firestine ocular and pulmonary pharmacology

3 divisions of the autonomic nervous system

sympathetic, parasympathetic, enteric

in the sympathetic response,

bp and heart rate __________

glycogenolysis __________

GI peristalsis __________

bp and heart rate __increase___

glycogenolysis _increases__

GI peristalsis _decreases__

in the parasympathetic system,

preganglionic neuron releases _______ onto _______,

postganglionic neuron releases _______ onto _______, leading to ___(constrict/dilate?)__

pre: ACh onto nicotinic

post: ACh onto muscarinic

= constriction

in the sympathetic system,

preganglionic neuron releases _______ onto _______,

postganglionic neuron releases _______ onto _______, leading to ___(constrict/dilate?)__

pre: ACh onto nicotinic

post: NE onto

alpha-> constriction

beta-> dilation

identify whether stimulation of the receptor leads to constriction or dilation

muscarinic:

alpha:

beta:

muscarinic: constriction

alpha: constriction

beta: dilation

t/f: acetylcholine acts at ALL junctions of the parasympathetic system

true

which nt do sympathetic neuroeffector junctions use primarily

norepinephrine

which nt does the adrenal medulla predominantly release

epinephrine

what allows for systemic activation of sympathetic sites even if there is no direct innervation

adrenal medulla-> releases epi/ne into blood

which receptors are activated and what is the response in symp/para stimulation of:

eye (iris)

symp: alpha1-> contraction of dilator/mydriasis

para: M->contraction of sphincter/ miosis

which receptors are activated and what is the response in symp/para stimulation of:

eye (ciliary muscle)

symp: beta2= relaxation, distant vision

[FFS: far, flat lens, symp]

para: M= contraction, near vision, increased aqueous humor OUTflow into canal of Schlemm

[PRN: para, round lens, near] / pronto: to canal

what kind of stimulation results in increased aqueous humor OUTflow into canal of Schlemm

parasympathetic stimulation of M receptors on ciliary muscle

what kind of stimulation results in increased aqueous humor production

sympathetic stimulation of B1

which receptors are activated and what is the response in symp/para stimulation of:

eye (ciliary body epithelium)

only sympathetic!

B1= increased aqueous humor production

which receptors are activated and what is the response in symp/para stimulation of:

lungs

symp: B2= dilates bronchioles

para: M= constrict bronchioles

summarize how ANS process affect aqueous humor

sympathetic: ciliary body epithelium B1= increases aqueous humor PRODUCTION

parasympathetic: ciliary muscle M= increases aqueous humor OUTFLOW

what explains why side effects may be seen in drugs meant for only one target area

receptors are found in multiple sites so even if you target a beta receptor in the eye, it may affect a beta receptor in the lungs, causing an undesired effect

what can minimize side effects

1. route of administration (topical eye drops, inhalation)

2. receptor subtype selectivity

muscarinic receptors are stimulated by _____ and blocked by _______

ACh; atropine

which ANS system controls pupillary constriction and how? whats another term for constriction?

parasympathetic control of sphincter pupillae- M; miosis

carbachol

moa

effect

-muscarinic agonist (like acetylcholine)

-Constricts pupils (miosis)

- used in lens replacement surgery

pupil dilation, or ________, can be caused by which drug classes

mydriasis

-muscarinic antagonists (relax circular/sphincter pupillae)

-alpha1 agonist (contract radial muscle)

alpha1 agonist effect on pupil

mydriasis (dilation)

- forces contraction of radial muscle

muscarinic agonists work to produce

a. miosis

b. mydriasis

c. miosis and aqueous humour drainage

d. mydriasis and aqueous humour drainage

e. none

c

pupil contraction and fluid drainage via parasymp stimulation

pilocarpine

brand

moa

effect

- Carpine

-muscarinic agonist

- drains fluid in eye; ocular hypertension and glaucoma

which enzyme terminates ACh activity

acetylcholinesterase (AChE)

physostigmine moa

inhibits AChE (INDIRECT M agonist since less ACh depleted)

