) - VC (prevents nonproductive absorption) - Induces dilator - Mydriasis >> TROPICAMIDE (anti-M3) - Blocks sphincter constriction and causes dilation by working on the dilator
48
Plasma conc of oral drug dep on...
Dose, Rate of absorption, Bioavailability, Rate of elim
49
Effects of binding of drug to plasma protein
(dec) tissue levels of drug/apparent vol of distrib/metabolism of drug, (inc) half life (depot effect) / excretion of drug
50
Drug affinity for albumin vs. globulin
Acidic (affinty for albumin) vs. Basic (affinity for globulin)
51
Effects that may result from repeated drug admin
(inc) drug metabolism / metabolism of another drug taken concurrently / metabolism of endogenous component, (dec) response to drug
52
Phase I biotransformation - Effects
Always inducible upon repeated drug admin - For drug elim >> 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
(Inc) IOP in glaucoma
(inc) IOP >> Change BVs >> (dec) BP, (dec) Blood flow >> Ischemia / Mech >> ONH damage / Shift in peak of diurnal fluctuation - (inc) IOP - (dec) Diastolic BP, (dec) Diastolic oc perfusion P
54
Conventional outflow
via TM, Schlemm's canal
55
Unconventional outflow
via Choroid, Sclera
56
Glutamate pathway
Glutamate (in higher levels of vitreous in glaucoma patients) >> NMDA receptor >> (inc) Ca >> Cell membrane failure >> Free radicals

FINAL. OPT 226A. Pharm (3 decks)

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