Exam 2 lecture 1 Flashcards
What is the second leading cause of blindness
glaucoma
Is glaucoma life long or one and done treatment
lifelong
two different types of glaucome
Open angle vs closed angle
difference between open vs closed angle glaucoma
Open agnle- most common (90%), happens gradually over time, painless, no vision change at first
Closed angle- Occurs when iris is very close to the lens or drainage angle and blocks it. It is a medical emergency
symptoms of open angle glaucoma
No symptoms during the early stages.
patchy blind spots in peripheral vision
Dificulty seeing in central vision
3 MOA to treat open angle glaucoma and the drugs to do it
Reduce aqueous humor production
increase aqueous humor outflow
Both
Which drugs can reduce aqueous humor production
B blockers
carbonic anhydrase inhibitors
Which drugs can increase aqueous humor outflow
prostaglandin analogs
cholinergics
RHo kinase inhibitors
Which drugs can reduce aqueous humor production and increase outflow
a-2 agonists
What are some 1st line options for open angle glaucome
prostaglandin analogs
B blockers
Name prostaglandin analog drugs
all end with prost
remember generic and brand
Bimatoprost (lumigan)
Travoprost (Travaton)
Latanoprost (xalatan)
Tafluprost (zioptan)
Bimatoprost (Latisse)
Which prostaglandin analog is indicated for eyelash hypotrichosis
Bimatoprost (latisse)
MOA of prostaglandin analogs
Increase aqueous humor outflow, (reduce IOP by 30%)
Dosing of prostaglandin
1 drop QHS
warnings of prostaglandin analogs
Darjkening of iris, increase eye lash length and number
side effects of prostaglandin analogs
Blurred vision
stinging
increased pigmentation
foreign body sensation
MOA of b blockers
decrease aqueous humor production
2 types of B blockers
non selective and selective
name non selective b blockers
Timolol (timoptic)
lartelol
levobunolol
name selective b blockers
Betaxolol (betoptic)
dosing of B blockers
1 drop daily or BID
contraindications of b blockers
sinus bradychardia
2nd or 3rd degree heart block
cardiogenic shock
uncompensated cardiac failure
side effects of b blockers
stinging
blurred vision
bradycardia
breathing problems
hypotension
diziness
fatugue
impotence
is betaxolol more effective than non selective
no
what is an alternative to 1st line therapy in glaucoma
a- agonist
moa of alpha agonist
increase aqueous humor outflow and reduce aqueous humor production
a-agonist drugs
Brimonidine (alphagan)
Aprachlonidine (iopidine)
Brimonidine (lumify)
dosing of a-agonist drugs
1 drop TID
Contraindication and warnings of a-agonist
CNS depression
Side effects of a-agonist
Dry eyes
xerostomia
blurry vision
sedation/confusion
Aprachlonidine clinical pearl
Does not have long term effects
xerostomia meaning
redness of eye
2nd line treatment of glaucoma
Carbonic anhydrase inhibitor
MOA of cAI
decrease aqueous humor production
Two ROA of CAI
opthalmic and oral
meds end with ide
Name opthalmic and oral CAI
Opthalmic- Dorzolamide (trusoft)
Brinzolamide (Azopt)
Oral- Acetazolamide
Methazolamide
Dosing of CAI
1 drop TID
warnings of CAI
sulfonamide allergy (meds end with amide )
side effects of opthalmic drugs
burning
blurred vision
blepharitis
taste disturbance
side effects of oral medications
Ataxia
Confusion
photosensitivity
What happens if CAI if bottles not capped
Can lead to crystallization
CAI not recommended in pts with
CRCL<30
3rd line treatment for glaucoma
Rho kinase inhibitor
MOA of rho kinase inhibitor
increased aqeous humor outflow
Rho-kinase inhibitor drugs
Netarsudil (rhopressin)
Dosing of Rho-kinase
1 drop QPM
side effects of rho kinase
Burning
Corneal disease
conjuctival hemorrhage
conjuctival hyperemia
remove contact lenses
Last line glaucoma treatment
Cholinergic
MOA of cholinergics
Increase aqueous humor outflow
Cholinergic drugs
carbachol (milostat)
pilocarpine (isopto carpine)
dosing of carbachol and pilocarpine
1-2 drops up to TID for carbachol
1-2 drops upto QID- pilocarpine
contraindications of cholinergics
Use with caution in patients with history of retinal detachment or corneal abrasion
Side effects of cholinergics
Pupil constriction
corneal clouding
hypotension
bronchospasms
tx algorithim for glaucoma
1st line- prostaglandin analog and B blocker
alternative a-agonist (brimonidine)
reassess response every 2-4 weeks.
