UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT
ANTIPYRETICS
PYREXIA
- aka FEVER
- Increase in the body temperature beyond the
normal range
- Important part of body’s defense against
infection
PYREXIA
- Substances that can produce pyrexia or fever.
- Most common are endotoxins, which are
lipopolysaccharides (LPS) produced by
Gram-negative bacteria (e.g. E. coli)
ANTIPYRETICS
- Agent that reduces fever or pyrexia.
- Every enzyme has an active site.
PHARMACOKINETICS
- ABSORPTION: stomach, intestinal mucosa
- DISTRIBUTION: blood plasma
- METABOLISM: liver
- EXCRETION: urine, bile
MECHANISM OF ACTION
- During infection and tissue injury
- Block the action of Prostaglandin production
in hypothalamus and reduce temperature
- FEVER -> PYROGENS (Interleukins,
TNF-alpha & Interferones) -> acts directly on
the thermoregulatory centers in Hypothalamus
-> Increase Body Temperature
- Note: This is associated with increase in brain
prostaglandins (pyrogenic). Aspirin prevents
the temperature rising effects of interleukin - 1
by preventing the increase in brain PGs
ACETYLSALICYLIC ACID / ASPIRIN
INDICATIONS
- analgesic, antipyretic and antiplatelet effects
MECHANISM OF ACTION
- Inhibits irreversibly cyclooxygenase (COX-1 &
COx-2) activity thereby reducing the synthesis
of Prostaglandins and Thromboxanes (TXA2)
- mainly effective in pains related
inflammation, tissue injury,
connective tissue and integument pain
- not much effective in visceral and
ischemic pain.
- Prevention of PG-mediated sensitization of
nerve endings.
- raising of pain threshold by acting
centrally (morphine like) but no
sedation, subjective effects, tolerance
or physical dependence
- resetting of hypothalamic thermostat -
fever reduction
- Note: Anti-inflammatory doses are higher
than analgesic doses
PHARMACOKINETICS
- Rapidly absorbed from the stomach and
proximal small intestine
- during absorption, it is partially hydrolyzed to
salicylic acid in gut, liver and plasma
- 80-85% bound to plasma protein;
salicylate can cross the placenta and
CSF
- Metabolized in the liver by conjugation with
glycine and glucuronic acid via gluconyl
transferase -- salicyluric acid
- Excretion: KIDNEY by both glomerular
filtration and renal tubular secretion
1 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

SIDE EFFECTS - petechial hemorrhage

- hyperglycaemia
1. Gastrointestinal disturbances - nausea, - hyperpyrexia
vomiting, epigastric distress and gastric - confusion
mucosal damage - coma
2. Hypersensitivity and Idiosyncrasy - FDE, - Management:
rash, urticaria, asthma (Bronchospasm - - Inducing emesis or administering
aspirin sensitive asthmatics) gastric lavage
3. Salicylism (on repeated admin of 3-5gm/day) - appropriate infusion measures to
- headache, mental confusion, lassitude correct abnormal electrolyte balance
and drowsiness and dehydration
- tinnitus and difficulty in hearing - alkalinization of the urine
- hyperthermia, sweating, thirst, - dialysis as required
hyperventilation, vomiting and - vitamin k injection
diarrhea
4. Hepatotoxicity ACETYLSALICYLIC ACID / ASPIRIN
- Rise in serum transaminases
- Reye’s Syndrome - rare disease of INDICATIONS ACETAMINOPHEN
hepatic encephalopathy when given in
viral conditions of influenza and - analgesic, antipyretic
varicella
5. Nephrotoxicity MECHANISM OF ACTION
- Sodium and water retention
6. Prolongation of Bleed Time
- or reduced prothrombin level
7. Respiratory problems
- Asthma, rhinitis

THERAPEUTIC USES

1. Analgesic
2. Rheumatoid Arthritis
3. Acute Rheumatic Fever
4. Osteoarthritis
5. Antipyretic
6. Post-myocardial infarction and post stroke
7. Others

