Pcol 211 Prelims ALL in
Pcol 211 Prelims ALL in
Pcol 211 Prelims ALL in
COLLEGE OF PHARMACY
PHARMACOLOGY 1
LECTURER: Mr. Jemar Wilian N. Labausa
• It is defined as the study of substancesthat interact with living
systems through chemical processes by binding to regulatory
molecules and activating or inhibitingnormal body
processes.
DRUG + RECEPTOR = EFFECT
PHARMACOKINETICS: WHAT THE BODY DOES TO THE DRUG
PHARMACODYNAMICS: WHAT THE DRUG DOES TO THE BODY
WHAT IS
PHARMACOLOGY
Clinical pharmacology
With added focus on the application of pharmacological principles and
methods in the medical clinic and towards patient care and outcomes.
-PATIENT ORIENTED PHARMACY PRACTICE (INDIVIDUAL PATIENT)
Neuropharmacology
Effects of medication on central and peripheral nervous system
CNS: BRAIN AND SPINAL CORD
PNS: MOTOR AND SENSORY
SO THEREFORE;WHAT ISA
DRUG?
DTCMP = DIAGNOSIS (SCREENING THE CONDITION)(DIAGNOSTIC AGENT),
TREATMENT( MANAGEMENT OF DISEASES) , CURE( TOTAL ERADICATION OF DISEASE),
MITIGATION(LOWERING OFF THE SYMPTOMS)(STAGE4 CANCER- ANALHESIC)
PREVENTION ( AVOIDING THE OCCURRENCE OFF DISEASE)
It is used in:
Prevention=Ex: YaGG1nes; Oral Contraceptive Pills (OCPs)
Diagnosis —Ex: BaS04 as contrast medium in the X-ray
examination of the gastrointestinal tract. Mitigation=Ex: Analgesic
drugs Treatment/Cure=Ex: Antibiotic
Size and MolecularWeight
Nature of Drugs
Drug-Receptor Bonds
• Drugs bind to receptors with
a variety of chemical bonds.
Nature of Drugs
*Strong covalent bonds (STRONG) (which usually
result in irreversible action).
*Somewhat weaker electrostatic bonds (WEAK)
(between a cation and an anion).
Much weaker interactions (hydrogen bond, van
der Waals interactions, and hydrophobic bonds).
REVERSIBLE
EXAMPLE:
• 2- (p-isobutylphenyl propionicacid)-
CHEMICALNAME
• IBUPROPEN-GENERIC NAME
• Motrin®-Trade name(proprietary
name/brand name)
ACETAMINOPHEN/PARACETAMOL
Classification of Drugs
according to use
1. Functional Modifiers
alter or modulate the normal physiologic
functions
Examples:
Analgesic drugs
Anti-pyretic drugs
Anti-inflammatory drugs
Anti-hypertensive drugs
Classification of Drugs
according to use
2. Replenishers
Supplement endogenous substances that are
lacking or deficient in the body
Examples:
Hormones
IV Fluids/Electrolyte/ORS
Multivitamins
Classification of Drugs
according to use
In the case of pernicious anemia (autoimmune disease) that
destroys parietal cells which secretes HCl and intrinsic factor,take
VIT B12
APPLICATION
3. Diagnostic Agents
Agents used to determine the presence or absenceof
a condition or a disease.
Examples:
Edrophonium (Tensilon’sTest)
Histamine
some Radiopharmaceuticals
Barium sulfate
Dobutamine and Dipyridamole for “Pharmacologic Stress
Testing” for CAD and MI.
Classification of Drugs
according to use
TENSILON- FOR MYASTHENIA GRAVIS
(AUTOIMMUNE DISORDER - OUR OWN IMMUNE SYSTEM
ATTACKS OUR OWN CELL) - muscle weakness
Dobutamine (Bl agonist) and Dipyridamole (Antiplatelet) for
"Pharmacologic Stress Testing for CAD - CORONARY ARTERY
DISEASE and Ml- MYOCARDIAL INFARCTION
Technetium 99m (for Dx of ischemia- BLOOD SUPPLY while
Thallium 209 for Dx of infarction - HEART ATTACK
4. Chemotherapeutic Agents
Agents used to kill or inhibit growth of
cells or nucleic acid considered as foreign
to the body. Selective toxicity is
considered
Antineoplastics/ANTI CANCER=
CYTOTOXIC ANTIBIOTICS =
DOXORUBICIN
Anti-infectives=AMINOGLYCOSIDES
Classification of Drugs
according to use
BUY AT 30S (AMINOGLYCOSIDE, TETRACYLINE)
CEL @ 50S (CHLORAMPHENICOL, ERYTHROMYCIN
AND LINCOSAMIDE)
PHARMACOKINETICS
PHARMACODYNAMICS
What is
Pharmacokinetics?
REVIEW OF
PHARMACOKINETIC
PRINCIPLES
LIBERATION-(NOT ALL DRUGS WILL UNDERGO LIBERATION -
ORAL AND SOLID DOSAGE)
ABSORPTION -SMALL INTESTINE
DISTRIBUTION - CELLS/TISSUE/ORGAN
METABOLISM - LIVER(MAIN ORGAN)
EXCRETION - KIDNEY (MAIN ORGAN)
RESPONSE-
TOXICITY -
ELIMINATION -METABOLISM + EXCRETION
DISPOSITION - DISTRIBUTION + METABOLISM + EXCRETION
.... LADME R T....
IN VIVO - performed or taking place in a living
organism
IN VITRO - performed or taking place in a test
tube, culture dish, or elseehere outside a living
organism
LIBERATION
ONLY ORAL AND SOLID DOSAGE FORM ARE
CAPABLE UNDERGO YOUR DELIVERATION PROCESS
DIVIDED INTO TWO ;
Disintegration--(process that a larger particle to
smaller particle)
Dissolution -Rate limiting step of absorption
(PROCESS WITH THE SLOWEST RATE CONSTANT)
-SOLID TO LIQUID
• Factors that influence the dissolution rate:
• Surface area – reducing the particle size increase the surface
area
• Salt forms – salt forms dissolve much readily when
compared to the drugs in its free form
Ex: Sodium and potassium salts of weak organic acids
and hydrochloride salts of weak organic bases dissolve
much more readily than the free forms.
• State of hydration – anhydrous form is more readily soluble
than the hydrated form
Ex:Ampicillin anhydrous was shown to have greater rate
of solubilitythan the trihydrate form.
LIBERATION
Surface area
DECREASE PARTICLE SIZE, INCREASE SURFACE AREA, INCREASE
ABSOPTION, INCREASE THE BIOAVAILABILITY
Salt forms
CAPTOPRIL FREE FORM
CAPTOPRIL HCL- SALT FORM – READILY DISSOLVE CAMPARED TO YOUR
FREE FORM
State ofhydration
ANHYDROUS VS HYDRATED
Anhydrous – MORE LIKELY TO BE ACTED UPON BY WATER
Bioavailability - The proportion of a drug
that is delivered to its site of action in the
body.
ABSORPTION
• If we put an acidic drug in an environment
with a lot of H+ (low pH) what will this
equilibrium do?
HA H+ +A-
System at Equilibrium
Non-ionized formpredominates!
ACIDIC DRUG + ACIDIC ENVIRONMENT = ABSORPTION
(NON-IONIZED) – EASILY ABSORBED
Why?
APPLICATION
ASPIRIN IS ACIDIC STOMACH
IS ACIDIC
=NON-IONIZED = ABSORPTION
Lipid Bilayer
Ionized form
(charged) A-
Non-Ionized
form HA HA
(uncharged)
ACIDIC DRUG are best absorbed from
acidic environments
Moral of thestory...
Gastric emptying – time it takes
for the stomach to empty its
contents
ABSORPTION
GASTRIC EMPTYING TIME –STOMACH WILL
EMPTY ITS CONTENT GOING TO SMALL
INTESTINE (MAIN ORGAN OF ABSORPTION)
ABSORPTION
SL-CATAPRES, ISDN (ISOSORBIDE DINITRATE)
BUCCAL – FENTANYL
a.k.a. “first pass effect”
Examples:
Morphine
Meperidine
Pentazocine
Catecholamines
Propanolol’ Beta
Blockers
TRANSPORT MECHANISMS
- means of movement of drug molecule across
cell membrane
PASSIVE Along concentration gradient, Without Weak organic acids, Weak organic bases,
the use of energy Organic nonelectrolytes (alcohol,
major transmembrane process for amidopyrine, urea), Cardiac glycosides
most drugs.
CONVECTIVE Passing through channels in the cell Inorganic and organic electrolytes up to
AKA: paracellular membrane (pores) 150 to 400MW
transport Ions of opposite charge of pore lining
Ionized sulfonamides
PASSIVE DIFFUSION – ALONG THE CONCENTRATION GRADIENT
-HIGHER CONCENTRATION TO LOWER CONCENTRATION
- NO ENERGY REQUIREMENT
- - NO CARRIER REQUIREMENT
Plasma-proteinbinding
FREE DRUG – NOT BOUNDED BY A PROTEIN
-EASILY DISTRIBUTED, ACTIVE DRUG (BIND INTO THE
RECEPTOR)
EXTRACELLULARFLUID 10-20L
INTRACELLULARFLUID 25-30L
Location of DRUGbased
on VD
• Metabolism
Biotransformation is the metabolic conversion of drugs,
generally to less active compounds but sometimes to isoactive or
more active forms.
Drug BiotransformationReactions
1. Active drug polarmetabolite
2. Active drug inactivemetabolite
3. Active drug activemetabolite
4. Inactive drug active metabolite
5. Active drug reactivemetabolite
More polar, inactive, non-toxic
• Phase II reactions
- Synthetic reactions that involve addition (conjugation) of subgroups to -OH,
-NH 2, and -SH functions on the drug molecule.