If no response try different 1st line response (prostaglandin analog or b blocker)
if only partial response- add an additional 1st or 2nd line option (CAI)
3.
if inadequate reponse
increase concentration and frequency
add 3rd or 4th line treatment
consider replacing CAI with oral CAI
- Inadequate response to max therapy
laser/surgery
if more than 1 drop of the same med, how long should we wait between drops? different meds?
5 mins
5-10 mins for different meds
2 ointments
30 mins
1 drop 1 ointment
drop 1st, 5 mins later, ointment
when should we rule out B blocker
if pt has low HR and/or COPD
when to rule out CAI
sulfa allergy
sx of closed angle glaucoma
halos around eyes
severe pain
severe headache
when should we treat closed angle glaucome=a
immediately, may cause blindness
treatment of closed angle glaucoma
-Hyperosmotic agents
-Mannitol IV (1.5-2 g/kg/dose over 30 min)
-glycerin PO
1-2 g/kg/dose every 5 H
-surgery (irridotomy)
What are some medications that increase IOP
anticholinergics (oxybutin, tolterodine)
Topiramate
SSRIs
sudafed
Use of lipoprotein
transports cholesterol and triglyceride around the body
structure of lipoprotein
Sperical particle with phospholipid, free cholesterol and protein making up the surface
lipoprotein core made of
triglyceride and cholesterol ester
How do lipoproteins determine where to go
Apoproteins determine where lipoproteins go
what is lipoprotein lipase system
release free fatty acid from lipoprotein
Classes of lipoproteins
chylomicrons
VLDL
ILDL
LDL
HDL
chylomicrons use size and what makes it up
Transport dietary lipids from gut to liver and adipose tissue
biggest lipoprotein
predominantly triglyceride
VLDL secreted by, made up of, and size
secreted by liver into the blood
lots of triglyceride, but less than chylomicron, more cholesterol than chylomicron.
it is big, but smaller than chylomicron
IDL
intermediate between VLDL and LDL
triglyceride depleted VLDL
LDL yse
main form of cholesterol in blood
HDL secreted by, made up of, and use
secreted by liver
mostly protein, some cholesterol, no triglyceride
main use is reverse cholesterol transport (bring cholesterol from peripheral tissue to liver)
when centrifuged, which lipids will be low? which will be high?
densest will be low
HDL will be low
Chylomicrons will be highest
Which apoprotein are on the Lipids
apoprotein A1 on HDL
apoprotein B on the others
Name important apoproteins
Apo A1
Apo B-100
Apo b-48
Apo C II
APO E
Apo A1 use? what lipid is it on?
Mediates reverse cholesterol transport back to liver
structural in HDL
Apo B 100 found on? produced by? use?
Dound on everything except HDL and chylomicro
produced in liver
ligand for LDL
APO B 48 found on? produced by?
found on chylomicrons, produced by intestines
difference between APO b 100 vs 48
-B 100 found on VLDL, IDL and LDL and produced by liver, bigger than B 48
-B 48 found on Chylomicron and producede by intestine
Apo C II found on? binds to? use?
-Found on chylomicrons and VLDL
-Binds to enzyme called lipoprotein lipase to enhance TG hydrolysis
APO E found in? Use?
found on HDL
ligand for LDL remnant receptor (helps get cholesterol into liver)
What is LPL? where is it found?
Lipoprotein lipase. Found in capillaries of fat, cardiac and skeletal muscle
What is HL? produced by? Use?
hepatic lipase
produced in liver
converts IDL to LDL
2 pathways for lipid absorption and trasnport
Exogenous pathway
endogenous pathway
describe the exogenous pathway
-eat food (dietary fat+cholesterol)
-absorbed into intestine and chylomicrons made
-chylomicrons encounter LPL (LPL break down trg into FFA, which are distributed into peripheral tissue.
