PCOL 2ND LONG EXAMINATION 1.

Subthreshold- initial; stimuli but can’t cause

action potential
Introduction to Nervous System 2. Threshold- enough energy/ potential to produce
-a complex network of nerves and cells that carry an action potential
messages to and from the brain and spinal cord to 3. Suprathreshold- also produces and action
various parts of the body potential but strength s higher that threshold
- responsible for regulating and maintaining stimuli
homeostasis together with the endocrine system
- through its receptors, it keeps us in touch with our Phases of Action Potential
environment, both internal and external 1. Hypopolarization- initial increase; when it
- major controlling, regulatory, communicating, reaches thethreshold standard, it opens voltage
and the center of all mental activity (thought, gated sodium channels
learning, memory) *sodium(Na+) - outside the cell
*potassium(K- )- inside the cell
Organs of the Nervous System
1. Brain 2. depolarization- sodium pump opening; sodium
2. Spinal cord entering cell making it electropositive
3. Nerve cells – its structural unit; consist of various
tissues (nerve, blood, and connective tissue); carry 3. overshoot- when the potential gets to the
out complex activities of nervous system electrochemical equilibrium for sodium; highest
*neuron/nerve cells- basic/primary functioning point ; extreme positivity
unit of nervous system
4. repolarization- sodium channels close and
Parts of the neuron voltagegated potassium will open
1. Dendrites- area where information are received 5. hyperpolarization-
2. Neurotransmitters- receptors in a form of *nerves transmit electrical activity (electrical in
chemicals that picks up information nature)
3. Soma- Cell Body; contains the nucleus *when neuron is connected to othe neuron it just
4. Nucleus- contains DNA transmits impulses to other neuron BUT when a
5. Axon hillock – connects cell body to axon neuron is connected to a muscle it causes activity
6. Axon- covered with myelin of muscle
*action potential- signals that reach the axon *transmission of impulses is electrochemical
* myelin- insulate axon; increase rate of action activity.
potential *electrical impulse- travels to the nerve
7. Axon terminal- very end of branch of nerve axon *chemical neurotransmitter- travels through the
8. Synapse/synaptic cleft- gap between neurons synapse/ synaptic cleft
Example: acetylcholine transfer from neuron to
Neurotransmitter- chemical substances that allow muscle
signals to cross synapse to transmit information *acetylcholine- synthesized inside the cell by
from nerve cell to neuron to a target cell acetyl
Some of the familiar identified neurotrasmitters: coenzyme A + choline stored in a vesicle
1. Dopamine- plays a role in how we feel pleasure 1. synthesis of acetylcholine
2. Gamma Aminobutyric Acid (GABA)- wide 2. storage of acetylcholine at vesicle
distributed in the brain; reduces activity of neurons 3. vesicle travels to edge of cell
3. Glutamate- powerful excitatory; for learning and 4. vesicle will fuse with pre synaptic membrane(of
memory neuron) with the help of calcium
4. Serotonin- key hormone that stabilizes mood, 5. creates a hole at fusion point
feelings of well –being, and happiness; impacts the 6. acetylcholine goes out
whole body; helps with sleeping, eating, and 7. acetylcholine attach to receptor of post synaptic
digestion membrane(of muscle)
5. Acetylcholine- contract smooth muscles, dilate 8. irritation of muscle to contract happens
blood vessels, increase bodily secretions, and
slows heart rate *After muscle contract…acetylcholine will be
6. Norepinephrine- increases heart rate and destroyed by acetylcholinesterase
bloodpumping of heart; improve vision, process of *acetylcholine must be destroyed after muscle
energy for the body contraction because if not muscle will continue to
7. Epinephrine- a.k.a adrenaline contract.
* Norepinephrine and Epinephrine are the same, *muscle must not contract all the time otherwise it
the difference is norepinephrine has more effect on will become tired and causing accumulation of a
the blood vessels while epinephrine has effect on lot of lactic acid in it without energy coming in to
the heart. the muscles

Action potential- sudden, fast, transitory, and *Myasthenia gravis- disease that uses
propagating change, of the resting membrane acetylcholine; deficiency of acetylcholine; stores
potential acetylcholine at night making you active in the
• Only neurons and muscle cells are capable of morning BUT the storage cannot patch up for the
generating an action potential whole day
• Excitability- generation of action potential *treat myasthenia gravis by inhibiting the reuptake
of acetylcholine and inhibiting
Types of Stimuli acetylcholinesterase
*inhibiting reuptake, all acetylcholine will go to the controls heart and respiration; found at base of
muscle and the muscle can act and contract brain above foramen magnum; area where tracts
*inhibiting acetylcholine allows you to have storage crossover(decussation);
of it at your muscle *foramen magnum- at the base of skull; exit of the
*reuptake- reabsorption of the secreted spinal cord
substances by the cell that originally produced and *brain herniation- brain gets out of the opening
secreted it (foramen
*acetylcholine can only live for a couple of minutes magnum)
*decrease of acetylcholine causes muscle *contralateral- different side
weakness * Ipsilateral- same side
3. Cerebellum- for coordination of voluntary
*NORMAL: more potassium inside and more muscular
sodium outside cell; no reaction of cell movement, posture, and balance
*irritability property- reaction of cell membrane *part of the body that is responsible for balance is
when irritated the ears and
cerebellum
Phases of Action Potential Spinal cord- highway for communication between
1. depolarization- when cell membrane is irritated ( the body and
more sodium inside and more potassium outside); the brain; midway station
causes contaction of cell
2. repolarization- going back to normal (more
potassium inside and more sodium outside cell)
*contraction of muscle is caused by opening of PERIPHERAL NERVOUS SYSTEM
sodiumpotassium pump - Contains the nerves outside CNS; connects CNS
*blocking sodium channel causes no contraction to organs limbs and skin
*calcium- used for contraction, blood clotting, and 1. Cranial Nerves – 12 pairs (olfactory, optic,
transmission of impulses oculomotor, trochlear, trigeminal, abducens,
*block calcium channel to relax muscle facial, auditory(vestibulocochlear),
*calcium blockers- used to relax blood vessel to glossopharyngeal, vagus, accessory, hypoglossal);
treat hypertension control much of motor and
sensory functions of the head and neck.
The various activities of nervous system can be *vagus- longest cranial nerve; reaches to stomach;
grouped stimulate
together as three general, overlapping functions: stomach to produce acid; parasympathetic
1. sensory- conveying nerve impulses from sense *parasympathetic activity increases gastric acid
organs to nerve centers production
2. integrative- process of integration combines and gastrointestinal movement
sensory perceptions and higher cognitive functions *serotonin- a parasympathetic drug that increases
(memories, learning, and emotion) to produce gastric
response motility
3. motor- something that produces or refers to
motion 2. Spinal Nerves- mixed nerves that send motor,
sensory, and autonomic signals between CNS and
CENTAL NERVOUS SYSTEM the body ; base on name of spine
-Brain and spinal cord

Brain Major Parts: NERVOUS SYSTEM AND PHARMACOLOGY RESULT

TO
1. Cerebrum- responsible for initiation of NEUROPHARMACOLOGY
movement, • Neuropharmacology- branch or pharmacology
coordination of movement, temperature, touch, that
vision, deals with the action of drugs in the nervous
hearing, judgement, reasoning, problem solving, system
emotions, and learning • Goal of neuropharmacology: apply information
4 lobes: about
a. Frontal lobe- motor movement: drugs and their mechanisms of actions to develop
b. Parietal lobe- integrative safer, more effective treatments and eventually
c. Occipital lobe- vission curative and preventive measures for a host of
d. Temporal lobe- hearing nervous system abnormalities.
