Hormones and reproduction Flashcards
1
Q
define glaucoma?
A
blanket term for a variety of conditions
common factor is acquired progressive neuropathy if untreated
2
Q
pathophysiology of glaucoma
A
optic nerve damage
visual field loss
eventual blindness
3
Q
symptoms of glaucoma?
A
usually asymptomatic
4
Q
what should happen if you’re over 40 years
A
yearly checks
5
Q
what is the normal range for interoccular pressure?
A
12-16 mmHg
6
Q
what is the IOP in people with glaucoma?
A
> 21mmHg
7
Q
risk factors for glaucoma?
A
family history race- africans systemic hypertension CVD migraine previous ocular disease r surgery
8
Q
what is glaucoma usually caused by?
A
impaired drainage of aq humour
can be primary or secondary- due to something else
9
Q
closed angle tends to be treated by?
A
surgery
10
Q
what does open angle refer to?
A
the angle between the iris and outer bit
11
Q
what is the trabecular meshwork?
how does this allow for aq humour flow
A
at the crook of the angle: with lots of spaces between the cells so the AH can flow through these spaces into the collector tunnel and into the episcleral vein
12
Q
once the AH has flowed through the spaces in the TM where does it go?
A
into the collector tunnel and into the episcleral vein
13
Q
where is the AH produced?
A
Cilary muscle, where the outer epithelial cells create the AH from the capillary fluid
14
Q
why does the AH flow into the episcleral vein?
A
as the pressure in the anterior chamber is higher than the vein
16mmHg compared to 8mmHg
15
Q
the trabecular network allows ___% of the AH to flow through
A
80
16
Q
what is another method of AH outflow besides the TM
A
scleral outflow- it can bypass the TM and go through the cells of the sclera and ciliary body into the venous system
17
Q
why is scleral outflow less than the TM
A
cells are held tighter together so there’s more resistance
18
Q
what do we look for in antiglaucoma treatment?
A
reduced IOP- as this is what causes neuropathy
<16-20mmHg
drug to have a sufficient duration of action
prevention of vision loss
compatible with other drugs
lack of side effects
no loss of effects over time
19
Q
why do we want IOP below 16-20 mmHg
A
as below 21 will prevent neuropathy
20
Q
why dont we want the drugs to lose effects over time
A
as usually life long
21
Q
what are first line glaucoma treatment?
A
prostaglandins and prostamide analogues
22
Q
PG__ has a huge impact of AH production
A
E
23
Q
why cant we use PGE for treatment?
A
as its very unstable so gets broken down quickly
24
Q
analogues of PG F2a are used as they are?
A
more stable
esters- more stable in formulation
25
why are prostaglandins a good treatment?
unique mechanism of action to decrease IOP
| most efficacious
26
examples of the prostaglandin (F2a) analogues?
latanoprost
travoprost
Tafluaprost
27
what do prostaglandin F2a act on?
PGF2a receptor (FP receptor)
28
what happens to the prostaglandin (F2a) analogues? they're _______
converted back to the acid (from the ester) so they're prodrugs
only the acid binds to the FP receptor
29
the FP receptor is a _______
GPCR
30
what happens once the FP receptor is stimulated?
Gaq
| once stimulated will activate PLC, dag and IP3
31
where are FP receptors present?
Hilary body
ciliary muscle
sclere
iris sphincter- doesn't have much effect on IOP
32
where do the prostaglandin (F2a) analogues have little effect on IOP? why?
iris sphincter
TM
as there's few of the receptors present
33
what are the 3 PG analogues?
latanoprost
tafluprost
travoprost
34
the 3 PG analogue are ______
prodrugs
| ester converted to acid
35
the 3 PG analogues have a _____ duration action, hence
short
| only need to take once at night
36
PG analogues lower IOP by?
35%
37
how well are PG analogues tolerated?
well!
