Cology Project

8/11/2019 Cology Project

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decrease rate of

absorption

Peak Plasma Time:

1.5-2 hr

Elimination

Half-Life: ~5 hr

acetylcholine), exhibits

high binding affinity for

muscarinic M3

receptors on lacrimal &

salivary gland

epithelium: incr

salivation

Nicotine - Oral gum, patch for

smoking

Agonist at both NN

and NM receptors

cessation

Medical use for

smoking cessation

nonmedical use in

smoking and in

insecticides

Activates autonomic

postganglionic neurons

(bothsympathetic and

parasympathetic and

skeletal

muscleneuromuscular

end plates •enters CNSand activates NN

receptor

Pilocarpine Isopto Carpine Oral lozenge and

topical

Like bethanechol,

partial agonist

Glau coma; Sjögren’s

syndrome

Activates M1 through

M3

receptors in all

peripheral

tissues • causes

increased

secretion, smooth

muscle

contraction (except

vascular

smooth muscle

relaxes), and

changes in heart rate



Varenicline Chantix Absorption

Completely absorbed

Bioavailability: High

Peak plasma time: 3-4

hr

Elimination

Excretion: Urine (92%)

Half-life: 24 hr

Excretion: Urine (92%)

Agonist at nicotinic

receptors; acts on

mesolimbic dopamine

system associated with

nicotine addiction,

Smoking Cessation Appetite changes

Chest pain

Constipation

Dry mouth Dyspepsia

Dyspnea

Ambenonium Mytelase Poor oral absorption

Onset: 20-30 min

Duration: 4-8 hr

Acetylcholinesterase

inhibitor;

Myasthenia Gravis Urinary urgency

Salivation Vomiting

Nausea Diarrhea

Lacrimation, miosis

Donepezil Aricept AbsorptionBioavailability: 100%


hr

Elimination

Half-life: 70 hr

Acetylcholinesteraseinhibitor

Alzheimer's Disease Nausea DiarrheaInsomnia Headache

Vomiting Cramping

Fatigue

Edrophonium Tensilon Onset: IV: 30-60 sec;

IM: 2-10 min

Duration: IV: 5-10 min;

IM: 5-45 min

Inhibits destruction of

acetylcholine by

cholinesterase

Myasthenia Gravis Urinary frequencyWeakness Hypotension

Arrhythmia BradycardiaLaryngospasm

Galantamine Reminyl, Razadyne Half-Life: 7 hr

Peak Plasma Time: 1

hr

Increases acetylcholine

from surviving

presynaptic nerve

terminals by modulating

Alzheimer Disease

Hepatic Impairment

Abdominal pain

Anorexia

Muscle cramp

Fatigue Dizziness





CHAPTER :8

TOPIC : Cholinoceptor-Blocking Drugs

NAME OF THE DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF

ACTION

THERAPEUTIC

INDICATION

ADVERSE EFFECT

Atropine Atreza Metabolism: Liver Half-

Life: 2.5 hr Absorption:

90% Onset: <1 hr

Duration: 4 hr Peak

plasma time: 1 hr Peak

effect: 2 hr

Antimuscarinic; inhibits

action of acetylcholine

at parasympathetic

sites in smooth muscle,

CNS, and secretory

glands. Increases

cardiac output and

dries secretions

Sialorrhea,

Pylorospasm & Other

Spastic Conditions of

the Gastrointestinal

Tract

Ataxia Coma

Confusion Delirium

Dizziness Drowsiness

Hallucinations

Headache Insomnia

Clidinium Quarzan Half-Life: 6-24 h

Metabolites: Metabolized

in liver to active

metabolites;

demoxepam,

Anticholinergic agent;

elicits antispasmodic

and antisecretory

effects on GI tract

Peptic Ulcer, IBS, &

Enterocolitis

Drowsiness Ataxia

Confusion Skin

eruptions, Edema

Menstrual irregularities

Nausea Constipation

Xerostomia

Cyclopentolate Cyclogyl Onset of action: 25-75

min (cycloplegia); 30-60

min (mydriasis)

Blocks action of

acetylcholine resulting

in relaxation of the

cholinergically

innervated iris

sphincter muscle

Mydriasis/Cycloplegia

Diaganosis

Blurred vision Burning

sensation in eye Light

intolerance

Tachycardia

Conjunctivitis Raised

intraocular pressure

Darifenacin Enablex Absorption !Protein

Bound: 98% Vd: 163 L

Competitive muscarinic

receptor antagonist of

Overactive Bladder Abdominal pain



Peak plasma time: 7 hr

Metabolism Liver, by

CYP3A4 and CYP2D6

Elimination Half-Life: 13-

19 hr Excretion: 60%

urine; 40% feces

the M3 muscarinic

receptor; receptor

blocking limits bladder

contractions, and

reduce symptoms of

bladder

irritability/overactivity

Dizziness Dry eyes

Dyspepsia Nausea

UTI

Dicyclomine Bentyl Available in oral and

parenteral forms short t½

but action lasts up to 6

hours

Competitive

antagonism

at M3 receptors

Irritable bowel

syndrome,

minor diarrhea

Reduces smooth

muscle and secretory

activity of gut

Fesoterodine Toviaz Absorption

Bioavailability: 52%

Protein Bound: 50% Vd:

169 L (5-HMT active

metabolite) Elimination

Half-Life: 7 hr Excretion:

Urine (70%); feces (7%)

Competitive muscarinic

receptor antagonist;

inhibition of receptors

in the bladder prevent

symptoms of urgency

and frequency

Abdominal pain

Constipation Dyspepsia

Insomnia Nausea

Urinary retention ,UTI

Overactive Bladder

Flavoxate Urispas Onset: 55 min

Peak Effect: 112 min

Excretion: Urine (10-30%)

Anticholinergic smooth

muscle relaxant that

inhibits

phosphodiesterase and

counteracts muscle

spasm in urinary tract;

nocturia, suprapubic

pain, urinary

incontinence, urinary

tract irritation,

Abdominal pain Blurred

vision Confusion

Constipation

Disturbance in ocular

accommodation

Drowsiness Dry

Glycopyrrolate Robinul Onset: 1 min (IV); 15-30

min (IM, SC) Duration: 2-

3 hr (parenteral, vagal

Competitively inhibits

action of ACh on

autonomic effectors

Peptic Ulcer Disease Dry mouth Dry skin

Anhidrosis Flushing

Blurred vision



block); 7 hr (parenteral,

inhibition of salivation);

8-12 hr (PO;

anticholinergic effects)

innervated by

postganglionic nerves

Inhibits salivation,

tracheobronchial

secretions,

bradycardia, and

hypotension

Cycloplegia

Photophobia

Palpitation

Xerophthalmia

Constipation

Homatropine , Isopto Homatropine N/A Blocks the responses

of the sphincter muscle

of iris & ciliary muscle

of the lens to

cholinergic stimulation,

thereby producingmydriasis and

cycloplegia

Cycloplegia/Mydriasis

for Refraction

Increased IOP

Follicular conjunctivitis

Vascular congestion

Edema Xerostomia

Burning Irritation

Stinging Blurred vision

Thirst

l-Hyoscyamine Anaspaz, Cystospaz-

M, Levsin,

Bioavailability: Tab

(100%), SR (81%)

Onset: IV/IM/SC (2-3

min), SL (5-20 min),

tab/SR (20-30 min)Duration:IV/IM/SC/tab/SL

(up to 4 hr), SR (12 hr)