2. Brain Stem- responsible for basic vital life
functions DRUGS ACTING ON THE CENTRAL AND
(breathing, heartbeat, and blood pressure) PERIPHERAL
a. Midbrain- vision, hearing, motor control, sleep NERVOUSSYSTEM
and wake cycle, awareness, and temperature
regulation A. Anxiolytics and Hypnotics- agents that are used
b. Pons- relay station between the core brain and to alter an individual’s responses to environmental
cerebellum that passes sensory information from stimuli.
the periphery to the thalamus; controls pattern of
respiration; pneumotaxic center These agents are referred to as…
c. medulla oblongata)- cardiorespiratory center, it 1. Anxiolytics- prevent feeling of tension are fear
2. Sedatives- help patient feel calm and unaware of
their environment
3. Hypnotics- help patients sleep THREE KNOWN REASONS

States affected by Anxiolytic and Hypnotic Drugs 1. Monoamine oxidase (MAO) –destroys amine
1. Anxiety- unpleasant feeling of tension, fear, or causing depression; cure hypertension
nervousness in response to an environmental *Amine theory- absence of monoamine causes
stimulus, whether real or imaginary depression; increasing amine can evade
2. Sedation- loss of awareness and reaction to depression
environmental stimuli * Monoamine oxidase inhibitor- to treat
3. Hypnosis- extreme state of sedation in which the depression; can cause hypertension
person no longer senses or reacts to incoming * Amines- sympathetics; Catecholamine
stimuli sympathetic
2. Rapid fire of the neurons may lead to their
Benzodiazepines- class of drugs primarily used for depletion
treating anxiety, but they also are effective in 3. Number or sensitivity of postsynaptic receptors
treating several other conditions. may increase
- Reduce anxiety and seizures, relax muscles, and 4. Inhibit the effects of MAOI
induce sleep. 5. Block the reuptake of neurotransmitters by the
- Work by affecting neurotransmitters in the brain. releasing nerves
6. Regulate receptor sites and breakdown of
* Gamma-aminobutiric acid (GABA) - main neurotransmitters
inhibitory neurotransmitter of brain; C. Psychotherapeutic Drugs- treat psychoses—
neurotransmitter (chemical) that nerve use to perceptual and behavioral disorders; targeted at
communicate with one another thought processes rather than affective states; do
*Glycine- main inhibitory neurotransmitter of not cure any psychotic disorders BUT help both
spinal cord adult and
❖ Effect: sedation pediatric patients to function in a more acceptable
❖ Side effect: severe sedation manner and carry on activities of daily living
which causes sedation; respiratory depression –
dreaded side effect Glossary of Terms:
Barbiturates- CNS depressants; reduce nerve ❑ Antipsychotic: drug used to treat disorders
activity causing muscle relaxation; reduce heart involving thought processes; dopamine receptor
rate, breathing, and blood preassure; affect blocker that helps affected people to organize their
gamma-aminobutiric acid (GABA) thoughts and respond appropriately to stimuli
*same MOA and side effects with benzodiazepins ❑ Attention deficit disorder: behavioral syndrome
characterized by an inability to concentrate for
Other Anxiolytic and Hypnotic drugs longer than a few minutes and excessive activity
❑ Bipolar disorder: behavioral disorder that
Antihistamine- can be very sedating in some involves extremes of depression alternating with
people; only use first generation because these are hyperactivity and excitement (either manic or
the ones sedating, new generations are non- depressed)
sedating buspirone (generic)- reduces signs and ❑ Major tranquilizer: former name of antipsychotic
sympyoms of anxiety without many of the CNS drugs; the name is no longer used because it
effects and severe adverse effects implies that the primary effect of these drugs is
associated with other anxiolytic drugs sedation, which is no longer thought to be the
* sedative drugs are depressant drugs desired therapeutic action
❑ Mania: state of hyperexcitability; one phase of
B. Antidepressants- alter the concentration of bipolar disorders, which alternate between periods
neurotransmitters in the brain; most effective of severe depression and mania
means of treating depression
❑ Narcolepsy: mental disorder characterized by
*amine- neurotransmitter used
daytime sleepiness and periods of sudden loss of
wakefulness
Glossary of Key Terms
❑ Neuroleptic: a drug with many associated
affect: feeling that a person experiences when he
neurological adverse effects that is used to treat
or she responds emotionally to the environment
disorders that involve thought processes (e.g.,
biogenic amine: one of the neurotransmitters
schizophrenia)
norepinephrine, anti- serotonin, or dopamine;
deficiency of these substances in key areas of the ❑ Schizophrenia: the most common type of
brain results in depression psychosis; characteristics include hallucinations,
* dopamine- absence of this will cause Parkinson’s paranoia, delusions, speech abnormalities, and
Disease affective problems
depression: affective disorder in which a person
experiences sadness that is much more severe and Mental Disorders and their Classification
longer lasting than is warranted by the event that once attributed to environmental influences and
seems to have precipitated it, with a more intense life experiences such as poor parenting or trauma
mood; the condition may not even be traceable to thought to be caused by some inherent
a dysfunction within the brain that leads to abnormal
specific event or stressor thought processes and responses
 chemical imbalance in specific areas within the * 2nd messengers- cyclic ANP, cyclic GNP, inositol,
brain Phosphoinositides, calcium.
based on distinguishing characteristics as * antimanics goes by way of the 2nd messenger (it’s
Because no diagnostic laboratory tests are not direct) by inhibiting conversion of IP 2 to inositol
available, patient assessment and response must that’s why it treats
be carefully evaluated to determine the basis of a mania
particular problem. * inositol- is for activity; part of calcium growth

A. Schizophrenia- most common; very debilitating; CNS stimulants- clinically used for treatment of
prevents affected individuals from functioning in attention-deficit disorders and narcolepsy; can
society; have a very strong genetic association; calm hyperkinetic children and help them focus on
may reflect a fundamental biochemical one activity for a longer period; redirect and excite
abnormality arousal stimuli from the RAS; majority are
Characteristics: controlled substances so it is important for
1. Hallucinations patients to be taught how to
2. Paranoia secure them to prevent inappropriate use and
3. Delusions distribution
4. speech abnormalities
5. affective problems ANTISEIZURE AGENTS - aka. anticonvulsants or
antiepileptic drugs (AEDs); used to treat epileptic
B. Bipolar disorder - involves extremes of seizures by stabilizing nerve cell membranes and
depression alternating with hyperactivity and suppress the abnormal electric impulses in the
excitement; reflect a biochemical imbalance cerebral cortex
followed by overcompensation on the part of
neurons and their inability to re-establish Epilepsy- group of chronic CNS disorders
stability characterized by recurrent seizures

C. Narcolepsy- characterized by daytime Seizures- sudden, transitory, and uncontrolled

sleepiness and sudden periods of loss of episodes of brain dysfunction resulting from
wakefulness; reflect problems with stimulation of abnormal discharge of neural cells with associated
the brain by the reticular activating system (RAS) or motor, sensory or behavioral changes
problems with response to that stimulation.
Nature of Seizures
D. Attention deficit disorders- involve various Primary Seizures- caused by abnormal cells with
conditions characterized by an inability to no underlying cause that can be identified
concentrate on one activity for longer than a few
minutes and a state of hyperkinesis; usually Secondary Seizures- caused by outside such as
diagnosed in school aged children but can occur in head injury, drug overdose, environmental
adults exposure and etc. can precipitate seizures
• Generalized seizures- Grand Mal Seizure
Antipsychotic/Neuroleptic Drugs-treat disorders • Tonic-clonic seizures- Grand Mal Seizure; most
that involve thought processes common; involves dramatic tonic-clonic muscle
• Because of their associated neurological adverse contraction
effects, these medications are also called
neuroleptic agents. • Absence seizures- Petit Mal Seizure; abrupt, brief
• At one time, these drugs were known as major within 3-5 second period of loss of consciousness;
tranquilizers but that name is no longer used usually occur in children; absence of seizure
because the primary action of these drugs is not activity; blank stares
sedation but a change in neuron stimulation and
response
• Myoclonic seizures- short periods of muscle
Orthostatic hypotension is a sudden drop in blood contraction that last for several minutes; rare;
pressure when you stand from a seated or prone often secondary seizures
(lying down) position. • Febrile seizures- very high fevers; involves tonic
You may feel dizzy or even faint. Orthostatic means clonic seizure; frequent in children
an upright posture. Hypotension is low blood * Simple Febrile seizures- below 6 years old
pressure. The condition is also called postural * Complex Febrile seizures- above 6 years old
hypotension. • Jacksonian seizure- begins in one area of brain;
Antimanic drugs- used to control mania that involve one part of body and spread to other body
occurs in individuals with bipolar disorder; due to parts then develop to generalized tonic-clonic
neuronal overstimulation. seizure
* Lithium -treatment for mania; treatment for • Psychomotor seizure- complex; involves
bipolar disorder. sensorimotor and psychic components; begin with
loss of consciousness and no memory of event
MOA: decreases amine turn-over (decreases both • Status epilepticus- most dangerous; recur again
norepinephrine and dopamine turn- over); and again with no recovery; even with medications
decreasing dopaminereceptor sensitivity; one of seizure won’t stop; cause death because muscles
the smallest substance which can penetrate wont relax; don’t breath
anywhere
General causes of seizure:
1. Infection esp. at nervous system 5. Cranial nerve affectations lead to a
2. Cancer of neoplasm mask-like expression.
3. Head injuries
4. Genetic factors Parkinsonism- Parkinson’s disease-like
5. Metabolic disorders (Electrolyte imbalances) extrapyramidal symptoms that are adverse effects
6. Toxins electrolyte imbalance that causes seizure associated with particular drugs or brain injuries
activity:
• Magnesium GLOSSARY OF KEY TERMS:
• Sodium- normal: 135-145 mEq; below 120 causes • Bradykinesia – “brady” slow, “kinesia”
hyponatremia(low sodium) can lead to neurologic kinetics; slowing of the movement
seizure symptoms • Corpus Striatum- part of the brain that
* do not be very anxious in returning the reacts with the substantia nigra to maintain the
normal level of sodium; rapid going back to normal balance of suppression and stimulation
levels of sodium causes brain stem edema • Dopamine- is a type of neurotransmitter.