CONTRAINDICATIONS - not completely understood

- produces analgesia and antipyresis via a weak,
1. Sensitive persons reversible, isoform-nonspecific inhibition of
2. Children with viral diseases cyclooxygenase (COX-3; COX-1-v1)
3. Peptic Ulcer disease and bleeding disorders - raises pain threshold but no PG inhibition
4. Chronic LIver diseases except COX inhibition in brain - no peripheral
5. Diabetes, CHF and juvenile Rheumatoid anti-inflammatory action
Arthritis
6. G-^-PD deficient persons PHARMACOKINETICS
7. Stop prior to surgery, near term pregnancy,
breastfeeding mothers etc - Rapidly and nearly completely absorbed from
the gut and is rapidly distributed into most
TREATMENT FOR ACUTE POISONING tissues.
- approximately, 25% is plasma protein bound
- Fatal dose: 15-30 grams - Metabolism by hepatic conjugation with
- low in case of children glucuronic acid (60%) and sulfuric acid (35%)
- Symptoms:
- vomiting
- dehydration
- acidosis

2 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

6. Renal - renal insufficiency, renal failure,

hyperkalemia and proteinuria
7. Allergic reactions and all types of skin rash

TOXICITY

- gastric lavage
- peritoneal dialysis
- activated charcoal
- hemodialysis
- IM Vit. K
- Antidote - Acetylcysteine
- IV Fluid and electrolyte supplements
- Acetaminophen metabolism. Acetaminophen
is metabolized primarily by sulfation and
glucuronidation. However, it can also be
oxidized by CYPs to form NAPQI. NAPQI can
then interact with cellular macromolecules,
resulting in toxicity, or it can be detoxified by
undergoing GSH conjugation.

SIDE EFFECTS

1. Severe liver and kidney damage

2. cyanosis
3. heinz body anemia
4. methemoglobinemia
5. jaundice
6. facial edema

ADVANTAGES

1. lesser gastric irritation, ulceration and

bleeding
2. does not prolong bleeding time
3. hypersensitivity rarely
4. no metabolic disturbances
5. can be given in all age
group-pregnancy-lactation
6. no significant drug interactions

THERAPEUTIC USES

- headache, mild migraine, musculoskeletal

pain, dysmenorrhoea etc
- 1st choice in osteoarthritis, not effective in
Rheumatoid arthritis

ADVERSE EFFECTS

1. CNS - headache, tinnitus, dizziness

2. CVS - fluid retention, hypertension, edema,
CHF (rarely)
3. GI - abdominal pain, dysplasia, nausea,
neutropenia or even aplastic anemia
4. Hematologic - abnormal liver function test
and rare liver failure
5. Pulmonary - asthma

3 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

BIOSTATISTICS DISTRIBUTION

STATISTICS - The distribution of a variable is the pattern of

frequencies, meaning the set of all possible
- Scientific study of numerical data based on values and the frequencies associated with
natural phenomena these values.
- The science of collecting, organizing,
interpreting and reporting data. FREQUENCY DISTRIBUTION
- Note: Statistics is an important tool in
pharmacological research that is used to - It can show either the actual number of
summarize (descriptive statistics) experimental observations falling in each range or the
data in terms of central tendency (mean or percentage of observations. In the latter
median) and variance (standard deviation, instance, the distribution is called a relative
standard error of the mean, confidence interval frequency distribution.
or range) but more importantly it enables us to - Note:
conduct hypothesis testing. This is of - Frequency distributions are portrayed
particular importance when attempting to as frequency tables or charts.
determine whether the pharmacological effect - Frequency distribution tables can be
of one drug is superior to another which used for both categorical and numeric
clearly has implications for drug development variables. Continuous variables should
only be used with class intervals,
PHARMACEUTICAL STATISTICS which will be explained shortly.
- Application to matters concerning the FREQUENCY OF DISTRIBUTION CURVE
industry.
- This can be from issues of design of
experiments, to analysis of drug trials, to
issues of commercialization of a medicine
- Evaluate drug activity
- Analysis of genomics data
- Demographic studies
- Design and analysis of clinical trials
- Public health (epidemiology, health
services research, nutrition,
environmental health and healthcare
policy and management)
- Many more

TABLE - A frequency distribution curve is a type of

descriptive statistics depicted as a graph that
- A table helps us to organize and analyze a set demonstrates the frequency of a given
of data values. variable's occurrence, where x represents some
measure of the variable's occurrence and y
FREQUENCY TABLE represents the number of cases at each
frequency.

