LOCAL
ANESTHETICS
Local Anesthetics
Historically the first local anesthetic
discovered was the tropane alkaloid
cocaine:
Cocaine is still used in ocular surgery (anesthetic)
and nasal/sinus surgery to decrease post-operative
bleeding due to its vasoconstrictive properties----cocaine addicts
Readily absorbed from the mucous membranes with
good local activity - Rapidly hydrolyzed and
inactivated due to the presence of two ester groups
Addiction includes both physical and psychological
addiction
Desirable Properties of Local Anesthetics
1) Reversible
2) Non-irritating to the tissues
3) Rapid onset of acting
4) Long duration of acting
5) High therapeutic index
6) Effective topically and by injection
7) Proper physical properties
solubility and stability in solution)
(water
LOCAL ANESTHETICS
CHEMISTRY
•It composed of hydrophilic domain
• Which either tertiary or secondary amine
• and hydrophobic domain
• it aromatic residue
• separated by alkyl chain
• The hydrophobic & hydrophilic domains linked
with either ester or amide
• This bonds determine the pharmacology of L.A.
ANESTHETICS
Pharmacological Classes of Local anesthetic
a- Amide
1- Lidocaine (lignocaine) Risk B & C
2- Prilocaine Risk B & C
3- Bupivacaine (Marcain) Risk C
4- Ropivacaine (Naropin) Risk C
5- Dibucaine Risk C
6- Mepivacaine ( Scandonest or Carbocaine) Risk C
7- Etidocaine (Dranest) Risk B
Pharmacological Classes of Local anesthetic
B- Ester
1- Tetracaine (Amethocaine) Risk C
2- Benzocaine Risk C
3- Cocaine Risk C & X
4- Proparacaine (Fluoracaine) Risk C
5- Procaine Risk C
6- Chloroprocaine Risk C
Pharmacological Classes of Local anesthetic
C- Miscellaneous
1- Dyclonine (ketone) Risk C
2- Pramoxine (ether)
MECHANISM OF ACTION
* Block initiation & propagation of action potential
* By preventing the voltage-Dependent increase in
sodium conduction
* Via physical plugging the transmembrane pore
* The binding site is in the inner end of sodium
channel
SEQUENCE OF EVENTS WHICH RESULT IN
CONDUCTION BLOCKADE
1. Diffusion of the base form across the
across the nerve sheath and nerve
membrane
2. Re-equilibration between the base
and cationic forms in the axoplasm
3. Penetration of the cation into and
attachment to a receptor site within the
sodium channel.
4. Blockade of the sodium channel
SEQUENCE OF EVENTS WHICH RESULT IN
CONDUCTION BLOCKADE
5. Inhibition of sodium conduction
6. Decrease in the rate and degree of
the depolarization phase of the action
potential
7. Failure to achieve the threshold
potential
8. Lack of development of a propagated
action potential
9. Blockade of impulse conduction
CONDUCTION OF A NERVE IMPULSE
Ionized
Common features of Local Anesthetics
• Weak bases (pKa > 7.4)
[poorly water soluble]
• Packaged as an acidic hydrochloride
[pH 4-7 now soluble]
• In solution- non-ionized lipid soluble (free
base) AND ionized water soluble (cation)
• Body buffers raise the pH, increase free
base
• lipid soluble form crosses axonal
membrane
• water soluble form blocks sodium
channel
Important Clinical Properties of Local
Anesthetics
• ONSET
• POTENCY
• DURATION OF ACTION
Important Clinical Properties of Local
Anesthetics
• ONSET = pKa
• pKa = pH at which 50% of drug
is ionized
• LA’s <50% exists in the lipid
soluble nonionized form
• Only the nonionized form
crosses into the nerve cell
ROLE of pH and pKa in LOCAL ANESTHETICS
Important Clinical Properties of Local
Anesthetics
Speed of Onset
• low pKa = fast onset
• Bupivacaine 8.1
Lidocaine 7.7
• ? LA action in septic tissue
– acid tissue -> é ionized % of LA
-> slow entry into membrane
-> low concentration of LA for block
Important Clinical Properties of Local
Anesthetics
Anesthetic Potency
• Potency <=> lipid solubility
• Higher solubility <=> can use a
lower concentration and reduce
potential for toxicity [LA]
Important Clinical Properties of Local
Anesthetics
DURATION OF ACTION
Duration <=> protein binding
• Bupivacaine 95%
• Lidocaine 65%
• Procaine 6%
Important Clinical Properties of Local
Anesthetics
CLEARANCE
• ESTERS
hydrolysis via
pseudocholinesterase
• AMIDES
metabolism via hepatic enzymes
Important Clinical Properties of Local
Anesthetics
Absorption of local at site
• LA’s cause some vasodilitation
• LA washout related to blood flow
• LA toxicity related to rate of
absorption via blood flow
Important Clinical Properties of LA’s
ADDITION of VASOCONSTRICTORS
1- Why it is combined with L.A. ?
• Vasoconstriction <=> slows systemic absorption &
increases duration
2- Epinephrine is commonly used in 1 in 200000 to 80000
(5ug-12.5ug/ml)
• Least effective with high lipid soluble LA’s
(bupivacaine/etidocaine)
• Epi may produce distal and systemic effects
ADDITION of VASOCONSTRICTORS
3- The total dose should not exceed 200-500ug
4- Epi-Drugs interaction
•Tricyclic anti-depressant
• Sympatholytic drugs
5- Contraindications ?
-not recommend for digits injection
6- Do you prefere Norepinephrine OR EPINEPHRINE?
Effect of pH on the efficacy
of local anesthetics
1- The activity of local anesthetic is strongly pH
dependent
2- L.A. need to penetrate the nerve sheath and axon to
reach the binding site of sodium channel
3- In acidic media penetration is very poor
7- Inflammed & infected tissues are acidic
ADDITION of Sodium Bicarbonate
•NaHCO3 - é pH & nonionized base
•Speeds onset of block
•1 mEq NaHCO3 per 10 ml Lido/Mepiv
•.1 mEq NaHCO3 per 10 ml Bupiv
Methods of administration of L.A.
