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Drug/Application Clinical Mechanism Drug Interactions/ CommentsUses Side Effects

Cholinergic Agonists Direct Acting Cause vasodilation by stimulating muscarinic type receptors on arteries

Increase Low viscosity saliva

CONTRAINDICTIONS: Bradycardia, hypotension, asthma, and peptic ulcer

All acetylcholine receptors are nicotinic except parasympathetic end organ receptors which are muscarinic

1st adrenergic receptor is nicotinic

Acetylcholine Eye surgery - topical Coronary angiography -

Coronary vasodilatation

Nicotinic and Muscurinic agonist

Broken down by AchE - Brief duration of action

No CNS

NT as sympathetic ganglia, pre and post- parasympathetic ganglia, adrenal medulla, and NMJ

Carbachol Nicotinic and Muscarinic agonist

NOT broken down by AchE No CNS

Bethanechol Used to stimulate intestine and bladder - increase contraction and tone

Muscarinic agonist Long duration of action NOT broken down by AchE No CNS

Decrease HR , decrease pupil diameter, increased secretions, bronchospasms, and increase GI and urinary function

In high does - causes vasodilatation and decreased BP due to activation of M3 receptors that release NO

Pilocarpine Glaucoma management - topical

Dry mouth - oral

Muscarinic agonist 2 - 3 hr duration of action NOT broken down by AchE CNS

Cholinergic crisis - salvation, lacrimination, urination, defecation, emesis (SLUDE syndrome)

Nicotine Smoking cessation - patch or gum

Nicotine receptor agonist CNS stimulant - respiration

stimulant and emetic effects

Nicotine poisoning causes depolarization block

Epinephrine Effects Bowel activity increase

Acetylcholinesterase reversible inhibitors

Indirect acting - temporarily blocks esteratic site of AchE

Physostigmine Antidote for atropine poisoning

Wide angle glaucoma

CNS - restlessness and agitation

Neostigmine Peripheral symptoms Treat myasthenia gravisNon-obstructive

intestinal/bladder atony

No CNS - due to positive charge

1


Edrophonium Diagnosis myasthenia gravis

Same as neostigmine, but shorter acting (less potent)

Acetylcholinesterase irreversible inhibitor

Indirect actine - permanently bind

Depolarization block causing respiratory failure

Antidote is Pralidoxime(peripheral) / Atropine (central)

Sarin – Nerve gas

Malathion (organophosphates) – pesticide

Treat lice

Penetrate CNS Humans break

Isoflourophate Glaucoma - not a first line drug

Duration of action - 1 week Overuse leads to toxicity (SLUD)

Acetylcholinesterase reactivator

Pralidoxime Antidote for AchE inhibitor

Reactivates AchE - only effective if given early

No CNS - positive charge

Peripheral antidote

Acetylcholine receptor antagonist

Muscarinic antagonist side effects:

Atropine - from belladonna or jimson weed plants

Treat Parkinson Treat intestinal spasms Best treatment for

organophosphate poisoning

Decrease nasal secretions Dilate eye to examine the

retina

CNS Muscarinic antagonist

Dry mouth Constipation Decreased sweating Mydriasis Urinary retention Tachycardia Decreased tears Precipitation of glaucoma

2

Acute iritis Physostgimine poisoning Bronchodilation (no

longer used)

Decreased respiratory secretions

Scopolamine - from belladonna plant

Treats motion sickness Increase CNS effect Muscarinic antagonist

Drowsiness Amnesia


Ipratropium COPD w/o dryness, bronchial dilation

NO CNS Muscarinic antagonist Decreases vagal tone - the

important bronchoconstrictor mechanism

Onset (15 - 30 min), peak (1 - 2 hrs), duration (6 - 8 hrs)

Do NOT block the direct effect of various mediators in asthma that act directly on airway smooth muscle

Effective in pts. With COPD

Muscarinic antagonist + B aginist = 1st line defense in COPD

Trimethaphan/ Mecamylamine None currently-was used to lower BP in Hypertensive crisis

Nicotinic ganglia specific Constipation Atony of bladder Cycloplegia Decreased sweating Postural hypotension Increased HR

Shock Management Catecholamines must be given IV due to 1st pass metabolism

Dopamine Low doses – D1

Moderate - 1

High - 1

D 1, 1, 1

Brief duration - inactivated by liver MAO

Used via IV

Epinephrine Dose dependent Cardiac stimulant (B1) Bronchodilator (B2) Glaucoma (A1) Given IV, topical,

inhalation

1 2 1 2 Agonist Vasoconstrictor - do NOT use at terminal arteries

Norepinephrine Infrequently used - increases BP and contractility

1 2 1 Agonist NO CNS

Constricts renal blood flow

3

Given IV


Phenylephrine To treat paroxysmal super ventricular tachycardia

Induces vagally mediated reflex

Decrease nasal secretions - topical

Induce mydriasis - does NOT effect accommodation

1 Agonist - vasocontriction

Indirect acting Sympathomimetics

Ephedrine Used orally Weight loss Performance enhancement

Release of NE B2 receptor agonist (minimum) CNS stimulant

Relax bronchial muscle Vasoconstriction of vessels

in nasal mucose Increased HR and BP Actions blocked by: cocaine

(block uptake), TCA (block uptake, and respirine (deplete NE content)