* parasympathetic stimulation will decrease Your body makes it, and your nervous system uses
incidence of seizure activity it to send messages between nerve cells. That’s
why it’s sometimes called a chemical messenger.
* GABA- main inhibitory brain neurotransmitter Dopamine plays a role in how we feel pleasure. It’s
* glycine- main inhibitory spinal cord a big part of our unique human ability to think and
neurotransmitter plans.

Ways of treatment for Seizure: • CAUSE OF PARKINSONISM- doesn’t cause

1. enhancing effect of GABA mentation; there is decrease in dopamine
2. decrease excitation – phenytoin acts secretion/stimulation of the substantia nigra of
here by using glutaminergic transmission. basal ganglia
3. modify ionic channels – blocks voltage-
gated channel Schematic Representation of the Degeneration of
* nystagmus Neurons That Leads to Parkinson’s disease
* diplopia and ataxia- most common side * when dopamine decreases, acetylcholine
effect of phenetoin increases which causes over stimulation of
* depressants can also be used for neurons then cause tremors and rigidity
epilepsy or seizure activity
* barbiturates is a depressant; watch out Treatment- use dopamine; no known treatment for
for respiratory depression Parkinson’s as of present and drug therapy remains
*lorazepam(Ativan)- date rape drug; one of to be the primary treatment. The goal of the therapy
the most potent benzodiazepine is to restore the balance between decreasing
* phenytoin- one of the most common dopamine levels (has inhibitory effect on the
drugs used in treating seizures neurons of the basal ganglia) and increasing
*dilantine- is a phenytoin cholinergic neurons (excitatory).
Phenytoin side effects:
• nystagmus * Parkinson’s Disease usually happens to elderly
• diplopia Dopaminergic - drugs that increase the effects of
• ataxia dopamine at receptor sites- have been proven to be
• gingival hyperplasia more effective than anticholinergics in the
treatment of parkinsonism
Drugs for Treating Generalized Seizure -Stabilize
the nerve membrane by blocking channels in the KEY POINTS: Levodopa- can pass through blood
cell membrane or altering receptor sites brain barrier BUT may cause problems because of
peripheral metabolism caused by 2 enzymes:
Drugs for Treating Partial Seizure- Stabilize nerve 1. peripheral dopamine decarboxylase –
membranes by directly, altering sodium and converts levodopa to dopamine
calcium channels or indirectly, by increasing the 2.catechol-o-methyltransferase (COMT)-
activity of GABA converts levodopa to 3-O-Methyldopa (3-OMD) the
standard dopaminergic used to treat parkinsonism
ANTIPARKINSONISM AGENTS- opposite of and Parkinson’s disease. Several order
antipsychotic drugs; giving antipsychotic drugs to a dopaminergic are used as adjuncts to levodopa to
parkinsonian patient can enhance parkinsonism increase the dopamine effects as long as possible.

Parkinson’s disease- debilitating disease, - levodopa is used in combination with other

characterized by the progressive loss of agents:- prolongs the time that levodopa is
coordination and function, which results from the available to the brain
degeneration of dopamine-producing cells in the 1. carbidopa – inhibits dopamine
substantia nigra decarboxylase to decrease to decrease conversion
Other manifestations: of levodopa
1. bradykinesia (extremely slowed 2. entacapone- inhibits peripheral COMT -
movements) levodopa when metabolized in the periphery will be
2. shuffling gait converted to dopamine, BUT do not let it be
3. drooling converted to dopamine because dopamine cannot
4. slow and slurred speech cross the blood-brain barrier.
 ❖ Dopamine is the thing needed to treat casing contraction, when returned to normal there
Parkinsonism BUT dopamine cannot pass the is relaxation. Preventing interaction of actin and
blood-brain barrier. Therefore, conversion of myosin prevents muscle contraction.
levodopa to dopamine must take place inside the Paralysis -Lack of muscle function; occur
brain. when acetylcholine cannot react with cholinergic
*dopamine is an inhibitory hormone for prolactin muscle receptor or when muscle cannot repolarize
secretion
*prolactin is the hormone for milk production * NEUROMUSCULAR JUNCTION-
Therefore, enhancing effect of dopamine will BLOCKING AGENTS
decrease milk production ➢ Non-depolarizing NMJs- those agents
that act as antagonists to ACh at the NMJ
Anticholinergics- oppose the effects of and prevent depolarization of muscle
acetylcholine at receptor sites in in the substantia cells.
nigra and the corpus striatum, thus helping to Curare –very effective/typical non-depolarizing
restore chemical balance in the area muscle relaxant; first non-depolarizing NMJ-
*dopaminergic drugs are more effective that blocker; first used by hunters as poison applied on
Anticholinergics arrow tips and spears to kill animals through
Adjunctive- used to improve patient response to respiratory muscle paralysis; safe for humans
traditional therapy because poison was destroyed by cooking process
and gastric acid; was purified for medical used as
MUSCLE RELAXANTS- used to treat muscle type NMJ-blocker tubocurarine
spasms or muscle spasticity ➢ Depolarizing NMJs
 Muscle spasms (Cramps) - often result • Why is it classified as muscle relaxant if
from injury to the musculoskeletal system. These it allows muscle to contract?
injuries can cause violent and painful involuntary - because with contraction esp.
muscle contraction. - caused by the flood of contained muscle contraction, the
sensory impulses coming to the spinal cord from receptors will be desynthesized)
the injured area.
 Muscle Spasticity –sustained muscle 2 Phases of depolarizing drug:
contraction or the result of damage to neurons *depolarization phase- allow contraction
within the CNS rather than injury to peripheral * desynthesizing phase- no further aCh
structures. - a continuous muscle spasm that can act on the receptor therefore can then
causes stiffness, rigidity or tightness that can be repolarized
interfere with normal walking, talking or *with continued exposure to
movement. succinylcholine (drug prototype of
depolarizing drug), depolarization cannot
Centrally-Acting Skeletal Muscle Relaxant -Used be allowed because it is already
for the relief of discomfort associate with acute, desynthesized thus letting relaxation *
painful musculoskeletal conditions as an adjunct when giving depolarizing drug there must
to rest, physical therapy, and other measures be initial muscle contraction
Direct-Acting Skeletal Muscle Relaxants –enters
the muscle to prevent muscle contraction directly. NARCOTICS, NARCOTIC
ANTAGONISTS, AND ANTIMIGRAINE
NEUROMUSCULAR JUNCTION BLOCKING AGENTS
AGENTS Narcotics and antimigraine
The Neuromuscular Junction-point which agents provide treatment for acute or
a motor neuron communicates with a skeletal chronic severe pain. These agents exert
muscle fiber; Synapse between a nerve and their effect on the brain and spinal cord to
muscle cell alter the way impulses from peripheral
Neuromuscular Junction-Blocking nerves are processed. As a result, pain
Agents- drugs that are used to prevent the nerve perception and tolerance are altered.
stimulation at the muscle cell and cause paralysis
of the muscle directly without total CNS PAIN- subjective experience of unpleasant
depression and its many systemic effects; affect sensation and emotional experience;
the normal functioning of muscles by interfering occurs whenever tissues are damaged.
with the normal processes that occur at the The injury to cells releases many
junction of nerve and muscle. chemicals, including kinins and
Sarcomere -functional unit of a muscle prostaglandins, which stimulate specific
cell; composed of actin and myosin molecules sensory nerves.
arranged in layers to give the unit a striped or • Acute Pain - typically lasts less
striated appearance. than 3 to 6 months; directly related to soft
Acetylcholine -Function as tissue damage such as a sprained ankle or
neurotransmitter a paper cut; short duration but it gradually
Acetylcholine-receptor site -area on the resolves as the injured tissues heal
muscle cell membrane where Acetylcholine(ACh) • Chronic Pain - ongoing and
reacts with a specific receptor site to cause usually lasts longer than six months; can
stimulation of the muscle in response to nerve continue even after the injury or illness
activity that caused it has healed or gone away
Sliding filament Theory- when actin (thin • Referred pain- perceived at a
filament) and myosin (thick filament) will interlace location other than the site of the painful
stimulus/ origin; result of a network of sensory A fibers, which are associated
interconnecting sensory nerves that with touch.
supplies many different tissues. EX: PAIN PERCEPTION FACTORS:
appendicitis- feel pain at epigastric area • Past experience
• Learned response
PAIN CLASSIFICATION ACCORDING TO • Environmental stimuli
SOURCE
Nociceptive Pain – caused by direct pain (These varied influences on pain
receptor stimulus. Neuropathic Pain- perception and response often make it
caused by nerve injury. Psychogenic Pain- very difficult to effectively evaluate and
associated with emotional, psychological, manage pain.)
or behavioral stimuli
PAIN MANAGEMENT- use scale system to
PAIN IMPULSE TRANSMISSION AND evaluate a patient’s pain [0 (no pain) and
PERCEPTION 10 (worst possible pain)]
Nonpharmacological treatments:
• Two small-diameter sensory nerves, • Warmth
called A-delta and C fibers, respectively, • Massage
respond to stimulation by generating nerve • Positioning
impulses that produce pain sensations. • Acupuncture
• meditation
• A-delta fibers are small, myelinated
fibers that respond quickly to acute pain. Pharmacological methods:
Responds quickly to acute pain. • non-steroidal anti-inflammatory
• C fibers are unmyelinated and are slow drugs or acetaminophen for
conducting. Response to chronic pain. tissue-related pain or atypical
antipsychotics
• Pain impulses from the skin, • other CNS depressants for
subcutaneous tissues, muscles, and deep the treatment of neurogenic
visceral structures are conducted to the pain
dorsal or posterior horn of the spinal cord • The goal is to achieve maximum
on these fibers. pain relief. One major method of
• In the spinal cord, these nerves form pain management involves the
synapses with spinal cord nerves that use of narcotics or opioids - were
send impulses to the brain first derived from the opium plant.
