Diabetes Flashcards
(231 cards)
1
Q
What cBG is hypoglycaemia?
A
<2.5mmol/L
2
Q
What cBG is normoglycaemia?
A
3-5mmol/L fasting
7-8mmol/L post-prandial
3
Q
What cBG is hyperglycaemia?
A
> 10mmol/L
4
Q
How is insulin synthesised?
A
From proinsulin. 23 amino acids removed to make insulin
5
Q
Insulin half life
A
3-5 mins
6
Q
What do the different cells in the Islets of Langerhans produce
A
β-cells; release insulin α-cell; release glucagon δ-cells; release somatostatin ε-cells; release ghrelin PP-cells; release pancreatic polypeptide
7
Q
How is insulin release triggered by presence of glucose?
A
- Uptake by B cells
- K channels close, depolarisation
- Ca2+ influx
- release of insulin
8
Q
How is insulin release triggered by gut hormones?
A
- rise in serum GLP-1
- activation of GLP-1 receptor on B cells
- cell signalling
- insulin release
9
Q
What is ghrelin?
A
Hunger hormone
10
Q
What effect does insulin have on cells?
A
- binds to insulin receptor on cell surface
- conformation change, switch on kinase activity of receptor (phosphorylates)
- activates many processes in the cell - cascade
- activates (and increases number of) transporters in the membrane, to increase glucose uptake
11
Q
How does insulin reduce blood sugar?
A
- increased glucose uptake into cells
- convert glucose to glycogen
- decrease glycogen breakdown
- increase fat stores
- increase protein production
12
Q
Which systems increase food intake (towards hyperglyc.)?
A
GI tract and CNS (through hunger)
13
Q
Which systems increase glucose production?
A
Liver and adipocytes
14
Q
Which systems increase glucose reabsorption?
A
Kidneys
15
Q
Which tissues increase glucose utilisation?
A
All of them. Especially liver and skeletal muscle
16
Q
Which systems increase glucose storage?
A
Liver and adipocytes
17
Q
Which systems increase glucose loss?
A
kidneys
18
Q
How to adipocytes control blood glucose?
A
Lipolysis, glucose uptake, leptin
19
Q
Definition of Diabetes?
A
When the pancreas doesn’t produce enough insulin, or the body cannot use it. Leads to hyperglycaemia
20
Q
Non-medical causes of hypoglycaemia?
A
- inadequate food intake
- insulin overdose
- sulfonylurea overdose
21
Q
Medical causes of hypoglycaemia?
A
- insulinoma
- hyperinsulinism
- nocturnal hypo with T1
- gastric bypass associated hypo
- transient neonatal hypo
22
Q
Symptoms of hypoglycaemia?
A
Autonomic: hunger, sweating, shaking, heart rate increased, nausea, headache
Neuroglycopaenic: confusion, drowsiness, odd behaviour, incoherent speech, poor co-ordination
23
Q
When to use glucagon therapy?
A
Severe hypoglycaemia when oral glucose not possible or desired
24
Q
What form is glucagon therapy in?
A
Injection (iv, im, sc). Must be reconstituted
25
Side effects of glucagon therapy?
Headache and nausea
26
What is diazoxide therapy?
For severe hypoglycaemia. Reverses the depolarisation effect that glucose has on B cells
27
Side effects of diazoxide?
Anorexia, nausea, vomiting, hypotension, oedema, tachycardia, arrhythmia, hypertrichosis (prolonged use)
28
4 T's of Type 1 Diabetes?
Toilet, Thirst, Tired, Thinner
29
How do the majority of T1 diabetics present?
Diabetic ketoacidosis (DKA)
30
What is DKA?
Response to absense of insulin
- hyperglycaemia
- increased urine output - dehydration
- suppressed lipolysis --> ketones
31
Why is DKA dangerous?
profound acidosis (often <7), severe dehydration
32
Symptoms of DKA
tachypnoea, altered mental state (drowsiness/coma, mistaken for drunkenness), nausea, vomiting, abdo pain
33
Fluid Resuscitation in DKA
First hour - isotonic only, give slowly (rapid leads to cerebral oedema and death)
34
Insulin administration in DKA
Given on a sliding scale (0.05-0.1unit/kg/hour), monitor cBG hourly, maintenance fluid once cBG <15
35
DKA Maintenance fluid amount in adults?