= for glaucoma

tropicamide

moa

effect

-muscarinic antagonist eye drops

- mydriasis (pupil dilation), vasoconstriction

phenylephrine

moa

effect

-alpha1 receptor agonist

- mydriasis, reduce red eyes via vasoconstriction, nasal decongestion

tetrahydrozoline

brand

moa

effect

Visine

-alpha-1 receptor agonist

-local vasoconstriction= reduce red eye

naphazoline

brand

moa

effect

Clear Eyes Redness Relief

-alpha-1 receptor agonist

-local vasoconstriction= reduce red eye

what contraindication do mydriatic drugs have?

individuals with glaucoma

what are the 3 anatomical pathways that control aqueous humour in the eye

(targets for glaucoma and intraocular pressure)

1. ciliary body receptors

-alpha decreases production [alpha2 agonist]

-beta increases production [beta1 blocker]

2. carbonic anhydrase [inhibitor] regulates bicarb (ion)- osmosis

3. prostaglandins [analog] increase uveoscleral outflow of fluid

brimonidine

brand

moa

effect

Alphagan P, Mirvaso

alpha-2 agonist

decrease aqueous humor (glaucoma)

timolol

brand

moa

effect

Betimol, Istalol, Timoptic

beta-1 blocker

decrease aqueous humor (glaucoma)

brimonidine/timolol

brand

moa

effect

Combigan

brimonidine (alpha2-agonist) and timolol (beta1 blocker)

decrease aqueous humor (glaucoma)

_______ is a prodrug of epinephrine, often used for ocular use

dipivefrin

what is the first line agent for glaucoma treatment?

topical prostaglandin analogs

- latanoprost, bimatoprost, travoprost

what are the brand names and moa for the following drugs?

latanoprost

bimatoprost

travoprost

moa: topical prostaglandin analogs (increase humour outflow)

latanoprost= Xalatan

bimatoprost= Lumigan

travoprost= Travatan Z

dorzolamide

moa

effect

carbonic anhydrase inhibitor

decreases bicarb production which reduces fluid into eye (glaucoma)

Cosopt

Generic: Dorzolamide (carbonic anhydrase inhibitor) and Timolol (beta1 blocker)

Drug Class: Ophthalmic glaucoma agents

muscarinic agonists favor ________ vision

near

muscarinic antagonists __(relax/contract?)___ the ciliary muscle, to produce a resting lens that ___(can/cant?)___ focus on near objects

muscarinic ANTAGONISTS

relax

cannot

strabismus

cross-eyed/ misalignment of the eye

what are 2 drug therapies for strabismus

1. atropine for underactive eye (forces eye to focus)

2. botox for overactive eye (paralyzes it)

pheniramine

moa/effect

ophthalmic H1 receptor antagonists

lowers eye inflammation

antazoline

moa/effect

ophthalmic H1 receptor antagonists

lowers eye inflammation

naphazoline

alpha 1 agonist= vasoconstriction

for eye redness; often added with antihistamines

cromolyn sodium

brand

moa

Opticrom

decreases histamine release from mast cells (for inflammation)

dexamethasone

moa

effect

glucocorticoid-> anti-inflammatory

- local and systemic side effects

prednisolone

moa

effect

glucocorticoid-> anti-inflammatory

- local and systemic side effects

diclofenac

brand

moa

Voltaren

NSAID (inflammation)

flurbiprofen

brand

moa

Ocufen

NSAID (inflammation)

cyclosporin ophthalmic

brand

moa

effect

Restasis

immunosuppressive that inhibits t lymphocyte activation->

decreases cytokines and inflammation in lacrimal gland

= for dry eyes; increases tear production

lifitegrast

brand

moa

effect

Xiidra

immunosuppressive that inhibits t lymphocyte activation->

decreases cytokines and inflammation in lacrimal gland

= for dry eyes; increases tear production

What did the AREDS study find?

Vit C and E, zinc, copper, and beta carotene slowed progression of age-related macular degeneration

What did AREDS2 find?

did not use beta carotene in study= less cancers but no improvement in eye

t/f: the FDA does not regulate whether supplements are beneficial, but they do regulate composition

false. they regulate neither

how is verteporfin used for age-related macular degeneration

-photodynamic therapy with verteporfin

-combats neo-vascularization (overgrowth of blood vessels)

-shining a light on cells treated with verteporfin makes free radicals= cell death

which drugs are given via intravitreal injection and target VEGF to treat age-related macular degeneration

-tanibizumab

-aflibercept

-pegaptanib

(TAP)

in the normal ANS system, what cause bronchodilation? constriction?

dilation= epi-> beta 2

constriction= vagus releasing ACh-> M3

dyspnea

difficulty breathing/ shortness of breath

t/f: emphysema is reversible with bronchodilator and anti-inflammatory therapy

false. lung parenchyma is destroyed; never reversible

methacholine

-Muscarinic receptor (M3) agonist.

