Post on 02-Jun-2018
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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
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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%
Peak plasma time: 3-4
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
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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
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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
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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
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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
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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%
Peak plasma time: 3-8 hr
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
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sphincter muscle
Trospium (Spasmex, Sanctura) Half-life: 20 hr
(immediate release)
Peak plasma time: 5-6 hr
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
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CHAPTER :9
TOPIC :Adrenoreceptor Agonist
NAME OF THE DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF
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
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Peak plasma time: 1-4
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
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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
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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
Hyperactivity Disorder
Dizziness, drugtolerance, dysphoricmood, euphoria,headache, insomnia,restlessness, tremor
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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
Hyperactivity Disorder
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
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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
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CHAPTER :10
TOPIC :Adrenoreceptor Antagonist
NAME OF THE DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF
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
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norepinephrine
Silodosin Rapaflow Bioavailability: 32%
Half-Life: 13 +/- 8 hr
Selective antagonist of
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
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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
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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
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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
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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
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CHAPTER 16
TOPIC :Histamine , Serotonin and Ergot Alkaloids
NAME OF THE DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF
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
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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
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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
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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
Selective antagonist of
kinin B2
receptors
Hereditary angioedema Blocks effects of kinins
on pain, hyperalgesia,
and inflammation
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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
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CHAPTER :18
TOPIC : The Eicosanoid , Prostaglandin , thromboxane, Leukotriene , Related compound
NAME OF THE DRUG BRAND NAME PHARMACOKINETICS MECHANISM OF
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
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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
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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
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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
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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
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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
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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
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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
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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
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CHAPTER 25
TOPIC : General Anesthetic
NAME OF DRUG BRAND NAME PHARMACOKINETIC MECHANISM OF ACTION
THERAPEUTICINDICATION
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)
Modulates postsynapticeffects of GABA-Atransmission, resultingin an increase inpresynaptic inhibition.
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
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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
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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
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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
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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
Blockade of sodiumchannels
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
Blockade of sodiumchannels
Short-durationprocedures •topical (mucosal),intravenous, infiltration,spinal, epidural, minorandmajor peripheral blocks
Slows, then blocks,actionpotential propagation
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
Slows, then blocks,actionpotential propagation
Procaine Novocain Parenteral • duration30 –60 min •60 – 90 min withepinephrine
Blockade of sodiumchannels
Very short procedures(notgenerally used topicallyor
Slows, then blocks,action
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CHAPTER 27
TOPIC : Skeletal Muscle Relaxant
NAME OF DRUG BRAND NAME PHARMACOKINETIC MECHANISM OF ACTION
THERAPEUTICINDICATION
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
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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
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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])
Modulates postsynapticeffects of GABA-Atransmission, resultingin an increase inpresynaptic inhibition.
Anxiety Atax
Euphoria
Somnolence
Rash
Gabapentin Neurontin Bioavailability:Inversely proportion to
dose; 60% (900
GABA analogue; Partial Seizure Ataxia DizzinessDrowsiness Fatigue
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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
Poorly understoodinhibition of musclestretch reflexin spinal cord
Acute spasm due tomuscleinjury • inflammation
Reduction inhyperactivemuscle reflexes• antimuscarinic effects
Orphenadrine Norflex Hepatic metabolism• duration, ~4 – 6 h
Poorly understoodinhibition of musclestretch reflexin spinal cord
Acute spasm due tomuscleinjury • inflammation
Reduction inhyperactivemuscle reflexes• antimuscarinic effects
Riluzole Rilutek Half-Life: 12 hr
Bioavailability: 60%
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
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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
Bioavailability: 49%
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
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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
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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