Peak plasma time:

Tab/SR (2.5 hr)

Parasympatholytic,

atropine-like effects,

especially peripherally;

blocks the action of

acetylcholine atparasympathetic sites

in smooth muscle,

secretory glands, and

CNS

Gastrointestinal

Disorders

Hypermotility of Lower

Urinary Tract

Blurred vision

Constipation

Dysphagia

Photosensitivity

Ipratropium Atrovent Minimal systemic

absorption

Anticholinergic

(parasympatholytic)

agent; inhibits vagally

Maintenance treatment

of bronchospasm,

including chronic

Bronchitis (10-23%)

Chronic obstructive



Onset: 15 min

Duration: 3-4 hr

Peak plasma time: 1-3 hr

mediated reflexes by

antagonizing

acetylcholine action;

bronchitis and

emphysema

pulmonary disease

(COPD) exacerbation

Sinusitis

Mepenzolate Cantil Absorption: Limited

Excretion: Urine (3-33%)& feces

Postganglionic

parasympathetic

inhibitor. Inhibits gastric

acid and pepsin

secretion and inhibits

spontaneous

contractions of the

colon

Peptic Ulcer Dizziness Confusion

Headache Insomnia

Nervousness

Weakness Drowsiness

Tachycardia

Methscopolamine Pamine Absorption: Incomplete

Onset of action: 1 hr

Duration: 4-6hr

Excretion: Urine,

unabsorbed drug in

feces

Reduces the volume of

the total acid content of

gastric secretion,

reduces gastric

secretion, and inhibits

salivation. Peripherally

blocks muscarinic

receptors

Peptic Ulcer Disease Blurred vision

Cycloplegia Mydriasis

Headache Dizziness

Drowsiness Palpitation

Oxybutynin Ditropan Bioavailability: 6% (~1.5-

2 times higher for

extended-release)

Onset: 30-60

Exerts antispasmodic

and antimuscarinic

effects on smooth

muscle

Overactive Bladder Asthenia Dizziness

Headache Blurred

vision Dry eyes

Diarrhea Nausea Pain

Propantheline Pro-Banthine Bioavailability: PO <50%,

take 30 min before meals

Competitively blocks

the action of ACh at

postganglionic

Peptic Ulcer

Antispasmodic

Constipation Dry

mouth Dry skin



Onset: 30-45 min (PO)

Duration: Upt to 6 hr

(PO)

parasympathetic

muscarinic receptor

sites

Decreased sweating

Scopolamine - Transdermal patch for

mation sickness

Unknown mechanism

in CNS

Prevention of motion

sickness andpostoperative and

nausea and vomiting

Reduces vertigo,

Postoperative nausea

Solifenacin Vesicare Bioavailability: 90%


Competitive

muscarinic-receptor

antagonist

Overactive Bladder,

Urge Incontinence

Blurred vision

Tiotropium Spiriva Onset: 30 min Duration:

>24 hr

Long-acting

antimuscarinic agent,often referred to asanticholinergic

Inhibits M3-receptors atsmooth muscle,leading tobronchodilation

Chronic Obstructive

Pulmonary Disease

Abdominal pain

Allergic reaction

Tolterodine Detrol Onset: Overactivebladder, 1 wk; urge

incontinence, 1 hr

Competitive muscarinicreceptor antagonist;

Overactive Bladder,Urge Incontinence

Blurred visionConstipation Dizziness

Drowsiness

Tropicamide Mydriacyl Onset: 15 min

Maximum effect: 60 min

Duration: 3 hr

Blocks acetylcholine

resulting in relaxation

of cholinergically

innervated iris

Mydriasis Dry mouth

Nausea

Vomiting



sphincter muscle

Trospium (Spasmex, Sanctura) Half-life: 20 hr

(immediate release)


Reduces the smooth

muscle tone of the

bladder by

antagonizing the

effects of acetyl choline

on muscarinic

receptors.

Overactive Bladder Constipation

Tachycardia

Mecamylamine (Inversine Half-Life: 24 hr Onset:

0.5-2 hr Duration: 6-12 hr

Excretion: urine 100%

Ganglionic blocker,

inhibits acetylcholine at

autonomic ganglia

Hypertession Fatigue Sedation

Constipation

Pralidoxime Protopam Onset: 5-15 min Binds to

organophosphates and

breaks alkyl

phosphate-

cholinesterase bond to

restore activity of

acetylcholinesterase

Organophosphate

Poisoning

Blurred vision Double

vision Hypertension



CHAPTER :9

TOPIC :Adrenoreceptor Agonist


ACTION

THERAPEUTIC

INDICATION

ADVERSE EFFECTS

Amphetamine Adderall Well absorbed

Onset of action: 30-60min

Duration: 4-6 h

Sympathomimetic

amine that promotes

release of dopamine

and norepinephrine

from their storage sites

in the presynaptic

nerve terminals

ADHD Abdominal painHeadache InsomniaLoss of appetite

Apraclonidine Iopidine Peak Plasma Time: 3-5hr (reduction inintraocular pressure)

Peak PlasmaConcentration (0.5%admin): 0.9 ng/mL

Alpha-1 & alpha-2

adrenergic receptor

agonist; may reduce

acqueous humor

formation

Glaucoma Discomfort HyperemiaPruritus BlanchingBlurred visionConjunctivitis

Armodafinil Nuvigil Peak plasma time: 2 hr Unknown; not

sympathomimetic (R-

enantiomer of

modafinil)

Narcolepsy Nausea

Dry mouth

Dizziness Anxiety

Diarrhea

Brimonidine Alphagan Metabolized by liver Alpha2 adrenergic Elevated IOP in

Patients with

Allergic conjunctivitis




hr (brimonidine)

receptor agonist; Glaucoma or Ocular

Hypertension

Conjunctival folliculosis

Conjunctival hyperemia

Eye pruritus

Dexmedetomidine Precedex Half-life, elimination: 6min; 2 hr (terminal)

Peak plasma: 0.3-1.5ng/mL

Centrally acting alpha2-

adrenoceptor agonist

that has sedative and

anesthetic properties

possibly by activating

G-proteins in the

brainstem

ICU Sedation Anemia Bradycardia

Fever Pleural effusion

Leukocytosis

Dexmethylphenidate Focalin Bioavailability: 22-25%

Onset of action: 12hr(extended release)

The more

pharmacologically

active CNS stimulant of

the d-threo-

enantiomers; blocks

reuptake of

norepinephrine and

dopamine

Attention Deficit

Hyperactivity Disorder

Abdominal pain

Headache Insomnia

Restlessness

Dextroamphetamine Dexedrine Peak plasma time: ~3hr (immediate release);~8 hr (sustainedrelease)

Onset of action: 1-1.5hr

Sympathomimetic

amine that promotes

release of dopamine

and norepinephrine

from their storage sites

in the presynaptic

nerve terminals

Narcolepsy Vomiting

Emotional lability

Nervousness

Fatigue Fever



Dobutamine Dobutrex Intravenous, required

dose titration to desired

effect

Activated adenylyl

cyclase, increasing

myocardial contractility

Cardiogenic shocks

acute heart failure

Positive inotropic effect

Dopamine Intropin Onset: 5 min (adults)

Duration: <10 min

Endogenous

catecholamine, acting

on both dopaminergic

and adrenergic

neurons

Hemodynamic

Conditions

Respiratory: Dyspnea

Gastrointestinal:Nausea, vomiting

Metabolic/nutritional: Azotemia

Central nervous system:Headache, anxiety

Ephedrine Half-Life: 2.5-3.6 hr

Duration: 3-6 hr (PO)