-The subgroups that are added include glucuronate, acetate, glutathione,
glycine, sulfate, and methyl groups.
- Most of these groups are relatively polar and make the product less lipid-
soluble than the original drug molecule.
- This metabolism phase reaction is responsible for the
formation of the final metabolic product of the drug to be
excreted
Phase 1 reactions - FUNCTIONALIZATION (POLAR FUNCTIONAL GROUP –
OH, SH, NH) PHASE
PHASE 2
1. GLUCORONIC ACID CONJUGATION / GLUCORONIDATION DRUG +
GLUCORONIC ACID = POLAR
2. SULFATE CONJUGATION / SULFATION DRUG + SULFATE = POLAR
3. GLUTATHIONE CONJUGATION
4. ACETYLATION (ACETYL GROUP)
5. METHYLATION (METHYL GROUP)
6. AMINO ACID CONJUGATION (GLYCERINE , CYSTEINE)
Maturation of Metabolic Processes in infant
AGE METABOLISM CAPACITY
DEVELOPED
Birth Sulfation
1st week Reduction, Oxidation
1 month Acetylation
2 months Glucoronidation
3 months Glycine conjugation
Glutathione conjugation
Cysteine conjugation
NEW BORN INFANTS
X CHLORAMPHENICOL – GLUCORONIDATION
- TOXIC METABOLITE – GRAY BABY SYNDROME
enzyme
inducers
Substances that increase the metabolic activity
of an enzyme either by binding to the enzyme and
activating it
usually decrease the pharmacologic action of
coadministered drugs
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DRUGS THAT INDUCES THE ENZYME TO SPEED UP
METABOLISM
INCREASE METABOLISM
DECREASE EFFECT
Enzyme Inducer
• Examples:
Carbamazepine
Phenobarbital
Phenytoin
Rifampicin
Smoking
Chronic Alcoholism
68
enzyme
inhibitors
Substances that inhibit cytochrome
P450 enzyme activity.
Reduce the metabolism of endogenous
substrates and coadministered drugs
through competitive inhibition
INHIBIT THE ENZYME TO SLOW DOWN THE
METABOLISM
DECREASE IN METABOLISM
INCREASE IN EFFECT
TOXICITY
Enzyme Inhibitor
Examples:
Cimetidine
Ketoconazole
Chloramphenicol
Disulfiram
Grapefruit Juice
AcuteAlcoholism
47
• EXCRETION:
• Clearance
• Clearance is defined as the volume of blood cleared of the drug in unit
time. It represents the relationship between the rate of drug elimination
and its plasmalevel.
• CREATININE CLEARANCE
-Volume of blood plasma that is cleared of creatinine by kidney filtration
per minute (mL/min)
-Normal adult male range is 75-125 mL/min
COMPUTED BY:
- Cockroft & Gault
- - JELLIFE- For adults with unstable renal function,
creatinineclearancemay be computed
1. GLOMERULAR FILTRATION
2. ACTIVE RENAL SECRETION
3.TUBULAR REABSORPTION
CLEARANCE – mL / min
Creatinine clearanceeq.
A. COCKCROFTANDGAULT
CrCl
(140-Age)(BW in kg)
(72)(serum conc. in mg/dL)
female = CrCl x0.85
unit: mL/min
EXCRETION
B. JELLIFE EQ
CrCl
98-[(0.8)(Age in years - 20]
EXCRETION
• Reabsorption of water and passive excretion of lipid
soluble drugs
• Depends on urinepH
• Based of Henderson-Hasselbalchequation
Tubular reabsorption
Pharmacodynamics
Pharmacodynamics
•
1. Non – target protein mediated mechanism
1. 1. Colligative mechanism – osmoticpressure
1. 2. Chemical reaction
• NEUTRALIZATION
• LOCAL
• SYSTEMIC
• CHELATION
• OTHERS
• CN + Sodium thiosulfate
1. 3. Counterfeit incorporation m e c h a n i s m Certaindrugs
that are structurally analogs of normal biological chemicals may be
incorporated may be incorporated into cellular components that may
alter its function. EXAMPLE: analogs of pyrimidines and purines that
can be incorporatedinto nucleic acids
SITES OF DRUG ACTION
1. Structural protein
Microtubule important site of
action
Drugs that inhibit microtubule
synthesis/ spindle protein
Griseofulvin
Vinca alkaloids
Colchicine
2. Regulatory Proteins
58
2.1. Channels/transport
Proteins that take part in
tranmembrane signaling and regulates
ionic composition Voltage-gated Na
channel
Voltage-gated Ca channel
e.g. drugs act on:
• Na channel Local
anesthetic, CBZ, PHENYTOIN
• Ca++ channel Ca++
channel blockers
2.2. Carrier molecules
Na+-K+ ATPase pump- Digitalis glycosides
(inhibitor)
H+-K+ ATPase pump- PPI
1. Type I Receptor
2. Type II Receptor
3. Type III Receptor
4. Type IV Receptor
HYPERPOLARIZATION- EFFLUX OF K,
INFLUX OF CL-, CHANGE IN
CELLMEMBRANE P O T E N T I A L NO
NERVE IMPULSE
Neurotransmitter
Ions
2. Type II receptors - G-protein linked receptor/
G-protein coupled receptor/Metabotropic
receptors
*7 transmembrane(7-TM or heptahelical)
receptors This means that the polypeptide
Chain traverses the membrane seven times.
When a chemical - a hormone or a pharmaceutical agent - binds to the
receptor on the outside of the cell, this triggers a series ofchemical reactions,
including the movement and binding of the G-protein, transformation of GTP
into GDP and activation of second messengers. Second messengers (e.g.,
cyclic AMP) start a cascade of enzymatic reactions leading to the cellular
response. This signaling method is quite fast and, more importantly, it
amplifies the signal
Second messengers
Cyclic Adenosine Monophosphate (cAMP)
Cyclic Guanosine Monophosphate (cGMP)
Inositol Triphosphate (IP3)
72
G proteins are so-called because they bind the guanine nucleotides GDP and GTP.
They are heterotrimers (i.e., made of three different subunits) associated with. the
inner surface of the plasma membrane and. transmembrane receptors of hormones,
etc. These are called G protein-coupled receptors (GPCRs).
PHOSPHORYLATION– ACTIVATESACTINANDMYOSIN
One of the major mechanism through
which the effects of Nitric Oxide are
mediated the production of the second
messenger cyclic GMP (cGMP). Nitric
Oxide can stimulate production of
cGMP by interacting with the haem
group of the enzyme soluble guanylate
cyclase (sGC). This interaction allows
sGC to convert GTP into cGMP.
Alpha receptors
Beta receptors
Muscarinic receptors
3. Type III receptors/Tyrosine Kinases-linked
receptors
location: nucleus
onset: hours
Examples:
Imatinib Gastrointestinal
stromal tumors (GIST)
Gefitinib Epidermal growth
factor receptor
Erythropoietin receptor
Receptor for Insulin utilization
of glucose
80
4. Type IV receptor/gene transcription-
linked receptors
Central dogma
-Replication (DNA copied
into complimentary DNA)
-transcription (DNA template is copied
to RNA)
-translation (RNA synthesize
protein)
-location: nucleus/cytosol (cytoplasm)
-onset: hours
Drugs that act on Type IV
receptors
Corticosteroids
Mineralocorticoids
Sex steroids
Vitamin D
Thyroid hormone
Theories of Drug Receptor Interaction
1. Clark Hypothesis
11
3. Induced-Fit Theory
-as the drug approaches the receptor, it
alters the conformation of its binding
site to producedrug-receptor complex.
4. Rate Theory
-the activation of receptors is directly
proportional to the total number of
encounters of the drug with its receptors
per unit time.
11
5. Hypothesis of Ariensand
Stephenson
A theory which states that
effectiveness lasts as long as the
receptor is occupied
6. Hypothesis of Paton-RATE
THEORY
“ Effectiveness of a drug does not depend on
the actual occupation of the receptor but by obtaining
properstimulus”
Dose & Response
relationships
Graded Dose-Response Relations
B. Maximal Efficacy
This parameter reflects the limit of the dose-response relation on
the response axis. Drugs A, C,and D have equal maximal
efficacy, while all have greater maximal efficacy than drug B.
C. Shape of Dose-Response Curves
reflects the ability of the drug to
produce an effect.
Idiosyncrasy
- Unusual drug Response
caused by genetic differences in metabolism of the
drug or by immunologic mechanisms, including allergic
reactions.
Hypo reactivity - the intensity of effect of a
given dose of drug is diminished
• Serum sickness
III Immune Complex • Systemic Lupus
IgG
Disease Erythematosus (SLE)
• Contact Dermatitis
IV Delayed-Type • Mantoux Test
T-cells
Hypersensitivity •Chronic Transplant
Rejection
• Multiple Sclerosis
* A n a p h y l a x i x is a serious, life-
threatening allergic reaction, SHORTNESS
OF BREATH, ITCHING AND FLUSHING
* A t o p a tendency to develop
allergic disease ( hay fever)
*Erythroblastosisfetalis hemolytic
anemia in neonates
*Graves D i s e a s e Results of over
active thyroid gland(hyperthyroidism)
Tolerance - it refers to a
decreased responsiveness to
the drug, a consequence of
continued drug administration
Tachyphylaxis - This refers to rapidly
acting tolerance
1. AGONIST
Able to bind (with affinity)
With intrinsic activity
1.1 Full agonist
Full response
Stimulate all different variant of
receptors even the new receptors
1.2 Partial agonist
Less than the expected
response
A drug that can activate receptor
but are unable to elicit the maximal
response.
