T4 Final Exam New Topics

A chronic progressive nervous disease chiefly of later life that is linked to decreased dopamine production in the substantia nigra and is marked by tremor and weakness of resting muscles and by a shuffling gait

Parkinson’s Disease

Hallmark pathology of PD

DA loss Lewy body formation

Most basically a lack of dopamine in the motor cortex (basal ganglia and reticular formation)

Parkinson’s Disease

regulates movement; responsible movement, balance, coordination, muscle tension/contraction

basal ganglia

in basal ganglia where DA produced

Substantia nigra

Cardinal features of PD

Tremor Muscle rigidity Bradykinesia Postural Instability

AAN recommends initiating therapy with a dopaminergic tx once there is

functional impairment

tx if tremor is predominant sx

Anticholinergic

may be useful for levodopa induced dyskinesias and has modest effect on sx

Amantadine

MAO-B inhibition preventing the breakdown of dopamine in the CNS

Safinamide, Selegiline, Rasagiline

Initial monotherapy in early disease

Safinamide, Selegiline, Rasagiline

At initiation, reduce levodopa dose by 10-30%

Selegiline

Antagonize the excitatory neurotransmitter acetylcholine in the substantia nigra to minimize the relative increase in cholinergic sensitivity

Benztropine, trihexyphenidyl

Limited use in older patients with PD

Benztropine, trihexyphenidyl

Augment dopamine release from the presynaptic nerve terminalS; Inhibit dopamine reuptake, stimulates release

Anticholinergic effects

N-methyl-D-aspartate receptor inhibitor

Amantadine

Synergistic effects with carbidopa/levodopa and Dopamine agonists when used as adjunctive treatment in later disease stages

Amantadine

Amantadine CIs

CHF, seizure disorder, other stimulants

Direct stimulation of striatal dopamine receptors

Bromocriptine, Ropinirole, and pramipexole

Non-ergot derived (2 &3)

Ropinirole, Pramipexole, Rotigotine, apomorphine

Recommended as 1st line monotherapy for most symptomatic patients

romocriptine, Ropinirole, and pramipexole

Adjunct/supplemental therapy for acute intermittent, treatment of hypomobility “off” episodes associated with “wearing off” and “on-off” in advanced stage pd Pharmacokinetics

Apomorphine hydrochloride

Apomorphine hydrochloride ADR

Significant nausea/vomiting

Adverse effects (class) Postural hypotension Confusion Hallucinations Lower extremity edema Sedation and vivid dreams Syncope Psychosis Compulsive behaviors and impulse control disorders

Dopamine Agonists

The most effective drug for PD and associated with decreased morbidity and mortality than pre-levodopa era. Almost all patients receive benefit

Levodopa

Gold-standard” All patients will end up needing CD/LD Place in therapy Benefits bradykinesia & rigidity the most In older pts (>60-70 y/o) with functional impairment, those with cognitive impairment/dementia or advanced disease Use lowest possible dose to control symptoms and avoid dyskinesias

Carbidopa/levodopa

Inhibits peripheral COMT – no central inhibition because it does not cross BBB

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Entacapone

Inhibits peripheral and central COMT

Tolcapone

Never monotherapy; always give with CD/LD

Catechol-O-methyltransferase (COMT) inhibitors

ASSOICATED WITH EXPLOSIVE Diarrhea (5/10%; delayed onset weeks to months) AND HEPATOTOXICITY,

tolcapone

inhibits the COMT enzyme

opicapone

Adenosine A2a receptor antagonist

istradefylline

Wearing- OFF solution

increase frequency of LD dose

Add a COMT inhibitor

Add MAOI-B

drugs approved to treat dementia in PD patients

rivastigmine and donepezil

What to do if patient is experiencing cognitive impairment in PD

Discontinue anticholinergics. Add cholinesterase inhibitor

What to do if patient is struggling with impulse control disorder

DC dopamine agonist or add clozapine, quetiapine, or naltrexone

Depression and anxiety treatment in PD

SSRIs; Mirtazapine venlafaxine TCAs Amitriptyline \[avoid lithium, amoxapine\]

Preferred antipsychotic in PD

Pimavanserin

Must be avoided in PD

Olanzapine

treating sleep disturbances in PD

Consider bedtime dose of levodopa/carbidopa CR, entacapone, dopamine agonist

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Physical blockage of space between iris and lens

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closed angle glaucoma

Sustained increases in IOP leads to

optic nerve damage

Comprehensive Dilated Eye Exam

Every 1-2 years

Glaucoma First-line therapy

Topical Prostaglandin Analogs or Topical Beta-Blockers

Topical Prostaglandin Analogs

Latanoprost, Bimatoprost, Travoprost, Travoprost

Topical Beta-Blockers

Timolol or Betaxolol

Mechanism: decrease aqueous fluid production

Topical Beta-Blockers

Mechanism: increase aqueous fluid outflow

Topical Prostaglandin Analogs

Adverse effects Conjunctivitis Eye irritation Exacerbation of pulmonary conditions Bradycardia Tachyphylaxis in 20-25% of patients

Topical Beta-Blockers

Second-line therapy

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Alpha-Agonists

Mechanism: decreases aqueous fluid production (may increase outflow as well

Alpha-Agonists

Alpha-Agonists

Brimonidine

Adverse effects Allergic reactions Dizziness Fatigue Dry mouth Somnolence?