Their actions in the body are
• A fibers are large –diameter sensory related to the stimulation of the
nerves enter the dorsal horn of the spinal various opioid receptors that they
cord; do not transmit pain impulses occupy; bind to opioid receptors
instead, they transmit sensations to relieve pain and promote
associated with touch and temperature; feelings of well-being or euphoria.
larger and conduct impulses more rapidly
than do the smaller fibers, can actually NARCOTIC DRUGS- vary with the type of opioid
block the ability of the smaller fibers to receptors with which they react. Regulated drugs
transmit their signals to the secondary because conducive to addiction.
neurons in the spinal cord. Pain relief and side effects depend on the type of
receptor site.
• The dorsal horn, therefore, can be both Different types of opioid receptors
excitatory and inhibitory with regard to * Reason why opioid is the other name of narcotics:
pain impulses that are transmitted from the initial narcotic agent developed is from opium
the periphery. The impulses reaching the of plants
dorsal horn are transmitted upward • Mu-receptors- primarily pain-blocking
toward the brain by a number of specific receptors BUT stimulating this will let patient suffer
ascending nerve pathways. These from respiratory depression, euphoria, and
pathways run from the spinal cord into the development of physical dependence.
thalamus, where they form synapses with • Delta-receptors- hallucinogenic effects
various nerve cells that transmit the and decreased GI secretions
information to the cerebral cortex, along • Kappa-receptors- associated with some
the spinothalmic tracts. analgesia, papillary constriction, sedation, and
dysphoria. ‘
• According to the gate theory of pain, • Sigma-receptors- papillary dilation,
impulses travel from the spine to the hallucinations, psychoses with narcotic use.
cortex via tracts that can be modulated Classes of Narcotic drugs
along the way at specific gates. These Narcotic Agonists - react with the opioid
gates can be closed to block the receptors throughout the body to cause analgesia,
transmission of pain impulses by sedation, or euphoria
descending nerves from the upper CNS, Narcotic Agonists-Antagonists – stimulate
which relate to emotion, culture, placebo certain opioid receptors but block other such
effect, and stress, and by large-diameter receptors; exert similar analgesic effect with that of
morphine but they have less potential for abuse.
However, they are associated with more psychotic rather than using one drug, commonly involves the
like reactions. following agents:
Narcotic Antagonists – bind strongly to • Preoperative medications, which may
opioid receptors without causing receptor include the use of anticholinergics that
activation; block opioid receptor effects as well as decrease secretions to facilitate
effects of too much opiods in the system intubation and prevent bradycardia
associated with neural depression.
GENERAL AND LOCAL ANESTHETIC AGENTS • Sedative-hypnotics to relax the patient,
Anesthetics - used to cause complete or facilitate amnesia, and decrease
partial loss of sensation; can be subdivided into sympathetic stimulation.
general and local anesthetics, depending on their • Antiemetics to decrease the nausea and
site of action vomiting associated with the slowing of GI
General anesthetics are central nervous activity.
system (CNS) depressants used to produce loss of • Antihistamines to decrease the chance
pain sensation and consciousness; - involves the of allergic reaction and help to dry up
administration of a combination of several different secretions.
general anesthetic agents to achieve the following • Narcotics to aid analgesia and sedation.
goals: Administration of General Anesthesia
(a) analgesia, or loss of pain
perception Stages of General Anesthesia Stage
(b) unconsciousness, or loss of awareness 1 (analgesia stage)- loss of pain sensation,
of one’s surroundings with the patient still conscious and able to
(c) amnesia, or inability to recall what took communicate
place also blocks the body’s reflexes. Stage 2, (excitement stage)- period of
excitement and often combative behavior, with
Blockage of autonomic reflexes prevents many signs of sympathetic stimulation (e.g.,
involuntary reflex response to bodily injury that tachycardia, increased respirations, blood
might compromise a patient’s cardiac, respiratory, pressure changes)
gastrointestinal (GI), and immune status. Blockage Stage 3 (surgical anesthesia)- involves
of muscle reflexes prevents jerking movements relaxation of skeletal muscles, return of regular
that might interfere with the success of the surgical respirations, and progressive loss of eye reflexes
procedure. and pupil dilation
Local anesthetics are drugs used to cause loss of ‘
pain sensation and feeling in a designated area of Surgery can be safely performed in stage 3
the body without the systemic effects associated Stage 4 (medullary paralysis)- is very deep
with severe CNS depression. CNS depression with loss of respiratory and
vasomotor center stimuli, in which death can
Risk Factors Associated with General Anesthesia occur rapidly. If a patient reaches this level, the
• CNS factors: underlying neurological anesthesia has become too intense and the
disease (e.g., epilepsy, stroke, myasthenia situation is critical
gravis) that presents a risk for abnormal
reaction to the CNS-depressing and General anesthesia administration
muscle-relaxing effects of these drugs. phases:
• Cardiovascular (CV) factors: underlying 1. Induction- the period from the beginning
vascular disease, coronary artery disease, of anesthesia until stage 3, or surgical
or hypotension, which put patients at risk anesthesia, is reached. The danger period
for severe reactions to anesthesia, such as for many patients during induction is stage
hypotension and shock, dysrhythmias, 2 because of the systemic stimulation that
and ischemia. occurs. Often a rapid-acting anesthetic is
• Respiratory factors: obstructive used to move quickly through this phase
pulmonary disease (e.g., asthma, chronic and into stage 3. NMJ blockers may be
obstructive pulmonary disease, used during induction to facilitate
bronchitis), which can complicate the intubation, which is necessary to support
delivery of gas anesthetics, as well as the the patient with mechanical ventilation
intubation and mechanical ventilation that during anesthesia.
must be used in most cases of general 2. Maintenance- the period from stage 3
anesthesia. until the surgical procedure is complete. A
• Renal and hepatic function: conditions slower, more predictable anesthetic, such
that interfere with the metabolism and as a gas anesthetic, may be used to
excretion of anesthetics (e.g., acute renal maintain the anesthesia once the patient
failure, hepatitis) and could result in is in stage 3.
prolonged anesthesia and the need for 3. Recovery- the period from
continued support during recovery. Toxic discontinuation of the anesthetic until the
reactions to the accumulation of patient has regained consciousness,
abnormally high levels of anesthetic movement, and the ability to
agents may even occur. communicate. During recovery, the
Balanced Anesthesia- combining of several drugs, patient requires continuous monitoring for
each with a specific effect, to achieve analgesia, any adverse effects of the drugs used, and
muscle relaxation, unconsciousness, and amnesia ensures support of the patient’s vital
functions as necessary.