Herbal supplement

Amphetamine Narcolepsy Hyperactivity in children Appetite control

Catecholamine release CNS stimulant

Increased BP and HR

Cocaine Vasoconstriction Local anesthetic in surgical

procedures

2 adrenergic agonist-blocks re-uptake of serotonin, dopamine, and Norepinephrine

CNS stimulant Produces a massive release of

DA

Increase BP and HR Highly Addictive

Diuretics HTN Nephrogenic diabetes

insipidus Hypercalcemia Hypercalciuria

Fluid and electrolyte imbalance

Mannitol Transiently control Osmotic diuretic (inert sugar) Dehydration Used in IV

4

cerebral edema during neurosurgery

Maintain renal blood flow during major vessel surgery

Manage drug interactions

Loop of Henle Increases delivery of Na and

water out of the loop into the blood - decreases viscosity

Expands ECF volume Decreases renin release

Hypernatremia Temporary volume

expansion CONTRAINDICTIONS:

Pulmonary edema, anuria, dehydration


Acetazolamide Glaucoma Antiepileptic Prevention of altitude

sickness

Inhibits carbonic anhydrase - both membrane bound and cytoplasmic CA

Increase urinary HCO3 excretion

Increased Na and Cl delivery to the loop of Henle

Causes metabolic acidosis CONTRAINDICTION:

Sulfa drug allergy

Rarely used as a diuretic

Thiazides (Hydrochlorothiazide) Edema states HTN Nephrogenic diabetes

insipidus

Inhibits the Na, Cl symport Distal tubule

Chronic use decreases Ca excretion

Less efficacious than loop diuretic

Loop Diuretics Furosemide Ethacrynic acid

Mobilize edema fluid Via IV - pulmonary edema Hypercalcemia

Ascending loop Inhibits the Na-K-2Cl transport Increase excreation of Ca, Mg,

Na, Cl

Dehydration Hyponatremia Hypernatremia Hyopkalemia Ototoxicity (deafness) CONTRAINDICTION:

Sulfa drug allergy, hypercalciuria, calcium kidney stones

K+ Wasting (does not require supplement)

Spironlactone Refractory edema associated with secondary hyperaldosteronism

HTN and edema Primary

hyperaldosteronism Co-administered with loop

diuretics and thiazides

Aldosterone receptor antagonist Late distal and collecting ducts

Hyperkalemia K sparing

Triamterene Used with loop diuretics and thiazides

Inhibit Na channels Late distal and collecting ducts

Hyperkalemia K sparing

B agonist Dobutamine Stimulate heart in

cardiogenic shock Short term - cardiac

decomensation

1 Agonist

5

Abuterol (metaproterenol) Dilate bronchial airways - used to manage asthma, COPD

2 Agonist Given orally - decrease BP and increase HR

Given via inhalation - jitters and tremors


Isoproterenol Mild or transient episodes of heart block

For cardiac arrest until cardioversion can be performed

Bronchodilator (minimum)

1 2 Agonist Tachycardia

-Blockers (Sympatholytic drugs)

HTN Cardiac arrhythmias (AF -

after cardiac inversion) Angina

Chronic use (months) - Increased ejection fraction, contractility, and improvement in systolic performance with decrease in systolic and diastolic volumes and left ventricular mass

DO NOT use with asthma patients, COPD, unstable CHF, Occlusive peripheral vascular disease

Can cause AV Heart block High Doses With Ca+ blockers With Digoxin

Gradual removal due to upregulation of receptors

In persons with mild, moderate, or severe heart failure - reduces morbidity (40%) and mortality (30%)

Use with ACE inhibitor when treating CHF

Propanolol Management of Hypertension Angina Cardiac arrhythmias Migraine headaches Anxiety