Max 2L / day
36
What fluid should be given for DKA management?
isotonic, glucose containing, with KCl (for kidneys, insulin lowers potassium)
37
At what point can you reduce iv insulin in DKA?
<3mmol/L (increase glucose and insulin if not dropping)
38
Correct order of treatment once a DKA patient is ready to eat?
1. Eat and give sc insulin
2. wait 30 minutes
3. stop glucose iv
4. stop insulin sliding scale
39
DKA in children - fluids?
50% volume of normal.
10kg - 2mL/kg/hour, 10-40kg - 1mL/kg/hour. >40kg, 40mL/hour (not weight based).
Replace deficit over 48 hours not 24
40
When to start sc insulin in children with DKA?
cBg <14mmol/L, ketones <3mmol/L, resolved acidosis, oral fluids tolerated
41
What are the complications of DKA?
fatality 0.15-0.31% of children. Most common cause is cerebral oedema (>4mL/kg/h, hypotonic fluid).
symptoms: bradycardia, dilated pupils, altered mental state
42
What insulin regimens are available for T1 Diabetics?
Basal bolus or biphasic
43
What is basal bolus insulin?
Long acting insulin OD or BD, plus rapid acting insulin with meals
44
What types of insulins are available for basal bolus?
Rapid acting, short acting, intermediate acting, long acting, super long acting
45
Onset time of short acting insulin?
30 mins - 1 hour
46
Peak time for short acting insulin?
2-3 hours
47
Duration of action for short acting insulin?
8-10 hours
48
Examples of short acting insulins?
Human Actrapid, Humulin S, Insuman Rapid
49
Onset time of rapid acting insulins?
5-15 mins
50
Structural changes to rapid acting insulins?
Changed last few amino acids - quicker penetration through s/c tissue
51
Peak time for rapid acting insulins?
30-90 mins
52
Duration of action for rapid acting insulins?
4-6 hours
53
Examples of rapid acting insulins?
Humalog (insulin lispro), Novorapid (insulin aspart), Apidra (insulin glulisine)
54
What is the insulin balancing act?
Decreased BG: exercise and insulin
| Increased BG: Food and stress hormones
55
Onset time of intermediate acting insulins?
2-4 hours
56
Peak time for intermediate acting insulins?
4-10 hours
57
Duration of action for intermediate acting insulins?
12-18 hours
58
Examples of intermediate acting insulins?
Human insulatard
Humulin 1
Insuman Basal
59
Onset time of long acting insulins?
2-4 hours
60
Peak time of long acting insulins?
no peak, mimics basal output in non-diabetics
61
Duration of action of long acting insulins?
20-24 hours
62
Examples of long acting insulins?
Insulin Glargine (Lantus or Abasaglar), Detemir (Levemir)
63
NICE indication for ultra long acting insulins?
3rd line when other long acting have failed
64
Duration of action of ultra long acting insulins?
up to 42 hours
65
When are ultra long acting insulins beneficial?
Troublesome nocturnal hypos, or non-adherent patients who forget their insulin
66
When is non-human insulin used?
Rarely. Only for patients who have used historically, or unable to tolerate human insulin
67
When should blood glucose be monitored?
before meals, before bed
68
Blood glucose monitoring requirements for driving?
Check before, then every 2 hours
69
Which dose would need to be adjusted if cBG was abnormal before breakfast?
evening long acting
70
Which dose would need to be adjusted if cBG was abnormal before dinner?
lunch quick acting
71
How much support should patients get in the first 6 months?
lots. help with dose titration based on cBG diaries
72
When can't patients move to self adjustment?
Non-adherent or those on biphasic insulins
73
What does DAFNE stand for?
Dose Adjustment For Normal Eating
74
What does DAFNE involve?
Calculating insulin dose based on carb content of meals
75
What are the benefits of DAFNE?
Saves NHS money, patients can eat more freely, reduced complications, reflects natural insulin response
76
What is biphasic insulin made up of?
Short or rapid acting insulin in a protamine suspension
| Some in a complex so isn't immediately released
77
Onset time for biphasic insulins?
approx 30 minutes
78
Duration of action of biphasic insulins?