- A frequency table is a tabular representation CLASS INTERVAL WIDTH

of a data set in an ascending order of
magnitude with their corresponding
frequencies. It is a simple device to provide a - Class interval width is the difference between
count of how often a data value occurs. the lower endpoint of an interval and the
- Note: The word 'frequency' means 'how often'. lower endpoint of the next interval.

FREQUENCY ENDPOINTS

- The frequency (f) of a particular value is the - The endpoints of a class interval are the lowest
number of times the value occurs in the data. and highest values that a variable can take.
- Upper Limit: It is the highest value of the
class interval. There could be no item greater

4 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

than the upper limit in that particular class.

- Lower Limit: It is the lowest value of the class
interval. There could be no item less than the
lower limit in that particular class.

RANGE

- Range is defined as the difference between the

highest and lowest values. - The mean (average) of a data set is found by
- The range is a measure of spread and it tells us adding all numbers in the data set and then
how much a data set is spread out or scattered. dividing by the number of values in the set.
The median is the middle value when a data
CLASS BOUNDARIES set is ordered from least to greatest. The mode
is the number that occurs most often in a data
- Class boundaries are the values that separate set.
the classes.
STANDARD DEVIATION
1. Subtract the upper class limit for the first class
from the lower class limit for the second class. - is a statistic that measures the dispersion of a
2. Divide the result by two. dataset relative to its mean and is calculated as
3. Subtract the result from the lower class limit the square root of the variance.
and add the result to the upper class limit for - The average amount of variability in your
each class. dataset.

CLASS MARK

- Class mark is the average of the upper limit

and the lower limit of a class in a frequency
distribution. In other words, the class mark is
the mid-value of the given class interval.

CLASS INTERVAL

- Class interval represents the difference

between the upper class limit and the lower
class limit.

Note: If a variable takes a large number of values, then

it is easier to present and handle the data by grouping
the values into class intervals. Continuous variables are
more likely to be presented in class intervals, while
discrete variables can be grouped into class intervals or
not.

Note:
- The standard deviation is the average amount
of variability in your dataset. It tells you, on
average, how far each value lies from the
mean.
- A high standard deviation means that values
are generally far from the mean, while a low
standard deviation indicates that values are
clustered close to the mean.

EQUATION

5 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

COEFFICIENT OF VARIATION

- Statistical measure of the dispersion of data

points in a data series around the mean. The
coefficient of variation represents the ratio of
the standard deviation to the mean, and it is a
useful statistic for comparing the degree of
variation from one data series to another, even
if the means are drastically different from one
another.
- Note:
- The coefficient of variation shows the extent
of variability of data in a sample in relation to
the mean of the population.

A set of measurements with a small standard deviation

and small coefficient of variation is deemed to be
precise. It is important to note that greater precision
does not necessarily mean greater accuracy!

6 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

CHOLINERGIC AGONISTS AND

ANTAGONISTS OF ANS
AUTONOMIC NERVOUS SYSTEM

- Involuntary (little to no control)

- acts on smooth muscles and glands
- control and regulation of the heart, respiratory
system, GI tract, bladder, eyes and glands

ANS NEURONS

AFFERENT (SENSORY)

- Send impulses to the CNS for interpretation

EFFERENT
- All have longer duration of action than ACH
- Receives impulses (information) from the brain - Some are more therapeutically useful drugs
and transmits from the spinal cord to the pilocarpine and bethanechol preferentially
effector organ cells bind to muscarinic receptors and are sometime
- 2 branches: referred to as muscarinic agents
- Sympathetic - As a group, this show little specificity in their
- parasympathetic acions, which limits their clinical usefulness.