1 2 –Antagonist (non-selective) - Decrease cardiac work and CO

Blocks renal 1 receptors to inhibit renin release - decrease angiotensin

No ISA

Bad dreams Depression Sexual dysfunction Aggravation of severe

congestive heart failure and occlusive peripheral vascular disease

Bronchospasms in asthma and COPD

INTERACTION: Calcium channel blockers and

6

Digoxin - causes AV blockMetoprolol Hypertension 1 –Antagonist - selective

No ISA Decreases CO and renin

SEE ABOVE SEE ABOVE

Timolol Glaucoma (major use) Antiarrythmia Treat hypertension

1 2 –Antagonist Decrease IOP by decreasing

aqueous humor production

topical

Central -Agonists Clonidine Centrally acting Anti-

Hypertensive (oral) 2-Agonists Inhibits release of NE - acts

pre-synaptically Decreased sympathetic outflow

to the heart- Decreased CO CNS

Sedation Withdrawal hypertension Decrease libido

Rebound hypertension

If given IV can cause direct vasoconstriction via A2 receptors


1-Blockers Phentolamine (Regitine) Lowers BP and HR of

pheochromacytoma Raynaud's diseases

(vasospasms) Erectile dysfunction

Competitive antagonist for both 1 2 receptors

Tachycardia

Prazosin Lowers BP - not widely used

BPH - relax bladder smooth muscle

1-Antagonist Decrease on total peripheral

resistance Increase in venous capacitance

Postural Hypotension Syncope - 1st full dose Favorable lipid shifts

Initiate with lower dose Give at night

Vasodilators Hydralazine Hypertension (not 1st line)

Reduce afterload in the treatment of heart failure when ACE inhibitors cannot be used

Direct SM relaxation by decrease in Ca and increase in NO

Decrease in TPR

Baroreceptors may cause tackycardia and increase oxygen usage (Blocked by B-blockers)

Immunogenic - Slow acetylators develop lupus like symptoms

Minoxidil Hypertension - drug resistant

Activates ATP dependent K channels resulting in hype-polarization and relaxation of SM

Decrease in TPR

Barrow receptors may cause tackycardia and increase oxygen usage

Tachycardia Pericardial effusion Fluid retention Hypertrichosis (xs. hair)

USE in combination with -Blockers and diuretics

Sodium Nitroprusside Hypertension Crisis - via IV

Fe-cyanide complex Increases release of NO -

Hypotension Cyanide and thiocyanate

Use only in patients with NORMAL liver

7

activates guanylcyclase cGMP relax SM

Decrease in cardiac preload and afterload

poisoning and kidney function so toxins can be metabolized and eliminated


Nitroglycerin Sublingual - venodilatation in the peripheral, splanchic, and pulmonary vascular beds

IV or high dose –decrease afterload

Abort acute angina attacks Angian prophylaxis

Releases NO upon contact Decreased venous return

(preload) decrease volume decreased contractility decreased oxygen consumption

Slight arteriolar dilatation Dilatation of epicardial

coronary a. and of the collaterals blood flow shifts to ischemic areas even though there is a decline in overall flow

Hypotension Decrease cardiac output Syncope Headache Possible dependence CONTRAINDICTION-

Sildenafil (Viagra) - increased vasodilation effect due to increased amount of cGMP

Develop tolerance Use: sublingual,

topical, buccal, oral spray, IV

Short duration of action

Isosorbide dinitrate Angina prophylaxis Heart failure - decreases

preload

Releases NO - long acting CONTRAINDICTION- Sildenafil (Viagra) - increased vasodilation effect due to increased amount of cGMP

Sublingual, chewed, or swallowed

Sildenafil (Viagra) Erectile dysfunction Inhibits phosphodiesterase-type 5

Inhibits the degradation of cGMP - vasodilation

Increases effects of NO Hypotension

ACE Inhibitors Captopril Management of

hypertension CHF Postmyocardial infarction

not treated with thrombolytics

Ejection fraction is <40% Delay renal insufficiency

Inhibits ACE Inhibits ACE from degrading

vasodilator bradykinin Indirectly inhibits Angiotensin

II from activating PIP pathway that causes the expression of protooncogene and growth factors

Hypotension on first dose Renal insufficiency

w/arterial stenosis due to efferent arteriole relaxation, therefore decrease in GFR

Cough due to kinin concentration

Proteinuria

Reduces mortality by 25%

8

w/type I diabetes and proteinuria (Unknown)

Decreases TPR (afterload) - w/o changes to heart rate

Decreases preload

Angioedema due to increased kinin

Hyperkalemia w/renal insuffiency, w/hypo aldosteronism (occurs with patients using K sparing diuretics)

CONTRAINDICTION: Do not give to pregnant, K-sparing diuretic


Angiotensin II Receptor Blockers

Losartan Diuretic Hypertension

Blocs binding of AII to its receptors

Vasodilator Decreases preload and after

load

CONTRAINDICTION: Do not give to pregnant

Does not cause cough Reduces mortality and

morbidity by 30% when combined with Spironolactone

Calcium Channel Blockers Hypertension (not a 1st line drug)

Arrhythmias - slows AV conduction and prolongs refractory period

Anti-Anginal

AV Block Hypotension Constipation, nausea,

vomiting Associated with

cardiovascular morbidity and mortality in hypertensive pts.