12 hours
79
Peak time for biphasic insulins?
1-2 hours
80
What patients is biphasic insulin suitable for?
Those that struggle with multiple injections, those unable to carb count
81
Examples of biphasic insulins?
Humulin M3, Insuman Comb 15,25, 50, Humalog Mix 25, 50, Novomix 30
82
Biphasic insulin regime?
2 injections a day, breakfastand evening meal
83
What is hypoglycaemia for people with medication controlled diabetes?
<4mmol/L
84
What to do when diabetic patient is hypoglycaemic?
Lucozade or other sugary drink, meal or snack.
If in hospital, dextrose tabs/glucogel, meal or snack.
If unconscious, Glucagon IM followed by 10% glucose 100mL/h
85
What 4 things need to be remembered on Sick days?
S - sugar. check every 2-3 hours
I - insulin. continue to avoid DKA
C - carbs. continue to take sugar to avoid hypo.
K - ketones. check urine, take rapid acting if present. drink plenty of water.
86
What route is insulin administered via?
S/c injection
87
Which insulins should always be timed with food?
short, biphasic or intermediate
88
When in relation to meals should insulin be given?
30 mins before, rapid acting can be given 5 mins after
89
When can IV insulin be given?
in hospital for close control - DKA or peri-op
90
How to remove air from the needle?
Eject 2 units
91
What angle should it be injected?
90 degrees
92
What types of insulin device can you get?
refillable pens, pre-filled pens, single use needles + vials (rarely used out of hospital)
93
Variations in insulin needles?
different lengths and thicknesses available. higher gauge = thinner needle.
some patients prefer short needles, others require longer ones
94
Benefits of needles that cover themselves?
good for needle phobics, safer for others administering to prevent injury
95
When should continuous sc infusion be considered?
- disabling hypos in attempt to reach target HbA1c
- HbA1c >69mmol/mol on MDI therapy, despite high care level
- patient (or carer) must have commitment and competience
96
Definition of disabling hypoglycaemia?
repeated and unpredictable episodes, persistent anxiety, significant impact on life
97
What is type 2 diabetes?
chronic hyperglycaemia due to insulin resistance and impairment of insulin secretion
98
Why does hyperglycaemia worsen T2 diabetes?
can impair B cell function and increase insulin resistance, so cycle of hyperglycaemia and worsening state
99
What is IGT?
Impaired glucose tolerance (prediabetes). insulin scretion/resistance and BG are increasing, but not yet in diabetic levels
100
When does T2D beome insulin dependent instead of resistant?
when insulin resistance becomes so high and secretion stops
101
Genetics and T2 risk?
1st degree - 5-10x increase, 90% concordance in identical twins
102
Ethnicity and T2 risk?
increased risk south asians, chinese, afro-caribbean, black african
103
Gender and T2 risk?
females more likely than men
104
Weight and T2 risk?
more men than women classified as obese, but more women than men have high waist circumference.
BMI: 1cm/m2 increases risk by 8.4%
WC: 1cm increases by 3.5%
105
What is epigenetics?
Underlying genetic risk factors and environment that favours development of disease
106
How does T2 present?
often asymptomatic, picked up in routine screening, or patient has complications.
some patients - increased thirst, urination
107
Diagnostic criteria for T2?
fasting cBG >7mmol/L
| HbA1c ≥48mmol/mol
108
Prediabetes diagnostic criteria?
Fasting cBG <7mmol/mol
| 2 hour venous BG after 75g load 7.8-11.1mmol/L
109
Treatment for T2D?
Diet, exercise, medication (that order).
Diet has most effect, followed by exercise
110
Goals from adjusting diet for T2D?
5-10% weight reduction short term, long term - normal BMI.
111
Good food choices for T2?
oily fish, complex carbs, high fibre, low fat dairy
112
Poor food choices for T2?
saturated and trans fats, simple carbs, food aimed at diabetics
113
Exercise goals for type 2?
150 mins/week moderate, or 75 mins intense
plus muscle strengthening 2x week
(any is better than none)
114
What do sulfonylureas target?
stimulates insulin release from B cells - inhibits ATP sensitive K channel
115
Examples of sulfonyl ureas?