2. ANTAGONIST
• With affinity but no intrinsic activity
• It prevents the binding of agonist
Types of Antagonism
A. PHARMACOLOGICANTAGONIST
PHARMACOLOGIC ANTAGONISM
B.PHARMACODYNAMIC ANTAGONISM
B1. Reversible Competitive Antagonism
receptor antagonist that binds to agonist receptor site and
equilibrates sufficiently rapidly with the receptors that its
occupancy is reduced when the agonist concentration is
increased
Chelating agents
Deferoxamine – Iron (Fe)
Allosteric Modulation
Is the regulation of an enzyme or
other protein by binding an effector
molecule at the proteins allosteric site
Allosteric activators areeffectors
that enhances the proteinsactivity
Allosteric Inhibitors are effectors
that decreases the protein’sactivity
Types of Allosteric Modulation
1. Positive Allosteric Modulation
Occurs when the binding of one
ligand enhances the
attraction between
substrate molecules and
other binding sites
A.K.A. “allosteric activation”
Example: Hgb and Oxygen
Haemoglobin is an allosteric protein. This means that the binding
of oxygen to one of the subunits is affected by its interactions with
the other subunits.
haemoglobin's oxygen binding affinity is inversely
related both to acidity and to the concentration of
carbon dioxide.
S i n c e carbon dioxide reacts with water to
form carbonic acid, an increase in CO2 results ina
decrease in blood pH, resulting in hemoglobin
proteins releasing their loadof oxygen.
C o n v e r s e l y, a decrease in carbon dioxide
provokes an increase in pH, which resultsin
hemoglobin picking up more oxygen.
Types of Allosteric Modulation
1. Negative Allosteric Modulation
Occurs when the binding of one
ligand decreases the affinity for
substrate at other binding sites
A.K.A “ allosteric inhibition”
Chemistry
Pre-Clinical Studies Physical Properties
Biological
Pre-formulation
Postmarketing (Phase 4)
Indirect drug design
Drug a- receptor a
New drug - receptor a
NDA- submission
FDA review preapproval plany inspection
FDA action
X TERATO Isotretinoin
Y Y GENIC
Thalidomide
Diethylstilbestrol
AUTACOIDS
Endogenous substances
with biological activity.
A.K.A. “Local hormones”.
Not released or stored in
glands.
Not circulated in blood.
Are formed at the site of
action.
Produce localized action.
Edongeneous there are naturally present in
our body.
CLASSIFICATION OF AUTACOIDS
4. Vasoactive Polypeptides
} Kinins
} Angiotensin
} Endothelin
} Natriuretic peptide
} Vasopressin
} Substance P
5. Endothelium Derived Autacoids
} Nitric oxide
HISTAMINE A.K.A imidazolyethylamine;
1H – imidazole-4-ethenamine (chemical name )
it is a small molecule
produced by
decarboxylation of the
amino acid L-Histidine.
it is catalyzed by the
enzyme L-Histidine
decarboxylase in a
reaction that requires
pyridoxal phosphate.
L- histidine when you remove the carboxyl group of
histidine amino acid it will be Histamine.
Metabolism
Monoamine oxidase
Diamineoxidase orHistamine
Imidazole N-methyl transferase / Histamine N-methyl
transferase
Aldehyde Dehydrogenase
TISSUE DISTRIBUTION
1. Histamine strongest
2.Betazole Isomer of histamine and acts on H2
receptor .
It is used for diagnosis of gastric acid secretion.
3.Betahistine It is analogue of histamine and
acts on H1 receptor , it is used in the treatment of
Meniere's disease.
4. Impromidine
5.R-alpha methylhistamine H3 SPECIFIC
AGONIST
8
Betahistine is used in the treatment of
Meniere's disease inner ear disorder causing tinnitus(ringing
of the ear) vertigo and hearing loss.
Anti vertigo drug
Agonist response
Antagonist babalikatrin mo lang siya
Clinical Uses: Adverse Effects:
¡ Allergy Testing ¡ Flushing
¡ Bronchial ¡ Hypotension
Hyperactivity ¡ Tachycardia
Test ¡ Headache
¡ Test of Gastric ¡ Wheals
Secretory ¡ Bronchoconstriction
Function ¡ Gastrointestinal upset
Flushing redness of the skin (because of Dilated
Blood Vessels) Decreasein Blood Pressurecausing
Hypotension Shock
Example:
Antihistamine +Antiserotonin
Cyproheptadine inc.apetite
Antihistamine +Anticholinergic
Diphenhydramine
Promethazine (Antihistamine +AntialphaAdrenergic +
Anticholinergic )
B. Histamine Antagonist
1. H1-Anti-histamines
MOA: Block H1 receptors especial y in Mast Cels
CLINICAL USES: allergic rhinitis, allergic contact
dermatitis
12
B.1.1.1.ETHANOLAMINE most sedating; has
significant anticholinergic; used as sleepingpills;
mx of EPS(atropine-likeeffects)
1. Diphenhydramine
2.Diphenhydramine+ Calamine Benadryl®,
Caladryl®
3. Dimenhydrinate Gravol®
4. Carbinoxamine. Palgic®
B.1.1.1.4. Doxylamine Unisom®
2. ETHYLENEDIAMINE
1. Pyrilamine
B.1.2.2.Tripelennamine
B.1.1.3.PIPERAZINE
1. Hydroxyzine Iterax®
2. Meclizine.Bonamine®,
B.1.3.1.Cyclizine Valoid®
ETHANOLAMINE Antihistamine+
Anticholinergic
Atropine(anticholinergic drug) likeeffect
5. PHENOTHIAZINE
1. Promethazine Phenargan®, Phenerzin®, Promet®, Zinmet®
6. MISCELLANEOUS
1. Cyproheptadine Periactin®
ALKYLAMINES
Paracetamol +Phenylephrine + Chlorphenamine Antihistamine drug
present in Bioflu,Neozep.
PHENOTHIAZINE
Promethazine as anesthetic (Antihistamine +Antialpha Adrenergic +
Anticholinergic)
MISCELLANEOUS
Cyphoheptadine Periactin® for serotonin syndrome ;has significant
blocking effects on 5 – HT receptors
Antihistamine +Antiserotonin
15
Sedation sleep aids , not use in day time
x pilot
18
PUD Peptic Ulcer Disease
GERD Gastro Esophageal Reflux Disorder
Gastric acid secretion
Common Symptoms
Sleep deprivation andPsychosis
Ergot Alkaloid
• Dihydroergotamine
• Methylsergide
Migraine
Sumatripan Imitrex
Ergotamine Ergomar
2. Hyperprolactinemia
¡ Increased serum levels of the anterior pituitary
hormone Prolactin are associated with secreting
tumors of the gland.
¡ Bromocriptine
¡ Pergolide
¡ Cabergoline
62
3. Postpartum Hemorrhage
¡ Oxytocin is the preferred agent for
control of postpartum hemorrhage,
but if this peptide agent is ineffective,
Ergonovine maleate, 0.2 mg usually
given intramuscularly, can be tried.
3
3
Ergonovine=Ergotrate
3
EICOSANOIDS- DEFINE AS INFLAMMATORY MEDIATORS
ORIGINATED FROM PHOSPHOLIPID PRECURSOR—
ARACHIDONIC ACID a 20 CARBON ATOM FATTY ACIDS
38
CELL MEMBRANE MADE UP OF PHOSPHOLIPID BY
LAYER CONVERTED TO AA BY PLA2
4
1
1. COX 1
} Located in the endothelial cells, kidneys,
gastrointestinal tract, and other locations.
} provide active action on the Gastric Mucosa and
in the kidney.
2. COX 2
} Found in abundance in connectivetissues.
} Highly inducible by numerous factors associated
with inflammation
4
2
b. Lipoxygenase Pathway
¡ Produces leukotrienes,
Hydroperoxyeicosatetranoic
acids (HPETE’s), and
Hydroxyeicosatetranoic acids
(HETE’s).
4
3
VASODILATOR DILATE BLOOD VESSELS
DECREASE BP
VASOCONSTRICTION NARROW OF BLOOD VESSELS
INCREASE BP
POLYMORPHO NUCLEIC LEUKOCYTES
27
4
27
5
27
6
27
7
ASPIRIN DECREASE COX- CAUSE ANTI
INFLAMMATORY AND INDUCED ULCER, AT THE
SAME TIME IT INCREASES LEUKOTRIENE.
BRONCHOSPAM ASTHMA
CARBOPLAST IS A NATURALLY
OCCURING PROTAGLANDIN USED IN
MEDICINE TO INDUCE LABOR AND AS
ABORTIFACIENT.
PGI2:
LTC4, LTD4
¡ MOA: Bronchoconstrictors important in
anaphylaxis; causeedema
ANTIPYRETICANDANALGESIC- 325-650 mg
orally/rectally once every 4-6 hours as needed
ASPIRIN (ACETYLATED)
A.K.A ACETYLSALICYLIC ACID
NON SELECTIVE- INHIBITS BOTH COX1 & COX2
PROTOTYPE AGENT OF NSAID
RAPIDLY ABSORBED IN STOMACH
RAPIDLY HYDROLYZED TO ACETIC ACID AND
SALICYLATE BY ESTERASE IN TISSUE AND BLOOD
USE AS ANTIPLATELET- 325 MG PER DAY
ANTI-INFLAMMATORY- 3.2- 4G PER DAY
ANTIPYRETIC/ ANALGESIC – 325-650 MG (EVERY 4-
6HRS AS NEEDED)
¡ SE:GI discomfort, GI ulceration, CNS
salicylism, vertigo, Hypersensitivity
reaction=Reye’s Syndrome,Asthma
¡ Reye’s Syndrome manifest as hepatic failure &
encephalopathy
happens when there is a previous or current
viral infection
WHEN MEDICATION SUCH AS NSAIDS OR ASPIRIN BLOCK THE
COX-1 ENZYME, PRODUCTION OF THROMBOXANE AND MORE
ANTI-INFLAMMATORY PROTAGLANDINS IS DECREASED, AND IN
PATIENTS WITH ASPIRIN INDUCED ASTHMA, THIS RESULTS IN THE
PRODUCTION OF PRO- INFLAMMATORY LEUKOTRIENES.