Alpha-Agonists

Mechanism: decrease aqueous fluid production

Topical Carbonic Anhydrase Inhibitors

Topical Carbonic Anhydrase Inhibitors

Dorzolamide, Brinzolamide

Adverse effects Blurred vision Stinging Tearing Conjunctivitis Photophobia Keratitis

Topical Carbonic Anhydrase Inhibitors

Mechanism: increases aqueous outflow

Parasympathomimetic Agents

Parasympathomimetic Agents

Pilocarpine

Adverse effects Accomodative spasms Blurred vision/irritation Eyelid twitching Retinal detachment May precipitate closed-angle glaucoma

Pilocarpine

Systemic Carbonic anhydrase inhibitors

Acetazolamide

Good for Acute elevation of IOP (closed-angle glaucoma)

Acetazolamide

Epineprine prodrug

Dipivefrin

Rho kinase inhibitor

netarsudil

Adverse effects Conjunctival hyperemia Corneal verticillata Instillation site pain Conjunctival hemorrhage

netarsudil

Decrease Fluid production

A B C= Alpha agonists, beta blockers, carbonic anhydrase inhibitors, rho kinase inhibitor

Increase fluid out flow

Prostaglandin analogs and parasympathetic agents

Rapid reduction needed

Acute Angle Closure Crisis, use pilocarpine, osmotics, or steroids

Staphylococcus aureus or Staphylococcus epidermidis

Streptococcus pneumoniae

H. influenzae (children)

Pseudomonas spp. or anaerobes (contact lens users)

Acanthamoeba-contaminated contact lens solution may cause keratitis (rare; \~30 cases/year in United States).

Neisseria gonorrhoeae and Neisseria meningitidis

Chlamydia trachomatis: gradual onset >4 weeks

Conjunctivitis bugs

Caused by Neisseria gonorrhoeae Rapid onset Characterized by eyelid edema, chemosis, severe, purulent discharge, and pain

Hyperacute

Lasts longer than a few weeks Commonly caused by Chlamydia trachomatis

Chronic

Treatment for Acute Infections

Watch and wait Most cases resolve independently (especially viral) Wait 2-3 days before initiating treatment (cool compress use may reduce antibiotic use) Avoid contacts while eye is red

require systemic AND topical treatment

Gonococcal and chlamydial infections

First line for dry eyes

Topical corticosteroids (e.g. prednisolone 1% sol’n) Recommended for a maximum of 4 weeks AE’s: ocular infection, cataracts, glaucoma

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Immunosuppressants Cyclosporine (Restasis) 0.05% emulsion AE’s: ocular irritation, scleral redness Lifitegrast (Xiidra)

Systemic agents for dry eyes

Cevimeline, Pilocarpine

Nonspecific term used to describe any intraocular inflammatory disorder

Uveitis

Uveitis treatment

Topical and/or systemic steroids \[May require intravitreal injections\] Immunosuppressants E.g., cyclosporine, tacrolimus, etc.

Corneal abrasion treatment

Topical and/or oral analgesics

Topical antimicrobials

Cycloplegics \[Cyclopentolate 1% or homatropine 5%\]

Preferred antibiotics for abrasions

erythromycin, polymixin, sulfacetamide

Antipseudo coverage for contact wearers

cipro, ofloxacin, gent

Topical corticosteroids are indicated for which ocular condition?

Xerosis

Which bacterial cause of conjunctivitis would be more likely in neonates?

Neisseria

Benefits: decreases inflammatory & non-inflammatory lesions, helpful with bacterial resistance Derivative of coal tar ANTIBACTERIAL, comedolytic, and anti-inflammatory

Benzoyl peroxide

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Standard for mild-to moderate papular-pustular acne

Benzoyl peroxide

Often used when unable to tolerate topical retinoid due to irritation

Salicylic acid

Useful for comedonal and inflammatory acne

Topical Retinoids

reduces sebum production

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Topical Retinoids

are drugs of choice for comedonal, non-inflammatory acne

adapalene or Trifarotene \[Topical Retinoids\]

Vitamin A analogues – reverse abnormal keratinization Do not decrease production of sebum, but primarily decrease inflammation, normalize keratinocyte differentiation, and increase keratinocyte proliferation and migration Retinoic acid (tretinoin, vita a acid) is powerful exfoliant that slows desquamation process 

tretinoin, adapalene, tazareotene

antimicrobial, anti-inflammatory, and comedolytic properties, reduces hyperpigmentation Mechanism: inhibits conversion of testosterone to 5-dehydrotestosterone

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Azelaic Acid

Treatment of mild to moderate inflammatory acne vulgaris. Treatment of inflammatory papules and pustules of mild to moderate rosacea.

Azelaic Acid

antimicrobials for p acnes topical

clinda, dapsone and erythro

Avoid with benzoyl peroxide

dapsone

Standard of care for moderate to severe acne and treatment-resistant inflammatory acne

Oral Antibiotics \[cyclines\]

Once daily PO antibiotic for non-nodular moderate-to-severe vulgaris 9 yo+

Salecycline

Mechanisms Oppose androgens at sebaceous gland Decrease androgen production Regulate gene production for sebaceous gland growth/lipid production

Estrogens

Mechanism: suppress adrenal activity, anti-inflammatory

often a bridge therapy option

corticosteroids

Mechanism: inhibits androgen activity

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Spironolactone

Severe recalcitrant nodular acne or treatment-resistant acne Mechanisms Induces atrophy of sebaceous glands Decreases sebum production Antibacterial Anti-inflammatory Alters keratinization Dosing (with food)

Isotretinoin

ALL patients, prescribers, wholesalers, and dispensing pharmacists must register Max 30-day supply each month Mandatory counseling and documentation Requires 2 forms of birth control for 1 month before, during and 1 month (usually 4 months) after treatment Routine pregnancy tests are required

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Isotretinoin

Comedonal, Non-Inflammatory Acne (Topical)

Adapalene +/- fixed benzoyl peroxide

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Mild to Moderate Papulopustular Inflammatory Acne (Topical)

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Fixed dose adapalene and benzoyl peroxide or fixed dose topical clindamycin and benzoyl peroxide are first line options

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