Local Anesthesia -loss of sensation in limited areas • Propofol- most common opioid IV anesthetic;
of the body; can be achieved by several different potentiates GABA receptor
methods: • Sedation- just to suppress • Hypnotics- also
1. Topical administration- involves the suppresses but focus is on sleep; sleep inducing
application of a cream, lotion, ointment, drugs
or drop of a local anesthetic to • Ketamine problems:
traumatized skin to relieve pain. It can also 1. causes a dissociated state – when the
involve applying these forms to the patient appears to be awake but is
mucous membranes in the eye, nose, unconscious and doesn’t feel the pain;
throat, mouth, urethra, anus, or rectum to you can ask the patient but response
relieve pain or to anesthetize the area to might be/not be true because the one
facilitate a medical procedure. Although functioning is only the subconscious
systemic absorption is rare with topical mind; if letting the patient talk, he will just
application, it can occur if there is damage repeat it over and over until drug effect is
or breakdown of the tissues in the area. gone; effect is shortlasting
2. Infiltration- involves injecting the 2. increases blood pressure; might cause
anesthetic directly into the tissues to be heart attack; the nurse must inform the
treated (e.g., sutured, drilled, cut). This anesthetist that the person has
injection brings the anesthetic into hypertension
contact with the nerve endings in the area • cocaine also increase blood pressure
and prevents them from transmitting nerve • local anesthetics WILL NOT have an anesthetic
impulses to the brain. effect if injected though the vein because blood
3. Field block- involves injecting the that flows through the vein goes to the heart and
anesthetic all around the area that will be throughout the body. Therefore, it will not locally
affected by the procedure or surgery. This affect but generally
is more intense than infiltration anesthesia • before injecting anesthesia to the vein, you have
because the anesthetic agents come in to exsanguinate the vein by ex. @arm- wrap with
contact with all of the nerve endings rubber from the fingertips to the axilla because by
surrounding the area. This type of block is doing so, you are pushing blood towards the body
often used for tooth extractions. thus eliminating the blood in the area. Then tie the
4. Nerve block- involves injecting the area with a tourniquet to prevent backflow of
anesthetic at some point along the nerve blood. After eliminating the blood that is the time
or nerves that run to and from the region in that you will inject anesthesia.
which the loss of pain sensation or muscle • exsanguinate- drainage of blood
paralysis is desired. These blocks are
performed not in the surgical field, but at DRUG LISTS and MECHANISM OF ACTION
some distance from the field. They involve
a greater area with potential for more UNIT 4: DRUGS ACTING ON THE CENTRAL AND
adverse effects. PERIPHERAL NERVOUSSYSTEM
types of nerve blocks: A. Anxiolytics and Hypnotics
• Peripheral nerve block: blockage of the 1. Benzodiazepines- GABA
sensory and motor aspects of a particular nerve for agonist/modulators; :. Increasing effect of GABA; -
relief of pain or for diagnostic purposes. pam
• Central nerve block: injection of a. alprazolam (Xanax)
anesthetic into the roots of the nerves in the spinal b. chlordiazepoxide (Librium)
cord. c. clonazepam (Klonopin) d. clorazepate
• Epidural anesthesia: injection of the drug (Tranxene)
into the epidural space where the nerves emerge e. diazepam (valium)
from the spinal cord. f. estazolam (generic)
• Caudal block: injection of anesthetic into g. flurazepam (generic)
the sacral canal, below the epidural area. h. lorazepam (Ativan)
• Spinal anesthesia: injection of i. midazolam (generic)
anesthetic into the spinal subarachnoid space. j. oxazepam (generic)
k. quazepam (Doral)
5. Intravenous regional (bier block)- involves l. temazepam (Restoril) m. triazolam
carefully draining all of the blood from the patient’s (Halcion)
arm or leg, securing a tourniquet to prevent the EX: person with seizure will be given GABA to inhibit
anesthetic from entering the general circulation, seizure activity
and then injecting the anesthetic into the vein of 2. Barbiturates- GABA
the arm or leg. This technique is used for very agonist/modulators
specific surgical procedures. a. amobarbital (Amytal Sodium)
• All depressants (esp. benzodiazepine) can be b. butabarbital (Butisol)
used as anesthetics c. pentobarbital (Nembutal)
• Naltrexone- opioid antagonist; antidote for opioid d. phenobarbital (Solfoton)
• Flumazenil- benzodiazepine antagonist/antidote e. secobarbital (Seconal)
• Drugs affecting CNS are lipid soluble drugs 3. Other Anxiolytic and Hypnotic
• Generally, anesthetics will cause hypotension drugs
• Opioid can also be used as IV anesthetic a. Antihistamine – H1 receptor antagonist
• Opioids increases blood pressure i. promethazine (generic)
 ii. diphenhydramine (Benadryl)- of norepinephrine and dopamine; for
histamine (H1) receptor antagonist smoking cessation because it mimics
*H1 blocker- antihistamine effect of nicotine
*H2 blocker- decrease formation of acid in b. desvenlafaxine (Pristiq)- blocks the
stomach (famotidine, ranitidine, reuptake of norepinephrine.
cimetidine) c. duloxetine (Cymbalta)- blocks the
b. buspirone (generic)- newer reuptake of norepinephrine
drug; serotonin agonist * d. milnacipran (Savella)- blocks the
serotonin (hydroxytryptamine 5- reuptake of norepinephrine
HT)- sleep juice; increases GI e. mirtazapine (Remeron)- blocks the
activity; comes from tryptophan reuptake of norepinephrine
c. dexmedetomidine (Precedex)- f. nefazodone (generic)- blocks the
alpha-2 adrenoceptor agonist reuptake of norepinephrine
d. eszopiclone (Lunesta)- react g. selegiline (Emsam)- MAOI type b
with GABA sites near inhibitor
benzodiazepine receptors h. trazodone (Desyrel)- blocks the
e. meprobamate (generic) reuptake of norepinephrine
f. ramelteon (Rozarem) - i. venlafaxine (Effexor, Effexor XR)- blocks
melatonin receptor agonists the reuptake of norepinephrine and
* melatonin- hormone secreted dopamine
by pineal gland; responsible for
sleeping; stimulated by darkness; C. Psychotherapeutic Drugs
light will decrease melatonin 1. Antipsychotic/Neuroleptic Drugs-
production dopamine receptor blockers
* hypnotics- sleep inducer; also a
sedative drugs because you a. Typical Antipyschotics (First Gen)-
cannot sleep without being a little dopamine inhibitors
bit sedated * psychosis- poor grasp of reality; the
g. suvorexant Belsomra)- orexin person doesn’t know that he has mental
receptor antagonists disorder
h. tasimelteon (Hetlioz)- * neurosis- the person knows that he has
melatonin receptor agonist mental disorder
i. zaleplon (Sonata) i. chlorpromazine (Thorazine)
j. zolpidem (Ambien) ii. fluphenazine (Prolixin)
B. Antidepressants iii. haloperidol (Haldol)
1. Tricyclic Antidepressants (TCAs)- inhibit iv. loxapine (Loxitane)
presynaptic reuptake (reabsorption) amines v. perphenazine (Trilafon)
a. Amines vi. pimozide (Orap)
i. amitriptyline (generic) vii. prochlorperazine (generic)
ii. amoxapine (generic) viii. thiothixene (Navane)
iii. clomipramine (Anafranil) ix. trifluoperazine (generic)
iv. doxepin (generic) b. Atypical Antipsychotics (Second Gen)-
v. imipramine (Tofranil) Block both dopamine and serotonin
vi. trimipramine (Surmontil) receptors
b. Secondary Amines i. aripiprazole (Abilify)
i. desipramine (Norpramin) ii. asenapine (Saphris)
. nortriptyline (Aventyl, Pamelor) iii. clozapine (Clozaril)
iii. protriptyline (Vivactil) iv. iloperidone (Fanapt)
c. Tetracyclic v. lurasidone (Latuda)
i. maprotiline (generic) vi. olanzapine (Zyprexa, Zyprexa
2. Selective Serotonin Reuptake Inhibitor Zydis)
(SSRI) vii. paliperidone (Invega)
a. citalopram (Celexa) viii. quetiapine (Seroquel,
b. escitalopram (Lexapro) Seroquel XR)
c. fluoxetine (Prozac, Sarafem) ix. risperidone (Risperdal,
d. fluvoxamine (Luvox) Risperdal Conta)
e. paroxetine (Paxil) x. ziprasidone (Geodon
f. sertraline (Zoloft) 2. Antimanic drugs- Inhibits the release of
g. vilazodone (Viibryd) norepinephrine serotonin and dopamine