38
what are protamine analogues?
analogues of prostaglandin F2a1
| ethanol amide
39
what do prostamide analogues act on?
also FP receptors
| prostamide receptors- more expressed in TM
40
where are prostamide receptors expressed more in comparison to PG
TM
41
effects of prostamide analogues?
increased uveoscleral and trabecular outflow
42
are prostamide analogues a prodrug
no
43
TF: PG analogues are more potent at FP receptors than prostamide analogues?
false- just as potent as each other
44
are the efficacy, tolerability and side effects of prostamide analogues the same as PG analogues? why?
yes
| as predominant action for both is via the same receptors
45
example of prostamide analogues?
only one
| bimatoprost
46
prostamide analogues mechanism of action?
increase uveoscleral outflow
reduced resistance to outflow by remodelling extracellular matrix which is achieved by: Increase matrix metalloproteinases
Degrades collagen and extracellular matrix
Decreases resistance of ciliary muscle and sclera to increase outflow
FPs on ciliary muscles and body and sclera
TB- negabile increase
47
how do protamine analogues cause reduced resistance to outflow?
Increase matrix metalloproteinases
Degrades collagen and extracellular matrix
Decreases resistance of ciliary muscle and sclera to increase outflow
48
how do prostamine analogues increase AH flow through the scleral cells?
change the cell structure
more enzymes introduced to break down collagen structure of the scleral cells
lose and holey cells like the TM
49
side effects of PG and PA analogues?
red eye- vasodilation
increased pigmentation in iris, eyelashes and periocular skin
eyelash growth and darker
sensitivity to light
pregnancy its contraindicated as PGs are needed for cell growth and can induce labour
50
will you always get vasodilation with PGs and PA analogues?
no decreases after the first couple of times
51
why does PGs and PA analogues cause pigmentation?
FP receptors are onmelanocytes
52
what are rare side effects fo PG and PA analogues?
sensitivity to light
| precipitate or worsen cymoid macular oedema in aphakic eyes
53
how do beta 2 cells contribute to AH production?
GPCR
cAMP production- which regulates ion transport in the ciliary epithelium
greater ion movement into the posterior chamber which = osmotic gradient
more fluid is thus filtered into the chamber
54
which ion channels does cAMP have an effect on in pigmented cells?
Na/ K/ 2Cl
55
which ion channels does cAMP have an effect on in non- pigmented cells?
Cl- efflux
56
what treatment can target B2 cells for glaucoma?
beta blockers to prevent AH production
57
mechanism of action: beta blockers
Decreased ion concentration
Decreased fluid along gradient
Decreased volume of aqueous humour
Better balance of production and drainage
58
advantages of beta blocker treatment?
well tolerated
rapid
very effective (75%)
compatible with other drugs
59
how effective are beta blockers?
work in 75% of patients
60
how much do BBs lower IOP?
lower IOP by 20-30%
61
TF: beta blockers are better than PG analogues?
false
62
disadvantages of beta blockers?
systemic absorption- effects on both eyes
| efficacy declines over time
63
administration of BBs?
twice daily
| od in some preparations
64
CV side effects of BBs?
bradycardia
hypotension
peripheral vasoconstriction
65
bronchial side effects of BBs?
construction
| cant be used in asthma or obstructive airway disease
66
diabetic side effects of BBs?
masks hypoglycaemia
67
can you use BBs and PGs in combination?
yes- additive effects
68
advantages of using BBs and PGs in combination?
decrease cost
avoids washout effect- with 2nd drop
reduced exposure to preservatives
patient compliance
69
what is the third line treatment for glaucoma
carbonic anhydrase inhibitors
70
when are CAIs used?
if BBs and PGs aren't tolerated or suitable
71
TF: CAIs are only used locally
false- also systemically but only in emergencies
72
so when are CAIs systemically used?
only in emergencies
73
where do the CAIs work in the eye?
in the ciliary epithelium
74
mechanism of action?
inhibits
CO2+H20 H2CO3 H+ HCO3-
bicarbonate formation is required for Aq secretion
75
______ formation is required for aq secretion
bicarbonate
76
what does bicarbonate do help aqueous secretion?
moves into the posterior chamber and fluid follows along a gradient
77
effects of CAIs?
```
prevent bicarbonate being moved into posterior chamber
decreased:
ion concentration
fluid along gradient
volume of AH
```
78
systemic CAIs? why not topical?
acetazolamide- not lipophilic so not topically absorbed
79
when is acetazolamide used?