-chylomicron remnants are reduced by LPL and HL and taken back up to liver through remnant receptor (APO E mediated profess)
-liver can secrete VLDLs, VLDLs encounter LPL and FFAare taken up.
-leads to reduction of VLDL into IDL
-IDL can be taken up into liver by APO E and remnant receptor OR it can be further hydrolized into LDL
HL is key for
converting IDL to LDL
What happens to IDL in exogenous pathway
some of the IDL gets taken up into liver and some of it gets converted to LDL
this is the way cholesterol is distrubuted in the body
most important apoprotein on LDL is
B-100
primary apoprotein for HDL? HDL importance
Apoprotein A1. HDLS are important for reverse transport cholesterol from peripheral tissue to liver
What does CETP stand for? What does it do?
Cholesterol ester transfer protein
move cholesterol esters from HDL into IDL in exchange for triglycerides
What is foam cell? how is it formed?
Foam cell is the basic unit of atherosclerotic plaque.
OXIDIED LDLs become tragets for scavenger receptors. leading to formation of foam cells.
what is the most critical way of reducing cholesterol
inhibiting synthesis of choletserol by liver.
What is the key building block for cholesterol
Mevalonate
What is a key enzyme that produces mevalonate
HMG-COA reductase
Lipoprotein disorders are detected by
measuring lipid in serum after a 10 hour fast
Ratio of total cholesterol to HDL and risk of CVD
Ratio of>4,5 is associated with increased risk of CVD
Ratio of < 3.5 is desirable
<3 is optimal
What are the two diseases associated with lipoprotein disorders
hyperproteinemia
Hypertriglyceridemia
What are hyperlipoproteinemia diseases
-Atherosclerosis - excess accumulation of cholesterol in smooth muscle
-Premature coronary artery disease
-neurologic disease (stroke)
What are hypertriglyceridemia diseases
-pancreatitis
-xanthoma
-increased risk of CHD
Atherosclerotic plaque and thrombosis are a deadly combo
Explain atherosclerosis
-Presence of a high number of LDLs lead to higher levels of oxidized LDL.
-Oxidized/modified LDLs get into the area between the endothelium and vascuar smooth muscle (entema)
-this stimulates T cells and they secrete pr inflammatory cytokines, cintributing to uptake of cholesterol
Name drugs used for high cholesterol
Bile acid binding resins
Inhibitors of cholesterol absorption
inhibitors of cholesterol synthesis
PCSK9 inhibitors
MTTP inhibitors
Drugs used for high triglycerides
Fibrates
Niacin
Omega 3 fatty acids
Bile acid binding resin MOA
inhibit reabsorption of bile acids from intestine by binding bile acids to form insoluble complex excreted in feces.
causes upregulation of LDL in liver to make more bile acids
all bile acid binding resins have positive charge
Bile acid binding resin drugs
Cholestyramine (queastran)
Olestipol (colestid)
all have positive charges on them.
What happens when liver is running low on LDL and needs to make bile (after we inhibit reabsorption of bile acids)
When liver is running low on cholesterol, there is an increase in LDL receptors, bringing LDL level in body to liver and away from peripheral tissues and entema.
by sequestering bile acids with bile acid resins, we can increase excretion of bile acid by
10 fold
bile acid binding resin side effects
Constipation and bloating
use of bile acid? how long does it take to work?
Used in hypercholesterolemia
reduce LDL in 2-4 weeks
may raise it 5%
May increase TG
Cholesterol absorption inhibitor drug
Ezetimebe
Ezetimebe MOA
inhibits intestinal absorption of cholesterol from dietary sources and reabsorption of cholesterol excreted in bile.
How does ezetimebe affect cholesterol in bile acid? how does it do it?
Binds NPCL4 and interferes with the ability of AP-2 to stimulate endocytosis of transporter
Indication of ezetimebe
Reduce LDL levels
used in combo with statins
How does ezetimebe affect statin action
May enhance statin action by 20%
ezetimebe adverse effects
Low incidence of liver and skeletal muscle damage