h. vortioxetine (Brintellix) while facilitating their reuptake into
3. Monoamine Oxidase Inhibitor (MAOI) presynaptic terminals
a. Lithium (Lithobid
a. isocarboxazid (Marplan) b. aripiprazole (Abilify)
b. phenelzine (Nardil) c. olanzapine (Zyprexa, Zyprexa
c. tranylcypromine (Parnate) Zydis)
d. quetiapine (Seroquel)
4. Other Antidepressants- amine reuptake e. ziprasidone (Geodon)
inhibitors f. lamotrigine (Lamictal
a. bupropion (Wellbutrin, Wellbutrin SR, 3. CNS stimulants
Wellbutrin XL, Zyban)- blocks the reuptake
 a. methylphenidate (Ritalin, d. Ezogabine (Potiga)- · Neuronal
Concerta, and others) Potassium Opener; Blocks repolarization;
b. dexmethylphenidate (Focalin) Inhibits Neuronal Firing
c. dextroamphetamine e. Gabapentin (Neurontin)- Potentiate
(Dexedrine) GABA; Inhibits Polysynaptic Responses;
d. lisdexamfetamine (Vyvanse) Blocks Increase of Stimulus
e. amphetamine; modafinil f. Lacosamide (Vimpat)- Inhibits
(Provigil) VoltageSensitive Sodium Channels
f. armodafinil (Nuvigil) g. Rufinamide (Banzel)- Inhibits
g. atomoxetine (Strattera) VoltageSensitive Sodium Channels
h. guanfacine (Intuniv) h. Oxcarbazepine (Trileptal)- · Inhibits
MOA: Voltage- Sensitive Sodium Channels;
• Amphetamine- direct releasers and re- Increase Potassium Conductance;
uptake inhibitors of dopamine and Modulates Calcium-dependent
norepinephrine Presynaptic release of Excitatory
• Non-Amphetamine- block dopamine neurotransmitters
and/or norepinephrine reuptake but i. Levetiracetam (Keppra)-
enhance dopamine release in vivo only potentiates/modifies synaptic release of
• Atomoxetine- NE inhibitor GABA and glutamate activity
D. Antiseizure Drugs j. Lamotrigine (Lamictal)- Inhibits
1. Drugs for Treating Generalized Seizure VoltageSensitive Sodium and calcium
a. Hydantoins- Blocks Voltage-gated Channels; Modulates Calcium-dependent
sodium channels Presynaptic release of Excitatory
i. Phenytoin (Dilantin) neurotransmitters
ii. Fosphenytoin (Cerebyx) k. Pregabalin (Lyrica)- High binding affinity
iii. Ethotoin (Peganone) for Voltage-gated calcium channels in the
Cerebrovascular System
b. Barbiturates and Barbiturate-Like Drugs l. Tiagabine (Gabitril)- Binds to GABA
Potentiates GABA action; Inhibits Impulse reuptake receptors
conduction in the Reticular Activating System m. Topiramate (Topamax)- Blocks Sodium
(RAS) Channels; Potentiate GABA activity
i. n. Vigabatrin (Sabril)- Blocks the enzyme
Phenobarbital(Solfoton,Luminal) GABA=se
ii. Primidone (Mysoline) E. Antiparkinsonism Drugs
c. Benzodiazepines- Potentiate GABA 1. Dopaminergics
action a. Amantadine (generic)- non-
i. Clobazam (Onfi) competitive antagonist of the NMDA
ii. Clonazepam (Klonopin) receptor; antiviral drug
iii. Diazepam (Valium) b. Bromocriptine (Parlodel)-
d. Succinimides- Decrease calcium influx stimulating the nerves that control
through the T-type calcium channels; treat movement; dopamine receptor agonist;
absence seisures promotes effect of dopamine; an ergot
i. Ethosuximide (Zarontin) alkaloid
ii. Methsuximide (Celontin) *apomorphine- another
e. Other Drugs for Treating Absence Seizures dopamine agonist
i. Acetazolamide (Diamox)- Alter Na+ and * pergolide- another ergot
Ca+ channels; is a diuretic; carbonic alkaloid
anhydrase inhibitor; use in seizure c. Levodopa (Dopar)- Precursor of
because decreases body fluid; the dopamine synthesis
problem of this is the tolerance is very high i. Carbidopa-levodopa
thus patient easily gets tolerated; used to (sinemet)- Decarboxylase
treat acidosis *carbonic anhydrase - enzyme inhibitor
enzyme that assists rapid inter - d. Pramipexole (Mirapex)- a
conversion of carbon dioxide and water nonergot dopamine agonist
into carbonic acid e. Rasagiline (Azilect)- irreversible
ii. Zonisamide (Zonegram)- Inhibits inhibitor of monoamine oxidase-B (MAOI-
voltage-sensitive sodium and calcium B)
channels; Modulate calcium –dependent f. Ropinirole (Requip)- stimulate
presynaptic release of excitatory dopamine D2 receptors
neurotransmitters g. Rotigotine (Neupro)- agonist at
iii. Valproic Acid (Depakene)- Potentiate all 5 dopamine receptor subtypes (D1-D5)
Gaba and decreases electrical activity
2. Drugs for Treating Partial Seizure 2. Anticholinergics- block acetylcholine therefore
a. Carbamazepine (Tegretol, Epitol)- reversing effect of parasympathetic activity;
Prolong inactivated sodium channel; muscarinic receptor blockers
Inhibits Polysynaptic Responses 1. Benztropine (Cogentin)- antagonizes
b. Clorazepate (Tranxene, Gen-Xene)- acetylcholine and histamine receptors
Potentiate effect of GABA 2. Diphenhydramine (Benadryl)-
c. Felbamate (Felbatol)- Potentiate effect intracellular sodium channel blocker
of GABA; Blocks NDMA receptors
 3. Trihexyphenidyl (generic)- viii. Morphine (Roxanol,
intracellular sodium channel blocker Astramorph)
3. Adjunctive- second treatment in conjunction ix. Opium (Paregoric)
with primary treatment x. Oxycodone (OxyContin)
1. Entacapone (comtan)- inhibit COMT xi. Oxymorphone (Generic)
(catechol-O-methyltransferase) xii. Remifentanil (Ultiva)
2. Tolcapone (tasmar)- inhibit COMT; alter xiii. Sufentanil (Sufental)
the plasma pharmacokinetics of levodopa xiv. Tapentadol (Nucynta)
3. Selegeline (eldepryl)- irreversible xv. Tramadol (Ultram)
inhibitor of monoamine oxidase (MAO)
b. Narcotic Agonist- Antagonists-
* side effect: constipation because of Stimulate certain opioid receptors but block other
blocking muscarinic receptors meaning blocking such receptors
parasympathetic activity i. Buprenorphine (Buprenex)
ii. Butorphanol (Generic)
F. Muscle Relaxants iii. Nalbuphine (Generic)
1. Centrally - Acting Skeletal Muscle iv. Pentazocine (Talwin)
Relaxants - not fully known; inhibit multisynaptic c. Narcotic Antagonists- Bind strongly to
reflex arcs opioid receptors without causing receptor
a. Baclofen (Lioresal) activation
b. Carisprodol (Soma) i. Naloxone (Evzio)
c. Chlorzoxazone (Parafon) ii. Naltrexone (ReVia)
d. Cyclobenzaprine (Amrix) 2. Antimigraine Agents
e. Metaxalone (Skelaxin) a. Ergot Derrivatives- Block alpha-
f. Methocarbamol (Robaxin) adrenergic and serotonin receptor sites in
g. Orphenadrine (Banflex,Flexon) the brain * avamigran- used to have
h. Tizanidine (Zanaflex ) ergotamine but now it is removed; now it is
i. Diazepam (Valium ) already and NSAID
2. Direct-Acting Skeletal Muscle i. Dihydroergotamine (Migranal,
Relaxants D.H.E. 45)
a. Dantrolene (Datrium) – causes calcium ii. Ergotamine (Ergomar)
efflux out of the cell; acts intracellularly in b. Triptan- Binds to selective
skeletal muscle to lessen the excitation – serotonin receptor sites
contraction coupling interaction between i. Almotriptan (Axert)
actin and myosin within the individual ii. Eletriptan (Relpax)
sarcomere iii. Frovatriptan (Froval)
b. Incobotulinum Toxin A (Xeomin) iv. Naratriptan (Amerge)
c. Onabotolunium toxin A (Botox botox v. Rizatriptan (Maxalt)
Cosmetics) vi. Sumatriptan (Imetrix)
* botulinum toxin- paralyzation of vii. Zolmitriptan (Zomig)
nerves causing relaxation (local I. Local and General Anesthetics
paralysis) 1. General Anesthetic Agents-
d. Rimabotulinum toxin type B (Myobloc) enhaled; administered for maintenance
G. Neuromuscular Junction Blocking Agents • All inhaled anesthetics cause
1. Depolarizing NMJs Blocking Agent- ACh hypotension
agonist; prevents repolarization resulting to a. Barbiturate Anesthetics-
paralysis of muscles; allow muscle to contract Enhanced GABA action
a. Succinylcholine (Anectine,Quelicin)- i. methohexital (Brevital)
ACh agonist b. Nonbarbiturate General
2. Non-depolarizing NMJs Blocking Agent- Anesthetics
ACh antagonist; not letting contraction; curare i. droperidol (Inapsine)
based medication ii. etomidate (Amidate)-
a. Atracurium (Tracrium) potentiates GABA
b. Cisatracurium (Nimbex) iii. ketamine (Ketalar)- NMDA
c. Pancuronium (Pavulon) receptor antagonist
d. Rocuronium (Zemuron) iv. midazolam (generic)
e. Vecuronium (Norcuron) v. propofol (Diprivan)- potentiates
H. Narcotics and Antimigraine Drugs GABA
1. Narcotic Drugs c. Anesthetic Gases
a. Narcotic Agonists- binds to mu-oppiate i. nitrous oxide (Blue)- 1st
and kappa-oppiate receptors on nerves; Inhibits inhalation anesthetics d. Volatile Liquids i.
