DIABETES Diseases and Drugs PH2113

lesson 1, lesson 2, lesson 3, lesson 4, lesson 5

high blood glucose outcome in non-diabetic

1. pancreas b-cells release insulin

2. insulin stimulates cells to use glucose

3. liver converts glucose to glycogen, fats and protein

4. blood glucose levels fall and less insulin is produced

low blood glucose outcome in non diabetic

1. pancreas a-cells produce glucagon

2. glucagon stimulates the liver to convert glycogen to glucose

3. blood glucose levels raise

4. less glucagon is produced

aims of insulin management

• prevent development of severe hypoglycaemia

• decrease microvascular complications

• avoid macrovascular complications in later life

rapid acting insulins

• lispro, aspart, glulisine

• onset = 10-20 mins

• timing = 0-15 mins before or soon after meals

• duration = 2-5 hours

long acting insulin

• detemir, glargine

• onset = steady state after 2-3 doses

• timing = once or twice daily - used as basal bolus regimen

• duration = 24 hours

note: limited peak/trough effect and limited inter or intra patient variability

short acting insulin

• insulin soluble, insulin porcine

• onset = 15-30 mins

• timing = 15-30 mins before meals

• duration = 6-12 hours

ultra rapid acting insulin

• insulin aspart

• onset = 5-10 mins

• timing = 2 mns before and up to 20 mins after meals

• duration = 3-5 hours

intermediate acting insulin

• sophane insulin

• onset = 1-2 hours

• timing = once or twice a day

• duration = 10-12 hours

note: need to be mixed before administration

ultra long acting insulin

• insulin degludec

• timing = once daily

• onset = steady state after 2-3 days

• duration = beyond 42 hours

pre mixed insulins

• combnation of short/rapid acting with intermediate

• ie novomix (aspart + aspart protamine)

• timing = twice daily, 0-15 mins before food

• onset = 10-20 mins

• duration = 15-24 hours

basal bolus regimen

• mealtime injections of fast acting insulin

• one or two injections of a basal insulin ie intermediate or long acting

twice daily insulin regimen

premixed insulin twice a day

framingham study

• study investigating the prevention and treatment of cardiovascular disease in the USA

• started in 1948 by president truman after the death of president roosevelt from undiagnosed hypertension

how is diabetes linked to cvd

thought to disrupt endothelial function

drives atherosclerotic progression in type 2 by:

• infection, inflammation, hyperglycaemia, insulin resistance, dyslipidaemia, thrombosis

Diabetes management in wales

• DESMOND diabetes education

• lfestyle, mental health, sexual health, immunisation

• HbA1c monitoring

• fitness to drive and DVLA

• assess cardiovascular risk and CKD risk

• complications!

NAFLD non alcoholic fatty liver disease

• diagnosed based on risk factors, elevated liver enzymes and negative findings for other causes

• liver ultrasound shows increased echogenicity

• fibrosis scoring tools

treat by lifestyle, optimise comorbidities, treatment on referral

peripheral vascular disease and diabetic foot

• annual foot examination

• mdt approach

• ulceration, infection, limb ischaemia, neuropathy, potential bone infection ie osteomyelitis

• can lead to amputation

diabetic retinopathy

• leading cause of preventable sight loss in the uk

• background = tiny bulges with slight bleeding

• pre-proliferative = more severe and widespread changes affecting vessels and bleeding into eye

• proliferative = scar tissue and new blood vessels, weak and easily bleed, some loss of vision

• ranibizumab licensed

diabetic nephropathy

check urine albumin-creatinine ration (protein in urine) and measure renal function

• kidney failure risk equation for risk of failure in 2-5 years

• glomerulosclerosis: basement membrane thickening, arteriole lumen thickening

tx: ACEi/ARB (prils and sartans), SGLT2i (flozins), ns-MRA (finerenone)

diabetic neuropathy

disruption of nerves leading to impaired sensory function

peripheral neuropathy ie hands and feet

• loss of touch, temp, (shooting) pain

• amitriptyline, duloxetine, gabapentin, pregablin

autonomic neuropathy (gut)