CHOLINERGIC AGONISTS

- Cholinergic and adrenergic drugs both act by EFFERENT

either stimulating or blocking receptors of the
ANS - A Tertiary amine and is stable to hydrolysis by
AChE
DIRECT-ACTING CHOLINERGIC AGONIST - Less potent but is uncharged and can
penetrate the CNS at therapeutic doses
- Cholinergic agonists (parasympathomimetics) - Exhibits muscarinic activity
mimic the effects of ACH by binding directly - Used primarily in ophthalmology
to cholinoreceptors
- Classified to 2 groups
- Choline esters, which include ACH
synthetic esters of choline, such as
carbachol and bethanechol
- Naturally occurring alkaloids, such as
pilocarpine

7 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

with xerostomia resulting from irradiation of

the head and neck
- Note: Miosis in eyes – spasm of
accommodation

Therapeutic used in Glaucoma

- Drug of choice in the emergency lowering of

intraocular pressure of both narrow-angle
(closed angle) and wide-angle (open-angle)
glaucoma
- Extremely effective in opening the trabecular
meshwork around Schlemm’s canal, causing an
immediate drop in intraocular pressure as a
result of increased drainage of aqueous humor.

Adverse effects

- Can enter the brain and cause CNS

Reaction Mechanism
disturbances
- It stimulates profuse sweating and salivation
- Bind to muscarinic receptor
- Activates receptor binds G-protein INDIRECT-ACTING CHOLINERGIC AGONIST
- Removal of GDP and addition of GTP to (reversible)
G-protein
- Dissociation of G-protein from muscarinic - AChE indirectly provide cholinergic action by
receptor preventing the degredation of Ach
- Separation of G-protein into alpha and - Results in an accumulation of Ach in the
beta-gamma subunits synaptic space
- Alpha subunits interacts with and activates - These drugs provoke response in both
Phospholipase C – Phosphatidyl inositol muscarinic and nicotinic receptors of the ANS,
biphosphate (PIP) complex also at NMJ and brain
- Phospholipase breaks down PIP into inositol - Classified:
1,4,5-triphosphate (IP3) and diacyglycerol - Short-acting
(both 2) - Intermediate acting
- IP3 interacts with ER membrane which
releases Calcium

Muscle Action

- Calcium bind to calmodulin forming a

complex
- This complex binds to caldesmon
- When caldesmon is bound by
calcium/calmodulin complex this allows
myosin-actin interactions to occur
- The muscle (pupils) contract

Muscle Action
- Note:
- AChE (Anticholinesterase agents or
- Applied topically to the eye, produces rapid
cholinesterase inhibitors)
miosis and contraction of the ciliary muscle
- Enzyme that specifically cleaves Ach
- One of the most potent stimulators of
to acetate and choline and thus
secretions (secretagogue) such as sweat, tears,
terminates its actions
and saliva but its use for producing these
effects has been limited due to its lack of
selectivity
- Beneficial in promoting salivation in patients

8 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

Mechanism of Action

INDIRECT-ACTING CHOLINERGIC AGONIST

(irreversible)

- A number of synthetic organophosphate

compounds have the capacity to bind
covalently to AChE.
- The result is a long-lasting increase in Ach at
all sites where it is released
- Note:
- Many of these drugs are extremely
toxic and were developed by the
military as nerve agents.
- Related compounds, such as parathion
and malathion, are used as insecticides ATROPINE

- Tertiary amine belladonna alkaloid with a high

CHOLINERGIC AGONISTS
- General term for agents that bind to
cholinoreceptors (muscarinic and nicotinic)
and prevent the effects of Ach and other
cholinergic agonists
affinity for muscarinic receptors
- Binds competetitively prevents Ach from
binding
- Acts centrally and peripherally
- General actions last about 4 hours, except
when placed topically in the eye, where the
action may last for days