Contraindication: B-blocker (A-V block with Verapamil), Digoxin (A-V block and increased serum digoxin levels with Verapamil)

Nifedipine Blocks voltage gated calcium channels

Noncardiogenic peripheral edema due to venous

Most hypotension No decreases in A-V

9

Marked Vasodilatation None or reflex increase in

contractility

relaxation conduction

Verapamil Blocks voltage gated calcium channels- in the activated and inactivated states

Moderate Vasodilatation Mild decrease in contractility

A-V block with B-blockers or digoxin

Most common for A-V block and bradycardia

Decreases Digoxin uptake

Diltiazem Blocks voltage gated calcium channels- in the activated and inactivated states

Moderate Vasodilatation

Headache Least hypotension No decrease in

contractility

Antiarrhythmic Drugs Quinidine Converts AF to sinus

rhythm Na+ channel blocker K+ Blocker Lengthens AP Prolongs refractory period

NVD

Procainamide Converts AF to sinus rhythm

Na+ channel blocker Lupus-like syndrome Caution in renal insuffiency


Lidocaine Ventricular ectopy Converts VT to sinus

rhythm - associated with hemodynamic instability

NOTE: not preferred over cardiac inversion

Na + channel blocker - esp. in depolarized cardiac tissue

Little effect on normal cardiac tissue - suppresses electrical activity of tissue causing arrhythmia

CNS stimulation

Toxicity - least cardiotoxic Extracardaic - Tremor and

seizures

Given IV because of extensive first pass hepatic clearance

- Blockers AF rate control Limits A-V conduction Do not use in asthma Depression

Verapamil AF rate control Ca channel blocker Limits A-V conduction

LV dysfunction AV block

Digoxin Atrial fibrillation - slows ventricular rate and increases CO (does NOT convert to sinus rhythm)

CHF

Inhibits membrane Na-K- ATPase activity - results in increase intracellular Ca

Increased myocardial contractility

Decreased intracellular K Use leads to a decrease in heart

Intoxication: Cardiac (arrhythmia) or extracardiac (fatigue, anorexia, naseua and vomiting, altered yellow-green vision, confusion, delerium and depression)

Does NOT reduce overall mortality, only morbidity

Small therapeutic index and long duration of action

Treatment of toxicity -

10

size, diuresis, decrease in blood volume and relief of edema

CNS stimulant Vagal stimulation, baroreceptor

sensitization, and sympathetic withdrawal

Encephalopathy Visual disturbances

hospitalization and monitoring - give IV K, stop digitalis, antiarrythmic drug, digoxin antibody (if severe)

Amiodarone Acute VT AND VF Long term treatment of AF

Blocks Na+ and some K+ channels

Sympatholytic Raises threshold for excitation Slows impulse conduction

Pulmonary fibrosis Liver dysfunction Thyroid dysfunction Corneal micro-deposits Skin color change

Adenosine (AMP) IV - Paroxysmal supraventricular tachycardia

Adenosine A 1 receptor agonist Directly inhibits AV nodal

conductance and increases AV nodal effective refractory period

Increase potassium conductance

Decreases cAMP induced Calcium influx

Flushing Inducing transient AV block INEFFECTIVE with the

drug theophylline - adenosine receptor antagonist

11


Antiplatelet/ Thrombolytics Bleeding

Aspirin Antiplatelet drug Transient cerebral

ischemic episode Cerebral vascular

disorders Unstable angina Post MI (preventative for

2nd MI) Maintain vein graft

patency after bypass

Irreversible COX inhibitor - prevents conversion of arachidonic acid to thromboxane A2, also prevents conversion to PGI2 - a vasodilator

TXA effected more then PGI

GI bleed Not used for primary prevention of stroke

Clopidogrel Antiplatelet drug Persons unable to take

Aspirin - requires several days before full effects are seen

Aspirin break through Expensive

Blocks ADP induced platelet aggregation and release of platelet granules

Leukopenia

Abciximab Antiplatelet drug Only available in IV form Prevent reocclusion and

restenosis following coronary angioplasty and atherectomy

Blocks platelet glycoprotein receptor IIb and IIIa (Thrombin and TF) – Inhibit the final common pathway of platelet aggregation

Bleeding IV only

Dipyridamole Antiplatelet drug Combined with aspirin

Inhibitor of adenosine uptake Weak inhibitor of

phosphodiesterase - increases cAMP

12


Streptokinase Thrombolytic drug MI (w/in 6 hrs of pain) Stroke (w/in 3 hr of

symptoms) Arterial Thrombus Infused parenterally $200

Noon-enzymatic protein Activates the fibrinolytic system Forms Plasminogen-

streptokinase activating complex to convert plasminogen to plasmin. Plasmin break fibrin.