release of neurotransmitters; Mu-receptor agonist desflurane (Suprane)
i. Codeine ii. enflurane (Ethrane)
ii. Fentanyl (Actic, Duragesic) iii. isoflurane (generic)
iii. Hydrocodone (Hysingla ER, iv. sevoflurane (Ultane)
Zohydro ER ) 2. Local Anesthetic Agents- inhibit
iv. Hydromorphone (Dilaudid) transmission of nerve impulses; block
v. Levarphanol (Generic) sodium channels; given as ointment;
vi. Meperidine (Demerol) Eutectic Mixture of Local Anesthetics
vii. Methadone (Dolophine) (EMLA)
• EMLA- composed of Lidocaine and • Muscarinic receptors-
Prilocaine; topical anesthetic; usually cholinergic receptors
used when injecting and you don’t want it that also respond to stimulation
to hurt much BUT it can easily evaporate; of muscarine
also used when removing tags/warts at • Nicotinic receptors- cholinergic
face and cover the area to avoid receptors that
evaporation and have a local topical also respond to stimulation by
anesthetic effect nicotine
a. Esters • Parasympathetic nervous
i. benzocaine (Dermoplast, system- “rest-anddigest”
Lanacane, Unguentine) response mediator that contains
ii. chloroprocaine (Nesacaine) CNS
iii. tetracaine (Pontocaine) cells from the cranium or sacral
b. Amides area of spinal
i. bupivacaine (Marcaine, cord, long preganglionic axons,
Sensorcaine) ganglia near or
ii. dibucaine (Nupercainal) within effector tissue, and short
iii. lidocaine (Dilocaine, postganglionic
Solarcaine, Xylocaine, Lidoderm, axons that react with cholinergic
Octocaine) receptors
iv. mepivacaine (Carbocaine, • Sympathetic nervous system-
Isocaine, Polocaine) “fight-or-flight”
v. prilocaine (Citanest Dental) response mediator; composed of
vi. ropivacaine (Naropin c. Other i. CNS cells fro
pramoxine (Tronothane, the thoracic or lumbar areas,
PrameGel, Itch-X, Prax) short preganglionic
axons, ganglia near the spinal
UNIT 5: Drugs Acting on the cord, and long
Autonomic Nervous System postganglionic axons that react
Introduction to the Autonomic with adrenergic
Nervous System receptors
Key Terms: AUTONOMIC NERVOUS SYSTEM-
• Acetylcholinesterase- enzyme sometimes called
responsible for the involuntary or visceral
immediate breakdown of nervous system because it
acetylcholine when mostly functions with the person
released from the nerve ending; having little conscious
prevent awareness of its activity.
overstimulation of cholinergic • Working closely with the
receptor sites endocrine system the ANS
• Adrenergic receptors- receptor helps to regulate and integrate the
sites on body’s internal
effectors that respond to functions within a relatively
norepinephrine/epinephrine. narrow range of normal
• Alpha-receptors- adrenergic on a minute-to-minute basis.
receptors found in • The ANS integrates parts of the
smooth muscles central nervous
• Autonomic nervous system- system (CNS) and peripheral
portion of central nervous system to
and peripheral nervous system automatically react to changes in
that, the the the internal and
endocrine system, functions to external environments
maintain internal Structure and Function of the
homeostasis Autonomic Nervous
• Beta-receptors- adrenergic System
receptors that are • The main nerve centers for the
found in the heart, lungs, and ANS are located in
vascular the hypothalamus, the medulla,
smooth muscle and the spinal
• Cholinergic receptors- receptor cord.
sites on • Nerve impulses that arise in
effectors that respond to peripheral structures are
acetylcholine carried to these centers by
• Ganglia- group of closely packed afferent nerve fibers.
nerve cell • These integrating centers in the
bodies CNS respond by
• Monoamide oxidase (MAO)- sending out efferent impulses
enzyme that along the autonomic
break down norepinephrine to nerve pathways.
make it inactive
• These impulses adjust the -Dilation
functioning of various 2
internal organs in ways that keep Divisions of ANS
the body’s internal 1. Sympathetic nervous system
environment constant, or (SNS)
homeostatic. 2. Parasympathetic nervous
• At every moment, signals flood system
from the visceral These two branches differ in three
organs into the CNS, and the basic ways:
autonomic nervous (1) the location of the originating
system makes adjustments as cells in the CNS
necessary to best (2) the location of the nerve
support body activities. ganglia
• For example, blood flow may be (3) the preganglionic and
shunted to more postganglionic neurons
“needy” areas, heart and Sympathetic Nervous System
breathing rate may be • The SNS is sometimes referred
speeded up or slowed down, to as the “fight-orflight” system,
blood pressure may be or the system responsible for
adjusted, and stomach preparing the body to respond to
secretions may be increased stress.
or decreased. • For the most part the SNS acts
Nerve Impulse Transmission much like an
• Throughout the ANS, nerve accelerator, speeding things up
impulses are carried for action.
from the CNS to the outlying Structure and Function
organs by way of a twoneuron • The SNS is also called the
system. thoracolumbar system
• In most peripheral nervous because the CNS cells that
system activities the CNS originate impulses for
nerve body sends an impulse this system are located in the
directly to an effector thoracic and lumbar
organ or muscle. sections of the spinal cord.
• The ANS does not send impulses • These cells send out short
directly to the preganglionic fibers
periphery. that synapse or communicate
• Instead, axons from CNS with nerve ganglia
neurons end in ganglia, or located in chains running
groups of nerve bodies that are alongside the spinal cord.
packed together, • Acetylcholine (ACh) is the
located outside of the CNS. neurotransmitter
• These ganglia receive released by these preganglionic
information from the nerves;
preganglionic neuron that started parasymthetic
in the CNS and • The nerve ganglia, in turn, send
relay that information along out long
postganglionic neurons. postganglionic fibers that
• The postganglionic neurons synapse with
transmit impulses to the neuroeffectors, using
neuroeffector cells—muscles, norepinephrine or
glands, and organs. epinephrine as the
COMPARISON ON HOW neurotransmitter for sympathetic
SOMATIC AND AUTONIMIC • One of the sympathetic ganglia,
NERVOUS SYSTEM SEND on either side of the
IMPULSES FROM CNS TO spinal cord, does not develop
EFFECTOR MUSCLE postganglionic axons
Functions but produces norepinephrine and
• The ANS works to regulate blood epinephrine, which
pressure, heart are secreted directly into the
rate, respiration, body bloodstream.
temperature, water • These ganglia have evolved into
balance, urinary excretion, and the adrenal
digestive medullae.
functions, among other things. • When the SNS is stimulated the
This system exerts chromaffin cells of
minute-to-minute control of body the adrenal medullae secrete
responses, which is epinephrine and
balanced by the two divisions of norepinephrine directly into the
the ANS. bloodstream.
Constriction -
*Adrenal medula- organ that thyroid-stimulating hormone,
erelease epinephrine which stimulates the
• When stimulated the SNS production and release of thyroid
prepares the body to flee hormone, which
or to turn and fight. increases metabolism and the
• Cardiovascular activity efficient use of
increases, as do blood energy.
pressure, heart rate, and blood *when sympathetic the bronchus
flow to the skeletal dilates to allow breathing
muscles. *when having asthma, not
• Respiratory efficiency also administer parasympathetic drug
increases; bronchi dilate because it constricts bronchus
to allow more air to enter with *Sympathetic drugs increase
each breath, and the heart rate that’s why asthma
respiratory rate increases. patients given these drugs can
• Pupils dilate to permit more light breathe well but extreme heart
to enter the eye, to rate
improve vision in darkened areas *sympathetic- pupils dilate
• Sweating increases to dissipate *Adrenergic=
heat generated by Sympathetic/Epinephrine
the increased metabolic activity. because
• Piloerection (hair standing on predominant neurotransmitter of
end) also occurs. sympathetic is Epinephrine
• Stimulation of the SNS causes *Cholinergic= parasympathetic
blood to be diverted because the predominant
away from the gastrointestinal neurotransmitter of
(GI) tract because parasympathetic is acetylcholine
there is no real need to digest food Adrenergic Response
during a flight-orfight situation. • Sympathetic postganglionic
• Blood is also diverted away from nerves that synthesize,
other internal store, and release norepinephrine
organs, including the kidneys, are referred to as
resulting in activation adrenergic nerves.
of the renin–angiotensin system • The chromaffin cells of the
and a further adrenal medulla also
increase in blood pressure and are adrenergic because they
blood volume as synthesize, store, and
water is retained by the kidneys. release norepinephrine, as well as
• Several other metabolic epinephrine.
activities occur that prepare Norepinephrine Synthesis and
the body to fight or flee. Storage
• For example, glucose is formed • Norepinephrine belongs to a
by glycogenolysis to group of structurally
increase blood glucose levels and related chemicals called
provide energy. catecholamines that also
• The hypothalamus causes the includes dopamine, serotonin,
secretion of and epinephrine.
adrenocorticotropic hormone, • Norepinephrine is made by the
leading to a release of nerve cells using
the adrenal hormones, including tyrosine, which is obtained in the
cortisol, which diet.
suppresses the immune and • Dihydroxyphenylalanine (DOPA)
inflammatory reactions is produced by a
to preserve energy that otherwise nerve, using tyrosine from the diet
might be used by and other
these activities. chemicals.