-Used in bronchial challenge test to help diagnose asthma. (constricts bronchioles even more)

t/f: cromolyn sodium can be used for both eye inflammation and asthma

true. it is a mast cell stabilizer

muscarinic _____ are used for bronchodilation in COPD

antagonists

which functional group is present in SAMAs and LAMAs to treat asthma

quaternary amine (permanent positive charge)

ipratropium

SAMA= short acting muscarinic antagonist used for bronchodilation

Combivent

Generic: Albuterol (SABA) and Ipratropium (SAMA)

Drug Class: Bronchodilator Combo

tiotropium

Spiriva

LAMA= long acting muscarinic antagonist used for bronchodilation

first line bronchodilator agents

beta 2 agonists (albuterol, salmeterol)

what is the principal endogenous ligand that causes bronchodilation

epinephrine; also used for anaphylaxis

albuterol

brand

moa

ProAir, Ventolin, Proventil

SABA= short acting beta agonist

for bronchodilation

salmeterol, formoterol

moas

effect

both are LABAs

long acting beta agonists

for bronchodilation

rank the following according to length of activity (short acting to longest acting). which drug class are these?

epinephrine, formoterol, albuterol, salmeterol

= beta 2 agonist

(shortest) epi, albuterol, salmeterol, formoterol (longest)

frequent use of a beta 2 inhaler often requires an additional drug class. which one? what does it do?

corticosteroid (ICS)

for inflammation

salmeterol + fluticasone

brand?

moa?

Advair

salmeterol is LABA, fluticasone is ICS

formoterol + budesonide

brand?

moa?

Symbicort

formoterol is LABA, budesonide is ICS

vilanterol + fluticasone + umeclidinium

brand?

moas?

Trelegy

vilanterol= LABA

fluticasone= ICS

umeclidinium= LAMA

theophylline

brand?

moa?

effect?

Elixophyllin

PDE inhibitor-> decreases cAMP-> bronchodilation

- available orally, but narrow therapeutic range

budesonide

Pulmicort

inhaled corticosteroid (ICS) for inflammation

most prominent endogenous glucocorticoid? 3 effects?

cortisol (hydrocortisone)

1. metabolic

2. anti-inflammatory

3. sodium-retentive

corticosteroids

systemic side effects?

local side effects?

systemic= cataracts, osteoporosis, growth suppression, adrenal suppression, metabolism

local= cough, oral thrush

t/f: corticosteroids work to both decrease the immune response and inflammatory responses

true

ciclesonide

brand?

moa?

Alvesco

an ICS PRODRUG!, less systemic side effects from steroid

which drug class is sometimes used to prevent newborn respiratory diseases and how? which drug and why?

-corticosteroids= produces surfactant

-betamethasone= best penetration into fetal circulation

omalizumab

-humanized monoclonal anti-IgE antibody

- for allergen-mediated asthma

meplizumab and reslizumab

-humanized mAbs against IL-5

- for eosinophilic asthma

benralizumab

-humanized mAB against IL-5 receptor

- for severe eosinophilic asthma

zileuton

5-lipoxygenase inhibitor

-blocks leukotriene synthesis, used for asthma

montelukast

Singulair

leukotriene receptor antagonist

for asthma and seasonal allergic rhinitis

t/f: opiates may suppress cough through central action

true

dextromethorphan

Robitussin

anti-tussive (cough)

benzonatate

Tessalon Perles

local anesthetic for cough suppression

driving cells of pulmonary fibrosis

activated myofibroblasts

pirfenidone

brand

moa

effect

Esbriet

- blocks TGF-beta stimulated collagen production

- for pulmonary fibrosis

nintedanib

brand

moa

effect

Ofev

ATP-competitive inhibitor of tyrosine kinase receptors

- lowers FGF

- for pulmonary fibrosis