Pulmonary Hypertension, Anti-Arrhythmics and Glaucoma Flashcards

Flashcards on Medicinal Chemistry, Pharmacology of Anti-arrhythmics, and Glaucoma

Arrhythmia

Alteration in the normal sequence of electrical impulse rhythm that leads to contraction of the myocardium

Resting heart rate

Normal sinus rhythm, typically between 60-100 beats per minute

Quinidine

Prodrug, found in cinchona bark, diastereomer of quinine; metabolites are hydroxylated derivatives at quinoline ring or quinuclidine ring

Procainamide

Effective in patients unresponsive to quinidine; more resistant to enzymatic and chemical hydrolysis

Disopyramide phosphate

Used orally to treat ventricular and atrial arrhythmias; Metabolized into n-dealkylated form

Lidocaine

For emergency treatment of ventricular arrhythmias

Tocaine

Orally active; an a-methyl group slows the rate of metabolism

Class IV Calcium Channel Blockers

Clinically used as antianginal, antiarrhythmic, and antihypertensive agents; includes dihydropyridines, benzothiazepine, aralkyl amine and diaminapropanol ether

Verapamil and diltiazem metabolism

N-demethylation by CYP3A4

Diuretics

Reduces blood volume and decreases central venous pressure and right ventricular stroke volume

Vasodilators

Decreases pulmonary vascular resistance

Examples of vasodilators in pulmonary hypertension

CCB, prostaglandins, PDE5 inhibitors

Arrhythmia commonality

They act to interfere with cardiac action potential

Two types of cell types in heart

Contractile (working horse of heart) and conductile

Skeletal muscle action potential initiation

Motor neurons via acetylcholine- initiation of action potential

Cardiac muscle action potential

Internal conduction system

Phase 0, rapid depolarization

Membrane potential reaches critical threshold; Na+ influx through fast sodium channels

Phase 1, rapid repolarization

K+ out, small outward current; Na+ channel closes

Phase 2, plateau

Ca+ in through L-type channels=K+ out; much slower time scale

Phase 3, repolarization

K+ out dominates; Ca2+ channels close and return to resting potential

Phase 4, resting membrane potential

K+ leak channels maintain -90mV, ready for next action potential; pacemaker function of heart, typically only observed in nodal and conducting tissue

Disorders of Impulse generation

Abnormal automaticity and triggered activity- early afterdepolarization and delayed afterdepolarization

Disorders of Impulse Conduction

Reentry

Atrial fibrillation

Very sporadic and disorganized (abnormal beats); can arise from multiple circuits

Atrial flutter

Rhythmic and organized (consistent beats but fast)

Ventricular fibrillation

Very sporadic and disorganized (abnormal beats)

Ventricular tachycardia

Rhythmic and organized (consistent beats but fast)

Goals of antiarrhythmic therapy

Increase or decrease conduction velocity, modulate the excitability of cardiac cells, suppress abnormal automaticity

Class 1: Sodium channel blockers

Block sodium channels, and reduce the maximum rate of depolarization; increase refractory period

Class two: Beta blockers

Blocked the effects of adrenaline and noradrenaline on the heart and blood vessels

Class three: Potassium channel blockers

Prevent potassium ions from passing through cell membranes, leading to prolongation of action, potentials and slowing of repolarization

Class 4: Calcium channel blockers

Work by inhibiting the influence of calcium ions into cells

Class 5: Digitalis

Inhibit the sodium potassium ATPase pump in the heart muscle

Aqueous humor

Serves to nourish the cornea and lens with nutrition (AA and glucose); no blood vessels in this part of eye

Primary Open Angle Glaucoma (POAG)

Elevated conventional outflow resistance

Primary Angle Closure Glaucoma (PACG)

Mechanical obstruction of trabecular meshwork due to pathological changes in ocular anatomy

Glaucoma

Progressive, irreversible optic nerve damage resulting in visual field loss

Intraocular pressure (IOP)

Balance of aqueous humor production and outflow, normal pressure=10-21 mmHg

Ocular hypertension

IOP> 21 mmHg

Groups at risk for glaucoma

Open angle (>65+, african american descent) and angle closure (asian descent)

Individual risk factors for glaucoma

Elevated IOP, T2DM, hypertension, first- degree family history, thinner central cornea

Meds that induce IOP

Topiramate, nasal/inhaled/systemic/ophthalmic corticosteroids, antihistamines, ophthalmic/systemic anticholinergics

Meds associated w/ angle-closure glaucoma

Alpha/beta AA, anticholinergic agents, antihistamines, diuretics, cholinergics, stimulants, beta2 AA, etc

Fundus Examination

Recommended screening frequency: 40-60 yoa w/o risk factors=Q3-5 yrs, 40-60 w/ risk factors=Q1-2 yrs, >60 yoa=Q1-2 yrs

α2-Adrenergic Agonists MOA

Decrease aqueous humor production; slightly increases aqueous humor outflow

α2-Adrenergic Agonists Examples

Epinephrine, dipivefrin, brimonidine BID or TID

α2-Adrenergic Agonists AE

Conjunctivitis, dry mouth, sedation, headache

α2-Adrenergic Agonists Warning

Increase risk of CNS

β-Adrenergic Blockers MOA

Decrease aqueous humor production

β-Adrenergic Blockers Examples

Betaxolol, timilol BID or Daily

β-Adrenergic Blockers AE

Burning, itching, vision changes, bradycardia, fatigue

β-Adrenergic Blockers Con

Sinus bradycardia, heart block, CHF

β-Adrenergic Blockers IOP reduction

20-25%

CAI MOA

Decrease aqueous humor production

CAI EX

Acetazolamide (monitor renal status), dorzolamide BID or TID

CAI AE

Blurred vision, dry eye, CNS effects

CAI Con

Sulfonamide allergy

CAI IOP reduction

15-30%

Cholinergics MOA

Increase aqueous humor outflow

Cholinergics Ex

Pilocarpine, Echothiophate

Cholinergics AE

Corneal clouding, poor vision at night, N/V, bradycardia

Cholinergics IOP reduction

20-25%

Prostaglandin Analogs MOA

Increase aqueous humor outflow

Prostaglandin Analogs Ex

Latanoprost QHS

Prostaglandin Analogs AE

Eyelid darkening, blurred vision, eyelash darkening/ lengthening

Prostaglandin Analogs IOP reduction

25-35%

Rho Kinase Inhibitor EX

Netarsudil (rhopressa) QHS

Rho Kinase Inhibitor AE

Conjunctival hemorrhage, pain at admin

Rho Kinase Inhibitor Precaution

Bacterial keratitis

Glaucoma Pharmacology

Use prostaglandins first, topical CAI used for pt that dont respond or tolerate preferred agents, cholinergic agonist are last line therapy

A2 AA=Drug-Drug interactions

CNS depressants, cardiac meds

B Adrenergic blockers= Drug-Drug interactions

Cardiac meds, oral antidiabetic agents

CAI=Drug-Drug interactions

NSAIDs