• constipation

• diarrhoea

• incontinence

• hypotension

• ed

• metclopramide

footcare in diabetes

lifestyle - stop smoking

check feet daily

cut toenails carefully and moisturise

appropriate fitting footwear

glaucoma cause

disturbance in the circulation of aqueous humour in the eye

glaucoma def

damage to the optic nerve resulting in deterioration of visual field caused by IOP being too high for normal functioning of optic nerve head

aqueous humour formation

• clear fluid from blood

• filtered in ciliary process arterioles

• enzymes involved: ATP-ase and Carbonic Anhydrase

Aqueous humour cycle

1. filtered in ciliary body

2. into posterior chamber

3. into anterior chamber between lens and iris

4. trabecular meshwork

5. drainage via canal of schlemm

6. into ocular veins

7. and uveoscleral outflow

normal intraocular pressure

16mmHg ± 2

if drainage cannot keep pace with secretion….

1. intraocular pressure is increased

2. restriction of blood supply to optic nerve

3. optic nerve atrophy

4. reduces field of vision

type of glaucoma depends on

1. poor aqueous humour drainage

• degeneration and subsequent collapse of trabecular meshwork

• mechanical blockage of trabecular meshwork by peripheral role of iris

• increase in filtration pressure

primary open angle glaucoma

most common

slow onset, commonly high iop

>40 years, short sighted

more common in afro-caribbeans

possible association with diabetes mellitus

secondary open angle glaucoma

rise in iop as a result of a known cause

inflammation, pigment dispersion syndrome, pseudoexfoliative syndrome, steroid-responsive glaucoma, trauma

congenital glaucoma

deformity - usually present at birth but onset may be in first 2 years of life

requires surgery

primary closed angle glaucoma

cause - blockage of trabecular meshwork

sudden onset - ocular emergency!

symptoms - dilated pupils, pain, inflamed eyes, blurred vision, reflex nausea

bad case - loss of vision (24hrs), blindness (2-3 days)

note: can be drug induced (atropine)

secondary closed angle glaucoma causes

inflammation, iris bombe, lens related

diagnosis of glaucomas

1. examine optic disc

   • optic disc appears cupped or white

2. measure intraocular pressure

   • via contact tonometry or air jet tonometry

3. gonioscopy

   • goniolens - viewing the rideocorneal angle via a mirror or prism

prostaglandin analogues

first line monotherapy

most powerful topical ocular hypotensive agents available, increases uveoscleral outflow

• ie latanoprost, xalatan, travoprost, tafluprost, bitamoprost

• instilled in the evening

• side effects: eye pigmentation, eye lash thickening/lengthening

note contraindication in pregnancy

B-adrenoceptor blockers glaucoma

first line monotherapy

used for chronic open angle glaucoma

decreases aqueous humour production therefore decreasing iop

mech 1: blocks b2 receptors in afferent ciliary bvs, vasoconstriction and decreased inflow, reduced iop

mech 2: blocks b2 receptors in ciliary process, decreased ultrafiltration, reduced iop

• eg timolol

• side effects: bradycardia, palpitation, hypotension, bronchospasm

• contraindicated in asthmatics

a2-adrenoceptor agonists in glaucoma

a1 mech - afferent ciliary vasoconstriction to reduce inflow

a2 mech - decrease aqueous secretion and inc. uveoscleral outflow

• eg brimonidine

carbonic anhydrase inhibitors in glaucoma

for open angle glaucoma, secondary glaucoma

• acetazolamide - po or iv

• dorzolamide - eye drops

• brinzolamide - eye drops

miotics use in glaucoma

closed angle glaucoma

mech: opens up drainage channels in trabecular meshwork, contracts constrictor pupillae

• eg pilocarpine - eye drops (single use units or long acting gel)

• side effects: transient headache, irritation

osmotic agents in glaucoma

increase extracellular osmomolarity, water leaves vitreous humour by osmosis into intravascular space. intraocluar volume is decreased so decreases iop

• eg mannitol

• emergency or surgery prep

reminder for opthalmic preparations

sterility

tonicity - eye will tolerate nacl

ph - range 3.5 - 10.5

stability - depends on ph and temp