1- Infilteration Lidocaine or Bupivacaine
2- Surface
Lidocaine, tetracaine, benzocaine
3- Intravenous regional anesthesia
prilocaine
4- Nerve block
mainly lidocaine ,
lidocaine or bupivacaine
5- Spinal anesthesia
mainly lidocaine , tetracaine
6- Epidural anesthesia
mainly lidocaine , marcain
A. Surface or Topical Anesthesia
1. The oral cavity, pharynx, larynx and tracheobronchial tree provide examples of
mucosal surfaces where local anesthetics are applied topically.
2. A great danger exists in these areas for overdosage since rapid absorption into the
circulatory system may occur and exceed the rate of detoxification of the drug.
3. To avoid this danger use a fine spray with a low concentration of the drug and
limit the volume of solution used.
4. Most often used agents cocaine (4-10%),
tetracaine (1-2%)
and
lidocaine (2-4%)
B. Local Infiltration
1. Used for superficial surgery such as removal of moles, warts, sebaceous cysts, etc.
Also for iv insertion.
2. Use the lowest concentration of drug which will block sensory perception. Large
volumes are generally used.
3. Epinephrine approximately doubles duration of action.
4. Most frequently used agents include lidocaine 0.5-1% and Bupivacaine 0.5%
C. Regional Nerve Block and Field Block
1. Field block: Similar to local infiltration, but the goal is
to specifically interrupt nerve transmission proximal to
the site to be anesthetized.
2. Nerve Block - The goal is to inject local anesthetic into
or about individual nerves or nerve plexuses. Produces
even greater areas distal of anesthesia with a smaller
amount of drug
8. Agents include Procaine (0.5-2.0%); Lidocaine (1-2%);
Mepivacaine (up to 7 mg/kg of 1-3%); Bupivacaine (0.250.75% up to 3 mg/kg ); Tetracatine (up to 1.5 mg/kg of
0.1-0.2%).
D. Intravenous Regional Anesthesia
1. Consists of iv injection of local anesthetic into vein of
exsanquinated extremity with proximal tourniquet.
2. Binding of drug occurs in tissues of extremity
- with tourniquet down (after 15-30 min minimum up time) only
15-30% released into systemic circulation.
3. More effective in upper extremity
4. Lidocaine (1.5 mg/kg of 0.5%) frequently used.
E. Epidural Anesthesia (caudal anesthesia)
1. Epidural space terminates cephically at the foramen magnum.
2. Epidural anesthesia consists of epidural injection into the
lumbar, or less frequently, the thoracic area.
3. Two sites of action
(a) diffusion into subarachnoid space
(b) diffusion into paravertebral area through intervertebral
foramina to produce multiple paravertebral blocks
Continue--. Epidural Anesthesia (caudal anesthesia)
4. Danger of inadvertent subdural and subarachnoid puncture.
* Lidocaine & Bupivacaine for longer action are used.
5. Unlike spinal, no differential zone of sympathetic blockade.
There is a zone of differential motor blockade 4-5 segments less
than sensory block.
6. Other dangers include anterior spinal artery syndrome,
hematoma, infection, and adhesions.
10. Advantages include
(a) blood pressure remains stable
(b) in obstetrical cases, the mother retains motor control of the
abdominal muscles and can assist in the delivery of the fetus
F. Spinal Anesthesia (subarachnoid block)
1. Injection of local anesthetic into the lumbar subarachnoid space
; usually at T2-T3 or T3-T4 interspace.
2. Distribution of the drug in the subarachnoid space determines
the level of anesthesia. This is controlled by:
a) Positioning of the patient
b) Speed of injection
c) Specific gravity of solution
d) Volume injected
3. Nerve fibers affected in the following sequence:
autonomic  sensory  motor
4. Zones of differential anesthesia: sympathetic block segments
higher than sensory - motor segments lower
Continue-- Spinal Anesthesia (subarachnoid block)
5. It causes sympathetic blockade. Most important changes are on
venous side of circulation.
6. Cardiovascular effects: hypotension, bradycardia, ↓preload
↓afterload
7. Respiratory complications: due to ischemic paralysis of medulla
and not usually phrenic paralysis
8. Other dangers:
* chemical transection of cord
* traumatic destruction of a spinal end artery
* traumatic damage of a nerve root & chronic arachnoiditis
* postural headache and infection.
9. Agents frequently employed include: Tetracaine & Lidocaine
Pharmacology of L.A.
•They interfere with function of all organs in
conduction occurs
A- CNS
Stimulate CNS leads to restlessness and may proceed
by clonic convulsion
•Then CNS depression
• Respiratory failure is main cause of death
• Drowsiness is the most complain
Pharmacology of L.A.
B- Cardiovascular
• Decrease mycardium excitability
•Conduction
• Decrease force of contraction
• Hypotension
• These effects occurred in high dose which cause
CNS toxicities
• Arteriodilation
• Rarely occurs in infilteration
Pharmacology of L.A.