Moderate beta-1 &

weak alpha effects

resulting in alpha- and

beta- adrenergic

stimulation

Hypotension

Associated with Spinal

Anesthesia

HypertensionTachycardiaDysrhythmias Anxiety

Anorexia Nausea

Epinephrine Adrenalin Chloride Half-Life: 44 min

Peak Plasma Time: 25-48 min

Local anesthetics

prevent

generation/conduction

of nerve impulses by

reducing sodium

permeability

Local, Infiltrative, or

Conductive Anesthesia

in Dental Procedures

Facial edema

Headache

Pain

Paresthesia

Sleepiness

Gingivitis

Fenoldopam Corlopam Requires dose titration Activates adenylyl Hypertension Vascular smooth muscle



to desired effect cyclase relaxation

Hydroxyamphetamine Paremyd Onset: 15 min

Maximum effect: 60

min

Duration: 3 hr

Blocks acetylcholine

resulting in relaxation

of cholinergicallyinnervated iris

sphincter muscle

Mydriasis Tachycardia PallorHeadacheParasympathetic

stimulation Transientstinging Dry mouth

Isoproterenol Isuprel Half-Life: 3-7 hr

Duration: cardiac arrest(IV): 8-50 min

Strong beta-1 & beta-2

effects resulting in incr

CO, decr PVR, &

variable BP & renal

perfusion changes

Adams-Stokes Attacks,

Cardiac Arrest, or

Heart Block

Tachycardia

Hypertension

Dysrhythmias

Angina

Metaraminol Aramine) Bioavailability: PO,96%

Duration: Short-acting

Glucocorticoid; elicits

mild mineralocorticoid

activity and moderate

anti-inflammatory

effects; controls orprevents inflammation

by controlling rate of

protein synthesis,

Acute Adrenal

Insufficiency

Adrenal suppression

Arthralgia

Bladder dysfunction

Cardiomegaly

Methamphetamine Desoxyn Half-Life: 4-5 hr

Absorption: Rapid

Metabolism: Liver

Amphetamine

anorexigenic agent;

sympathomimetic

amine related to

Attention Deficit


Dizziness, drugtolerance, dysphoricmood, euphoria,headache, insomnia,restlessness, tremor



ephedrine and

amphetamine with CNS

stimulant activity

Methylphenidate Ritalin Bioavailability: ~30%;large individualdifferences (11-52%)

Duration: 3-6 hr (IR); 3-8 hr (ER, SR); 8-12 hr(CD, LA, Concerta)

Peak plasma time: 6-8hr (PO); 7.5-10.5 hr;(patch)

Unknown; may block

reuptake of

norepinephrine and

dopamine into

presynaptic neurons;

Attention Deficit


Headache

Hypertension

Nausea

Nervousness

Toxic psychosis

Seizures

Midodrine ProAmatidine Oral prodrug converted

to active drug with 1h

peak effect

Activated

phospholipase C.

resulting in increase

intracellular calcium

and vasoconstriction

Orthostatic

hypotension

Vascular Smooth

muscle contraction

increasing blood

pressure

Modafinil Provigil Peak plasma time: 2-4

hr

Unknown; not

sympathomimetic

Obstructive Sleep

Apnea/Hypopnea

Syndrome (OSAHS)

Hypotension

Hypertension

T-wave changes

Amnesia

Anxiety

Naphazoline Privine Absorption: minimalsystemic

Alpha 1 adrenergic

agonist; stimulates

Nasal Decongestant Burning StingingSneezing Dryness Local





Tetrahydrozoline Visine Duration: 2-3hr

(vasoconstriction)

May stimulate alpha-

adrenergic receptors in

the arterioles of the

conjunctiva; produces

vasoconstriction

Conjunctival

Congestion

Irritation/burning

Blurred vision

Headache

Tremor

Tizanidine Zanaflex Bioavailability: 40%

Peak serum time: 1-4hr

Alpha-2 adrenergic

receptor agonist

structurally related to

clonidine; increases

presynaptic inhibition of

motor neurons

Muscle Spasticity Dry mouth

Somnolence

Dizziness Asthenia

Xylometazoline Otrivin Onset: 5-10 min

Duration: 5-6 hr

Metabolism: unknown

Alpha adrenergic

agonist

Nasal Congestion Anxiety

Dizzy

Tremor



CHAPTER :10

TOPIC :Adrenoreceptor Antagonist


ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECT

Alfuzosin (Uroxatral) Bioavailability: 49%

Peak Plasma Time: 8

hr Peak Plasma

Concentration: 13.6

ng/mL AUC: 194

ng.hr/mL

Selective antagonist of

postsynaptic alpha-1-

adrenoceptors;

Benign Prostatic

Hyperplasia (BPH)

Back pain Brochitis

Constipation Dizziness

Doxazosin Cardura Bioavailability:

Immediate release,65%; extended release,

54-59%

Blocks alpha1

receptors in prostaticstromal and bladder

tissues;

Benign Prostatic

Hyperplasia

Dizziness Fatigue

Headache

Phenoxybenzamine Dibenzyline Half-Life: 24 hr Onset:

several hours

Alpha blocker,

noncompetitive alpha-

adrenergic blockade of

post ganglionic

synapses in smoothmuscle, exocrine

glands

Hypertension

Pheochromocytoma

Tachycardia Dizziness

Drowsiness Fatigue

Phentolamine Regitine Half-Life:19 min (IV)

Duration: 30-45 min

(IM); 15-30 min (IV)

Blocks alph-adrenergic

receptors to briefly

antagonize circulating

epinephrine and

Pheochromocytoma Nasal congestion Post-

treatment pain Injection

site pain Diarrhea



norepinephrine

Silodosin Rapaflow Bioavailability: 32%

Half-Life: 13 +/- 8 hr


postsynaptic alpha-1-

adrenoceptors

Benign Prostatic

Hyperplasia

Diarrhea HeadacheInsomnia Dizziness

Tamsulosin Flomax Bioavailability: Fasting,30%

Onset: 4-8 hr

Tamsulosin is slightly

selective for α1A

Benign prostatic

hyperplasia

α1A

Blockade may relax

prostatic smooth

muscles more

than vascular smooth

muscle

Terazosin Hytrin Bioavailability: 90%

Onset (hypertension): 3hr

Blocks postsynapticalpha-1 receptor; alphablockade causesarterial and venousdilation

Benign Prostate

Hyperplasia

HypotensionRhinitis/nasalcongestionLightheadednessSomnolence

Tolazoline (Priscoline) Bioavailability: ~100%Onset: 30 min

Duration: 4-6 hr

Inhibits synthesis ofprostaglandins in body

tissues by inhibiting at

least 2 cyclo-

oxygenase (COX)

isoenzymes, COX-1

and COX-2

Pain Dizziness DyspepsiaEpigastric pain



Acebutolol Sectral Oral • β1β2 , with intrinsic

sympathomimetic

(partial agonist) effect

Hypertension •

arrhythmias • migraine

• may avoid worsening

of bradycardia

Lowers BP • modestly

lower HR

Atenolol Tenormin Bioavailability: 46-60%Onset:

Antihypertensiveresponse, 3 hr

Duration: 12-24 hr(normal renal function)

Block β1> β2 Angina pectoris •

hypertension

arrhythmias

Lower HR and BP •

reduce renin • may be

safer in

asthma

Betaxolol Betoptic Onset: Within 30 minDuration: 12 hr

Block β1> β2 Angina pectoris •hypertension

arrhythmias

Lower HR and BP •reduce renin • may be

safer in asthma

Bisoprolol Zebeta Half-Life: 9-12 hr

(normal renal function);

27-36hr (<40 mL/min);

8-22 hr (hepatic

cirrhosis)

Blocks response to

beta-adrenergic

stimulation;

cardioselective for

beta-1 at low doses

with little or no effect on

beta-2 receptors.