Risk of bleeding CONTRAINDICTIONS: hx

of peptic ulcers, IDDM, internal bleeding, CVA, recent surgery or trauma, brain tumor, aneurysm, bleeding diathesis, age over 70, or uncontrolled severe HNT

Prolongation of PT or APTT indicates lytic state

Follow by use of heparin

t-PA Thrombolytic drug $2000

Converts plasminogen to plasmin. Plasmin break fibrin

t-PA selectively binds to bound fibrin-plasminogen

Releases plasmin – systemic fibrinolytic

Not used to treat: DVT or PE

Prolongation of PT or APTT indicates lytic state

Must be followed up with Heparin

Anticoagulants Heparin - Injection Hemodialysis

Cardiopulmonary bypass DVT (IV) and DVT

prevention (subcu) PE and PE prevention

SEE BELOW Hemorrhage Thrombocyopenia Arterial thromboembolism Hypersensitivity Osteoporosis

Monitored by APTT of >50 sec and PTT - heparin plasma [0.2 - 0.4 U/ml)

IV Only Does NOT cross

placenta Unfractionated (UFH) Initial treatment for

DVT PE

Enhances antithrombin III and IIa, which deactivates Thrombin and Factors Xa and Iia

Short half-life (0.5 - 1 hour)

Heparin induced thrombocytopenia (HIT) - Activates antiplatelet Ab (IgG) that activate platelets via their Fc Iia receptors

OK for breast feeding or pregnancy

Widespread binding - unpredictable

Low molecular weight(LMWH)

Subcutaneous b.i.d DVT - prophylaxis Venous

thromboembolism

Enhances antithrombin IIIa only , which deactivates factor Xa more than Iia

Long half-life (4 - 6 hours) Eliminated in kidney

Spinal or epidural hematoma

Less likely: HIT, but if already HIT DON’T use

Predictable ↑ ½ life, ↑

bioavailability

13


Warfarin - Oral DVT - begin during heparin treatment

PE - begin during heparin treatment

Atrial fibrillation Acute MI Valvular heart disease Recurrent systemic

embolism

Interferes with vit K therefore reducing factors VII, IX, X, and Thrombin

Long duration (35-45 hrs) Metabolized by cytochrome

P-450

Hemorrage Teratogenic - CROSSES

placenta CONTRAINDICTIONS:

Rifampin - increases metabolism; Nafcillin - loss of activity; alcohol - chronic: decrease activity, acute: increased; Metronidazole, trimethoprim, and sulfamethoxazole - decreases metabolism of S isomer; Amiodarone - decreases metabolism of S and R isomer; Aspirin - risk of bleeding

½ life 35-45 hrs Therapeutic delay (3-4

days) PT or INR 2-3 Treat OD with Vit K

Protamine Sulfate Reversal of Heparin's (LMWH) actions

Basic protein that binds the acidic heparin to for a stable compound

Partially reveses the anti-factor Xa activity

Vitamin K Reverse warfarin's anticoagulant effects

In the process of carboxylation of Factors Vii, IX, X and thrombin, vit. K is oxidized to am epoxide - a required step

Pulmonary All 2 agonists Palpitations 2 dilation

which leads to barrow receptors increasing HR

Tremor – caused by stimulation of 2 in skeletal muscles - Na-K ATPase causing hypokalemia

Asthma:o 1) Mild-Albuterolo 2) Low dose ICSo 3) Low - Med dose

ICS + LABAo 4) High dose ICS +

LABACOPD:o 1st line- B agonist +

anticholinergic bronchodilators

o Symptomatic -ICSo Acute exacerbation

-inhales B agonist and anticholinergic, plus systemic CS

14


Abuterol (metaproterenol) Bronchodilator - inhalation

Acute attacks

2 Agonist Activates adenylyl cyclase

increased cAMP PKA relaxation of smooth muscle

Duration of action 3 - 6hr

Tremors - B2 receptors on skeletal muscle

Palpitations - B2 receptors on peripheral vasculature vasodilatation reflex- increased cardiac force and rate of contraction

Hypokalemia - stimulate K+ uptake by skeletal muscle via muscle Na-K-ATPase pump cardiac arrhythmias

Salmeterol Bronchodilator - prevention of attacks, b.i.d.