C- Hypersensitivity
• Mostly occurred with ester type
• Allergic dermatitis
• asthmatic attack
• Amide almost free of hypersensitivity
Lidocaine 2%
1- DOSE
*OVER 10 YRS: Not exceed 6.6 mg/kg or 300
mg per dental appointment
2- under 10 years 100-150 mg per dental
CH
appointment
H
3
N
3- Drug interaction
-beta blockers
-antiarrhythmia agents
4- Metabolism
O
CH3
N
CH3
CH3
Lidocaine HCl - Xylocaine®,
Octocaine®, Dilocaine®, Duo-Trach®
Also available with or without Epinephrine
CH3
Prilocaine 4%
1- DOSE:
-Less than 10 yrs
CH3
H
N
O
N
H
CH3
Prilocaine HCl - Citanest®
40 mg per setting or less
- greater than 10 yrs and adult 40-80 mg
-Not exceed 400-600 mg in adult
1- Toxicities
* Methemoglobinemia
2- under 10 years 100-150 mg per dental
appointment
BUPIVACAINE 0.5%
1- DOSE:
-Less than 10 yrs
NOT ESTABLISHED
- greater than 10 yrs and adult 9 mg
-Not exceed 90 mg in adult per dental
appointment
CH3
2- duration
H
N
-Nerve block 5-7 hrs
O
CH3
3- Toxicities
- much greater than lidocaine
N
CH3
Bupivacaine HCl - Marcaine®,
Sensorcaine®
MEPIVACAINE
Amide Products: Longer duration of action
CH3
H
N
O
CH3
N
CH3
Mepivacaine HCl - Carbocaine®,
Polocaine®, Isocaine®
1- Indications: Peripheral, transvaginal, paracervical, caudal,
epidural and infiltration nerve block, dental procedures
2- protein bound 78%
3- Warnings:
* NOT recommended for obstetrical epidural anesthesia due
to cardiac arrest and death
* Reserve the 0.75% solution for surgical procedures where
prolonged activity is needed—danger of inadvertent IV
injection and cardiac arrest
ETIDOCAINE
Amide Products: - Longer duration of action
CH3
CH3
H
N
N
O
CH3
CH3
CH3
Etidocaine HCl - Duranest®
1- Indications: peripheral, central or lumbar peridural
nerve block; intra-abdominal/pelvic/lower
limb/ceasarean section surgery; caudal or maxillary
block
2- Onset of action 3-5 minutes
3- with a duration of action of 5-10 hours
4- surprisingly epinephrine addition does NOT increase
the duration—why?----Partition coefficient is 7050X of
procaine---94% protein bound
ROPIVACAINE
Amide Products: - Longer duration of action
CH3
H H
N
O
CH3
N
CH3
Ropivacaine HCl - Naropin®
1- Indications: local or regional anesthesia for surgery,
post-operative pain management and obstetrical
procedures
2- Avoid rapid administration of large doses---use
fractional or incremental administration
3- ideal for continuous infusion for epidurals during birth
4- Onset of action is 10-15 minutes
5- with a duration of action of 2-8 hours---safe to use this
as an epidural product for up to 24 hours
CH3
O
TETRACAINE
O
Ester Products:
N
CH3
HN
CH3
Tetracaine HCl - Pomntocaine®
1- Indications: Spinal anesthesia including high, median,
low and saddle blocks including prolonged action of 2-3
hours
2- Slower onset of action than procaine but duration is 2-3
hours ------ can increase to 3-5 hours by including
epinephrine
3- This drug should not be used in children due to a lack of
safety data
COCAINE
(1)- Mechanism of action
A- Blocks sodium channel
B- inhibit NE UPTAKE-1
(2) Direct vasoconstrictor action and potentiation sympathetic
system
(3) Extensive cardiovascular actions
(4) Powerful CNS stimulant
(5) Considered a narcotic with potentially for psychic dependence
(6) Used for surface anesthesia in 1.0-10.0% solutions,
occasionally with epinephrine
(7) Metabolized by esterases and hepatic enzymatic degradation;
t1/2 after oral or nasal administration, approximately 1 hour
LOCALLY ACTING AGENTS
LOCAL HAEMOSTATIC AGENTS
LOCALLY ACTING AGENTS
LOCAL HAEMOSTATIC AGENTS
1- Sympathomimetic
•Epinephrine with LA
•Epinephrine-imprignated cord to retract and control
gingival haemorrhage
2- Astringents & STYPTICS
-They react with proteins of oral cavity and make
protective layer:
•Aluminum chloride (Sansilla)
–Example of Styptics : Silver nitrate rod
LOCAL HAEMOSTATICS
•Aluminum chloride retraction cord (HEMODENT
25%)
• Tannins: Pyralvex
-it is an oral paint contains tannic acid and salicylic acid
- It is used for mild peri-oral lesion & less effective in oral lesion
3- Mechanical haemostatics
•They forms matrices in which blood cells and fibrin
can trapped
•They are more effective than astringent, styptics or
sympathomimetics
• in controlling capillary oozing & surface bleeding
Types of mechanical haemostatics
1- Absorbable gelatin (Gel Foam)
* Advantages of absorbable gelatin
-It does not interfere with the followings:
•Thrombin
•Epithelization
•Bone regeneration
2- Oxidized cellulose (Oxycel &Novocel)
• It has high affinity to haemoglobin & it is form of gauze of cotton pellets
•It is more effective than Gelfoam
•It interfere with followings:
- Epithelization & bone regeneration (not suitable for packing in bone fracture
- Inactivates thrombin
3- Oxidized regenerated cellulose (Surgicel)
•Advantages
- It does not interfere with epithelization
-Therefore , it is suitable for surface dressing
•Disadvantages
- It interferes with bone regeneration
- Inactivates thrombin
3- Microfibrillar collagen hemostat (Avitene)
It is in the form of powder & used to control bleeding after oral surgery
* Advantages
- It does not interfere with:
* epithelization
* bone regeneration
* activity of thrombin
SYSTEMIC HAEMOSTATICS
HAEMOSTATIC SYSTEMS
•1- Formation of fibrin via clotting factors
2- Fibrinolysis
3- Platelets aggregation
4- Blood vessels (PGE12)
Examples of systemic haemostatic agents
VITAMIN K
•Role of vitamin K in clotting system
- Vit K is necessarly for final stage of clotting factors synthesis
such as prothrombin ,factor vii, ix &x
Premature
Clotting factors
Mature clotting factor
CAUSES OF VIT K DEFICIENCY
1- Obstructive jaundice
2- malabsorption
3- Reduced GIT flora
-Rarely after broad spectrum antibiotics
CLINICAL USES OF VITK
1-Reverse bleeding induced by oral anticoagulant
2- Inadequate vit k availability
3- new born baby
VIT K Preparations
vit k1 (phytomenandione) konakion
- it is lipid soluble and injected in new born baby
-onset within 12 hours
-Menadiol sodium phosphate (vitk3)
• it is water soluble
• onset 24 hrs
• prefered in malabsorption or obstructive jaundice
•It has tendency to induce hemolytic anemia
TRANEXAMIC ACID
1- MECHANISM OF ACTION
•Prevents plasminogen not to attach to fibrin
• resulting in inhibition fibrinolysis
• inhibits the proteolytic activity of plasmin
2- Clinical uses
•Use as Mouthrinse 4.8% to prevent bleeding in hemophiliac &
patient under warfarin due to dental extraction
• ORAL: 25 MG/KG FOR 2-8 DAY in haemophiliac
•Hereditary angioedema & menorrhagia
•Thrombolytic over dose
TRANEXAMIC ACID
3- pregnancy Risk factor B
•to prevent bleeding in hemophiliac & patient under
warfarin due to dental extraction
3- Adverse effects
•If taken orally
-GIT Disturbances such as diarrhea
-Hypotension
-Thrombosis
-Blurred vision requires regular eye examination
--Regular liver function tests in long term oral use for hereditary
angioedema
AMINOCAPROIC ACID
1- Mechanism of action
•Inhibits the activation of plasminogen to plasmin
2- Clinical uses
•Treatment of excessive bleeding from
fibrinolysis
• 5-30
g/day in divided dose at 3-6 hrs interval
AMINOCAPROIC ACID
3- pregnancy Risk factor C
•4- Adverse effects
•Hypotension
• bradycardia
•Arrhythmia
•Myopathy
•GIT irritation
APRPTONIN (Trasylol)
It is inhibitor of plasmin (plasmin causes fibrin lysis)
•CLINICAL USES
- Over dose of thrombolytic drugs such streptokinase
- Hyperplasminia as a result of mobilization and
dissection of malignant tumor
SIDE EFFECTS
-Hypersensitivity
--localized thrombophlebitis
ETHAMSYLATE OR ETAMSYLATE
DICYNENE®
1- Mechanism of action
•CORRECT ABNORMAL PLATELETS ADHESION
2- Clinical uses
•Short term use in blood loss in menorrhagia(500mg tablets four
times daily during menses
•Prophylaxis and treatment of periventricular haemorrhage in low
birth weight infants (i.v. or i.m.)