Hypertension Dizziness DyssomniaBradyarrhythmia

Carteolol Ocupress Oral • β1β2 , with intrinsic

sympathomimetic

(partial agonist) effect

Hypertension •

arrhythmias • migraine

• may avoid worsening

Lowers BP • modestly

lower HR



of bradycardia

Carvedilol Coreg Bioavailability: 25-35%(immediate release)

Onset(antihypertensive):Initial response, 1 hr;peak response, 1-2 hr

Nonselective beta-

adrenergic and alpha1-

adrenergic blocking

agent with no intrinsic

activity for use in

congestive heart failure

and hypertension

Congestive heart failure Dizziness FatigueHypotension

Weight gainHyperglycemia

Esmolol (Brevibloc) Pa renteral only • half -

life ~ 10 min

β1> β2 Rapid control of BP and

arrhythmias,

thyrotoxicosis and

myocardial ischemia

intraoperatively

Very brief cardiac β

blockade

Labetalol Normodyne, Trandate Bioavailability: 25%(PO)

Onset: PO, 20-120 min;

IV, 2.5 min

Nonselective beta

blocker with intrinsic

sympathomimetic

activity; also alphablocker

Hypertension DizzinessLightheadednessNausea

Levobunolol (Betagan Liquifilm Peak Plasma Time: 30min

Onset of action: 1hr

Peak effect: 2-6hr

Nonselective beta-

adrenergic receptor

blocker; reduces IOP

by reducing production

of aqueous humor

Open-angle Glaucoma Ataxia BurningLethargy DiscomfortBand keratopathy



Metipranolol Optipranolol Onset: 30 min Duration:24 hr Maximum effect:2 hr

Nonselective beta-

blocker

Open-Angle Glaucoma Burning sensation ineye , BlepharitisBlurred visionLight intolerance

Metoprolol Lopressor, Toprol Bioavailability:

Immediate release, 40-

50%; extended release,

65-77% relative to

immediate release

Blocks response to

beta-adrenergic

stimulation;

cardioselective for

beta1 receptors at low

doses, with little or no

effect on beta2

receptors

Acute Myocardial

Infarction

Dizziness Headache

Tiredness Depression

Diarrhea

Nadolol Corgard Oral, parenteral • Block β1and β2 Hypertension • angina

pectoris • arrhythmias •

migraine •

hyperthyroidism

Lower HR and BP •

reduce

renin

Nebivolol Bystolic Block β1> β2 Angina pectoris •

hypertension

arrhythmias

Lower HR and BP •

reduce renin • may be

safer in

asthma

Penbutolol Levatol Half-Life: 5 hr Beta adrenergic Arterial Hypertension Aggravate CHF





hyperthyroidism

Metyrosine Demser Half-Life: 3-4 hr

Bioavailability: Wellabsorbed

Metabolism: liver

Inhibits synthesis of

endogenous

catecholamines thru

inhibition of tyrosine

hydroxylase

Chronic

Pheochromocytoma

DiarrheaExrapyramidalSymptoms



CHAPTER 16

TOPIC :Histamine , Serotonin and Ergot Alkaloids


ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECT

Azelastine Astelin Nasal Onset: 1-3 hr

Duration: 12 hr

H1-receptor antagonist;

inhibits release of

histamine and other

mediators involved in

allergic response

Seasonal Allergic

Rhinitis

Bitter taste

Headache

Somnolence

Cold symptoms/rhinitis

Cough

Brompheniramine Brovex Half-Life: 11.8-34.7 hr

Onset: 30 min

Histamine H1-receptor

antagonist

Perennial & seasonal

allergic & vasomotor

rhinitis, relief of

symptoms from colds,

urticaria, angioedema,

anaphylactic reactions,

pruritus, allergic

conjunctivitis

Restlessness,

insomnia, tremors,

euphoria, nervousness,

delirium, palpitation,

seizures is less

common

Buclizine Bucladin-S Softabs

Carbinoxamine Histex Half-Life: 10-20 hr

Metabolism: Hepatic

Excretion: Urine

Histamine H1-receptor Allergies Dizziness Lassitude



Cetirizine Zyrtec Oral • duration 12– 24 h Competitive

antagonism/inverse

agonism at

H1receptors

IgE immediate

allergies, especially hay

fever, urticaria

Reduces or prevents

histamine effects on

smooth muscle,

immune cells

Chlorpheniramine Chlor-Trimeton N/A Chlorpheniramine

blocks muscle

responses in histamine

and acts as an

antagonism of the

constrictor effects of

histamine on

respiratory smoothmuscle.

Relief of Cold & Flu

Symptoms

Hypotension

Palpitations

Tachycardia

Confusion

Convulsion

Clemastine Tavist Onset: 5-7 hr Duration:

8-12 hr

Histamine H1-receptor

antagonist in blood

vessels, respiratory

tract, and

gastrointestinal tract

Allergic Rhinitis Dizziness Lassitude

Disturbed coordination

Muscular weakness

Diphenhydramine Benadryl Oral and parenteral •

duration 4 –6 h •

Competitive

antagonism/inverse

agonism at H1

receptors

IgE immediate

allergies, especially hay

fever, urticaria • often

used as a sedative,

antiemetic, and anti-

motion sickness drug

Reduces or prevents

histamine effects on

smooth muscle,

immune cells • also

blocks muscarinic and

α adrenoceptors •

highly sedative



Sumatriptan Imitrex Oral, nasal, parenteral •

duration 2 h

Partial agonist at

5-HT1B/1D receptors

Migraine and cluster

headache

Effects not fully

understood • may

reduce release of

calcitonin gene-related

peptide andperivascular edema in

cerebral circulation



CHAPTER :17

TOPIC : Vasoactive Peptide

NAME OF THE DRUG BRAND NAME PHARMACOKINETIC MECHANISM OF

ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECT

Valsartan Diovan Bioavailability: 25%Onset: 2 hr

Selective competitiveantagonist of

angiotensin AT1

receptors

Hypertension Arteriolar dilation.Decrease aldosterone

secretion. Increase

sodium and water

excretion

Enalapril Lexxel enalapril: initial 1-4 hr,

peak 8-18 hr

Inhibits conversion of

angiotensin I to

angiotensin II

Hypertension • heart

failure

Arteriolar dilation •

decreased aldosterone

secretion • increased

sodium and water

excretion

Aliskiren Valturna Onset: (valsartan) 2 hr Inhibits catalytic activity

of renin

Hypertension Arteriolar dilation •

decreased aldosterone

secretion • increased

sodium and water

excretion

Icatibant Firazyr Bioavailability: 97%

Peak Plasma Time: 45

minutes


kinin B2

receptors

Hereditary angioedema Blocks effects of kinins

on pain, hyperalgesia,

and inflammation





PO: 60-65% vomiting

Meclinertant N/A N/A Antagonist of central

and peripheral

neurotensin receptors

None identified Blocks some central

and peripheral

(vasodilator) actions of

neurotensin

Telcagepant N/A N/A Antagonists of the

calcitonin gene-related

peptide (CGRP)

recepto

Migraine

1

Blocks some central

and peripheral

(vasodilator) actions of

CGRP

Palosuran N/A N/A Antagonist of urotensin

receptors

Diabetic renal failure

1

Blocks vasoconstrictor

action of urotensin



CHAPTER :18

TOPIC : The Eicosanoid , Prostaglandin , thromboxane, Leukotriene , Related compound


ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECTS

Alprostadil Half-Life: 5-10 min Relaxes arterial smoothmuscle, producing

vasodilation

Inhibits platelet

aggregation

(prostaglandin E1)

Erectile Dysfunction BradycardiaHypotension Seizures

Tachycardia

Bimatoprost Lumigan Absorption: no

significant systemic

accumulation

Half Life: 45 min

Prostaglandin analog;

outflow of aqueous

humor

Elevated Intraocular

Pressure

Ocular dryness (3-10%)

Visual disturbance

Carboprost

tromethamine

Hemabate Peak plasma time: 20-

30 min Concentration:

1-1.6 ng/mL Half-life: 3

hr

Inhibits or stimulates

smooth muscle

contraction

Refractory Postpartum

Uterine Bleeding

Nervousness Epistaxis

Sleep disorder

Dinoprostone Prepidil, Cervidil Onset: In most first and

second trimester

pregnancies, slight

uterine contractions

begin within 10 min

Relaxes cervical

smooth muscle;

Cervical Ripening Fever/temperature

elevations (1%)

GI upset

Epoprostenol Flolan Half-life: 3-6 min Potent peripheral Pulmonary Jaw pain Headache



Metabolism: rapidly

hydrolyzed in blood to

metabolites

vasodilator of all

vascular beds; also

prevents platelet

aggregation

Hypertension Myalgia

Iloprost Ventavis) Vd: 0.7-0.8 L/kg Protein

Bound: 60% Duration:30-60 min

Synthetic analog of

prostagladin PGI2

Pulmonary Arterial

Hypertension

Flushing Cough

Hypotension NauseaHeadache

Latanoprost Xalatan Absorption: ocular and

systemic Half-Life: 17

min

Prostaglandin F2-alpha

analog;

Elevated Intraocular

Pressure

Blurred vision Burning

and stinging Foreign

body sensation

Misoprostol Cytotec Onset: 2-3 hr (initial

response for acid

secretion) Duration: ≥3

hr (inhibition of acid

secretion)

Synthetic prostaglandin

E analogue

NSAID-Induced Ulcer Anaphylaxis Anemia

Cardiac dysrhythmia

Chest pain

Montelukast Singulair Peak plasma time:

Tablet, 3-4 hr;

chewable tablet, 2-2.5

hr; granules, 1-3 hr

Blocks binding of

leukotriene D4 to its

receptor;

Asthma Abdominal painEczema InfluenzaLaryngitis Pharyngitis

Travoprost Travatan Absorption: through thecornea

Peak Plasma Time:within 30 min

Prostaglandin F2-alpha

analog

Open-Angle Glaucoma Decreased visual acuity(

Ocular discomfort

Foreign body sensation

Pain Pruritus



Treprostinil Remodulin Bioavailability: ~100%

(SC); 64-72%

(inhalation) Peak

plasma time: 10 hr

Peripheral prostacyclin

vasodilator of both

pulmonary and

systemic arterial

vascular bed

Pulmonary Arterial

Hypertension

Nausea DiarrheaVasodilation

Jaw pain Rash

Zafirlukast Accolate Half-Life: 8-16 hrOnset: 3-14 days

Inhibitsbronchoconstriction as

competitive receptor

antagonist of

leukotrienes D4 & E4

Asthma Abdominal painInfection Nausea

Diarrhea Generalized

pain

Zileuton Zyflo Half-Life: 2.5 hr Onset:

2-5 hr

Inhibitor of 5-

lipoxygenase, which

inhibits formation ofLTB4, LTC4, LTD4, &

LTE4

Asthma Abdominal pain ALTelevation AstheniaDyspepsia Diarrhea

Generalized pain



CHAPTER :20

TOPIC : Drug in Asthma

NAME OF DRUGS BRAND NAME PHARMACOKINETICS MECHANISM OF

ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECTS

Albuterol Proventil, Ventolin Aerosol inhalation •duration several hours •

also available for

nebulizer and

parenteral use

Selective β2agonist Asthma, chronicobstructive pulmonary

disease (COPD) • drug

of choice in acute

asthmatic

bronchospasm

Asthma prophylaxis

Prompt, efficaciousbronchodilation

Albuterol/Ipratropium Combivent Peak plasma time:

Albuterol, 3 hr (from

portion swallowed)

Peak plasma

concentration:

Albuterol, 419-802

pg/mL (from portion

swallowed)

Albuterol: Beta2-

adrenergic

bronchodilator

Ipratropium:

Anticholinergic

(parasympatholytic)

agent

COPD Lung disease

Headache Dyspnea

Montelukast Singulair Oral • duration hours Block leukotriene D4

receptors

Prophylaxis of asthma,

especially in children

and in aspirin-induced

asthma

Block airway response

to exercise and antigen

challenge



Zafirlukast Accolate Oral • duration hours Block leukotriene D4

receptors

Prophylaxis of asthma,

especially in children

and in aspirin-induced

asthma

Block airway response

to exercise and antigen

challenge

Omalizumab Xolair Parenteral • duration 2–

4 d

Humanized IgE

antibody reduces

circulating IgE

Severe asthma

inadequately

controlled by above

agents

Reduces frequency of

asthma exacerbations



CHAPTER 23

TOPIC : The Alcohol

NAME OF DRUG BRAND NAME PHARMACOKINETIC MECHANISM OF ACTION

THERAPEUTICINDICATION

ADVERSE EFFECT

Chlordiazepoxide HCI Librium

Diazepam Valium AbsorptionBioavailability: 90%(PR)Duration: Variable,dependent on dose andfrequency (PO[hypnotic action]); 15-60 min (IV [sedativeaction])

DistributionProtein bound: 98%EliminationHalf-life: 20-70 hr(active metabolite)

Modulates postsynapticeffects of GABA-Atransmission, resultingin an increase inpresynaptic inhibition.

Appears to act on partof the limbic system, aswell as on the thalamusand hypothalamus, to

induce a calming effect

Alcohol WithdrawalEndoscopyMuscle SpasmSeizure DisorderStatus Epilepticus

NeutropeniaJaundice MuscleweaknessRespiratory depressionUrinary retentionDepressionIncontinenceBlurred visionDysarthria HeadacheSkin rash

Lorazepam Ativan Bioavailability: 90%

Onset: 1-3 min (IV insedation); 15-30 min(IM in hypnosis)Duration: Up to 8 hrPeak plasma time: 2 hr(PO); <3 hr (IM)DistributionProtein bound: 85-93%

(neonates)

Sedative hypnotic with

short onset of effectsand relatively long half-life; by increasing theaction of gamma-aminobutyric acid(GABA), which is amajor inhibitoryneurotransmitter in thebrain, lorazepam maydepress all levels of the

CNS, including limbic

Anxiety Disorders

Short-Term Treatmentof InsomniaPreoperative Sedation,

Anxiety Relief, & Anterograde AmnesiaStatus Epilepticus

Anxiolytic/Sedation inICUChemotherapy-InducedNausea/Vomiting

Sedation Dizziness

UnsteadinessWeakness FatigueDrowsiness AmnesiaConfusionDisorientationDepression Suicidalideation/attempt Vertigo

