Eye drugs Flashcards
Explain the pharmacology of atropine
CLASS
Antimuscarinic/parasympatholytic
PHARMACOLOGY
Target: muscarinicreceptors(GPCR)
Action: non-selective, competitive antagonist
Very long lasting
PHYSIOLOGY
Mydriasis, cycloplegia (paralysis of ciliary muscle = no accomodation), unilateral amblyopia (‘lazy’ eye) → in good eye; anterior uveitis
Explain the pharmacology of cyclopentolate
CLASS
Antimuscarinic/parasympatholytic
PHARMACOLOGY
Target: muscarinicreceptors(GPCR)
Action: non-selective, competitive antagonist long-lasting action (up to 24 hours)
PHYSIOLOGY
(multiple effects) incl. mydriasis, cycloplegia
CLINICAL
Eye examination; unilateral amblyopia (‘lazy’ eye) → in good eye; anterior uveitis; ↓posterior synechiae
Explain the pharmacology of tropicamide
CLASS
Antimuscarinic/parasympatholytic
PHARMACOLOGY
Target: muscarinic receptors(GPCR)
PHYSIOLOGY
Action: non-selective, competitive antagonist
Short-acting (up to 6 hours - as less potent) mydriasis, cycloplegia
CLINICAL
Eye examination (funduscopy)
Explain the pharmacology of phenylephrine
CLASS
Sympathomimetic
PHARMACOLOGY
Target: α1receptors (GPCR)
Action: full agonist
Signalling: Gq/11
PHYSIOLOGY
Mydriasis, vasoconstriction
CLINICAL
Eye examination and surgery
Explain pharmacology of heroin/diamorphine
CLASS
Opiate
PHARMACOLOGY
Target: μ receptors(GPCR)
Action: full agonist
CLINICAL
Stimulates nuclei oculomotor (CNIII) → miosis, (respiratory depression, analgesia etc…) analgesic etc…
What is the pharmacology of pridostigmine?
CLASS
Cholinesterase inhibitor
PHARMACOLOGY
Target: acetylcholinesterase(enzyme)
Action: competitive reversible inhibitor
PHYSIOLOGY
↑ [ACh] at cholinergic synapses →↑ nicotinic activity at NMJ (myasthenia gravis)
In overdose
→↑ muscarinic activity (many side effects!) incl. miosis
CLINICAL
Myasthenia gravis
Explain how theophylline causes brochial smooth muscle relaxation
Theophylline is a non-selective competitive antagonist of adenosine receptors (A1, A2A, A2B, A3)
Adenosine induces bronchoconstriction and production of inflammatory mediators and cytokines
Some hypotheses:
A1 and A3 may contribute to clinical signs and therapeutic effect
A2B activation by autocrine adenosine may desensitise β2 receptors
Alternative signalling pathways for A2B (i.e., Gq/11) may be present
Theophylline is also an inhibitor of PDE, so may increase cAMP
How can sildenafil cause visual disturbances?
As inhibits phosphodiesterases (usually PDE5)
PDE6 is found in the cones hence, affects vision (COMMON)
Explain MOA of prostaglandins in the eye
PHARMACOLOGY
Target: FP receptor (GPCR)
Action: agonist
1° signalling: Gq
PHYSIOLOGY
↑permeability of sclera
↑aqueous outflow via uveoscleral route • No effect on aqueous production
CLINCAL
1st line treatment for glaucoma in many cases
Topical application
Prostaglandins are prodrugs and are either:
‘prost’ = agonists
‘iprant’ = antagonists
Explainn the MOA of Beta-blockers (in the eye)
CLASS
B-blockers (-olol)
PHARMACOLOGY
Non-selective (propranolol)
B1 selective
B2 selective
PHYSIOLOGY
Sympathetic tone DECREASE in ciliary body
DECREASE aqueous humour formation
CLINICAL
Open-angle glaucoma
Ocular hypertension
Explain MOA of apraclonidine (in the eye)
CLASS
Sympathomimetic
PHARM
Target: α2-adrenergic receptor (GPCR)
Action: full agonist
1° Signalling: Gi
PHYS
↓sympathetic tone (pre-synaptic) →↓aqueous formation
↑uveoscleral drainage →↑ outflow
also: mydriasis, disruption of accommodation
Limited access to CNS (cf. clonidine)
CLIN:
Glaucoma
Explain the MOA of clonidine
CLASS
Sympathomimetic
PHARM
Target: α2-adrenergic receptor (GPCR)
Action: partial agonist
1° Signalling: Gi/o
PHYS:
Can enter CNS (cf. apraclonidine)
Direct action in ventrolateral medulla (rich in α2) →↓ABP
Pre-synaptically: Gi/o →↓[cAMP] →↓Ca+ influx (VGCC) →↓NA release
Acts on central I1 sites →↓sympathetic tone
CLIN
Hypertension
Explain the MOA of acetazolomide
CLASS
Carbonic Anhydrase Inhibitor
PHARMACOLOGY
Target: carbonic anhydrases
Action: Competitive inhibitor
PHYSIOLOGY(complex!)