ASPIRIN IS COINTRADICTION WITH VIRAL INFECTION IT WILL
PRODUCE REYES SYNDROME.
SIDE EFFECT OF ASA: REYES SYNDROME, ASTHMA, GI
DISCOMFORT
¡ ADMINISTRATION: Must be given w/ orafter
heavy meal
Or take proton-pump inhibitor before taking
aspirin
¡ RISK FACTORS:Taking multipleNSAIDS:
causesGastritis (blood in the stools)
¡ Concurrent use of Glucocortcoids:Increase
inhibition of cytoprotectant action of COX
NON-SELECTIVE COXINHIBITOR
Phenylpropionic acid Ibuprofen Advil®, Dolan FP®, Medicol®,
Midol®, Nuprin®,Motrin®
Pyrrolealkanoic acid derivative TolmetinTolectin®
PropionicAcid D e r i v a t iv e Flurbiprofen Ocufen® ophthalmicsoln
Ketoprofen Orudis®
Oxaprozin
Indole derivative Indomethacin Infree® , VI-Gel®
Pyrazolone derivativePhenylbutazone, Oxyphenbutazone,
Sulfinpyrazone -Anturane®
Phenylacetic acid derivativeDiclofenac
Fenamate Meclofenamate acid
O x i c a m Piroxicam Feldene®
Non-acid N S A I D Nabumetone
Naphthylpropionic acid derivative Naproxen Flanax®, Naprosyn®
Anthralinic acid FlufenamicAcid
MeclofenamicAcid
MefenamicAcid olfenal®,Gardan®,Ponsran®
DICLOFENAC IS USED TO TREAT MILD TO
MODERATE PAIN, OR SIGNS AND SYMPTOMS
OFOSTEOARTHRITIS OR RHEUMATOID
ARTHRITIS.
1.SE: Hematologic toxicities-Aplastic Anemia,Agranolocyte;
ATN(Acute tubular necrosis)
2.USED FOR PDA/ Patent DuctusArtriosusfailure to close ductus
preferredfor the mx of pain of an acute attacks of gout
3.sulfur-containingdrugs
causesSJS(StevenJohnsonSyndrome)
for ArthritisOsteoarthritis
AnkylosingSpondylitis
7.is an arylaceticacidderivative
appears comparable to aspirinIn the tx of RA, with a lower incidenceof
side effects also been approved for use in primary dysmenorrheal
prescribedforHemophiliacPatientfor RA
existsboth as R-& S- enantiomers(S-enantiomeristhe only active form)
1. PYRAZOLONE DERIVATIVES
2. INDOMETHACIN
3. SULINDAC
4. ETODOLAC
5. NABUMETONE
6. FENAMATES
7. IBUPROFEN
¡ (Advantage: Less incidence of gastric
irritation or ulceration)
¡ MOA: Selectively reversibly inhibits COX-2
CLINICALUSE/S: Analgesia, antipyretic,and
anti-inflammatory
Toxicity: Nephrotoxicity; hypersensitivity dueto
increased leukotrienes; less risk of GI toxicity
than nonselective
¡ NSAIDs; greater risk of thrombosis than
nonselective NSAIDs
Celecoxib (CELEBREX) 10-20times selectivefor COX-2 than COX-1
CLINICAL USES: ANALGESIA, It is a sulfonamide derivative, therefore it may cause
ANTIPYRETIC AND ANTI- rashes
INFLAMMATORY
It interacts with Warfarin due to CYP2C6
ANTI-RHEUMATIC DRUGS.
DMARDS METHOTREXHATE
SAARTS HYDROXYCHLOROQUINE,
CHLOROQUINE, PENICILLAMINE, GOLD AND
SULFASALAZINE
Methotrexate 1st line DMARDS in RA
Zexate®, Alltrex® Important to pyrimidine synthesis
MOA:
1. Cytotoxic to rapidly dividing immune cells due to inhibition of
dihydrofolate reductase
2. Inhibit AICAR (aminoimidazole carboxanide tribonucleotide)
3. Inhibits DNA transcription
CLINICAL USE/S: Anticancer, rheumatic disorders
S E : Hepatotoxicity ( FolicAcid- hepatoprotectant)
TOXICITY: Nausea, Mucosal Ulcers, Hematotoxicity,
Hepatotoxicity,Teratogenicity
ALTERNATIVE: Leflunamide
Anti-MalarialAgents
Chloroquine Chloromax®
Hydroxychloroquin Hydroxychloroquine Plaquenil®
AICAR INVOLVED IN PURINE BIOSYNTHESIS
PURINE INVOLVE DNA SYNTHESIS
RHEMATOID ARTHRITIS (RA) IS THE MOST COMMON TYPE
OF AUTOIMMUNE ARTHRITIS. IT IS CAUSED WHEN THE
IMMUNE SYSTEM (THE BODYS DEFENSE SYSTEM) IS NOT
WORKING PROPERLY.
RHEMATOID ARTHRITIS CAN CAUSE PAIN, SWELLLING AND
DEFORMITY. AS THE TISSUE THAT LINES YOUR JOINTS (SYNOVIAL
MEMBRANE) BECOMES INFLAMEF AND THICKENED, FLUID BUILDS
UP AND JOINTS ERODE AND DEGRADE.
RHEMATOID ARTHRITIS CAUSE PAIN AND SWELLING IN WRIST
AND SMALL JOINTS OF THE HAND AND FEET.
TREATMENT OF RHEMATOID ARTHRITIS CAN STOP JOINT PAIN
AND SWELLING.
Gold Auranofin Ridaura®
Compound Aurothiomalate Myochrysine®
s Aurothioglucose Solganal®
SE:hypersensitivity reaction
Formation of UricAcid:
Purine hypoxanthinexanthineuric acid
w/ allopurinol alloxanthine cannot be converted to
uric acid
PURINES ARE NITROGEN CONTAINING COMPOUNDS.
WHICH ARE MADE INSIDE THE CELLS OF YOUR BODY
(ENDOGENOUS), OR COME FROM OUTSIDE OF YOUR
BODY, FROM FOODS CONTAINING PURINE (EXOGENOUS).
PURINE BREAKS DOWN INTO URIC ACID. INCREASED
LEVELS OF URIC ACID FROM EXCESS PURINES MAY
ACCUMULATE IN YOUR TISSUES, AND FORM CRYSTALS.
3.Glucocorticoids (GC)
¡ Methyl Prednisolone
¡ to inhibit inflammation systemic management of RA,
¡ Life threatening SLE(Systemic Lupus Erythematus)
Intrasynovial
1.Colchicine
1st line initial treatment of chronic gout after 2-3 weeks
MOA: Inhibits the synthesisofMicrotubules
4. Sulfinpyrazone Anturane®
¡ Uricosurics
¡ Similar toprobenecid
5. Penicillamine C u p r i m i n e
Angiotensin
¡ A peptide, causes blood vessels to constrict,
and drives blood pressure up.
¡ It is part of the renin-angiotensin system,
which is a major target for drugs that lower
blood pressure.
¡ It stimulates the release of aldosterone from
Aldosterone Function:
Promotes Na (sodium) retention
Action: Inc. Na, Inc. in Water, Inc. in Blood
Volume, Inc, BP.
Juxtaglomerular cells(synthesized / realease renin) present in
nephron of kidney
Low BP our body try to adopt with this changes in the BP
stimulates the release of renin
32
1
¡ An aspartyl protease that specifically
catalyzes the hydrolytic release of the
decapeptide angiotensin I from
angiotensinogen,
¡ it is synthesized as a preprohormone that
is processed to prorenin, which is inactive,
and then to active renin, a glycoprotein,
consisting of 340 amino acids.
¡ Within the kidney, it is synthesized and
stored in the juxtaglomerular apparatus of
the nephron. 32
2
Renin comes from PRORENIN
2nd reason
Decrease Na (sodium), Dec.
Water, Dec. BV, Dec. BP
4. Angiotensin II
¡ inhibits renin secretion.
5. Pharmacologic Alteration of Renin Release
¡ Stimulated by vasodilators
(Hydralazine,Minoxidil, Nitroprusside), B-
adrenoceptor agonist (isoproterenol), a-
adrenoceptor antagonists, phosphodiesterase
inhibitors (theophylline, Milrinone, Rolipram),
and most Diuretics and Anesthetics.
32
6
A2 inc. BP, Dec. Amount of renin
release, dec BP
32
8
Angiotensin I
¡ It acted on the plasma or tissue
aminopeptidases to form
angiotensin I; this in turn is
converted to angiotensin II by
converting enzyme.
32
9
Angiotensinogen by the
action of (renin) it will be
converted to A1.
10
0
Actions of Angiotensin II
1. Blood Pressure
¡ Increase the release of Epinephrine and
Norepinephrine.
2. Adrenal Cortex
¡ Acts directly on the zona glomerulosa to
stimulate aldosterone biosynthesis.
3. Kidney
¡ Cause renal vasoconstriction, increase
proximal tubular sodium reabsorption, and
inhibit renin secretion. 82
BLOOD PRESSURE
INCREASE IN EPI AND NOR EPI – INC BP
EPI & NE ARE PRIMARY NEURO
TRANSMITTER AT SYMPATHETIC NERVOUS
SYSTEM
4. Central Nervous System
¡ Stimulate drinking (dispogenic effect) and
increase the secretion of vasopressin, and
adrenocorticotropic hormone (ACTH).