Ataxia Sleep apnea Asthenia



MetabolismMetabolites: InactiveUndergoes glucuronicacid conjugationEliminationHalf-life: 18 hr (children2-12 years); 42 hr

(neonates); 28 hr(adolescents); 18 hr(end stage renaldisease); 14 hr (adults)

and reticular formation Chronic Insomnia

Oxazepam Serax Half-life elimination:2.8-5.7 hrPeak plasma time: 3 hrPeak plasma

concentration: 450ng/mLMetabolism: Glucuronicacid conjugationProtein binding: 86-99% Excretion: Urine

Binds receptors atseveral sites within theCNS, including thelimbic system andreticular formation.Effects may bemediated throughGABA receptor system.Increase in neuronalmembrane permeabilityto chloride ionsenhances the inhibitoryeffects of GABA; theshift in chloride ionscauseshyperpolarization (lessexcitability) andstabilization of thenuronal membrane

Anxiety Alcohol Withdrawal

Sedation AtaxiaConfusionMemory impairmentDizziness Drowsiness

Muscle weaknessSyncope edemaLeukopenia, blooddyscrasias

Thiamine HCI - Distribution: Distributesmainly to heart, brain,kidney, and liverExcretion: Urine

Absorption: Adequate

(PO); rapid and

Forms thiaminepyrophosphate bycombining withadenosinetriphosphate; essential

coenzyme in

WernickeEncephalopathyBeriberiRDA

Warmth AnaphylaxisCyanosis DiaphoresisRestlessness

Angioneurotic edemaPruritus Urticaria

Pulmonary edema



complete (IM) carbohydratemetabolism

WeaknessTightness of the throatNausea

Acamprosate Campral Protein Bound:NegligibleVd: 1 L/kgPeak PlasmaTime: 3-8hrConcentration: 350ng/mL for a dose of 666mg TIDBioavailability: 11%,decreased by foodMetabolism: NoneExcretion: UrineHalf-life: 20-33 hr

Not fully understood;may act by interactingwith glutamate & GABAneurotransmitter

systems

AlcholismRenal Impairment

Accidental injury Anorexia Anxiety Asthenia DepressionDizziness Dry mouthFlatulence InsomniaNausea Pain

Disulfiram Antabuse AbsorptionPeak plasma time: 4 hrPeak plasmaconcentration: 2.4mcg/mLDuration: up to 2 wkOnset: 2-12 hrMetabolismHepatic 80-90%

Metabolites:DiethyldithiocarbamateEnzymes inhibited:hepatic CYP2C9,CYP2E1EliminationExcretion: Feces andexhaled gases

Produces sensitivity toEtOH via blocking itsoxidation atacetaldehyde stage,resulting in unpleasantreactions includingpalpitations,hypotension, chestpain, nausea, vertigo,thirst, flushing, and

nausea

Alcoholism Fatigue HeadacheImpotenceMetallic aftertaste

Acneiform eruptionsPolyneuritis RashHepatitisPeripheral neuropathyOptic neuritisPsychotic disorder

Naltrexone HCI ReVia 96% absorbed fromgastrointestinal tract,but because of first-

Opioid competitivereceptor antagonist;shows highest affinity

Opioid Dependence Alcohol Dependence

Nausea HeadacheDecreased appetite



pass metabolism, only5-40% reachessystemic circulation

for mu receptors;congener ofoxymorphone

Insomnia VomitingDiarrhea Dizziness

Ethanol - Metabolism: LiverHalf-life elimination: 15-20 mg/dL/hrExcretion: Urine; lungs

Vd: 0.6-0.7 L/kg

Competes withmethanol & ethyleneglycol for alcoholdehydrogenase to

inhibit production oftoxic metabolites

Methanol Toxicity,Ethylene GlycolPoisoningTreatment of congenital

venous and lymphaticmalformations

IntoxicationFlushing hypotension

Agitation HypoglycemiaN/V PolyuriaIntoxication

Fomepizole Antizol Onset of action: 1.5-2hr Vd: 0.6-1.02 L/kgExcretion: Urine

Inhibits alcoholdehydrogenase, whichcatalyzes themetabolism of ethanol,methanol and ethyleneglycol; has no effectupon CNS or need formonitoring levels (likeEtOH currently)

Methanol & EthyleneGlycol PoisoningRenal Impairment

Bad/metallic tasteDizzinessDrowsiness BackacheNystagmus Fever

Abdominal pain



CHAPTER 25

TOPIC : General Anesthetic



ADVERSE EFFECT

Desflurane Suprane Onset: 1-2 min Absorption: <0.02%(systemic)Metabolism: Liver(minimal)Elimination: Via the lungs(exhaled gases)

Volatile liquid inhalationanesthetic; mayenhance inhibitorypostsynaptic channelactivity and may inhibitexcitatory synapticactivity

General Anesthesia Cough ApneaInterrupted breathingLaryngeal spasmNausea VomitingCardiovascular:hypotensionBradyarrhythmia

Dexmedetomidine Precede Half-life, elimination: 6min; 2 hr (terminal)Peak plasma: 0.3-1.5ng/mL

Centrally actingalpha2-adrenoceptoragonist that hassedative andanesthetic propertiespossibly by activatingG-proteins in thebrainstem, whichresults in the inhibitionof norepinephrinerelease

ICU SedationFiberoptic IntubationProcedural Sedation Renal Impairment

AnemiaBradycardiaFeverPleural effusionLeukocytosisPulmonary edema

Diazepam Valium AbsorptionBioavailability: 90% (PR)Duration: Variable,dependent on dose andfrequency (PO [hypnoticaction]); 15-60 min (IV[sedative action])DistributionProtein bound: 98%EliminationHalf-life: 20-70 hr (active

metabolite)


Appears to act on partof the limbic system, aswell as on the thalamusand hypothalamus, toinduce a calming effect

Alcohol WithdrawalEndoscopyMuscle SpasmSeizure DisorderStatus Epilepticus

NeutropeniaJaundice MuscleweaknessRespiratory depressionUrinary retentionDepressionIncontinenceBlurred visionDysarthria HeadacheSkin rash



Droperidol Inapsine Half-Life elimination: 2 hr(parent drug), 8-12 hr(metabolites)Onset: 3-10 min

Duration: 2-4 hr, maypersist up to12 hr

dopamine receptorblockade in brain,predominantlydopamine-2 receptor &

when reuptake isprevented, a strongantidopaminergic,antiserotonic responseoccurs

Antiemetic , Delirium ,Hepatic and RenalImpairment

Restlessness AnxietyExtrapyramidalSymptomsDystonic reactionsPseudoparkinsoniansigns and symptomsTardive dyskinesiaSeizure

Enflurane Ethrane Onset of action: 7-10minutesPeak PlasmaConcentration:

biotransformation resultsin low serum fluoridelevels (average 15micromol/L); can exceed50 micromol/L ifanesthesia >2 MAC h

Inhalation anesthetic Anesthesia , Analgesia HypotensionRespiratory depressionHypoxia

ArrhythmiasShiveringNauseaVomiting

Etomidate Amidate Onset: Within 60 secDuration: 3-5 min due toredistribution from CNS

Nonbarbituratehypnotic used for theinduction ofanesthesia; lacksanalgesic activity; hasminimal cardiovasculareffects

General AnesthesiaInduction

ArrhythmiasHyperventilationHTNHypotensionHypoventilationLaryngospasmNausea/vomiting

Fospropofol Lusedra Peak Plasma Time: 2-4min to propofol; 8-12 minof propofol fromfospropofol:Protein Bound: 98%Onset: ~8 min

Sedative-hypnotic,prodrug of propofol;interacts with GABA Areceptor

HeadacheHypotensionNausea/vomiting



Half-life: 0.8-0.96 hrDuration: ~5 min (time tofully alert)

Halothane Fluothane 1.08 in neonates to 0.64in the elderly, Addition ofN20 in adults reducesMAC to 0.29%.

inhalation anestheticHalothane anesthesiaalso causes dilation ofthe vessels of the skin

and skeletal muscles. Itdoes not cause therelease ofcatecholamines fromadrenergic stores.

inhalational generalanesthetic,

Liver damage, heartarrest and abnormalincrease in bodytemperature.