↓Na+ reabsorption in PCT → ↑urine flow (~3 ml.min−1)
~1⁄3 PCT Na+ reabsorption is through Na+/H+ antiporter
Diuretic effect is mild and self-limiting
→ ↓ preload → ↓ venous congestion → symptomatic relief
Heavy loss of HCO3− → alkaline urine/metabolic acidosis → ↓diuresis
↑Na+ at DCT → ↑K+ loss → hypokalaemia
acetazolamide
CLINICAL
First ‘modern’ diuretic, superseded mercurials, now obsolete as diuretic
Still in use for glaucoma: I.V. for acute ↑IOP as topical treatment cannot enter the eye across cornea
Is given IV (intravenously) - otherwise is NOT absorbed
What is the MOA of dorzolamide
CLASS
Carbonic anhydrase inhibitor (CAI)
PHARM
Target: carbonic anhydrases
Action: Competitive inhibitor
PHYS:
CAI →↓[HCO3−]i in ciliary epithelia
↓[HCO3−]→↓[Na+]i →↓substrate for Na+/K+-ATPase
↓[HCO3−]→↓pH →↓ Na+/K+-ATPase activity
↓[HCO3−] →↓ co-transport into aqueous with Na+
→↓ Na+ movement into aqueous →↓ aqueous formation
CLIN
Open-angle glaucoma (eye drops - topically)
What is the MOA of pilocarpine?
CLASS
Parasympathomimetic
PHARM
Target: muscarinic receptors (GPCR)
Action: non-selective, partial agonist
1° Signalling: M1, M3, M5 → Gq; M2, M4 → Gi
PHYS
M3 on ciliary muscle → contraction of LCM →
opening of trabecular meshwork/Schlemm’s canal →
↓outflow resistance → ↑ocular aqueous outflow
also: miosis, disruption of accommodation, headache!
(also: vasodilation → blood flow to ciliary body - partial agonist ??)
CLIN
Glaucoma (in use since 1877!); acute closed-angle glaucoma
What is the MOA of VEGF-A?
PHARM
Binds to VEGF receptors (in blood vessels)– receptor tyrosine kinase (RTKs)
PHYS
Endothelial cell proliferation
Promotes cell migration
Inhibits apoptosis
Induces permeabilization of blood vessels
CLIN:
ANTI-VEGF used in tumours, AMD and diabetic eye disease
What is the MOA of bevacizumab?
CLASS:
Angiogenesis inhibitor
CHEM:
IgG
- mab = monoclonal antibody
- zu- = humanized
- ci- = cardiovascular
PHARM:
Target:VEGF-A (growth factor)
Action: binding/blocking
PHYS:
VEGF promotes angiogenesis
↓ blood vessel formation slows degeneration of retina
CLIN:
Multiple types of solid tumour (licensed)
Wet-type age-related macular degeneration (unlicensed)
What is the MOA of Ranibizumab?
CLASS:
Angiogenesis inhibitor (HAS NO Fc fragment thus, much smaller)
PHARM:
Target: VEGF-A (growth factor)
Action: binding/blocking
PHYS:
VEGF promotes angiogenesis
↓ blood vessel formation slows degeneration of retina
CLIN:
Wet-type age-related macular degeneration (licensed)
What is the MOA of aflibercept?
CLASS
Angiogenesis inhibitor
PHARM:
Target: VEGF-A and VEGF-B (growth factors)
Action: binding/blocking
PHYS:
VEGFs promotes angiogenesis
↓ blood vessel formation slows degeneration of retina
CLIN:
Wet-type age-related macular degeneration (licensed)
