Pharmacology

ASTHMA

Heart

Relievers

Maintenance

ICS

SABA

SAMA

Agonist

antagonist

methylxanthines

LABA

LAMA

Leukotriene
midfiers

Anti-IgE antibodies

Receptors

Beta 2

Muscarinic

Activation = bronchodilation

Early phase

BD + increased mucous clearance

SABA + extended side chain

COPD

Ultra-LABA

ACh receptors

Activation = constriction
Antagonism = dilation

Prevents PSNS ACh contraction of SMCs

Less effective than B2

Inhibits constriction and mucus

Corticosteroids

reduce PLA2 activity

Late phase asthma

suppresses activated inflammatory genes CBP, CREB binding protein

inhibition of immune mediators froom

Leukotrine activation = constriction of bronchial smooth muscles

Reduces stimulation of mast cells and release of inflammatory mediators

Pain management

SAIDS

NSAIDs

Opioids

Inflammatory synthetic process

Inflammatory stim

PLA generates cytosolic AA

COX 1

5LP

COX 2

PGD + thromboxane

Leukotriene

Inhibitors

Exogenous glucocorticoids

Endogenous corticosteroids

Hydrocortisone
Prednisolone
Dexamethasone

Glucocorticoids
(steroid hormones)

Powerful reducer of inflammation (immune suppression)

Increase synthesis of anti-inflammatory proteins

decrease synthesis of pro-inf mediators

++ side effects

MOST POWERFUL ANTI-INF

Inhibits PLA2

Reduces COX enzyme expression

REDUCES PGD

Suppresses Th2

Inhibits

Effects

Analgesic

Anti-pyretic

Anti-inflammatory

COX1

COX2

Protective prostaglandin

Inflammatory prostaglandin

Permanently inhibited by aspirin

inhibits thromboxane = prolongs clotting time

INHIBITORS

IRREVERSIBLY INHIBITED BY ASPIRIN
COX1 x10 > COX 2

Effects

Anti-platelet

anaglesic

antipyretic

Indomethacin
COX 1 x7 > COX 2
competitive/reversible

Effects

Most potent anti inflammatory

10x better analgesic than aspirin

++ toxicity; cant use in kids <14 and preg

COX 2 inhibitors

click to edit

Ibuprofen
competitive, reversible inhibitor

Diclofenac
Competitive
reversible
inhibitor

Naproxen
competitive reversible inhibitor

COX 1 and 2 Inhibitor 2:1

Good for menstrual pain
(lasts longer than ibuprofen as well)

Well tolerated. Less SEs. Can increase thrombosis risk

COX 2 > COX 1

Potent NSAID
++ pain relief

Longest lasting NSAID

Chronic inflammation. Topical

CVD, GI, Renal, hypersensitivity risks

COX 1 = COX 2
Slightly COX 2 selective

Analgesic
Antipyretic
Menstrual pain analgesic
RA

Risks: Thrombosis, mild GI irritation
Well tolerated.
Safe for children.

Celecoxib

COX 1: COX2 = 1:30

Stroke, MI
GI bleeding

RA and OA

CV effects d/t inhibition of PGl2
leads to platelet aggregation

Inhibition of COX2 reduces PGl2 and PGE2 --> HTN and edema as arterial pressure hemostasis is disrupted

Paracetamol

Not a traditional NSAID

Selective COX 3 inhibitor in CNS

Strong anti-pyretic
Good analgesic for mild pain
Weak anti-inflammatory
most well tolerated analgesic

Good for those with GI problems.