3- Clinical uses
- Rashes , Nausea and Headache
DESMOPRESSIN ACETATE(Stimate®)
1- Mechanism of action
•Enhance reabsorption of water in kidney
•Increase Von Willebrand factor & factor viii
2- Clinical uses
•Control bleeding in mild hemophilia & Von
Willebrand disease during dental extraction
•Diabetes insipidus
•Nocturnal enuresis
•CAUTION : Avoid overhydration (it has ADH activity)
DESMOPRESSIN ACETATE
3- pregnancy Risk factor B
•4- Adverse effects
•Facial flushing
• Dizziness
•Nasal congestion
•hyponatremia
•Water intoxication
BLOOD PRODUCTS
1- Anti-hemophilic factor (Kogenate®)
•It is factor viii derived from recombinant DNA
- CLINICAL USES
- Control bleeding in hemophilia A
- Life threatening haemorrhage
2- FACTOR VIIa (NovoSeven®)
-It is recombinant DNA
CLINICAL USES:
* PATIENT WITH INHIBITORS TO FACTORS VIII & IX
BLOOD PRODUCTS
3- FACTOR IX (Replenine®)
•- CLINICAL USES
- it indicated in patient with factor ix deficiency (Hemophilia B)
- CAUTION : Risk for thrombosis
FIBRIN GLUE (Beriplast)
1- Composition
•Two separate solutions
a- fibrinogen
b- thrombin & calcium
•It is completely reabsorb within 2 –4 weeks
•Some products contain
-tranexamic acid or aprotonin
2- Effective in preventing bleeding in bleeding
disorders
Management of patient under warfarin
1- Minor surgery
•Use tranexamic mouth rinse
• without adjustment of anticoagulation if INR
is less than 4
2- Major surgery
•Stop warfarin preoperative
• use low molecular weight heparin
Intrinsic Pathway
Extrinsic Pathway
Tissue Injury
Blood Vessel Injury
Tissue Factor
XIIa
XII
Thromboplastin
XIa
XI
IXa
IX
Xa
X
Factors affected
By Heparin
VIIa
Prothrombin
Vit. K dependent Factors
Affected by Oral Anticoagulants
Fibrinogen
XIII
VII
X
Thrombin
Fribrin monomer
Fibrin polymer
ANTI-COAGULANTS
1- Drugs inhibit vit k actions (oral anticoagulant)
-By prevents maturation of the clotting factors
- slow onset (3 days)
2- Drugs directly acting on the clotting factors
- Rapid onset (Heparin)
3- Drugs inhibit platelets aggregation
4- Fibrinolytic drugs (dissolve clot)
ORAL ANTI-COAGULANTS
WARFARIN (Coumadin®)
1- CLINICAL USES OF WARFARIN
•Prophylaxis and treatment of venous
thrombosis such as :
- Deep vein thrombosis (DVT)
- Atrial fibrillation
- prosthetic cardiac valves with antiplatelets
- thromboembolic disorders such post MI
or Stroke and embolism
ORAL ANTI-COAGULANTS
WARFARIN (Coumadin®)
2- MOA OF WARFARIN
•Warfarin interferes with hepatic synthesis of
vit K-dependent factors (ii, vii, ix, x)
• PREVENT RECYCLING OF VIT K by
inhibiting reductase enzyme which convert
epoxide vit K to vit K
3- ONSET OF WARFARIN
-Within 36-72 hours
Mechanism of action
Descarboxy Prothrombin
Prothrombin
Reduced Vitamin K Oxidized Vitamin K
NAD
NADH
WARFARIN
ORAL ANTI-COAGULANTS
WARFARIN (Coumadin®)
4- MONITORING ITS EFFICACY
•Prothrombin time expressed by :
•International Normalized Ratio (INR)
determined daily initially then at longer intervals depends on
the response
• INR 2-2.5 For prophylaxis of DVT, AF, Cardioversion,
dilated cardiomyopathy, MI, Rheumatic valve disease
• INR 3.5 For recurrent DVT , pulmonary embolism and
mechanical prosthetic heart valve
ORAL ANTI-COAGULANTS
WARFARIN (Coumadin®)
4- ADVERSE EFFECTS OF WARFARIN
• The main is hemorrhage
•Skin necrosis in patient with protein c & s
deficiency
5- PREGNANCY
•AVOID RISK FACTOR D
•REPLACED BY HEPARIN
ORAL ANTI-COAGULANTS
WARFARIN (Coumadin®)
6- DRUG INTERACTION
•INCREASE EFFECTS:
- NSAIDs
- Sulfa drugs
- cimetidine
•Decrease effects
liver enzyme inducer such as:
-phenobarbitone, rifampicin, phenytoin
HEPARIN
1- RAPID ONSET, inject only S.C. OR I.V.