ANTIMUSCARINIC AGENTS

- These agents block muscarinic receptors,

causing inhibition in muscarinic functions
- Block the few exceptional sympathetic
neurons that are cholinergic
- Have little to no action at skeletal NMJs or
autonomic ganglia
- Note: Commonly known as anticholinergic
drugs

9 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

Action Therapeutic Uses

A. EYE A. Ophthalmic
- Blocks muscarinic activity resulting in - Exerts both mydriatic and cycloplegic
mydriasis, unresponsiveness to light, effects and permits the measurement
and cycloplegia of refractive errors without
interference by accommodative
B. GASTROINTESTINAL capacity of the eye
- Can be used as antispasmodic to
reduce GI tract activity B. Antispasmodic
- Although gastric motility is reduced, - Relax the GI
hydrochloric acid production is not
significantly affected. Thus, not C. Cardiovascular
effective for tx of peptic ulcer - Used to treat bradycardia of varying
- Doses that reduce spasms also reduce etiologies
saliva secretion, ocular
accommodation and urination D. Antisecretory
- Block secretions in the upper and
C. CARDIOVASCULAR lower respiratory tracts prior to
- Produces divergent effects depending surgery
on the dose
- Low doses - slight decrease in heart E. Antidote for cholinergic agonists
rate by blocking the M1 receptors on - Used for tx of organophosphate
the inhibitory prejunctional poisoning, of overdose of clinically
(presynaptic) neurons thus permiting used Ache’s and in some types of
increased Ach release mushroom poisoning
- High doses – cause progressive
increase in heart rate by blocking m2 Pharmacokinetics
receptors on sinoatrial node
- Readily absorbed, partially metabolized by the
D. SECRETIONS
liver
- Blocks muscarinic receptors in
- Eliminated primarily in urine
salivary glands, producing xerostomia
- Half-life of about 4 hours

Adverse Effects

- Depending on dose, may cause dry mouth,

blurred vision, “sandy eyes”, tachycardia,
urinary retention and constipation
- Effects on CNS include restlessness,
confusion, hallucinations and delirium, which
may progress to depression, collapse of the
circulatory and respiratory systems and death
- May also induce urinary retention
- May be dangerous in children because they are
sensitive to its effects, particularly to rapid
increases in body temperature that it may
elicit.

NOTE:
- Mydriasis -pupil dilation
- Cycloplegia - inability to focus for near vision
- Xerostomia - dryness of the mouth

10 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

NEUROMUSCULAR BLOCKING - Note: Depolarization is caused when

DRUGS
- Drugs that cause skeletal muscle relaxation by
interrupting the transmission of nerve
impulses at the neuromuscular junction
- Note:
- Have no analgesic or amnestic
properties.
- Inappropriate use leads to a state
where the patient is paralyzed but not
anaesthetized
positively charged sodium ions rush into a
neuron with the opening of voltage-gated
sodium channels. Repolarization is caused by
the closing of sodium ion channels and the
opening of potassium ion channels
NON-DEPOLARIZING NEUROMUSCULAR
DRUGS
Mechanism of Action

- Each Ach-receptor has two receptive sites and

activation of the receptor requires binding to
both of them.
- Each receptor site is located at one of the two
- Acting presynaptically via the inhibition of a-subunits of the receptor.
acetylcholine (ACh) synthesis or release, or by
acting postsymaptically at the acetylcholine
receptors of the motor nerve end-plate.
- Note:
- Causes paralysis of the affected
skeletal muscles
- While some drugs act presynaptically
(e.g. botulinum toxin and tetanus
toxin), those of current clinical
importance work postsynaptically.