Isoflurane Forane Onset: rapidDuration: shortMinimum Alveolar Conc:1.3%

Volatile liquid inhalationanesthetic

Anesthesia Induction &Maintenance

Nausea VomitingShiveringMalignant hyperthermia(rare) Elevations inwhite blood countIleus, severe (fatal)Hepatic dysfunction

Ketamine Ketalar Onset: 30 sec (IV); 3-4min (IM) Duration: 5-10min (IV); 12-25 min (IM):dissociative state maylast >20 min Peakplasma concentration:0.75 pg/mL

Blocks NMDA receptor Anesthesia Induction Bradycardia DiplopiaHypotensionIncreased IOPInjection-site painNystagmus

Lorazepam Ativan Onset: 1-3 min (IV insedation); 15-30 min (IMin hypnosis)

Duration: Up to 8 hr

Peak plasma time: 2 hr(PO); <3 hr (IM)

Sedative hypnotic withshort onset of effectsand relatively long half-life; by increasing theaction of gamma-aminobutyric acid(GABA), which is amajor inhibitoryneurotransmitter in thebrain, lorazepam may

depress all levels of the

Short-Term Treatmentof Insomnia

Anxiety Disorders

Sedation DizzinessUnsteadinessWeakness FatigueDrowsiness AmnesiaConfusionDisorientationDepression



CNS, including limbicand reticular formation

Methohexital Brevital Half-Life: 3-6 hrOnset: Immediate (IV); 2-10 min (IM); 5-15 min(PR)Duration: 10-20 min (IV);

45 min (PR)

Ultra short-actinganesthetic barbiturate;no muscle relaxantactivity

Anesthesia Hiccups, coughing,muscle twitching &laryngospasm, whichmay impair pulmonaryventilation

Midazolam Versed Onset: 15-20 min (IM,PO); 3-5 min (IV)Duration: 1-6 hr (IM)Duration of anterogradeamnesia: 1 hr (IM); 20-40min (IV)Metabolized by liver viaCYP3A4

Metabolites: 1-hydroxymethylmidazolam

Binds receptors atseveral sites within theCNS, including thelimbic system andreticular formation;effects may bemediated throughGABA receptor system;increase in neuronalmembrane permeabilityto chloride ionsenhances the inhibitoryeffects of GABA; theshift in chloride ionscauseshyperpolarization (lessexcitability) andstabilization of theneuronal membrane

Anesthesia HeadacheSedationHiccoughsDeliriumEuphoriaPediatricDesaturationHypotension

Propofol Diprivan Onset: 30-45 secDuration: 3-10 min (MetabolismMetabolized by hepaticconjugation to inactivecompoundEliminationHalf-life: 40 min (initial);24-72 hr (after 10-day

infusion)

Short-acting, lipophilicsedative/hypnotic;causes global CNSdepression,presumably throughagonist actions onGABAa receptors

AnesthesiaMAC SedationPostoperativeNausea/Vomiting

Hypotension Apnea lastingMovementInjection siteburning/stinging/pain







through intact skin anesthetics stabilizeneuronal membranesand preventgeneration/conductionof nerve impulses

Flushing Eye/skinirritation N/V DiarrheaChest pain

Levobupivacaine Chirocaine Parenteral • duration 3–6 h

Blockade of sodiumchannels

Longer-durationprocedures

(but not used topicallyorintravenously)

Slows, then blocks,action

potential propagation

Lidocaine Xylocaine Parenteral (eg,peripheral block, butvaries significantlybased on specificsite) • duration 1–2 h •2 – 4 h withepinephrine


Short-durationprocedures •topical (mucosal),intravenous, infiltration,spinal, epidural, minorand

major peripheral blocks

Slows, then blocks,actionpotential propagation

Mepivacaine Carbocaine Parenteral (eg,peripheral block, butvaries significantlybased on specificsite) • duration 1–2 h •2 – 4 h withepinephrine


Short-durationprocedures •topical (mucosal),intravenous, infiltration,spinal, epidural, minorandmajor peripheral blocks


Prilocaine Citanest Parenteral (eg,peripheral block, butvaries significantlybased on specificsite) • duration 1–2 h •2 – 4 h withepinephrine

Blockade of sodium

channels

Short-durationprocedures •topical (mucosal),intravenous, infiltration,spinal, epidural, minorandmajor peripheral blocks


Procaine Novocain Parenteral • duration30 –60 min •60 – 90 min withepinephrine


Very short procedures(notgenerally used topicallyor

Slows, then blocks,action





CHAPTER 27

TOPIC : Skeletal Muscle Relaxant



ADVERSE EFFECT

Atracurium Tracurium Half-Life: Alpha: 2-3.4 minBeta: averages 20 minOnset: 2-2.5 min; maybe slightly delayed inpatients with renalfailureDuration: 20-35 minProtein Bound: 82%

Non-depolarizingskeletal musclerelaxant; cholinergicreceptor antagonist

EndotrachealIntubation, MechanicalVentilation

ErythemaWheezing Increasedbronchial secretionsPruritusUrticaria

Cisatracurium Nimbex Half-Life, Elim: 22-29minOnset: 2.4-2.6 min(mean for 0.15-0.2mg/kg adult dose)Duration: 55-65 minVd: 145 mL/kg

Non-depolarizingskeletal musc. relaxant;cholinergic receptorantagonist; a cis-isomerof atracurium

NeuromuscularBlockade

Adjunct to generalanesthesia-inducemuscle relaxation forendotrachealintubation, mechanicalventilation

BronchospasmBradycardiaFlushingHypotensionRash

Mivacurium Mivacron Onset: Within 60 sec

Duration: 3-5 min dueto redistribution fromCNS

Nonbarbituratehypnotic used for theinduction of anesthesia;lacks analgesic activity

General AnesthesiaInduction

Transient injection sitepain

Skeletal musclemovements, mainlymyoclonic

Opsoclonus Adrenalsuppression

Pancuronium - Half-Life:2 hr (terminal phase)

Renal dysfunction may

Non-depolarizingskeletal musclerelaxant; cholinergic

General Anesthesia Adjunct/CesareanSection

Slight elevation in pulserate

Elevations in blood



incr half-life 50% receptor antagonist pressureExcessive salivation

Rocuronium Zemuron Half-Life1.4-2.4 hr (elimination)