2- CLINICAL USES
•Preventive and treatment of thromboembolic
disorders such as DVT, MI, pulmonary emobolism
• patient undergoin general surgery (low dose)
• orthopedic surgery
• unstable angina & Pregnancy
•Extracorporeal circuits such as hemodialysis &
cardiopulmonary bypass
HEPARIN
3- DOSES OF HEPARIN
• PROPHYLAXIS DOSE
A- Post-operative & MI 5000 units s.c. every 8-12
hrs
B- pre-surgery 5000 units 2 hours before surgery
C- Pregnancy 5000 -10,000 units every 12 hours
(REQUIRED APTT monitoring
HEPARIN
4- MECHANISM OF ACTION OF HEPARIN
• Heparin enhances the activity of anti-thrombin
• It inhibits factor X in small dose
5- MONITOR THE EFFICACY
Prophylaxis dose does NOT require
APTT (Activated partial thromboplastin)
APTT should be in the ranges 1.5-2.5
Heparin mechanism of action
Heparin
Antithrombin III
Thrombin
HEPARIN
6- ADVERSE EFFECTS
•Bleeding if APTT more than 3 or
- impaired hepatic or renal functions
•Thrombocytopenia
• Osteoporosis (long term use)
• skin necrosis & hypersensitivity
• It may induce hyperkalemia by inhibition of
aldosterone secretion
•7- ANTIDOTE OF HEPARIN
- Protamine sulfate 100mg neutralizes 100 unit
LOW MOELCULAR WEIGHT
HEPARIN
1- EXAMPLES:
•Enoxaprin , Dalteparin & Ardeparin
2- Advantages
A- Do not required APTT monitoring
B- because it has little effects on antithrombin but it
potent inhibition on factor Xa
•C- Long duration (once daily)‫اىل هنا‬
HEPARINOID
1- EXAMPLES:
•DANAPAROID
2- MOA : inhibits Xa & IIa factors
3- Advantages
A- Low incidence of thrombocytopenia
* therefore it can be used in patient had history of
thrombocytopenia due to heparin
4- Disadvantage : not effectively antagonized by
protamine sulfate
ANTIPLATELETS AGGREGATION
1- EXAMPLES:
•Aspirin
•Clopidogrel
•Dipyridamole
•Ticlopidine
•Abciximab
•Eptifibatide
•Tirofiban
ANTIPLATELETS AGGREGATION
2- THEY DECREASE PLATELETS
AGGREGATION and inhibit thrombus formation in
the arterial circulation where anti-coagulants have
little effects.
3- General Clinical uses
•cerebral vascular diseases such as Transient
ischemic attack (TIA)
•Unstable angina
•Post MI
•Coronary artery bypass surgery & Angioplasty
ASPIRIN
1- CLINICAL USES OF ASPIRIN (small dose)
Prophylaxis for MI (75mg- 81mg-160-325 mg)
• Transient ischemic episode & stroke (600 mg twice daily)
•Following coronary bypass surgery
• percutaneous transluminal coronary angioplasty
•Eclampsia in small dose ? Unlabelled
2- MOA : Irreversibly inhibits COX (cyclooxygenase)
leading to inhibit thrombane A2 in platelets
ASPIRIN
3- ADVERSE EFFECTS OF ASPIRIN
•GIT upset may develop ulcer
•May precipitate bronchial asthma in patient has histry of
bronchial asthma
• Some patient develop subcutaneous hemorrhage (as spots)
4- contraindication
* children under 12 years and breast feeding mother
* active peptic ulcer
* bleeding disorders
5- Caution:
* asthma , pregnancy
CLOPIDOGREL (PLAVIX)
1- CLINICAL USES
*Reduces atherosclerosis events such as MI, Stroke
& peripheral artery diseases
•Prevent of thrombotic complications after
coronary stenting
•Acute coronary syndrome such as unstable angina or non-Q-wave
MI
• It can be used instead of aspirin if patient allergic to aspirin
2- MOA
It blocks the ADP receptors in platelets which prevent fibrinogen
CLOPIDOGREL (PLAVIX)
3- ADVERSE EFFECTS
•Bleeding (GIT & Brain) & leukopenia
•GIT upset such as gastritis (less than aspirin)
4- CONTRAINDICATIONS
•Active bleeding avoid first few days after MI & 7
days after stroke
•Not recommend for angioplasty
•Stop it 7 days before surgery
TICLOPIDINE (TICLID)
1- CLINICAL USES
•It is reserved for patients who are intolerant to
ASPIRIN
•Prophylaxis of major ischemic events in patient
with a history of ischemic stroke
•Adjuvant therapy with aspirin following coronary
stent to reduce stent thrombosis
2- MOA
Similar to plavix
TICLOPIDINE (TICLID)
3- ADVERSE EFFECTS
•Bleeding
•Neutropenia , agranulocytosis & pancytopenia
•Thrombotic thrombocytopenic purpura
•Increases liver enzymes
•Jaundice
•hyperlipidemia
DIPYRIMADOLE (PERSANTIN)
1- CLINICAL USES: Maintains patency after surgical
grafting include coronary artery bypass
•Used with Warfarin to decrease thrombosis in patient
after artificial heart valve replacement
•Use with ASPIRIN to prevent thromboembolic disorders
•It can be given 2 days prior open heart surgery
2- MOA: Inhibits adenosine deaminase &
phosphodiesterase leading to accumulation of:
•Adenosine , adenosine nucleotides These inhibit platelets
aggregation
DIPYRIMADOLE (PERSANTIN)
3- ADVERSE EFFECTS
•Hypotension
•Headache
•Increased bleeding during or after surgery
•Worsening symptoms of coronary heart disease
4- CAUTIONS
•Rapidly worsening angina
•Aortic stenosis
ABCIXIMAB(REOPRO)
1- CLINICAL USES
•Adjunct to percutaneous transluminal coronary
angioplast
•Prevention of acute ischemic complications in
patients at high risk for abrupt closure of treated
coronary vessels
•Use with heparin in unstable angina
2- MOA
It binds with platelets iib/iiia receptors preventing
FIBRINOLYTIC DRUGS
1- EXAMPLES
•Alteplase (recombinant DNA tissues plasminogen
activator)
•Reteplase
•Streptokinase
•tenecteplase
ALTEPLASE (ACTIVASE)
1- CLINICAL USES
•Management of acute MI
•& pulmonary embolism for lysis of thrombi
2- MOA
* It initiates local fibrinolysis by binding to fibrin