5. Cell Growth
¡ a mitogenic for vascular and cardiac muscle
cells and may contribute to the development
of cardiovascular hypertrophy.
10
2
VASOPRESSIN A.K.A “ANTIDIURETIC
HORMONE”
PREVENTS URINATION
Angiotensin II Receptors
1. AT1
¡ Have high affinity for Losartan(LOSARTAN –
ARBS ANGIOSENTIN RECEPTOR BLOCKER’s)
and low affinity for PD123177 (an experimental
non-peptide antagonist).
¡ Binding of angiotensin II in vascular smooth
muscle results in activation of phospholipase C
and generation of IP3 and DAG.
10
3
2. AT2
¡ Have high affinity for PD 123177 and a low
affinity for Losartan.
¡ Involves the serine and tyrosine
phosphatases, phospholipase A2, nitric oxide,
and cyclic guanosine monophosphate
(cGMP).
¡ Upregulated in pathologic conditions
including heart failure and myocardial
infarction.
10
4
Drugs that block Renin
Secretion
¡ Clonidine (CATAPRESS®)
)Propranolol (INDERAL®)
Renin Inhibitors
¡ Remikiren
¡ Enalkiren 86
Angiotensin Converting Enzymes (ACE)
Inhibitors
¡ Captopril (CAPOTEN®) & Enalapril (VASOTEC®) are the
prototype agents.
¡Lisinopril (ZESTRIL®)
¡ Benazapril
¡ Fosinopril (MONOPRIL®) ACE when inhibits will result
dcrease of A2 (No
¡ Moexipril vasoconstriction)(decrease in BP)
¡ Perindopril
¡ Quinapril (ACCUPRIL®)
¡ Ramipril (ALTACE®)
¡ Trandolapril
339
Angiotensin Receptor Blocking
Agents®
¡ Losartan & Valsartan (DIOVAN®)
were the first marketed blockers of
angiotensin II type 1 (AT1) receptor.
¡ Candesartan ATACAND®
¡ Eprosartan TEVETEN®
¡ Irbesartan AVAPRO®
¡ Telmisartan MICARDIS®
340
Kinins
¡ Formed enzymatically by the
action of enzymes known as
kallikreins or kininogenases acting on
protein substrates called kininogens.
¡ Potent vasodilator peptides.
KININOGENS (KALLIKRENS ENZYME)
KININS
341
Kallikreins
¡ Are glycoprotein enzymes produced in the liver
as prekallikreins and present in plasma and in
several tissues, including the kidneys,
pancreas, intestine, sweat glands, and salivary
glands.
¡ They are serine proteases with active sites and
catalytic properties similar to those of enzymes
such trypsin, chymotrypsin, elastase, thrombin,
plasmin, and other serine proteases.
342
KALLIKREINS ARE SERINE PROTEASES THAT
LIBERATE KININS
345
3. Role in Inflammation
¡ Kallikreins and kinins can produce
redness, local heat, swelling, and pain,
and the production of kinins is increased
in inflammatory lesions.
4. Effects on Sensory Nerves
¡ Are potent pain-producing substances
when applied to a blister base or injected
intradermally. 346
Metabolism of Kinins
1. Kinnase I
} Synthesized in the liver, is a
carboxypeptidase that releases the
carboxyl terminal arginine residue.
2. Kinnase II
} Present in plasma and vascular
endothelial cells throughout the body.
347
Arginine becomes nitric oxide-a blood vessels
–widening agent called a vasodilator) in the
body
Drugs Affecting the Kallikrein-Kinin System
1. Icatibant
} Second generation B2 receptor antagonist.
} Used to evaluate the role of kinins in pain,
hyperalgesia, and inflammation.
2. 3rd Generation B2 Receptor Antagonist
} FR 173657
} FR 172357
} NPC 18884
} Inhibit bradykinin-induced broncho-constriction.
349
Vasopressin
¡ a.k.a. “Antidiuretic Hormone”.
¡ Plays an important role in the long-term
control of blood pressure through its
action on the kidney to increase water
reabsorption.
VasopressinAntagonist
¡ Lithium
¡ Demeclocyline
350
VASOPRESSIN DEC URINATION, INC WATER
REABSORPTION, INC BV, INC BP
TAKE NOTE:
DEMECLOCYLINE INHIBIT THE ACTION OF
ANTIDIURETIC HORMONE IN THE RENAL TUBULE
CAN INDUCE SENSITIVITY TO SUNLIGHT
(PHOTOSENSITIVE DRUG)
LITHIUM = BRANDNAME: LITHASE
352
ACTH- ADRENO CORTICOTROPIC HORMONE
A HORMONE PRODUCED IN THE PITUITARY
GLAND THAT STIMULATES THE ADRENAL GLAND
TO RELEASE A HORMONE CALLED CORTISOL
Natriuretic Peptides
¡ One of the peptides that causes natriuresis, the excretion of an excessively
large amount of sodium in the urine. The natriuretic peptides are produced
by the heart and vasculature:
A-type natriuretic peptide is secreted largely by the atrial
myocardium in response to dilatation.
B-type natriuretic peptide is manufactured mainly by the
ventricular myocardium. It useful in the diagnosis of heart
failure. The finding of a low level of B-type natriuretic peptide
tends to exclude heart failure.
C-type natriuretic peptide is produced by endothelial cells
that line the blood vessels.
354
Natriuretic promotes Excretion of Sodium
Natri salt
Uretic urine
Clinical Significant:
Increase Heart failure, renal failure
Actions:
Decrease the secretion of renin, aldosterone and
vasopressin; decrease BP and increase sodium
excretion.
Acts via activation of guanalyl cyclase.
Vasopeptidase Inhibitors
¡ are new class of cardiovascular drugs
that inhibit two metalloprotease
enzymes,NEP(NEUTRAL
ENDOPEPTIDASES) 24.11 andACE.
¡ Omaprilat
¡ Sampatrilat
¡ Fasidotrilat
356
Endothelins
¡ is the source of a variety of substances with
vasodilator (PGI2 and Nitric Oxide) and
vasoconstrictor activities.
Three Isoforms
1. ET-1
¡ Is the predominant endothelin secreted by the
vascular endothelium
¡ Produced by the neurons and astrocytes in the CNS
and in endometrial, renal mesangial, Sertoli, breast
epithelial, and other cells.
357
2. ET-2
¡ Produced dominantly in the kidneys
and intestine
3. ET-3
¡ Found in highest concentration in the
brain but is also present in
gastrointestinal tract, lungs, and
kidneys. 358
Physiologic and Pathologic Roles of Endothelins
¡ *Essential/Primary Hypertension-there's no identifiable cause of high blood pressure
¡ *Cardiac Hypertrophy-myocardiumresponse to various physiologic and pathologic
stimuli that cause the heart to work harder ex. Hypertensionand MI that causes
stretching of myocardial walls
¡ *Heart Failure-sometimes known ascongestive heart failure, occurs when yourheart
muscle doesn't pump enough blood
¡ *Atherosclerosis-hardening and narrowing of the arteries.
¡ *Coronary Artery Disease-Coronary heart disease (CHD) is a disease in which a waxy
substance called plaque builds up inside the coronary arteries. These arteries supply
oxygen-rich blood to your heart muscle. When plaque builds up in the arteries, the
condition is called atherosclerosis.
¡ *Myocardial Infarction-Most heart attacks are caused by a blood clot that blocks one of
the coronary arteries. The coronary arteries bring blood and oxygen to the heart. If the
blood flow is blocked, the heart is starved of oxygen and heart cel s die.The medical term
for this ismyocardial infarction.
¡ *Pulmonary HTN-high blood pressure that affects the arteries in your lungs and the
right side of your heart.
¡ *Asthma-airways narrow and swell and produce extra mucus. This can make breathing
difficult and trigger coughing, wheezing and shortness of breath.
359
Endothelin Antagonist
¡ Bosentan
¡ Sitaxentan
¡ Ambrisentan
Adverse Effects:
¡ Systemic hypotension, increased
heart rate, facial flushing, nausea,
and headache.
360
Bosentan a complete antagonist of both ETA
and ETB receptors and blocks the action of
endothelin at different target sites.
Is indicated for pulomonary hypertension.
362
Substance P
¡ is a neuropeptide: an undecapeptide that functions
as a neurotransmitter and as a neuromodulator.
¡ It belongs to the tachykinin neuropeptide family.
¡ Its closely related neuropeptide neurokinin A (NKA)
and neurokinin B (NKB) are produced from a
polyprotein precursor after differential splicing of
the preprotachykinin Agene.
¡ Aprepitant-NK1 receptor antagonist approved for
the prevention of chemotherapy induced nausea
and vomiting.
363
SUBSTANCE P(PAIN) – A COMPOUND
THOUGHT TO BE INVOLVED IN THE SYNAPTIC
TRANSMISSION OF PAIN AND OTHER NERVE
IMPULSES. IT IS A POLY PEPTIDE WITH 11
AMINO ACID RESIDUES (PRESENT IN DORSAL
HORN OF SPINAL CORD ACTS AS AN AFFERENT
NT FROM THE SENSORY FIBERS, PLAYS
NEUROGENIC INFLAMMATION)
365
Calcitonin Gene-Related Peptide
¡ Is a member of the calcitonin family of
peptides which also includes calcitonin,
adrenomedullin and amylin.
¡ Consists of 37 amino acids and displays
approximately 30% structural homology
with salmon calcitonin.
¡ Causes hypotension and tachycardia.
¡ Most potent vasodilator yet discovered.
366
Calcitonin Gene-Related Peptide(CGRP)
present in the parafollicular cells of the thyroid
gland similar to calcitonin
368
Pheochromocytoma(disease)
tumor on the adrenal
medulla(chromaffin cells)that
secretes cathecolamines.