Long Lasting B2 Agonist Long duration >12 hrs

Should NOT be repeated for acute attacks

Theophylline (Caffeine) 2nd line therapy for COPD and asthma

Must be monitored 5-15 mcg/ml therapeutic

range; 30 mcg/ml toxic range

In elderly and pts. with COPD - max 12 mcg/ml

Methylxanthine compound Unclear mechanism - results in

smooth muscle relaxation, improved diaphragmatic contraction, and increased mucociliary clearance

Some anti-inflammatory effects Well absorbed for GI tract Volume of distribution: 0.5L/KG - 1mg/kg increases 2mcg/ml Clearance varies among and

within individuals - cleared by cytochrome p450 in liver

Common side effects- nausea, tremor, HA, agitation, and insomnia

Severe toxicity > 30 mcg -Seizures, arrhythmias

Conditions that decreased elimination: CHF Liver disease Cor pulmonale -

increased pulmonary a. pressure

Ciprofloxacin ErythromycinConditions that increase Elimination Smoking

Corticosteroids Asthma COPD Rhinitis - use topically See below for specifics

Binds to GC receptor in cytoplasm and enters nucleus

Forms homodimer and binds to GRE - results in transcriptional regulation of specific target genes

See below for specifics

15


Prednisone COPD - acute excerbations

Asthma Give twice dailyGood on: Sneezing Rhinorrhea Pruritis Nasal Blockage

Oral corticosteroids - systemic Binds to GC receptor in

cytoplasm and enters nucleus Forms homodimer and binds to

GRE - results in transcriptional regulation of specific target genes

CHRONIC EFFFECTS Adrenal insufficiency Glucose intolerance Osteoporosis?Compression

fractures Myopathy - esp. quads Osteonecrosis Cataracts Glaucoma Psychosis Cushingoid appearance Obesity Hypokalemia Immune Suppression/

infection Purpura Delayed wound healing In children - stunted growth

Inhaled w/precautions avoid most if not all side effects

20% reaches respiratory tract when inhaled

Osteoporosis is treated by bisphosphonate /Ca+

+

Beclomethasone 1st line therapy in asthma Symptomatic COPD -

chronic use <800 micro g / day no

problems <1600micro g/day no

adrenal problems

Inhaled corticosteroid - same mechanism as above

20% of inhaled steroid reaches lung and absorbed into body

Limited systemic effects Oropharyngeal candidias

(thrush) Dysphonia (hoarseness) In children - stunted growth

Use of spacer limits amount deposited in the oropharynx (nl. up to 80% deposited) or with rinsing mouth

Chromolyn and Nedochromil Inhalation ProphylacticOK on: Sneezing Rhinorrhea Pruritis Nasal Blockage

Not well defined - prevents degranulation of mast cells, t-lymphocytes, eosinophils, and macrophages

Anti-inflammatory effects Improve bronchial

hyperresponsiveness Protects against

bronchoconstrictive stimuli

None

16


Ipratropium COPD w/o dryness, bronchial dilation

Rhinitis

NO CNS Muscarinic antagonist Decreases vagal tone - the

important bronchoconstrictor mechanism

Onset (15 - 30 min), peak (1 - 2 hrs), duration (6 - 8 hrs)

Nasal administration - blocks rich parasympathetic innervation of mucosa - decrease secretion

Do NOT block the direct effect of various mediators in asthma that act directly on airway smooth muscle

Effective in pts. With COPD

Muscarinic antagonist + B aginist = 1st line defense in COPD

Montelukast (Accolate) Leukotriene receptor antagonist Antihistamines Good on:

Sneezing Rhinorrhea Pruritis NOT nasal congestion

H1 receptor antagonist 1st generation blocked muscarinic receptors causing sedation and anticholinergic effects (dry mouth, urinary retention)

2nd generation selective w/o sedation of sedation

Diphenhydramine (1st Gen) Benadryl Blocks rhinitis, uticaria,

eczema

H1 blocker Muscarinic receptors blocker CNS

Sedation Anticholinergic side effects

Terfenadine (2nd Gen) Relief of allergic rhinitis Blocks H1 receptors Blocks delayed rectifiers –

voltage gated K channels Metabolized By CTY450 3A4 to

fexophenadine (the H1 active metabolite - Allegra)

NO CNS

Torsades de pointes - due to blocked delayed rectifier channels (prolonged QT interval and Ventricular Tachycardia)

Block metabolism: Ketoconazole Itraconazole Erythromycin Clarithromycin

Decongestions Good on: Nasal Blockage

1 2 Agonist

Phenylephrine 1 2 Agonist Increase BP due to fluid retention

Insomnia Not used w/MAO

inhibitors Caution w/BPH

Pseudoephedrine Common in OTC oral Vasoconstrictor 1 2 agonist

Not used w/MAO inhibitors

17


Oxymetazoline (Afrin) Nasal sprays 1 2 agonist topical vasoconstriction

Rebound congestion with prolonged use

Rhinitis medicamentosa - Chronic rhinitis, secondary hyperemia, tachyphylaxis, and mucosal irritability