in clot and converts entrapped plasminogen to
plasmin
ALTEPLASE (ACTIVASE)
3- adverse effects
•Multiple emboli
•Arrhythmia due to cardiac reperfusion
•bleeding
ANTICOAGULANT DRUGS TO TREAT
THROMBOEMBOLISM
Drug Class
Anticoagulant
Parenteral
Prototype
Heparin
Action
Inactivation of clotting
Factors
Effect
Prevent venous
Thrombosis
Anticoagulant Warfarin Decrease synthesis of
Oral
Clotting factors
Prevent venous
Thrombosis
Antiplatelet
drugs
Aspirin
Prevent arterial
Thrombosis
Thrombolytic
Drugs
Streptokinase Fibinolysis
Decrease platelet
aggregation
Breakdown of
thrombi
ORAL PROTECTIVE AGENTS
1- CLINICAL USES :Protectives are used for
non-specific mouth ulceration such as aphthus
ulcer
•It is usually combines with local anesthetic and
antiseptics such as [ORAL B®] composed of:
-lidocaine, cetylpyridinium, menthol & cineole
2- examples of oral protectives
•Carmelose gelatin (ORABASE®)
•Choline salicylate dental gel (BOJELA®)
•Benzdamine (DIFFLAM®)
ANTI-SEPTIC MOUTH RINSE
1- Chlorhexidine
2- Cetylpyridinium chloride & Triclosan
3- phenols
4- Hexitidine (oraldene mouth rinse)
5- Domiphen bromide (Bradoral lozenges)
CHLORHEXIDINE 0. 2% CORSODYL® & Hexidine®
1- PROPERTIES OF CHLORHEXIDINE
* It is used in 0.2% as mouth rinse
* It is the most effective mouth rinse
•It Reduces gingival pathogen
•The anti-microbial last several hours
• it is effective in gingivitis associated with bleeding &
PUS
• it cause permanent stain of restorative
•But reversibly stains natural teeth & dorsum of the
tongue
CHLORHEXIDINE 0. 2% CORSODYL® & Hexidine®
2- MOA
•It broad spectrum antiseptic
• its bacterial action exerts by disruption of bacterial
membrane of both gram positive & negative bacteria
3- CLINICAL USES
•Oral hygeine especially if there heavy plaque
•Inhbition of plaque formation
•Gingival infection
•It may help in recurrent aphous ulcer
CHLORHEXIDINE 0. 2% CORSODYL® & Hexidine®
4- ADVERSE EFFECTS
•Reversible brown staining of natural teeth
•Irreversible brown staining of artificial teeth
(restorative)
•Idiosyncratic Epithelial irritation of oral
cavity
•Rarely parotid gland swelling
•Inflammation of salivary glands
• It may mask periodontitis
CETYLPYRIDINIUM CHLORIDE0.5%
SCOPE®
1-PROPERTIES
•It is surface active agent
•It is ineffective in present of bleeding, sputum
& pus
•It is weak antibacterial
2- MOA
•It acts as detergent which help removal of
bacteria & Disrupts the membrane of bacteria
PHENOLS
CHLORASEPTICS®
•It contains phenol
• Available as spray , mouth rinse & lozenges
2- ADVERSE EFECTS OF PHENOL
•Nephrotoxicity if exceeds the dose
• It inhibits polymerization of resin restoration
• It damage the cavity liner
Agents used in dental procedures
1- HYDROGEN PEROXIDE
• It is used for root canal irrigation
• Its action is mediated by releasing nascent
oxygen which kills bacteria
2- SODIUM HYPOCHLORITE 5%
•It is used to irrigate root canal
• It is irritant to mucous membrane of oral cavity
Agents used in dental procedures
3- OBTUNDANTS
A- DEFINTION OF OBTUNDANT
Chemical precipitates cellular protein of nerve fiber
Causing paralysis of nerve fiber which leads to
diminish sensation of dentine
B- IDEAL PROPERTIES OF OBTUNDANTS
•Acts without initial pain
•Does not stain teeth, dentine or enamel
•It penetrates quickly through the dentine but not too
deep otherwise it may lead to inflammation of the
pulp
Agents used in dental procedures
C- MOA OF OBTUNDANT
•It precipitates cellular protein of nerve fiber
• Causing paralysis of nerve fiber which leads
to diminish sensation of dentine
D- CLINICAL USES
Obtundants allow painless excavation
EXAMPLES OF OBTUNDANTS
1- Eugenol
•It causes initial stimulation followed by paralysis
of nerve
2- Zinc chloride
•It stains teeth and has poor penetration
3- Absolute Alcohol
•It requires the oral cavity to be dry
4- Cresote
Agents used in dental procedures
4- MUMIFYING AGENT
A- Definition of mumifying agents
•It is a chemical causes aseptic dryness and
hardness of pulp tissues and root canal
•They have astringent and antiseptic
properties
• All mumifying agents are obtundant but not
all obtundants are mumifying agents
B- CLINICAL USES
* They applied when pulp or content of the
root can NOT be removed
EXAMPLES OF MUMIFYING AGENTS
1- Iodinated cresol
2- beta-naphthol 1% in alcohol
3- iodoform
4- Ammonical silver nitrate (it stains teeth)
5- Forlmaldehyde
FLOURIDE PREPARATIONS
1- NATURAL SOURCE OF FLOURIDE
•Water (1PPM iseffective cincentration)
• Fish (20 PPM)
• Tea (100 PPM)
2- METABOLISM & ABSORPTION OF FLOURIDE
•Calcium and magnesium decrease flouride absorption
• Flouride concentrates in bone & teeth
•In children, the flouride concentrates in bone and
teeth than elderly
FLOURIDE PREPARATIONS
3- MECHANISM OF ACTION OF FLOURIDE
•Flouride converts hydroxyapatite to
FLOUROAPATITE which leads
- Makes the apatite structure more stable which
improve CRYSTALLINITY of the structure
- FLOUROAPATITE is less soluble in acid
- FLOURIDE inhibits bacteria enzymes
EXAMPLES FLOURIDE PREPARATIONS
1- ACIDULATED PHOSPHATE FLOURIDE (APF)
• It contains flouride between 10,000 to 20,000 PPM
• It is the preparation of choice for professional
flouride application
• It benefits last 2-3 years after application on the teeth
• Contact time upon application is (1-4 minutes)
depends on the type of preparation.