Septic shock
Neuropeptide Y
1
9
0
CNS Inc. food intake and Decraese physical
activity
Urotensin
¡ Was originally identified in fish, but isoforms
are now known to be present in mammalian
species including mouse, rat, pig, and
human.
¡ In vitro, it is a potent constrictor of vascular
smooth muscle.
¡ Occurs primarily in arterial vessels, where
urotensin II can be more potent than
endothelin 1.
¡ Upregulated in the heart of humans with
end-stage heart failure.
¡ Increase levels in patients with cardiovascular diseases
110
Isoforms a protein that has the same
functions as another protein but which is encoded
by a different gene and may have small
differences in its sequence.
1. Nedrocromil
2. CromolynSodium/ Na Cromoglycate
Hydocortisone Solucortef®
Methylprednisolone Solumedrol®
¡ Locally-actinginhaledGC(Low dose)1st line control ers for BASystemic
GC(parenteral)1st line in statusasthamticus
MOA: Inhibit the synthesisof phospholipaseA2
¡ Inhibit the late phaseal ergic reactions
¡ Inhibit the releaseof interleukin by the macrophagesInhaledCorticoids
adjunctivecontrollers; COPD
¡ SE: oral candidiasisvocal cord nodulesOral thrush hoarseness
¡ Prevention of oral candidiasis:gargling(3-4x);use of spacers
¡ PO: Prednisone;Prednisolone
are given not more than 10days(ifexceed,adrenal suppression)
¡ ShortCourseTherapy:AcuteBAExacerbation
¡ Exacerbation: Early phase airway obstruction (brochodilation) Late Phase
2-8hrs ; inflamation
¡ IV: Methylprednisolone;Hydrocortisone
managementof severeacuteasthma exacerbation
Review Well !!!
GoodLuck!!!
Review Well !!!
GoodLuck!!!
PCOL Topic 1.1 Others – Cyanide + sodium. thiosulfate
Na2S3O3 - Most common antidote for
Pharmacology divided into two
cyanide toxicity.
1. Pharmacodynamics – What the drug does to the 3. Counterfeit incorporation mechanism
body – mechanism of action. - Example: pyrimidines (Pyrimidine Cytosine Uracil
2. Pharmacokinetics – What the body does to the drug thymine) and purines (Purine Guanine Adenine)
– biopharmaceutics. Flucytosine – Antifungal drug that inhibit DNA
and RNA synthesis –
Mechanism of drug action
incorporate into RNA of the fungi that cause
- Non-target protein mediated mechanism. death to fungi,
Not targeting any protein but it is able to elicit its SITE OF DRUG ACTION
mechanism of action.
- TARGET PROTEIN
- Target protein mediated mechanism. 1. Structural protein
- Have targeting protein in order to a drug exert its Griseofulvin – Antifungal drug (famous drug
pharmacologic effect or action it has to target protein. it absorb increase
This protein upon targeting protein will produce a when there is a administration of fatty meal.
mechanism of action. Vinca alkaloids – Antineoplastic drug.
Non-target protein mediated mechanism Example:
Vinblastine – Example of vinca alkaloids that
1. Colligative mechanism derived from Vinca Rosea – Source.
- A good example is osmotic pressure – Example drug Vincristine – Alkaloids derivative that is
in osmotic pressure. MAGNESIUM SULFATE- closely related to vinblastine.
acting as purgative – An osmotic pressure targeting an Vinorelbine – Semi synthetic derivative of
osmotic pressure in our gastrointestinal tract. vinblastine.
Neutralization
2. Chemical reaction – A good example is Colchicine – Autumn crocus, colchicine
3 example
ANTACID, neutralize the acidic of stomach in autumnale – The
order to counter act the acidity. sources. for acute gout.
Treatment
Chelation – Used in case of metal toxicity, a
good example is Deferoxamine – Iron toxicity. 2. Regulatory protein
- Example of calcium channel blockers
– Dipine – Used for antihypertensive.
Hyperpolarization
- Efflux- Going outside. Potassium will go outside the
Carrier molecule – Carry certain ion or chemical which is
cell.
very essential biological processes in our body.
- Influx- Ion will go inside the cell.
Digitalis glycosides – Ex. Digoxin – acting in atrophic - Efflux and Influx will cause a change in cell
agent. membrane potential (Negative)
Proton pump inhibitor (PPI)- Used as antacid reduce (handout)
gastric acid secretion. Meaning wala/decrease ang amount ng
neurotransmitter.
- Eg: Omeprazole and Pantoprazole. Loop diuretics Eg: There will be a drug acting to
– Example FUROSEMIDE. Enzyme promote hyperpolarization. Beneficial for people with
- Allopurinol (for chronic gout) anxiety.
- Ace inhibitors – Anti-hypertensive. Depolarization- Influx of Sodium and Calcium ion.
- MAO (Monoamine oxidase) Tataas yung amount ng neurotransmitter.
- Acetylcholinesterase – Responsible breaking down
- Not beneficial for people with anxiety and seizure.
acetylcholine example drug EDOPHONIUM – used
- Find a drug that will block depolarization. Eg:
to diagnosis of Myasthenia Gravis – Auto immune
Carbamazepine and Phenytoin Acting to
disorder.
blockyour voltage gated sodium channel thereby
- COMT (Cathecol o Methyl transferase)- Responsible
blocking depolarization.
for breaking down dopamine.
Eg: Entacapone and Tolocapone Repolarization- Opposite of depolarization. No nerve
Used in
Receptors- Parkinson’s
The disease.
most common site of action of drug. impulse. Similar with Hyperpolarization.
Type of Receptor
Specificity- Drug will only act in the specific type
of receptor there are specific functional group 1) Type I Receptor (Ionotropic receptor)
acting on the specific receptor. (Handout under GABA receptors control Cl- ions)
Selectivity- Selective drug acting only in the
single receptor. Benzodiazepines and Barbiturates
Affinity- Capacity of the drug to form complex Common examples of Anti-anxiety drugs. An agonist of
GABA receptors.
with its receptor.
Intrinsic activity- Efficacy of drug – “Once a drug is an agonist receptor this will
Pharmacologic response. increase the movement of Chloride ion inside the cell.”
It will produce Hyperpolarization.
Nicotinic receptors- (Handout) Inhibited by neuromuscular cGMP- Originates from GTP (Guanosine Triphosphate)
blocker. Eg: Succinylcholine Inhibit your nicotinic Guanylyl Cyclase cGMP.
receptors thereby inhibiting the movement of Sodium ion.
Guanylyl Cyclase- Enzyme. GTP
(Picture) Once a drug binds into the receptor, the chloride cGMP.
ion will go inside the cell causing hyperpolarization.
An increase in cGMP will produce a common effect
2) Type II Receptors (G-protein linked receptor/G- (handout).
protein coupled receptor/Metabotropic receptors)
- AKA 7 transmembrane (7-TM or heptahelical - Beneficial in tx of hypertension.
receptors) Phosphatidyl Choline- Precursor of your IP3 and DAG.
- Increase in calcium responsible for common
G-protein linked receptors- Type II
effect (handout)
receptors are associated or closely related to G-
protein. Phospholipase C- Enzyme. Responsible for converting
Phosphatidyl Choline IP3,DAG.
“Once a receptor is linked in your G-protein this is
responsible for producing an intracellular second Examples of G-proteins:
messenger.” Gs- there would be increase in the cAMP.
- Cholera toxin came from Vibrio chloreae
Second messenger- Inositol Triphosphate (IP3) and DAG Blocks your GTPase
(Diacylglycerol)
Gi- Decrease the cAMP.
cAMP- Comes from ATP (Adenosine Triphosphate) - Blocks by pertussis toxin came from
Adenylyl cyclase cAMP. Bordatella pertussis.
Gq- Increase in calcium
Adenylyl Cyclase- Enzyme. ATP cAMP. Contraction of the muscle.
Type III receptors/Tyrosine Kinases- linked
“When there is an increase in the amount of cAMP, it will receptors
activate protein kinase.”
JAK-STAT pathway- Responsible for modulating a
Protein kinase- Is responsible for the common effect number of biochemical processes.
(handout)
Tyrosine kinase- Belong to the family of Janus kinase.
Eg: If you have an asthma, an increase of cAMP is
Type IV receptor/gene transcription- linked receptors-
beneficial in tx of asthma because it will produce
Responsible for modulating the different processes in
bronchodilation.
your
If you are experiencing hypertension and you have
increase in amount of cAMP will not be beneficial in the tx
of hypertension because it causes contraction of the heart
may increase the blood pressure.
DNA and RNA synthesis and protein synthesis. factor wherein a drug will produce its
effectiveness.
Clark Hypothesis- The effect pf the drug is directly - Kapag maraming stimulus, mas matindi ang
proportional to the number of receptors that would be effectivity ng isang drug.
occupied.
Graded Dose-Response Relations- We are studying the
- If receptors are occupied, maximum effect is effect of the drug in relation to the dose.
obtained.
Linear dose scale- Zero 100 600. Range
Lock and Key Theory- Eg: If the receptor has a spherical is 200.
shape type of receptor. The drug with spherical shape
molecule should fit in this into the receptor. Logarithmic dose scale- The dose or drug concentration
will be by 10s, 100s and 1000s
- Kung hindi kasukat ng drug ang receptor or vice
versa, they will not produce its effect. 3 Factors of Quantal Dose- Effect curves.
Configuration 1. The number of patients.
2. The response of the patient.
Drug- must fit into the receptor. They must have the 3. Specified dose of the drug.
same configuration in order for the drug to produce *Graded Dose Response
its effect.