About 2x as long inhepatic dysfunction

Nondepolarizingskeletal musclerelaxant; cholinergicreceptor antagonist

Tracheal Intubation Dose-relatedtachycardia

Apnea

Residual muscleweakness

Succinylcholine Anectine, Quelicin Onset: IV: 30-60 sec;IM: 2-3 min

Duration: IV 2-10 min;IM 10-30 min

Depolarizing skeletalmuscle relaxant; noeffect onconsciousness, pain

Adjunct to generalanesthesia-inducemuscle relaxation forendotrachealintubation, endoscopicexaminations,orthopedic procedures

Jaw rigidity

Apnea

Respiratory depression

Bradycardia

Hypotension

Cardiac arrhythmiasSinus tachycardia

Vecuronium Norcuron Distribution phase: 3.3-9 min

Terminal phase: 31-80min

Non-depolarizingskeletal musclerelaxant; cholinergicreceptor antagonist

General Anesthesia Hypersensitivityreactions associatedwith histamine release(e.g., bronchospasm,flushing, erythema,acute urticaria,

hypotension,tachycardia)

Baclofen Lioresal, Gablofen Onset: 3-4 days

Duration: 4-8 hr

Inhibits synaptictransmission throughspinal reflex arcs, viahyperpolarization ofprimary afferent fiberterminals, which mayresult in musclespasticity

Spasticity Drowsiness, transient

Dizziness

Nausea

Confusion



Carisoprodol Soma Onset: 30 min

Duration: 4-6 hr

Not clearly known; mayblock interneuralactivity and depresspolysynaptic neurontransmission

MusculoskeletalConditions

Dizziness Headache

Chlorzoxazone - Half-life: 66 min

Onset: 1 hr

Duration: 6-12 hr

Blocks interneuronalconduction in spinal

cord and subcorticalbrain areas bydepressingpolysynaptic reflexes

MusculoskeletalConditions

Dizziness

Drowsiness

Excitement,Paradoxical

Cyclobenzaprine Amrix, Fexmid, Flexeril Hepatic metabolism• duration, ~4– 6 h

Poorly understoodinhibition of musclestretch reflexin spinal cord

Acute spasm due tomuscleinjury • inflammation

Reduction inhyperactivemuscle reflexes• antimuscarinic effects

Dantrolene Dantrium, RevontoPeak plasma time: 5 hr

Concentration: 100 to>600 ng/mL

Half-life elimination: 4-8hr

Duration: 3 hr or longer

Interferes with calciumrelease within skeletalmuscle cells (fromsarcoplasmic reticulum)

MalignantHyperthermia (PerMHAUS

Diarrhea

Anorexia

Nausea

Vomiting

Gastric irritation

Diazepam Diastat, Valium Duration: Variable,dependent on dose andfrequency (PO[hypnotic action]); 15-60 min (IV [sedativeaction])


Anxiety Atax

Euphoria

Somnolence

Rash

Gabapentin Neurontin Bioavailability:Inversely proportion to

dose; 60% (900

GABA analogue; Partial Seizure Ataxia DizzinessDrowsiness Fatigue



mg/day); 47% (1200mg/day); 34% (2400mg/day); 33% (3600mg/day); 27% (4800mg/day)

Metaxalone Skelaxin Onset: Within 1 hr

Duration: 4-6 hr

Peak plasma time: 3 hr

General CNSdepression

Acute PainfulMusculoskeletal

Conditions

Nausea

Vomiting

Dizziness

Headache

Somnolence

Nervousness

Methocarbamol Robaxin Hepatic metabolism• duration, ~4– 6 h




Orphenadrine Norflex Hepatic metabolism• duration, ~4 – 6 h




Riluzole Rilutek Half-Life: 12 hr


Benzathiazole; inhibits

glutamate release,inactivates voltage-dependent Na+channels, inhibitseffects of excitatoryneurotransmitters

Amyotrophic Lateral

Sclerosis (ALS)

Headache

Abdominal pain

Diarrhea DizzinessHypertension

Tizanidine Zanaflex Bioavailability:40%Peak serum time:1-4 hr

Alpha-2 adrenergicreceptor agonist

Muscle Spasticity Dry mouth SomnolenceDizziness Asthenia



CHAPTER 36

TOPIC : Non- steroidal Anti inflammatory drug disease modify antirheumatic Drug, non- opiod Analgesic , Drug use in Gout

NAME OF DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF

ACTION

PHARMACEUTICAL

INDICATION

ADVERSE EFFECT

Acetylsalicylic Acid Easprin Bioavailability: 80-100% Onset: PO, 5-30

min; PR, 1-2 hr

Duration: PO, 4-6 hr;

PR, >7 hr Peak plasma

time: PO, 0.25-3 hr

Inhibits synthesis ofprostaglandin by

cyclooxygenase;

inhibits platelet

aggregation; has

antipyretic and

analgesic activity

Pain & Fever AcuteCoronary Syndrome

Ischemic Stroke &

Transient Ischemic

Attack

AngioedemaBronchospasm CNS

alteration Dermatologic

problems

GI pain, ulceration,

bleeding Hepatotoxicity

Hearing loss Nausea

Platelet aggregationinhibition Premature

hemolysis

Bromfenac Xibrom Absorption : Negligible

systemic absorption

Half-life: 0.5-4 hr

Nonsteroidal anti-

inflammatory agent;

inhibits COX-1 and

COX-2, which results in

decreased formation of

prostaglandin

precursors

Cataract Postoperative

Ocular

Inflammation/Pain

Abnormal sensation in

eye Conjunctival

hyperemia Eye irriation

(burning/stinging) Eye

pain Eye pruritus Eye

redness Headache Iritis

Febuxostat Uloric Absorption


Peak plasma time: 1-

1.5 hr Distribution

Protein bound: 99.2%

Xanthine oxidase

inhibitor; inhibits

conversion of

hypoxanthine to

xanthine to uric acid; at

Chronic Gout Arthralgia Elevated liver

function test (LFT)

results Liver function

abnormalities Nausea



Vd: 50 L

Metabolism

Metabolized by

UGT1A1, UGT1A3,

UGT1A9, and UGT2B7;

oxidized by CYP1A2,CYP2C8, and CYP2C9;

also metabolized by

non-CYP450 enzymes

Elimination Half-life: 5-8

hr Excretion: Feces

(45%; 12%

unchanged), urine

(49%; 3% unchanged)

therapeutic dosages,

decreases production

of uric acid without

disrupting synthesis of

vital purines and

pyrimidines

Rash

Pegloticase Krystexxa Onset of action: 24 hr

Duration: 12.5 days

Half-life: 14 days

Recombinant,

pegylated uric acid

specific enzyme;

achieves its therapeutic

effect by catalyzing

oxidation of uric acid to

allantoin, therebylowering serum uric

acid levels

Gout Gout flares

Infusion reactions

Nausea Urticaria

Probenecid Benamid Half-Life: 3-17 hr

Onset: 2 hr (effect on

penicillin levels) Peak

Plasma Time: 2-4 hr

Bioavailability: >90%

(Uricosuric) inhibits

tubular reabsorption of

urate; increasing uric

acid excretion . Also

inhibits tubular

Gout, Pelvic

Inflammatory Disease

Gonorrhea

Headache Nausea

Vomiting Loss of

appetite GI upset Rash

Flushing Dizziness

Fever Aplastic anemia



Protein Bound: 85-95%

(albumin) Metabolism:

Liver Metabolites:

hydroxylated

metabolites, N-

despropyl metabolite,

probenecid

acylglucuronide

Excretion: Urine

secretion of weak

organic acids like PCNs

& cephalosporins

Hemolytic anemia

Leukopenia

Date post:	02-Jun-2018
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