DR and ARMD Flashcards
_________________ means the RATE and EXTENT to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action
Bioavailability
HIGHLY SIMILAR TO THE REFERENCE PRODUCT notwithstanding minor differences in clinically inactive components, and there are NO CLINICALLY MEANINGFUL DIFFERENCES between the biological product and the reference product in terms of the safety, purity, and potency of the product.
Biosimilar or biosimilarity
Drug products that contain the same therapeutic moiety but as DIFFERENT SALTS, ESTERS, OR COMPLEXES.
Pharmaceutical alternatives
Different dosage forms and strengths within a product line by a single manufac- turer are pharmaceutical alternatives (eg, an extended- release dosage form and a standard immediate-release dosage form of the same active ingredient)
The FDA currently considers a tablet and capsule containing the same active ingredient in the same dosage strength as pharmaceutical alternatives.
Drug products in IDENTICAL DOSAGE FORMS that contain the same active ingredient(s), but different amounts of inactive drug that is, the same salt or ester, are of the same dosage form, use the same route of administra- tion, and are identical in strength or concentration
Pharmaceutical equivalents
Pharmaceutically equivalent drug products are formulated to contain the same amount of active ingredient in the same dosage form and to meet the same or compendial or other applicable standards (ie, strength, quality, purity, and identity), but they may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (including colors, flavors, preservatives), expiration time, and, within certain limits, labeling.
The process of dispensing a pharmaceutical alternative for the prescribed drug product.
Pharmaceutical substitution
For example, ampicillin suspension is dispensed in place of ampicillin capsules, or tetracycline hydrochloride is dispensed in place of tetracycline phosphate. Pharmaceutical substitution generally requires the physician’s approval.
Drug products containing different active ingredients that are indicated for the same therapeutic or clinical objectives.
Therapeutic alternatives
Active ingredients in therapeutic alternatives are from the same pharmacologic class, for example, ibuprofen is given instead of aspirin; cimetidine may be given instead of ranitidine.
Therapeutic equivalents:
Drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents and if they can be expected to have the same clinical effect and safety profile when administered to patients under the con- ditions specified in the labeling.
The availability of the absorption product compared to the recognized standard
Relative bioavailiabilty
AB=F
Absolute bioavailability = fraction of dose absorbed
The macula is located behind the:
Pupil
TorF: low concentration of cones facilitate clear and crisp central vision
False. High concentration of cones facilitate clear and crisp central vision
The initial stage of DR is called
Nonproliferative DR (NPDR; previously termed “background” retinopathy)
Advanced stage of diabetic retinopathy can be termed:
Proliterative DR
TorF: DME occurs at the end of the disease
False:
Diabetic macular edema (DME) or diabetic macular ischemia can occur at any stage of the disease
Chronic intracellular hyperglycemia triggers a cascade of biochemical
mechanisms at the cellular level that drive the disease process incl:
Aldose reductase (sorbitol) and protein kinase C (PKC) pathways
Renin‐angiotensin system (RAS)
Oxidative stress (OS)
Accumulation of advanced glycation end products (AGE)
Release of inflammatory mediators and vascular endothelial growth factor (VEGF) that damage ophthalmic vascular endothelial cells.
tiny swellings, or microaneurysms, in the retinal capillary walls:
Mild NPDR
severe hemorrhages, microaneurysms and exudate formation
Severe NPDR
Moderate NPRD
Exudates: Lipid‐rich deposits formed by fluid‐containing lipids
seeping from leaky damaged capillaries
Edema and retinal hemorrhages
Capillary occlusions – formed as body attempts to repair vessel damage leads to ischemic retina
Cotton wool spots – formed by oxygen‐deficit distal to capillary
occlusion
Clinical findings of PDR
Occlusion of blood vessels with ensuing ischemia leads to upregulation of growth factors which stimulate
neovascularization (formation of new blood vessel) that are abnormal (thin,fragile) vessels that rupture easily and bleed into the
vitreous and retina
Activation of ___________ stimulates endothelial cell proliferation, migration, survival and angiogenesis
VEGFR‐2
CORTICOSTEROIDS used to tx DR:
Dexamethasone
Fluocinolone
VEGF INHIBITORS drugs used to tx DR:
Ranibizumab
Aflibercept
MOA of corticosteroids:
Decreased release of vasoactive and chemo‐attractive factors
at inflammation sites
Decreased secretion of lipolytic and proteolytic enzymes
Decrease migration of leukocytes to inflammation sites
Increase tight junctions between capillary endothelial cells
What is dexamethasone used for?
Used for the treatment of:
Macular edema following branch or central retinal vein occlusion
Diabetic macular edema
Non‐infectious uveitis affecting the posterior segment of the eye
What is Fluocinolone used for?
Used for the treatment of diabetic macular edema in patients who have been treated with a course of corticosteroids without a significant rise in IOP
What VEGFI drugs are used in the tc of DR:
ranibizumab and aflibercept
MOA of VEGF?
Acts by inhibiting VEGF production and preventing retinal neovascularization
RANIBIZUMAB
A recombinant, humanized antibody fragment active against all isoforms of VEGF‐A
RANIBIZUMAB can be used in the tax of:
Diabetic retinopathy
Diabetic macular edema
Neovascular (wet) age‐related macular degeneration*
Macular edema following retinal vein occlusion
Myopic choroidal neovascularization*
AFLIBERCEPT
A recombinant fusion protein comprising the key VEGF‐binding domains of human VEGF receptors.
AFLIBERCEPT can be used in the tx of:
Diabetic retinopathy
Diabetic macular edema
Neovascular (wet) age‐related macular degeneration*
Macular edema following retinal vein occlusion
DRY ARMD is characterized by
Drusen (yellow deposits of lipids and proteins)
RPE abnormalities
Atrophy of RPE and choriocapillaris
WET ARMD
Growth of abnormal new blood vessels (neovascularization) causes more damage to retina, with subsequent scarring at the macula (disciform scar).
WET ARMD:
Primary dysfunction: hypoxic insult to choriocapillary blood vessels leads to increase in growth factors (e.g., VEGF), resulting in growth of blood vessels underlying the macula
Early ARMD Tx:
Vit C (1.1‐0.5 g/day; Vit E (50‐100 IU/day); Beta‐carotene (100‐ 300 mg/day);
Mineral supplementation ‐ Zinc oxide; cupric oxide & selenium
*AREDS found that the combination of Vitamins and minerals offered maximal protection
Reduced progression of intermediate to advanced stages of ARMD by 25% after 5 years
Drugs to tx WET ARMB:
VEGF INHIBITORS
VERTEPORFIN
VEGF INHIBITORS
Pegaptanib
Brolucizumab
Ranibizumab*
Aflibercept*
pegylated RNA aptamer that binds to the VEGF‐A 165 isoform
PEGAPTANIB
PEGAPTANIB
Inhibits VEGF formation
humanized, single chain antibody that I nhibits VEGF‐A
BROLUCIZUMAB
VERTEPORFIN
Photosensitizing agent utilized in Photodynamic Therapy
Administered by IV; transported bound to LDL; absorbed by defective choroidal blood vessels
Then activated by a non‐thermal light source (689 nm wavelength laser light) to release free radicals that damage dysfunctional tissue
Can halt the progression of vision loss in patients with ARMD who have subfovea choroidal neovascularization
Side effects include injection site reactions (pain, edema, rash), visual disturbances (blurred vision, decreased visual acuity, flashes of light) Used for the treatment of choroidal neovascularization due to ARMD