Induced-fit Theory- Kahit hindi same ng configuration
2 Factors
yung drug and receptor, once the drug binds to its receptor,
the receptor will adjust or will alter the conformation in 1. The effect of the drug.
order for the drug to bind with the receptor. 2. The dose of the drug.
Induced- Ipinilit sa mismong receptor. Important consideration- LD50 (Lethal Dose 50)
Dose which produces toxiceffect at 50% of the population.
Rate Theory- The binding of the drug and the receptor
will be dependent kung ilang receptor yung naeencounter Therapeutic Index (TI)- TD50 (Toxid Dose
ni drug. 50) / ED50 (Effective Dose 50)
The more na marami syang naeencounter na receptor, the Therapeutic Window (TW)- Range between MEC
more na maactivate na receptor producing now the effect. (Minimum Effective Concentration) and MTC (Minimum
Toxic Concentration).
Hypothesis of Ariens and Stepheson- Duration of the
effectivity of the drug as long as nakabind yung drug sa - Margin of safety.
receptor may effect yung isang drug.
Trapezoidal Rule- Used to determine AUC Therapeutic
Hypothesis of Paton-RATE THEORY- It summarizes the Window/Margin of Safety/Therapeutic Range (safe &
proper stimulus is the main effective).
Exceeded- Toxic, not safe. Slide 116: Eg: smoking.
Below- Not effective. 1-stick Nicotine Low response.
ED50 (Median Effective Dose)- Effective dose at 50% of Stick- 1 pack (Increase in intake)
the population.
✖ Stop/Abrupt Withdrawal- Withdrawal symptoms.
Quantal Dose Effect Curves- Measured by ED50 and
TD50. Withdrawal- Can produce serious adverse drug effect.
Duration of Action: How long the drug will it takes its Slide 119: Agonist have both affinity – The ability to bind
effectivity. to the receptor as well as intrinsic activity – The ability to
produce a measurable effect.
- Max – Maximum concentration.
Slide 120: It is a drug that is capable at a sufficiently high
Tmax- Maximum time/the time it takes for the drug to concentration producing maximal cellular response (full
reach its maximum effectivity. response)
Idiosyncrasy- Type B (Bizarre)- Adverse effect. BETA RECEPTOR
- Dose independent/unpredictable. Beta 1- heart.
A: Allergic reaction – Type I (Immediate) – Allerge. Beta 2- lungs.
C: Cytotoxic – Type II (Autoimmune dxn) – immune system Eg: Isoproterenol- BN = Isuprel = B1 and B2 agonist.
attacks your own cell.
It acts on B1 receptor- Increase heart rate.
I: Immune complex – Type III (More antigen
compared to antibodies) B2 receptor- Bronchodilation- It is a symphatomimetic
drugs that can be used in asthma.
D: Delayed Type – Type IV – Not immediate.
Slide 122: When used alone partial agonist will act as a
*Flushing- all – Redness of the skin.
Vasodilation
Slide 113 memorize WEAK AGONIST pero in the presence of FULL
*Mantoux/PPD/Tuberculin Skin Test- 48- 72hrs after AGONIST it will acts as an ANTAGONIST.
exposure to tuberculin toxin.
BASIC AND CLINICAL EVALUATION OF NEW DRUGS
SLIDE 143 1.) Ligand based drug design – may sinusundan na design.
Drug target – molecular structure / cellular structure
- e.g.: Drug A acting on receptor A. Your goal is to design
- it can be a receptor, a certain tissue of our body, the organ a new drug that will also bind on receptor A. This drug is
of our body that will be involved in the pathology of the more active than drug A.
disease that the drug is treating or managing. 2.) Structure based drug design – it finds
the composition of the molecule/composition of the structure
- protein, enzyme, tissue, receptor that is responsible for
of the biological target.
the pathology of the disease.
Drug design – each drug has a unique drug design. - based on the structure amide, amine, carboxylic acid,
etc.
- e.g.: if a drug is reacting to the receptor enzyme, they 3.) Computer aided drug design – uses computational
have a separate or unique drug design for each of the new chemistry to develop new drug.
chemical entities. SLIDE 145
New chemical entity – the new
Drug repositioning – finding new therapeutic use if an old drug/chemical compound that will be the product of the drug
- e.g.: Sildenafil – Viagra
drug. discovery.
w a s initially designed to lower bloodpressure but is now - the product will be examined/synthesized
typically used to treat erectile dysfunction or impotence. through organic synthesis, molecular modification through
pre-clinical studies.
Pre-clinical studies – usually uses animals
SLIDE 144 - should obtain of the new information of the new chemical
TYPES OF DRUG DESIGN entities chemistry, physical
properties, biological properties, and pre- formulation - main purpose: safety bur mainly effectiveness
properties.
- inaalam na yung dosage form yung appropriate sa new - 100-500 patients
chemical entity. goalIf it is safe, it will proceed to Phase 3 – 3- 4 years
Investigational New Drug. - main purpose: safety, effectiveness, and dosage.
Investigational New Drug – its main goal is to provide data
showing that it is reasonable to begin tests of a new drug to - 500-5,000 patients
humans. This is to protect the rights and safety of the
subjects and to ensure that the investigational plan is sound *After providing that the drug is safe and effective on
and design to achieve the stated objectives. humans, you will proceed to New Drug Application.
- safe and effective on humans.
*After NDA, the drug is ready for the market.
* after IND, it will continue to pre-clinical studies for the
long-term toxicity. It then proceeds to clinical trials: Phase Phase 4 – AKA Post-marketing surveillance to
4.
*NDA submission – only applied kapag safe and effective. *10-20 years drug discovery.
- Treatment of Meniere’s disease. If there is a drug blocking your histamine receptor, decrease
Impromidine (INN)- Is a highly potent and specific ang allergic reaction, neurotransmission in the CNS.
histamine H2 receptor
- Used agonist. gastric
to increase acid If there is a drug blocking your histamine 1 receptor,
secretion.
naapektuhan din ang serotonin, adrenergic receptor, and
- It has been used diagnostically as a gastric secretion
cholinergic receptor.
indicator. Kapag mababa ang neurotransmitter sa brain, nakakaantok
Agonist- (slide 7 organ system effects) response.
sya and that would be increase in sedation. That’s why
antihistamine ay nakakaantok.
Antagonist- Babaliktarin yung organ system effects.
Ano ang example ng antihistamine + antiserotonin =
R-Alpha Methylhistamine- Acts on H3 receptor. Cyproheptadine increasein appetite.
SEROTONIN
Some serotonin receptor – they are excitatory
Serotonin – AKA 5-hydroxytryptamine also written to 5-HT
(responsible for increasing the amount of other
neurotransmitter) or inhibitory (responsible for
- potent vasoconstrictor other called
- Constrictor – responsible for constructor for decreasing the amount of neurotransmitter)
Other enzyme is 5-hyroxy protein coupled receptor (the rest of 5HT receptor)
MECHANISM OF ACTION
tryptophan decarboxylase or N- 5HT1 RECEPTOR – release serotonin which is
aromatic L-amino acid inhibitory, inhibit aldehyde cyclase, inhibit cAMP
decarboxylase – two enzyme (CNS)
responsible for converting 5- hydroxyl
5HT2 receptor – linked to PLC raising IP3 and DAG
tryptophan into serotonin
linked levels (smooth muscles, platelets, CNS)
Enzyme responsible for metabolism
of serotonin 5-hydroxy indole acetic acid 5HT3 receptor – linked to membrane ion channels
Remember that when there is abundant amount linked (sensory and enteric nerves)
of monoaminoxidase kapag masyadong madami the
amount of serotonin will decrease
SEROTONIN AND RELATED DRUGS
triptan that cause toxicity of triptan Peritol, is a first-generation antihistamine with additional
Hyperprolactinemia
Postpartum hemorrhage
Eicosanoids – inflammatory mediators
- from phospholipid precurson – AA (Arachidonic
a c i d ) a 20 carbon fatyacids.
2. Leukotrienes
*Eicosanoids – derived from Arachidonic acid
considered as a 20 carbon atom
Eicosanoids – inflammatory mediators
- from phospholipid precurson – AA (Arachidonic
a c i d ) a 20 carbon fatyacids.
2. Leukotrienes
*Eicosanoids – derived from Arachidonic acid
considered as a 20 carbon atom
SUMMARY DRUGS WITH ACTIONS ON HISTAMINE AND SEROTONIN RECEPTORS; ERGOT ALKALOIDS
Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions
H1 ANTIHISTAMINES
FIRST GENERATION:
Competitive Reduces or IgE immediate Oral and parenteral • duration 4–6 h Toxicity: Sedation when used in
hay fever,muscarinic blockade symptoms, orthostatic hypotension
antagonism/ prevents histamine allergies; especially
•Interactions: Additive sedation with other sedatives, including alcohol
inverse effects on smooth hay fever, urticaria
agonism at H1 muscle, immune • often used as a •some inhibition of CYP2D6, may prolong action of some β blockers
DIPHENHYDRAMINE receptors cells sedative,antiemetic,
• also blocks and anti-motion
muscarinic and α sickness drug
adrenoceptors
• highly sedative
SECOND GENERATION:
Competitive Reduces or IgE immediate Oral • duration 12–24 h
Antagonism prevents histamine allergies; especially • Toxicity: Sedation and arrhythmias in
CETIRIZINE /inverse effects on smooth hay fever, urticaria overdose
agonism at H1 muscle, • Interactions: Minimal
receptors immune cells
Other first-generation H1 blockers: CHLORPHENIRAMINE is a less sedating H1 blocker with fewer autonomic effects.