GI Drugs Erythromycin Increase intestine motility

Antibiotic Motilin agonist - prokinetic

effects Diarrhea

Kaolin/ Pectin (Kaopectate) Makes solid stool Forms clay in lumen Does not stop fluid loss Cimetidine (Tagamet) Decrease acid secretion

Peptic ulcer disease (no longer used)

Parietal cell H2 Blocker - inhibits both basal and meal induced acid secretion

Short duration of action (4 -6 hrs)

Mental confusin Antiandrogenic effects -

decreased libido, gynecomastia

Metabolized by CYP450 - decreases metabolism of other drugs inc. coumadin and diazepam

Ranitidine (Zantac) Peptic ulcer disease Decrease acid secretion Stage I and II GERD

H2 Blocker Long duration of action - Lasts

12hrs

No significant side effects

Loperamide (Imodium AD) Diarrhea Opioid receptor agonist Poor CNS penetration Increases mixing contractions Decreases motility

Do NOT give to treat diarrhea induced by infections with invasive organisms

Metoclopramide Diabetic gastroparesis Antiemetic For constipation

Dopamine Antagonist (D 2) Seratonin Agonist (5-HT 4)

Misoprostol Adjunct therapy for peptic ulcer disease

NSAID gastric ulcers

Prostaglandin receptor agonist - In parietal cells (opp. happens elsewhere) inhibit adenyl cyclase stimulated by histamine indirectly acid secretion

Also, protect mucosa damage induced by acid, alcohol, and NSAIDS (aspirin)

Diarrhea - secretory Uterine stimulation (avoid

during pregnancy) Do NOT give - IBS pts.

Marked for co-administration with anti-inflammatory - prevent side effects

18


Sucralfate (Carafate) Stress/ Peptic ulcers Mucoprotective

Basic aluminum salt - 3 actions:- Complexes with proteins and forms a protective layer over ulcer site

- Decreases back-diffusion of H+ ions - Binds pepsin and bile salts

Non-toxic Constipation, diarrhea,

nausea, dry mouth, etc.

Omeprazole (Prilosec R and S isomer /Nexium - S isomer)

Peptic ulcer disease - inhibits both basal and meal induced acid secretion

Esophagitis Stage II and III GERD

Proton pump inhibitor Irreversible H+, K+ pump

inhibitor - inhibits gastric secretion

Need low pH to be active 24-48 hour action Metabolized by CYP2C and

CYP3A

Gastric hyperplasia due to oversecretion of gastrin (?) (linked to gastric cancer in animals)

Given with Amoxicillin to treat H. Pylori - 80% effective

Bismuth (Pepto Bismol) Diarrhea - esp. microorganism caused

Inhibit toxin-induced formation of prostanoid substances in intestinal mucosa

Prophylactic Treat

Diphenoxylate Diarrhea Opioid agonist CNS

Overdose- respiratory deprssion

Treat OD with naloxone Do NOT give to treat

diarrhea induced by infections with invasive organisms

Mixed with Atropine to deter abuse

Magnesium Hydroxide Antacid - Stage 1 GERD Laxative Pro osmotic

Weak base that neutralizes acid Non-systemic Rapid onset Raises intragastric pH to 8 - 9

Increased acid secretion Laxative (con when used as

an antacid) Xs. can induce muscle

weakness and fatigue

Propantheline Decrease acid secretion Anticholinergic Cholestyramine Diarrhea Binds osmotically active agents Endocrine Drugs Lispro Insulin Injected prior to meal Insulin analog - with penultimate

and antepenultimate (pro-lys) AA at carboxy-termainal end have been reversed (lys-pro)

Fast acting, high peak, and short duration

Subcutaneous

19


Tolbutamine Type 2 diabetes Sulfonyureas - promote first phase insulin releas

Potentiate the effects of insulin in target tissues (action at post-receptor level)

Decrease hepatic glucose output Half-life = 6 hrs Liver metabolism

Hypoglycemia From sulfa antibacterial drugs

Oral

Metformin Hyperglycemia Biguanide drug Reduces hyperglycemia by

decreasing hepatic glucose output - blocks hepatic glucose production

Increases peripheral uptake and metabolism of glucose

Takes 1 -2 weeks to decrease hyperglycemia

Renal excretion

Diarrhea Loss of appetite Nausea Rare - lactic acidosis

Oral

Acarbose Reduce sugar absorption Inhibits intestinal disaccharidase enzymes

Retards absorption of sucrose and starch in the intestine

Gas productin Oral

Rosiglitazone Type 2 diabetes Anti-hyperglycemic agent

Thiazolidinediones - sensitizes peripheral tissues to insulin

Enter nucleus, and bind the gamma subunit of the portein regulator PPAR, which modifies gene transcription of the glucose transporter