Short acting: gliclazide, glipizide, tolbutamide, glimepiride
Long acting: glibenclamide
116
Which sulfonylureas are preferred?
Short acting as lower hypo risk. gliclazide most common
117
When should sulfonylureas be taken?
Always with food. don't take if no meal
118
Dosing information for gliclazide?
start 40mg with breakfast
up to 160mg BD with meals
119
Advantages of sulfonylureas?
Can be OD or BD, quickly lowers cBG soimproves symptoms, fewer GI effects than metformin
120
Disadvantages of sulfonylureas?
Can cause hypos, can cause weight gain, need some pancreas function, unpredictable in renal impairment and the elderly, need to monitor liver function
121
What are meglitanides?
same mechanism as sulfonylureas, different B cells. less likely to cause hypos. repaglinide/nateglinide. not often used in UK
122
What class is pioglitazone?
Thiazolidinediones. only one licensed in UK
123
What does pioglitazone target?
Decreases peripheral insulin resistance. increases glucose utilistation in muscles and adipose, and decreases glucose production in liver.
124
Pioglitazone dosing info?
Start 15mg OD, max 45mg OD
125
Advantages of pioglitazone?
OD dosing, low risk of hypo, suitable in renal impairment
126
Disadvantages of pioglitazone?
Linked to bladder cancer, heart failure and fracture risk (CI), liver monitoring required, weight gain, can take 3-6 months to show benefit
127
What class is metformin?
Biguanide. First line!
128
What does metformin target?
Inhibits gluconeogenesis in the liver, increase glucose utilisation in peripheral tissues
129
Metformin dosing info?
start 500mg OD, max 1g TDS (rarely go over 2g)
130
Alternative form metformin suitable when?
Modified release may improve GI side effects
131
Advantages of metformin?
Cheap, weight neutral, low hypo risk
132
Disadvantages of metformin?
GI effects, lactic acidosis risk (avoid if other risk factors e.g. post MI, sepsis), short t1/2 so TDS, not suitable in renal impairment,
133
Metformin dose adjustment in renal impairment?
half dose when eGFR gets to 45 (caution), stop when 30 (CI)
134
What class is acarbose?
Alpha glucosidase (UK only)
135
What does acarbose target?
inhibits enzymes that convert poly - monosccharides, slows glucose absorption
136
Acarbose dosing info
start 50mg OD, increase daily to TDS. max 200mg TDS
have to chew, take with meals
137
Side effect of acarbose?
GI side effects, poorly tolerated
138
Which classes of antidiabetic target GLP-1 hormone?
GLP-1 agonists, DPP-1 inhibitors
139
What does GLP-1 do?
Gut derived incretin hormone, stimulates insulin release and suppresses glucagon production. also inhibits gastric empyting and suppresses appetite
140
What do GLP-1 agonists do?
Stimulate insulin secretion and cause minor delay in gastric emptying - reduced hunger
141
What forms of GLP-1 agonists are there?
Exenatide, liraglutide, lixisenatide (daily)
albiglutide, dulaglutide, lond acting exenatide (weekly)
s/c injections
142
What are the criteria for GLP-1 agonist use?
- BMI >35 (adjusted for non-europeans)
- BMI < 35 but psychological/medical problems associated with weight
- BMI <35 but insulin is unsuitable due to occupation
143
What must patients demonstrate in order to continue use of GLP-1 agonists?
Weight loss and improved HbA1c
144
Advantages of GLP-1 agonists?
Weight loss, once a day (or week) preparations, rarely cause hypos, suitable in moderate renal impairment
145
Disadvantages of GLP-1 agonists?
Injections, severe GI effects are common, can cause pancreatitis
146
What do DPP-4 inhibitors target?
block rapid degradation of GLP-1
147
Examples of DPP-4 inhibitors?
sitagliptin, vildagliptin, saxagliptin, alogliptin (all need dose adjustment in renal impairment)
linagliptin (suitable in all renal functions)
148
Advantages of DPP-4 inhibitors?