OAG
| secondary glaucoma and peri-operatively in acute glaucoma
80
how is acetazolamide administered?
emergency injection
81
side effects of acetazolamide?
increased risk of allergy and blood disorders as it has a sulphonamide group
```
GI problems
diuresis
acid/base disturbances
drowsiness and depression
parasthesias
```
82
acetazolamide is a _______ derivative
sulfonamide
83
why is there an increased risk of allergy and blood disorders in acetazolamide?
as it has a sulphonamide group
84
how can CAIs be developed to make a better glaucoma treatment
better lipid solubility for corneal absorption
decrease side effects
more selective- CA II enzyme
= Dorzolamide and brinzolamide
85
CA __ are mostly expressed in the eye. so...
II
| so if you can target those it will decrease systemic side effects
86
what drugs are a result of CAI modification?
dorzolamide
| brinzolamide
87
can CAIs be used with BBs or PGs?
yes
88
when is CAIs indicated as sole therapy?
when BBs cant be used
89
CAIs produce an approximate reduction in IOP of?
20%
90
topical CAIs side effects?
transient burning and stinging- acidic
blurred vision
conjunctival hyperaemia (redenning)
taste disturbances, dry mouth and headache
91
why do CAIs (topical) cause burning?
acidic
92
pH of brinzolamide drops?
7.5
93
pH of dorzolamide drops?
5.6-6
94
where are A2 receptors in the eye?
ciliary epithelial cells
| conjunctival and corneal epithelial cells
95
advantages of A2 adrenoceptor agonists
no mydriasis
no vasoconstriction
little effect on CV system- a2 selective
96
why do A2 agonists have little effect on CV system
A2 selective
97
A2 agonist mechanism of action?
Decrease secretion of aqueous
Decreases cAMP (Gi coupled; inactivates adenylate cyclase)
Decreases ion transport and ion efflux. Decreased osmotic gradient
Decreases aqueous secretion
Decreases ultrafiltration- less fluid filtered from the capillaries
(reduced blood flow, vasoconstriction)
Increases uveo-scleral outflow
Neuroprotective
98
why are a2 agonists thought to be neuroprotective
preserve optic nerve
| retinal ganglion cells
99
a2 agonists show tachyphylaxis, what does this mean?
rapid, non selectivity to agonists
| therefore limited lifetime of action
100
why do a2 agonists have a limited lifetime of action?
as they show tachyphylaxis:
| rapid, non selectivity to agonists
101
due to the tachyphylaxis, what are a2 agonists used for?
NOT chronic management
| post surgery and pre surgery to prevent changes in IOP
102
why are a2 agonists used pre and post surgery?
to prevent changes in IOP
103
2 a2 agonists used?
brimonidine
| apraclonidine
104
Brimonidine are ____ selective.
| _____ onset
a2
| rapid- 2 hours
105
apraclonidine are ____ selective for a2 agonists than brimonidine
used _____ term
limited because of its?
less
short
side effects
106
local side effects of a2 agonists?
allergies
stining
blurred vision
photophobia
107
systemic side effects of a2 agonists?
```
hypotension
droziness
fatigue
dry mouth
taste disturbances
```
108
what is pilocarpine?
muscarinic agonist- M3
109
pilocarpine mechanism of action?
Contract ciliary muscle M3. Those in the iris doesn’t contribute to the MOA for glaucoma treatment
Ciliary muscle contracts which
Pulls scleral spur (bit that juts into the eye)
Opens trabecular meshwork
Increases trabecular outflow- drainage
Decreases IOP
110
pilocarpine effects last for?
6 hours
111
how often do you use pilocarpine?
4 times a day
| COMPLIANCE!!
112
Pilocarpine has a _____ effect on lowering IOP.
Cyclical
113
```
Which of the drugs used to treat glaucoma would bring an increased intraocular pressure of 32mmHg back within an acceptable range?
Alpha 2 adrenoceptor agonist
Beta blocker
Carbonic anhydrase inhibitor
Parasympathomimetic
Prostaglandin analogue
```
Prostaglandin analogue- only just into the normal range. At pressures above this you will probably used a fixed dose combination for 2 different mechanism
114
```
Which class of drug most effectively reduces ion transport in the ciliary epithelium?
Alpha 2 adrenoceptor agonist- <20%
Beta blocker
Carbonic anhydrase inhibitor- <20%
Parasympathomimetic
Prostaglandin analogue
```
Beta blocker- about 20-30% reduction