EXAMPLES FLOURIDE PREPARATIONS
ACIDULATED PHOSPHATE FLOURIDE (APF)
A- Advantages of APF
• Stable in solution
• Not irritant to gingiva
• Agent of choice for professional application
B- Disadvantages of APF
• APF is acidic solution may affect CEMENTUM
• Not suitable for dentrifrices
EXAMPLES FLOURIDE PREPARATIONS
2- SODIUM FLOURIDE
• It is available in tablets such as Zymaflour® 1mg
• 0.25 MG (1/4 Tablet) per day required for 5-16 years old
A- Advantages of sodium flouride
•Stable in solution
• Neutral solution (Ph 7.0)
B- Disadvantages of sodium flouride
• It is NOT compatible with many abrasives in
tooth-paste because:
- it reacts with CALCIUM & PHOSPHATE
- and becomes insoluble compound
EXAMPLES FLOURIDE PREPARATIONS
MOUTH RINSE CONTAINS SODIUM FLOURIDE
• It is more effective than MFP present in tooth-paste
• but combination of sodium flouride mouth rinse with
dentrifrices are more effective than either product alone
• Mouth rinse containing FLOURIDE 100 PPM
recommend to use it twice daily
• Mouth rinse containg 250 PPM used once daily
• mouth rinse contains 1000 ppm used once weekly or
every other week (‫هنا‬
EXAMPLES FLOURIDE PREPARATIONS
3- SODIUM MONOFLOUROPHOSPHATE (MFP)
• It is commonly used in tooth-paste
A- Advantages of (MFP)
•Stable in various pH
• It is compatible with tooth-paste abrasives
B- Disadvantages of (MFP)
• It is weak flouride source
• Efficacy is questionable
EXAMPLES FLOURIDE PREPARATIONS
4- STANNOUS FLOURIDE
A- Advantages of STANNOUS FLOURIDE
•Both cation & anion are effective
B- Disadvantages of STANNOUS FLOURIDE
• Unstable in solution
• Stain teeth
• bitter taste
TOXICITY OF FLOURIDE
A- ACUTE TOXICITY
•It is common during applying APF IN CHILDREN
•Fatal dose 50-225 mg/kg
• Symptoms of toxicity
- Nausea, vomiting
- Abdominal pain
- Sweating
- Convulsion
- Death
TOXICITY OF FLOURIDE
B- CHRONIC TOXICITY
It is occurs at concentration ranges between 2-8 ppm
consumed in drinking water
• Flourosis occurs when the crown of permanent teeth
are forming
• DEFINITION OF FLOUROSIS
- Is hypoplastic defect resulting from disturbance in
the function of AMELOBLAST (enamel) during teeth
development
Symptoms of chronic toxicity
- endemic flourosis is associated with
- mottled enamel & deformed teeth
DENTRIFERICES
1- It is a pharmaceutical preparations are used
locally on the teeth & oral cavity to perform the
followings:
•Clean
•Polish
•Prevent bacterial fermentation
•Prevent gingivitis
•Prevent dental caries
EXAMPLES OF DENTRIFERICES
•TOOTH PASTE
•POWDER
•LIQUID IN FORM OF SOLUTION
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
1- Abrasive
•It is am inert , insoluble and finely powdered
•Examples of abrasives
- calcium pyrophosphate
- dicalcium phosphate
•Main action of abrasive
- it cleans and polish
- removes stain and plaque
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
2- Flavouring agents
•They have the following properties:
• good odor
• mild antiseptic
• mild local anesthetic
• counter irritant
•Examples of flavouring agents
- peppermint
- cinnamon
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
3- SWEETNER
•Examples of sweetner
- Saccharin
- aspartame
- glycerin
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
4- HUMICTANT
• FUNCTIONS OF HUMICTANTS:
- Keep moisture of the tooth-paste
- prevents dryness of the tooth paste
- it gives plasticity to the tooth-paste
- it has demulcent action on the gum
•Examples of sweetner
-GLYCERIN
- SORBITOL
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
5- DETERGENT & FOAMING AGENTS
• FUNCTIONS OF HUMICTANTS:
- they lower surface tension(emulsifying agents)
- emulsify fatty materials
- Promote good penetration and mixing of
constituents of the tooth-paste
- they assists in removal mucous deposit and
debris
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
EXAMPLES DETERGENT
& FOAMING AGENTS
Examples of detergent and foaming agents:
- sodium lauryl-sulfate
- magnesium lauryl-sulfo-acetate
- monoglyceride
- dioctyl-sodium-sulfo-succinate
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
6- THICKENING AGENTS
•FUNCTIONS
- Improve & maintain the consistency of the paste
- they prevent separation of the tooth-paste
contents under extreme temperatures (high & low)
Examples of thickening agents:
- glycerin starch
- carboxy-methyl-cellulose
- sodium alginate
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
7- PRESERVATIVES
•FUNCTIONS
- prevent bacterial , fungal growth which prevents
fermentation of the tooth-paste
Examples of preservatives:
- methylparaben 0.15%
- propylparaben 0.15%
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
8- FLOURIDE
•FUNCTIONS
- It is anti-cariogenic agent and significantly reduces
caries
- it is commonly used sodium-mono-flourophosphate (MFP) because :
* it is stable at various Ph
* compatible with many abrasives
TOOTH-PASTE
MAIN INGREDIENTS OF TOOTH PASTE
9- DESENSITIZING AGENTS
•Not present in most of tooth-paste
• examples of desensitizing agents
- Potassium nitrate
- Potassium oxalate
GLUCOCORTICOIDS
•Adrenal steroids are synthesised from zona
fasciculata of adrenal cortex as needed
•It is stimulated by ACTH which is release from
pituitary gland
• ACTH is regulated by CRF in hypothalamus
•Glucocorticoids is synthesised from chlosterol
• Stress also stimulate glucocorticoids
Adrenal Gland
Glucocorticoids
MECHANISM OF ACTION
•Glucocorticoids bind with specific receptors in
the cytoplasms
• The complex binds with DNA which leads to:
* prevent transcription such as
- COX-2
- Block Vit D3 –mediated induction of