Once a day, no weight gain, low hypo risk, suitbale in renal impairment
149
Disadvantages of DPP-4 inhibitors?
commonly causes Gi effects, rash and UTIs, risk of pancreatic inflammation
150
What do SGLT-2 inhibitors target?
block active transport (reabsorption) of glucose in glomerular filtrate
151
Renal requirements for SGLT-2 inhibitors?
Don't start if eGFR <60
| Stop when eGFR <45
152
Examples of SGLT-2 inhibitors?
Canagliflozin, empagliflozin (cheapest), dapagliflozin
153
Advantages of SGLT-2 inhibitors?
Weight loss, can lower BP, low risk of hypo
154
Disadvantages of SGLT-2 inhibitors?
Thrush and UTIs (especially on starting treatment), only effective if good renal function, lower BP can increase fall risk, safety concerns around AKI and DKA
evidence of increased amputation incidence with canagliflozin
155
NICE guidance on SGLT-2 inhibitors?
only as part of dual therapy when patient is unable to take sulfonylureas - due to hypo risk, intolerance or contraindications
156
Step 1 of NICE guidelines for T2 drug therapy?
When HbA1c >48mmol/mol, metformin
157
Step 2 of NICE guidelines for T2 drug therapy?
When HbA1c >58mmol/mol, add ONE OF:
DPP-4 inhibitor, Sulfonylurea, pioglitazone, SGLT-2 inhibitor
53mmol/mol HbA1c target
158
Step 3 of NICE guidelines for T2 drug therapy?
Triple therapy:
- metformin + DPP-4i + SU
- metformin + pioglitazone + SU
- metformin + pioglitazone or SU + SGLT-2i
if not effective, consider metformin + SU + GLP-1 (criteria)
Consider insulin therapy
159
First step of insulin treatment in T2?
Basal insulin only - start with NPH (intermediate) BD
long acting insulin can be given for patients having hypos that restrict dose increases, or are unable to administer themselves and nurse is needed
160
Second step of insulin treatment in T2?
Basal bolus regime or biphasic - HbA1c >75mmol/mol
161
1st step if metformin is contraindicated or not tolerated?
HbA1c >48mmol/mol
DPP-4i, pioglitazone or SU
SGLT-2i if DPP-4i not possible
HbA1c targets: 48mmol/mol (53 if SU)
162
2nd step if metformin contraindicated or not tolerated?
HbA1c >58mmol/mol
- DPP-4i + pioglitazone OR SU
- pioglitazone + SU
aim for 53mmol/mol
163
3rd step if metformin contraindicated or not tolerated?
insulin therapy
164
% HbA1c reduction with lifestyle changes?
1-2%
165
% HbA1c reduction with metformin?
1-2%
166
% HbA1c reduction with insulin?
1.5-3.5%
167
% HbA1c reduction with Pioglitazone?
0.5-1.4%
168
% HbA1c reduction with GLP-1 agonist?
0.5-1%
169
% HbA1c reduction with DPP-4i?
0.5-0.6%
170
% HbA1c reduction with SGLT-2i?
0.5-1.5%
171
Main aims of medicines optimisation in diabetes?
blood sugar control and reducing complications
172
Types of microvascular complications?
retinopathy, nephropathy and neuropathy
173
What is diabetic retinopathy?
micro-thrombi in retina, blocks capillaries
174
What are the three mechanisms of retinopathy?
1. increased retinal blood flow due to impaired autoregulation
2. increased sorbitol production - osmolarity and swelling leads to cell rupture
3. glycosylation end products (e.g. glucose + amino acid) results in vasculature damage
175
What is proliferative retinopathy?
New blood vessels form and leak blood into vitreous - blocking light
176
What is non-proliferative retinopathy?
No new vessels form, damage occurs to existing ones
177
Is diabetic retinopathy treatable?
No - irreversible
Laser treatment can help to slow the progress
178
What is diabetic neuropathy?
High blood sugars lead to reduced blood flow and death of nerves - most common is peripheral neuropathy
179
Symptoms of neuropathy?
Pain, unusual sensations, complete loss of sensation
180
Treatment for neuropathy?
Topical - capsacin
Antidepressants - amitriptyline, duloxetine, nortriptyline
Anticonvulsants - gabapentin, pregablin (lyrica only licesned)
181
Order of treatment for diabetic neuropathy?