PURPOSE OF SKELETAL MUSCLE RELAXATION

- To facilitate tracheal intubation

- To facilitate mechanical ventilation
- To optimize surgical working conditions
CLASSIFICATIONS OF DRUGS
NON-DEPOLARIZING
- Does not depolarize the motor end plate
- Quaternary ammonium muscle relaxants
belong to this class
DEPOLARIZING
- It binds to the nicotinic acetylcholine receptor
and inhibit or interfere with the binding and
effect of Ach to the receptor.
- They are competitive agonists combine with
the nicotinic Ach receptor at the end plate and
thereby competitively block the binding of
Ach
- A decrease in binding of ACh leads to a
decrease in its effect and neuron transmission
to the muscle is less likely to occur.
- Note: It is generally accepted that
non-depolarizing neuromuscular drugs block
by acting as reversible competitive inhibitors.

- Depolarize the motor end plate

11 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

- Non-depolarising neuromuscular drugs also
block facilitatroy presynaoptic autoreceptors,
and thus inhibit the release of ACh during
repetitive stimulation of the motor nerve
resulting in the phenomenon of tetanic fade.
Tetanic Fade
- Failure of muscle tension to be maintained
during a brief period of nerve stimulation at a
frequency high enough to produce a fused
tetanus,
TYPES OF NON-DEPOLARIZING BLOCKERS
LONG ACTING
- Pancuronium
- Gallamline
- Pipercuronium
- Doxacurium (longest acting)
Vecuronium
- commonly used muscle relaxant
Rocuronium
- choice for precurazation (Precurarization is
the administration of a small dose (10% of
ED95) of a non-depolarizing neuromuscular
blocking agent (NDMBA) a few (3.5-4) minutes
before Succinylcholine (SCH) to minimize
these complications of SCH use like
fasciculations, rise in intragastric pressure and
rise in ICP.)
Atracurium
- unique method of degredation/elimination. Its
metabolism is independent of hepatic or renal
functions. It undergoes spontaneous
degradation in plasma called HoffMan
degradation.

Mivacurium
INTERMEDIATE ACTING
- Choice for day care surgery; release histamine
- Atracurium thus can cause transient hypotension and
- Vecuronium brochospasm
- Rocuronium
- Cisatracurium
- Metocurine

SHORT ACTING

- Mivacurium
- Rapacuronium
- Gantacurium (shortest acting)

12 | AC OCFEMIA
 UNIVERSITY OF SANTO TOMAS - LEGAZPI
COLLEGE OF HEALTH SCIENCES - BATCH 2024
DRUG DISCOVERY AND DEVELOPMENT

DEPOLARIZING NEUROMUSCULAR DRUGS SUCCINYLCHOLINE

Mechanism of Action - The only depolarizing neuromuscular blocker

in use.
- Onset of action: 20 – 30 seconds
- Work by depolarizing the plasma membrane of
- Duration of action: 5 - 10 minutes
the muscle fiber, similar to acetylcholine.
- Elimination: Plasma cholinesterase
- These agents are more resistant to degradation
- Side effects: Bradycardia, muscle pain day after
by acetylcholinesterase, the enzyme
surgery due to initial fasciculation and
responsible for degrading acetylcholine, and
hyperkalemia
can thus more persistently depolarize the
- Note:
muscle fibers. This differs from ACh, which is
- Because of its early onset and short
rapidly degraded and only transiently
duration.
depolarizes the muscle.
- It is an ideal muscle relaxant for
intubatiin due to its side effects it
should be used in rapid sequence and
difficult airway management.

REVERSAL OF NEUROMUSCULAR BLOCK

- Residual neuromuscular block, at the end of

the surgical procedure, is reversed with the
help of anticholinesterases.

Mechanism of Action

- Anticholinesterases inhibit acetyl

cholinesterase which is responsible for rapid
hydrolysis of acetylcholine at NMJ.
- As a result concentration of ACH risesat NMJ,
more number of molecules ar then available to
interact with nicotinic acetylcholine receptors,
thereby overcoming the effects of NMBs
- The constant depolarization and triggering of
the receptors keeps the endplate resistant to
activation by acetylcholine
- A normal neuron transmission to muscle
cannot cause contraction of the muscle
because the endplate is depolarized and
thereby muscle is paralyzed

13 | AC OCFEMIA