osteocalcin
* or induce particular gene
- Such as LIPOCORTIN-1 & Tyrosine hydroxylase
MECHANISM OF ACTION
•Glucocorticoids bind with specific receptors in
the cytoplasms
• The complex binds with DNA which leads to:
* prevent transcription such as
- COX-2
- Block Vit D3 –mediated induction of
osteocalcin
* or induce particular gene
- Such as LIPOCORTIN-1 & Tyrosine hydroxylase
Direct effects come from receptor
binding
CBG
albumin
HSP70
IP
IP
HSP70
HSP90
HSP90
transcription
GRE
GRE GRE
Altered cellular function
protei
n
Example of indirect inhibition of gene induction
Cytokines
COX-2
NOS-2
NF-B
NF-B
TNF-  TNFR
NF-B
IB
GCR
IB
GC
IB 
GCR
GLUCORTICOIDS
(PAF)
Phospholipase A2
Pharmacological action of
glucocorticoids
1- General effects on metabolism
- Water, edlectrolyte balance and organ systems
2- Negative feedback on Pituitary & Hypothalamus
3- Anti-inflammatory and immunosuppressive
GENERAL METABOLIC & SYSTEMIC
EFFECTS
1- Carbohydrate and protein metabolism
2- Decrease glucose utilization
3- increase gluconeogenesis which may induce
hyperglycemia
4- Decrease in protein synthesis breakdown
5- It has permissive effects on the lipolytic response to
catecholamines
GENERAL METABOLIC & SYSTEMIC
EFFECTS
6- Redistribute fat in large dose
7- It has some mineralocorticoids activities
8- Increase calcium secretion & decrease its absorption
9- Reduce function of osteoblast
10- and Increase the activity of osteoclast (Digest bone)
* by hypocalcemia-induced parathyroid hormone secretion
* These lead to osteoporosis
NEGATIVE FEEDBACK EFFECTS
1- Both endogenous and exogenous glucocorticoids
have a negative feedback on CRF & ACTH
2- The inhibitory effects of endogenous glucocorticoids
due to exogenous steroids is prolonged (months)
3- lipocortin-1 play negative feedback on hypothalamus
and pituitary
3- and leads to atrophy of adrenal cortex
Atrophy due to negative feedback
inhibition of ACTH
3rd
vent
(-)
(+)
CRF neuron
IL-1
IL-2
IL-6
TNF-
(+)
immune
system
(-)
(-)
ACTH
(+)
Adrenal
d
Cortisol
administered glucocorticoid
Anti-Inflammatory
1- Inhibit production of prostaglandins due to
decrease the expression of COX-2
2- inhibit early and late manifestation of
inflammation
3- Which leads to prevent chronic inflammation
4- Decrease fibroblast which leads to inhibition
of chronic inflammation (less fibrosis) and
wound healing and repair
Continue anti-inflammatory effects
5- Inhbits Phospholipase A2 by inducing
lipocortin which leads to:
•Decrease production of PAF
• Arachidonic acid which is the
precursor for:
* Production of prostaglandins
* Leukotrienes (slow reacting substance of
anaphylaxis
Continue anti-inflammatory effects
6- Decrease histamine release
7- decrease production of nitric oxide
8- Decrease production of PAF
9- Decrease the production of GM-CSF which
is essential for production of:
-platelets
-Monocyte, neutrophil & eosinophil
-RBCs
IMMUNOSUPPRESSIVE EFFECTS
* Drug binds only to certain targets
•Supress initiation generation of immune
response
•It is non-selective
** Supress cellular immunity
** and Humeral
* It induces apoptosis of lymphocyte
ADVERSE EFFECTS OF
GLUCOCORTICOIDS
• Adverse effects occur after prolonged used
• or large dose
1- Supress response to infection or injury
2- Impair wound healing
3-Slight incidence of peptic ulcer
4- Cushing’syndrome
5- Osteoporosis
6- Hyperglycemia
ADVERSE EFFECTS OF
GLUCOCORTICOIDS
7- Muscle wasting
8- Inhibit growth in children
9- Euphoria & Psychosis
10- decrease blood supply to bone leading to
necrosis the head of the femur
inhalation
ADVERSE EFFECTS OF
GLUCOCORTICOIDS
11- cataract
12- glaucoma
13- increase in intracranial pressure
14- disorder of menestrual cycle
15- oral thrush especially when taken by
inhalation
16- Adrenal insufficiency
* It may take two months or more up to 18
months
GUIDELINES FOR
GLUCOCORTICOID THERAPY
1- It should based on the severity of diseases
2- Dosage, frequency, duration & preparation
influence the response and adverse reactions
3- Administered locally when possible inorder to
minimize the adverse effects & efficacy
4- The pharmacological dose should be tapered in order
to avoid adrenal crisis
CLINICAL USES OF
GLUCOCORTICOIDS
1- Replacement therapy (Addison’disease
2- Asthma
3-Topically in various inflammatory condition
-skin , eye, nose
4- Post neurosurgery &head and spinal injury
5- Autoimmune diseases
-Inflammatory bowel disease
- haemolytic anemia
CLINICAL USES OF GLUCOCORTICOIDS
6- Anti-cancer with other cytotoxic agents
7- Autoimmune diseases
8- Inflammatory diseases
- haemolytic anemia
- organ transplant with other
immunosuppressants
9- Anti-emetic in conjunction with other antiemetic
GLUCOCORTICOIDS USES IN
DENTAL PRACTICE
10- Temporary relief of sympton associated with
Oral inflammation and ulcerative lesion such as
A- Recurrent aphthus stomatitis
Triamcinolone acetonide (Kenalog orabase)
B- Erosive lichen planus
-- Dexamethasone
C- Major aphthae
- Kenalog orabase
CLASSIFICATION OF GLUCOCORTICOIDS
DURATION OF ACTION
Pregnancy Risk
Potency
Short (8-12hrs)
- Hydrocortisone
- Cortisone
C
D
1
0.8
C
C
B
C
5
4
4
5
Intermediate (18-36)
- Methylprednisolone
- Prednisolone
- Prednisone
- Triamcinolone
CLASSIFICATION OF GLUCOCORTICOIDS
Duration of action
Pregnancy Risk
Potency
Long acting (36-54)
- Betamethasone
C
25
- Dexamethasone
C
25-30
INHALER GLUCOCORTICOIDS
DRUG
Pregnancy
Risk
Potency
Compare to
dexamethasone=1
Fluticasone
C
1200
Budesonide
C
980
C
600
(Pulmicort, Rhinocort)
Beclomethasone
(Beconase, Beclovent)
Triamcinolone
330
SEE YOU NEXT TIME
Thank you