Topical agent first, then patient choice for systemic
182
Why are regular foot and eye checks necessary?
To monitor for foot ulcers and retinopathy
183
How to diabetic foot ulcers arise?
Lack of sensation (neuropathy) increases risk of damage to feet
high blood sugar increases infection risk, poor blood flow delays healing
poor antibiotic penetration
often leads to amputation
184
What is diabetic nephropathy?
Nephrons become thickened and scarred due to chronic hyperglycaemia, ineffectiveness
185
Treatment for nephropathy?
Blood pressure control - ACE or ARB
186
Macrovascular complications associated with diabetes?
High insulin levels lead to atherosclerosis
diabetes related dyslipidaemia
leads to MI, stroke, vascular disease
187
Prevention of macrovascular complications?
Control BP, cholesterol
aspirin if evidence of CVD
obviously glucose control
188
Blood pressure targets for T2?
140/80
130/80 if kidney, eye or cerebrovascular damage
ACE inhibitor (CCB for black or pregnant patients)
189
When to offer atorvastatin to T1D?
20mg
| older than 40, diabetes for >10y, established nephropathy or otehr CVD risk factors
190
When to offer atorvastatin to T2D?
anyone scoring over 10% on QRISK
191
Goals of statin treatment in diabetics?
reduce HDL by 40% in 3 months - titrate dose as needed
192
What is glaucoma?
a blanket term for several conditions caused progressive neuropathy, leading to optic nerve damage, visual loss and eventual blindness
usually due to impaired drainage of aqueous humour (imbalance of production and drainage)
193
What are the risk factors for glaucoma?
(usually asymptomatic)
- raised IOP (>21)
- family history
- race (black, asian, hispanic)
- hypertension, CV disease
- migraine
194
What are the two types of glaucoma?
Open angle, closed angle
most drugs are to manage open angle
195
Where in the eye is aqueous humour produced?
Ciliary epithelium
196
Where does aqueous humour sit within the eye?
Anterior chamber
197
What rate is aqueous humour produced?
2.75microL/min
198
Where does aqueous humour drain?
Between iris muscle and trabecular meshwork (into here), then down into Schlemm's canal
angle must be sufficient for drainage to occur, and this is where the types come from
199
What is a normal Intra-occular pressure?
around 16 mmHg (up to 20)
200
What are the goals of glaucoma treatment?
Reduce IOP to 16-20mmHg
Drug to have sufficient duration of action (for compliance)
Provide preservation of vision, no loss of effect over time, compatibility with other treatments (comorbid), no topical or systemic side effects
201
How is aqueous humour formed?
Aq. substances and ions transported from blood into occular cells, to produce humour which is then released into the posterior chamber
202
What are the first choice treatment for glaucoma and why?
Prostaglandins
Have a unique mechanism for decreasing IOP - increase outflow
203
What are examples of the prostaglandin analogues?
Latanoprost, Travoprost, Tafluprost (esters, converted to acid as absorbed across cornea - prodrug)
204
How to prostaglandin analogues work to treat glaucoma?
Analogues of Prostaglandin F2a, and act on the FP receptor (dont use PGE as shorter half life than F)
reduce the outflow of aqueous humour
205
What effect do the prostaglandin analogues for glaucoma have on the FP receptor?
The FP receptor is a GPCR, which is coupled with GåQ
activates phospholipase C, which increases production of diacylglycerol and inositol phosphate
206
Where are the FP receptors found?
ciliary body/muscle and sclera, iris sphincter, trabecular meshwork cells (little effect here as damaged due to glaucoma)
207
Benefits of using prostaglandin analogues?
Long duration of action, lower IOP by up to 35%, well tolerated (good compliance)
208
Example of a prostamide analogue?
Bitamoprost
209
How to prostamide analogues differ from prostaglandin analogues?
Not prodrug - analogues of prostamide F2alpha
slightly more effective, because work on both prostamide and FP receptors
210
What is the mechanism of action of prostaglandin analogues?
Increased uveoscleral outflow (reduces resistance by remodelling the extracellular matrix:
- increase matrix metalloproteinases
- degrades collagen
- decreases resistance of ciliary muscle and sclera to increase outflow
211
What are some side effects of PG analogues?