Also decrease hepatic glucose production

Weight gain Liver function abnormalities

- check

Oral

Propylthiouracil Overactive thyroid gland Antithyroid - block the organification of iodide

Decreases the peripheral conversion of T4T3

I-131 radioiodine Persistent hyperthyroidism

Induces radiation injury to the cells - occurs gradually over wks - mo

Hypothyroidism - give thyroid

CONTRAINDICATION: pregnancy - destroy fetus thyroid

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Parahormone Diagnostic test - distinguish pseudohypoparathyroidism from hypoparathyrodism

Increase bone density in osteoporosis (not yet in US)

Acts like parathyroid hormone - promotes intestinal and renal absorption of Calcium, and Ca resorption from bone

Injection

Calcitonin Hypercalcemia Paget's disease Osteoporosis

Decreases calcium and phosphorus resorption from bone

Subcutaneous Nasal spray

Dihydroxycholecaciferol Renal enzyme deficiency to convert vit. To active form

Convert vit. D to active form

Etidronate Paget's disease Osteoporosis -

intermittent treatment (2 wks q 3 mo)

Diphosphonate - decreases bone resorption

Oral

Alendronate Osteoporosis - qd before breakfast with water

Diphosphonate - decreases bone loss

Gastrointestinal Epigastric pain

Clomiphene Citrate Anovulation - given 5 day courses to induce ovulation

Estrogenantagonist - causes reflex stimulation of GnRH that leads to LH surge ovulation

Bromocriptine Prolactin tumors Prolactine overscretion Acromegaly

Dopamine superagonist - suppresses secretion and growth of prolactin secreting cells

InhibitingGH secretion

Nausea

Raloxifene (Evista) Osteoporosis Estrogen receptor modulator - inhibits bone resportion and turnover

Do NOT use - hx. of DVT

Mifepristone (RU 486) Postcoital contraception Abortion in early

pregnancy

Synthetic steroid - inhibits progesterone receptors

For abortion - follow with prostaglandin after 48 hours

Hydrocortisone 1 or 2 adrenal insufficiency

Congenital adrenal hyperplasia

Cortisol - increase gluconeogenesis, potentiation of effects of lipolytic agents, improve stress response

Cushing like symptoms Oral or parenterally

Prednisone Treat diseases with strong inflammatory reactions

Glucocorticoids - potent glucorticoid effects

Longish duration of action Very potent

HTN Hypokalemia Edema

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Dexamethasone Decrease cerebral edema Diagnostic agent to

suppress endogenous secretion of mineralcorticoid activity

Potent glucocorticoid Long duration of action

See above

9-fluorohydrocortisone Aldosterone replacement Very potent mineralcorticoid - adrenocorticoid analog

125 times more active than hydrocortisone

Metyrapone Diagnostic test of pituitary, eliciting a compensatory ACTH release, which is reflected in increased 11-deoxycortisol in plasma and urine

Inhibits 11-beta-hydroxylation in adrenocortical cells

Decreases hydrocortisone production

Cholestyramine an Colestipol Decrease plasma LPL High molecular weight Ion- exchange resins that bind bile acids in intestine

Forces the formation of new bile acids from cholesterol

Nausea, vomiting, constipation, and steatorrhea

Reduced absorption of compounds that depend on bile acids - fat soluble vit, thyroid hormone, iron, digitalis, thiazide diuretics, tetracycline, and anticoagulants

Mix with water or fruit juice - give before meal

Atorvastatin (Lipitor) Lower LDL levels Lower VLDL

HMG-CoA reductase inhibitor Increased synthesis of the LDL

receptor - esp. in liver

Liver and muscle enzyme elevations

Side effects increase with Cyclosporin, nicotinic acid, an fibric acid derivatives

Gemfibrozil Decreased VLDL production

Not known -lipid regulating drug Decreases hepatic uptake of FFA

and decreases synthesis of triglyceride and of VLDL carrier apoprotein

Increases plasma HDL

Gastrointestinal Liver function abnormalities

- check

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Nicotinic acid Familial hypercholesterolemia elevated VLDL and IDL levels

Unknown - B- group vitamin Lipid lowering properties Decreases hepatic synthesis of

triglycerides Augments fecal excreting of

neutral sterols (cholesterol end-products)

Decreases adipose tissue lipolysis

Enhanced lipoprotein lipase activity

Incresed HDL levels Decreases VLDL, LDL and

TAG

Cutaneous flushing Pruritis Side effects treated with

NSAIDS Provoke cardiac

arrhythmias Liver function abnormalities GI - heartburn, nausea, and

diarrhea Increased serum uric acid gout

Impaired glucose tolerance

Overall lipoprotein reduction is 10 - 15 %

Combine with resins treatment

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