AEs

highly hepatotoxic when overdosed

Chronic use can be hepatotoxic over time
d/t toxic intermediate
liver enzymes and bili rises
Hepatic dmg appears in 2 - 4 days

Know:

benefits of different NSAIDs
uses of the NSAIDS
common side effects

Angina pectoris = NBC + r

Lipid disorders
(dysllipidemia)

Anti-dysrhythmic

Nitrates

Beta-2 adrenergic blockers

Ca2+ ion channel blockers (CCBs)

Statins

Fibrates

bile acid binding resins

Ezetimibe

Bempedoic acid

PCSK9i

Symptoms d/t O2 demand > O2 supply

VD -> increase O2 supply

Decrease HR -> decrease O2 demand

Ca2+ blockers; statins

Organic nitrates; Ca2+ blockers

Nitroglyceryn

Sublingual

Oral

Transdermal

Converted to NO by liver;
dilates veins and arteries

Low dose

High dose

Dilates veins

Decreases venous return

dilates arteries and veins

NO relaxes SMCs

Reduce myocardial O2 demand
by reducing cardiac work d/t negative
ionotropic effects

Bind reversibly to alpha subunit of L-Ca2+ channels

Inhibit Ca2+ movement --> inhibits contraction

Nodal and myocardial effects

Smooth muscles of coronary and peripheral muscles

Coronary artery dilation

peripheral arteriole contraction

Systemic decrease in TPR and BP

Effects on cardiac conduction

Blocks inward Ca2+ current in SA node.

Decreases automaticity --> decreases HR

Slow AV conduction; prolong AV refractory time

Fewer atrial impulses --> rate of contraction slowed

Rabolazine

Reduces cardiac muscle stiffness

Used when other Rx fail

Blocks inward Na currents in cardiomyocytes

Goal = reduce LDL-C
raise HDL-C
reduce TG

-statin

Inhibit HMG-coA reductase

rate limiting step in cholesterol synthesis

Reduces mevalonate

reduced LDL-C
c = cholesterol

Effects

Reduce LDL, improve lipid profile

Increased NO production

Antiplatelet

Stabilize plaques

-fibrate

PPAR alpha agonists

Reduction of inflammation

Effects

Large VLDL and TG reduction

modest LDL reductions

modest HDL increases

used when issues d/t DM

Contraindication: renal issues

Effect

Inhibits sterol transporter at brush border

blocks ~50% of C absorption

10 - 20% reduction in LDL

Malabsorption syndrome.
Joint pain.

Effects

Cholesterol converted to bile acid by liver, which are then re-absirbed

BABRs prevent re-absorption of bile acids, and promote excretion

Used in severe disease

PCSK9 secreted by liver. Degrades LDL receptors when cholesterol too high

Causes increase in serum cholesterol

Given as injection x2/year

Increases LDL receptors on cell by increasing recycling

Pro drug. Upstream inhibition of cholesterol synthesis

Reduces LDL-C 18% when used with Statins; reduces MIs by 23%

Anti-hyperensive

Consequences of HTN

LV Hypertrophy

Stroke/MI

Endothelial damage

Renal Failure

Retinal Damage

First line drugs

ACE inhibitors OR ARB

CCB

Thiazide diruetics

Class 1

Class 2

Class 3

Class 4

Na channel blocker

Beta-2 channel antagonist

K+ channel blocker

Ca2+ channel blocker

disopyramide

medium speed dissociation

Slows phase 0

qunidine

Tx for VTac

Slowest dissociation form Na channels

Fastest dissociation

limited effect on conduction v elocity

binds active and refractory channels

Greatest effect in depolarized tissue. Limited impact on nodes

lignocaine

Used for MI related ventricular arrhythmia

More specific for voltage gated channels.
Frequency dependent. Works best with high HR

flecainide

Slow conduction in ventricles

works on tissue and nodes

Prolongs QT and QRS

uses

Afib

Aflut

SVT

contra with HB

Blocks sympathetic stim of heart

reduces HR

Depress SA and AV node activity

beta 1 selective

Atenolol

Metoprolol

Post MI

tachyarrhythmias

Reduce calcium influx

Negative ionotrope (shorter plateau phase)

coralan

Prolonged AP by delaying
repolarization by increasing Na
channel refractory period

amiodarone

Sotalol

Drugs

Verapamil

Diltiazem

Adenosine

Bradyarrythmias

Atropine

Isoprenaline

Cardiac glycosides

Digoxin