- red eye (initial)
- increased pigmentation in iris, eyelashes and perocular skin
- eyelash growth
- precipitate or worsen cystoid macular oedema in aphakic eyes
- light sensitivity
- C/I in pregnancy (theoretical general effect on cell division)
212
What is the mechanism of action of beta blockers for glaucoma?
blocks cAMP:
cAMP activates the cotransporter than transports ions in pigmented epithelial cells, controls Cl efflux in non-pigmented
- blocking these processes reduces the aq. humour production
- decreased ion concentration
- decreased fluid gradient
- better balance of production and drainage
213
What are the advantages of beta blockers for glaucoma treatment?
well tolerated, rapid onset, effective in 75% of patients, lower IOP by 20-30%, compatible with other drugs, OD or BD administration
214
What are the disadvantages of beta blockers for glaucoma treatment?
can have effect on the other eye also, systemic side effects, efficacy declines over time
215
What side effects can occur from beta blockers for glaucoma treatment?
generally systemic:
bradycardia, hypotension, vascoconstriction, impotence etc
C/I in heart block/failure
bronchial effects - constriction - C/I in asthma and other airways disease
diabetic - masks hypoglycaemia
216
What are fixed dose combinations?
Preparations that contain both drugs, as combinations can be more effective than singular ones
217
What are the benefits of fixed dose combinations?
patient compliance, reduced preservative exposure, no washout effect for second drop
cheaper for patient (one charge), cheaper treatment
218
What are carbonic anhydrase inhibitors?
INhibit carbonic anhydrase in ciliary epithelium - which produces bicarbonate needed for aq humour production
decreased ion conc leads to decreased fluid gradient
219
What are the systemic carbonic anhydrase inhibitors?
Acetazolamide (not absorbed topically) - used only in emergencies
used in open angle glaucoma, secondary glaucoma, or peri-op for closed angle
side effects limit use
220
What are the side effecs of acetazolamide?
sulfonamide derivative so increased risk of allergy and blood disorders
enzyme is present throughout body so effect on GI tract, diuresis, acid/base balance disturbance, drowsiness, depression, parasthesias
221
How were topical carbonic anhydrase inhibitors developed?
modified acetazolamide to improve lipid solubility (for corneal absorption) and reduce side effects by increasing selectivity for CA-II enzyme
222
Examples of topical carbonic anhydrase inhibitors?
Dorzolamide and brinzolamide
223
When are topical carbonic anhydrase inhibitors indicated?
adjunct with beta blockers or PG analogues
sole therapy if patient cannot tolerate beta blockers
224
What % reduction in IOP can you expect from topical carbonic anhydrase inhibitors?
20%
225
What are ethe side effects of topical carbonic anhydrase inhibitors?
burning/stinging (pH brinzolamide drops 7.5, pH dorzolamide drops 5.6-6.0)
Blurred vision, conjunctival hyperaemia, transient myopia, blepharitis, allergic conjunctivitis
taste disturbances, dry mouth, headache
226
Alpha-2 receptor agonist use for glaucoma?
same as beta blockers/ stimulated alpha-2 receptors reduce cAMP so subsequently aq humour production (receptors on ciliary, corneal and conjunctival epithelial cells)
also decreases blood flow so less ultrafiltration (from vasoconstriction)
increases uveo-scleral outflow (thought to be from increased PGs from alpha stimulation)
potentially neuroprotective
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Examples of alpha-2 agonists in glaucoma treatment?
Brimonidine and Apraclonidine
b. is more selective for alpha-2
apraclonidine is only for short term use as can cause tachyphylaxis, used post laser surgery to prevent IOP rise
228
Side effects of alpha-2 agonists?
local: blurred vision, stinging/burning, photophobia
systemic: hypotension, drowsiness, fatigue, dry mouth, taste disturbances
229
What type of drug is pilocarpine?
Parasympathomimetic
230
What is the mechanism of pilocarpine for glaucoma treatment?
```
Contract ciliary muscle
Pulls scleral spur
Opens trabecular meshwork
Increases trabecular outflow
Decreases IOP
```
231
What is the main problem with using pilocarpine for glaucoma?
Only lasts about 6 hours so multiple daily doses - compliance issue