Doxylamine, a strongly sedating H1 blocker, is available
over-the-counter in many sleep-aid formulations and in DICLEGIS (in combination with PYRIDOXINE) for use in nausea and vomiting of pregnancy
Other second-generation H1 blockers: LORATADINE, DESLORATADINE, and FEXOFENADINE are very similar to
cetirizine
H2 ANTIHISTAMINES
CIMETIDINE
RANITIDINE
NIZATIDINE
FAMOTIDINE
SEROTONIN AGONISTS
5-HT1B/1D:
Partial agonist at Effects not fully understood Migraine Oral, nasal, parenteral
5-HT1B/1D •may reduce release of calcitonin gene-related peptide and cluster • duration 2 h
SUMATRIPTAN and perivascular edema in cerebral circulation
receptors headache • Toxicity:
Paresthesias, dizziness, coronary vasoconstriction • Interactions: Additive with
other vasoconstrictors
Other triptans (ALMOTRIPTAN, ELETRIPTAN, FROVATRIPTAN, NARATRIPTAN, RIZATRIPTAN,
ZOLMITRIPTAN): Similar to sumatriptan except for pharmacokinetics (2–6 h duration of action); much more expensive than generic sumatriptan
5-HT2C
LORCASERIN Agonist at 5-HT2C receptors Appears to reduce appetite Obesity Oral • duration 11 h
• Toxicity: Dizziness, headache, constipation
5-HT4:
TEGASEROD
PRULALOPRIDE
SEROTONIN BLOCKERS
5-HT2: jrc
KETANSERIN Competitive Prevents vasoconstriction Hypertension Oral
(not blockade at 5-HT2 and • carcinoid syndrome • duration 12–24 h
5-HT3:
ONDANSETRON
ALOSETRON
TEGASEROD
GRANISETRON
DOLASETRON
SEROTONIN
ERGOT ALKALOIDS
VASOSELECTIVE:
Mixed partial agonist effects at 5-HT2 and Causes marked smooth muscle Migraine and cluster Oral, parenteral
α adrenoceptors contraction but blocks α-agonist headache • duration 12–24 h
ERGOTAMINE
vasoconstriction •Toxicity: Prolonged vasospasm causing angina, gangrene; uterine
spasm
UTEROSELECTIVE:
Mixed partial agonist effects at 5-HT2 and Same as ergotamine • some Postpartum bleeding Oral, parenteral (methylergonovine)
α adrenoceptors selectivity for uterine smooth •migraine headache • duration 2–4 h
ERGONOVINE
muscle • Toxicity: Same as ergotamine
CNS SELECTIVE :
Central nervous system 5-HT2 and Hallucinations None • widely abused Oral • duration several hours
LYSERGIC ACID DIETHYLAMIDE dopamine agonist • psychotomimetic •Toxicity: Prolonged psychotic state, flashbacks
•5-HT2 antagonist in periphery
BROMOCRIPTINE, PERGOLIDE: Ergot derivatives used in Parkinson’s disease (see Chapter 28) and
PROLACTINOMA (see Chapter 37). Pergolide used in equine Cushing’s disease
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GENERIC NAME AVAILABLE AS
ANTIHISTAMINES (H1 BLOCKERS)*
AZELASTINE Generic, Astelin (nasal),
Optivar (ophthalmic)
BROMPHENIRAMINE Brovex, Dimetapp, others
BUCLIZINE Bucladin-S Softabs
CARBINOXAMINE Generic, Histex
CETIRIZINE Generic, Zyrtec
CHLORPHENIRAMINE Generic, Chlor-Trimeton
CLEMASTINE Generic, Tavist
CYCLIZINE Generic, Marezine
CYPROHEPTADINE Generic, Periactin
DESLORATADINE Generic, Clarinex
DIMENHYDRINATE† Generic, Dramamine
DIPHENHYDRAMINE Generic, Benadryl
DOXYLAMINE Diclegis (combination with pyridoxine), Unisom Sleep Tabs
ENDOTHELIN ANTAGONISTS
Nonselective antagonists
BOSENTAN, MACITENTAN Vasodilation Pulmonary arterial hypertension
of endothelin ETA and ETB receptors
SITAXSENTAN, AMBRISENTAN: Selective antagonists for ETA receptors
COMBINED ENDOTHELIN-CONVERTING ENZYME/NEPRILYSIN INHIBITORS
Blocks formation of Vasodilation
SLV306, DAGLUTRIL endothelins and breakdown of natriuretic • increased sodium and water excretion Heart failure
peptides • hypertension1
SUBSTANCE P ANTAGONISTS
Prevention of chemotherapyinduced
Selective antagonist of tachykinin NK1 Blocks several central nervous system effects of
APREPITANT nausea and vomiting
receptors substance P
NEUROTENSIN ANTAGONISTS
Antagonist of central and peripheral Blocks some central and peripheral (vasodilator) actions
MECLINERTANT None identified
neurotensin receptors of neurotensin
CALCITONIN GENE-RELATED PEPTIDE ANTAGONISTS
Antagonists of the calcitonin gene-related Blocks some central and peripheral (vasodilator) actions
TELCAGEPANT, Migraine1
peptide (CGRP) receptor of CGRP
OLCEGEPANT
NEUROPEPTIDE Y ANTAGONISTS
Selective antagonist of neuropeptide Y1
BIBP3226 Blocks vasoconstrictor response to neurotensin Potential antiobesity agent
receptors
• BIIE0246: Selective for Y2 receptor
• MK-0557: Selective for Y5 receptor
UROTENSIN ANTAGONISTS
• PALOSURAN Potential for treatment of diabetic renal
• GSK1440115: Antagonist of urotensin receptors Blocks vasoconstrictor action of urotensin failure and asthma1
More potent than palosuran
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GENERIC NAME AVAILABLE AS
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
Captopril
ANGIOTENSIN RECEPTOR BLOCKERS
Losartan
RENIN INHIBITOR
Aliskiren Tekturna
KININ INHIBITOR
Icatibant Firazyr
KALLIKREIN INHIBITORS
C1 esterase inhibitor, human Cinryze, Berinert
Ecallantide Kalbitor
AVP RECEPTOR ANTAGONISTS
Conivaptan Vaprisol
Tolvaptan Samsca
SUBSTANCE P ANTAGONIST
Aprepitant Emend
NATRIURETIC PEPTIDE AGONIST
Nesiritide Natrecor
DRUGS USED IN PULMONARY HYPERTENSION
Ambrisentan Letairis
Bosentan Tracleer
Epoprostenol Flolan, Veletri
Iloprost Ventavis
Macitentan Opsumit
Riociguat Adempas
Selexipag Uptravi
Treprostinil Tyvaso, Remodulin
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GENERIC NAME AVAILABLE AS
Alprostadil
Penile injection, mini-suppository Caverject, Edex, Muse
Parenteral Generic, Prostin VR Pediatric
Bimatoprost Lumigan, Latisse
Carboprost tromethamine Hemabate
Dinoprostone [prostaglandin E2] Prostin E2, Prepidil, Cervidil
Epoprostenol [prostacyclin] Generic, Flolan, Veletri
Iloprost Ventavis
Latanoprost Generic, Xalatan
Misoprostol Generic, Cytotec
Montelukast Generic, Singulair
Selexipag Uptravi
Travoprost Generic, Travatan, Travatan-Z
Treprostinil Remodulin, Tyvaso, Orenitram
Zafirlukast Generic, Accolate
Zileuton Zyflo, Zyflo CR
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
Aspirin, acetylsalicylic acid Generic, Easprin, others
Bromfenac Prolensa, Bromday
Celecoxib Celebrex
Choline salicylate Various
Diclofenac Generic, Cataflam, Voltaren
Diflunisal Generic, Dolobid
Etodolac Generic, Lodine
Fenoprofen Generic, Nalfon
Flurbiprofen Generic, Ansaid, Ocufen (ophthalmic)
Ibuprofen Generic, Motrin, Rufen, Advil (OTC), Nuprin (OTC),
others
Indomethacin Generic, Indocin
Ketoprofen Generic, Orudis
Magnesium salicylate Doan’s Pills, Magan, Mobidin
Meclofenamate sodium Generic
Mefenamic acid Generic, Ponstel
Meloxicam Generic, Mobic
Nabumetone Generic
Naproxen Generic (OTC), Naprosyn, Anaprox, Aleve (OTC)
Oxaprozin Generic, Daypro
Piroxicam Generic, Feldene
Salsalate, salicylsalicylic acid jrc Generic, Disalcid
Sodium salicylate Generic
Sodium thiosalicylate Generic, Rexolate
GENERIC NAME AVAILABLE AS
DISEASE-MODIFYING ANTIRHEUMATIC DRUGS
Abatacept Orencia
Adalimumab Humira
Anakinra Kineret
Auranofin Ridaura
Aurothioglucose Solganal
Belimumab Benlysta
Canakinumab Ilaris
Certolizumab Cimzia
Cyclophosphamide Generic, Cytoxan
Cyclosporine Generic, Sandimmune
Etanercept Enbrel
Gold sodium thiomalate Generic, Aurolate
Golimumab Simponi
Infliximab Remicade
Leflunomide Generic, Arava
Methotrexate Generic, Rheumatrex
Mycophenolate mofetil Generic, Cellcept
Penicillamine Cuprimine, Depen
Rilonacept Arcalyst
Rituximab Rituxan
Sulfasalazine Generic, Azulfidine
Tocilizumab Actemra
Tofacitinib Xeljanz
ACETAMINOPHEN AND OTHER ANALGESICS
Acetaminophen Generic, Tylenol, Tempra, Panadol, Acephen, others
Ketorolac tromethamine Generic, Toradol
Tramadol Ultram
DRUGS USED IN GOUT
Allopurinol Generic, Zyloprim
Colchicine Generic*, Colchrys
Febuxostat Uloric
Pegloticase Krystexxa
Probenecid Generic
Sulfinpyrazone Generic, Anturane
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