• The corticosteroid hormones • With the help of the enzyme
also block protein DOPA decarboxylase
production, another energy- the DOPA is converted to
saving activity, and dopamine, which in turn is
increase the release of glucose to converted to norepinephrine in
provide energy. adrenergic cells.
• Aldosterone, also released with • The norepinephrine then is
adrenal stimulation, stored in granules or
retains sodium and water and storage vesicles within the cell.
causes the excretion • These vesicles move down the
of potassium in the urine. nerve axon to the
• The hypothalamus also causes terminals of the axon, where they
the release of line up along the
cell membrane.
• To be an adrenergic nerve the • Once norepinephrine has been
nerve must contain all released into the
of the enzymes and building synaptic cleft, stimulation of the
blocks necessary to receptor site is
produce norepinephrine terminated and disposal of any
Norepinephrine Release extra norepinephrine,
• When the nerve is stimulated as well as the neurotransmitter
the action potential that has reacted with
travels down the nerve axon and the receptor site, must occur.
arrives at the axon • Most of the free norepinephrine
terminal. molecules are taken
• The action potential then up by the nerve terminal that
depolarizes the axon released them in a
membrane. process called reuptake.
* Pupils-dilate • Enzymes are also in the area, as
* Bronchi-dilate well as in the liver,
* Urinarydecrease to metabolize or biotransform any
* GI decrease remaining
3 norepinephrine or any
This action allows calcium into norepinephrine that is
the nerve, causing the absorbed into circulation.
membrane to contract and the • These enzymes are monoamine
storage vesicles to fuse with oxidase (MAO) and
the cell membrane, releasing catechol-O-methyl transferase
their load of norepinephrine into (COMT).
the synaptic gap or cleft. Parasympathetic Nervous System
Adrenergic Receptors + In many areas the
• Adrenergic receptors can be parasympathetic nervous system
stimulated by the works in opposition to the SNS.
neurotransmitter released from This allows the
the axon in the autonomic system to maintain a
immediate vicinity, and they can fine control over
be further stimulated internal homeostasis.
by circulating norepinephrine and + Whereas the SNS is associated
epinephrine with the stress
secreted directly into the reaction and expenditure of
bloodstream by the adrenal energy, the
medulla. parasympathetic system is
• The receptor sites that react associated with activities
with neurotransmitters that help the body to store or
at adrenergic sites have been conserve energy, a
classified as alphareceptors and “rest-and-digest” response
beta-receptors. These receptors Structure and Function
are • Parasympathetic system
further classified as alpha1- someties called
,alpha2-, beta1-, and craniosacral system because the
beta2-receptors CNS neurons that
Alpha-Receptors originate parasympathetic
• Alpha1-receptors are found in impulses are found in the
blood vessels, in the cranium (one of the most
iris, and in the urinary bladder. mportant being the vagus)
• Alpha2-receptors are located on and sacral area of the spinal cord
nerve membranes Parasympathetic system
and act as modulators of stimulation resultd the following
norepinephrine release. actions:
Beta-Receptors • Increased motility and
• Beta1-receptors are found in secretions in GI tract to
cardiac tissue, where promote digestion and absorption
they can stimulate increased of nutrients
myocardialactivity and • Constriction of bronchi, with
increased heart rate. increased secretions.
• They are also responsible for Relaxation of the GI and urinary
increased lipolysis or sphincters, allowing
breakdown of fat for energy in evacuation of waste products
peripheral tissues. • Pupillary constriction, which
• Beta3-receptors are found in the decreases the light
kidney and help to entering the eye and decreases
stimulate the renin–angiotensin– stimulation of retina.
aldosterone system. 4
Termination of Response Cholinergic Response
• Neurons that uses Ach as their ➢ also called a sympathomimetic
neurotransmitter are called drug because it mimics the
cholinergic neurons effects of the sympathetic
4 basic kinds of cholinergic nervous system (SNS).
nerves: ➢ A drug that stimulates the
1. All preganglionic nerves in ANS, adrenergic receptors of the
both sympathetic and sympathetic nervous system,
parasympathetic either directly (by reacting
2. Postganglionic nerves of with receptor sites) or indirectly
parasympathetic system and few (by increasing
SNS nerves, such as those that norepinephrine levels)
reenter the spinal cord and A. ALPHA- SPECIFIC
cause general body reactions ADRENERGIC AGONIST
such as sweating. B. BETA- SPECIFIC ADRENERGIC
3. Motor nerves on skeletal AGONISTS- Most of the
muscles drugs that belong to the class of
4. Cholinergic nerves within the beta-specific adrenergic
CNS agonists, or beta-agonists,are
Acetylcholine Synthesis and beta2-specific agonists and
Storage are used to manage and treat
• Ach is an ester of acetic acid and bronchial spasm, asthma,
an organic alcohol called and other obstructive pulmonary
choline. Cholinergic nerves use conditions.
choline, obtained in diet, to C. BOTH ALPHA AND BETA-
produce Ach. RECEPTOR- Alpha- and
• Just like norepinephrine, the Ach betaadrenergic agonists
is produced in the nerve stimulate all of the adrenergic
and travels to the end of the receptors
axons, where it is packaged in the SNS. They induce a fight-or-
into vesicles flight response and are
• To be a cholinergic nerve the frequently used to treat shock.
nerve must contain all the II. ANDRENERGIC ANTAGONIST-
enzymes and building blocks also called sympatholytic drugs
necessary to produce ACh. because they lyse, or block, the
Acetylcholine release effects of the sympathetic
• The vesicle full of ACh move to nervous system (SNS). The
the nerve membrane; when therapeutic and adverse effects
an action potential reaches the associated with these drugs are
nerve terminal, calcium related to their
entering the cell causes the adrenergicreceptor-site
membrane to contract and specificity; that is, the ability to
secrete the neurotransmitter into react with specific
the synaptic cleft. adrenergic receptor sites without
• The ACh travels across the activating them, thus
synaptic cleft and reacts with preventing the typical
very specific cholinergic receptor manifestations of SNS activation.
sites on the effector cell. By
Cholinergic/ACh receptors- found occupying the adrenergic
on organs and muscles; receptor site, they prevent
classified as muscarinic norepinephrine released from the
receptors and nicotinic receptors. nerve terminal or from the
Muscarinic Receptors-stimulate adrenal medulla from activating
muscarine; found in visceral the receptor, thus blocking the
effector SNS effects.
organs (GI tract, bladder, heart, A. Nonselective Adrenergic
sweat glands, some vascular Blocking Agents- Drugs that
smooth block both alpha- and beta-
muscle adrenergic receptors are
Nicotinic receptors- at CNS, primarily used to treat cardiac-
adrenal medulla, autonomic related conditions.
ganglia, B. Nonselective Alpha-Adrenergic
and neuromuscular junction Blocking Agents
Termination of Response- once C. Alpha1-Selective Adrenergic
the effector cell has been Blocking Agents
stimulated by ACh, Stimulation of D. Nonselective Beta-Adrenergic
receptor site must be terminated Blocking Agents
and destruction of any ACh must E. Beta1-Selective Adrenergic
occur. Blocking Agents- have an
DRUGS advantage over the nonselective
I. ANDRENERGIC AGONIST beta-blockers in some
cases. Because they do not Cholinergic Agonists
usually block beta2-receptor CHILDREN
sites, they do not block the + Children may be more
sympathetic bronchodilation that susceptible to the adverse effects
is so important for patients with associated with the cholinergic
lung diseases or allergic agonists, including GI upset,
rhinitis. diarrhea, increased salivation
III. CHOLINERGIC AGONISTS that could lead to choking,
GLOSSARY OF KEY TERMS and loss of bowel and bladder
• acetylcholinesterase: enzyme control, a problem that could
responsible for the cause stress in the child.
immediate breakdown of ~ bind to alpha-receptors
acetylcholine when released from Ldopamine
the nerve ending; prevents 5
overstimulation of cholinergic + Bethanechol is approved for the
receptor sites treatment of neurogenic
• Alzheimer’s disease: bladder in children older than 8
degenerative disease of the cortex years of age.
with loss of acetylcholine- + Neostigmine and
producing cells and cholinergic pyridostigmine are used in the
receptors; characterized by control
progressive dementia of myasthenia gravis and for
• cholinergic agonists: reversal of neuromuscular
responding to acetylcholine; junction blocker effects in
refers children.
to receptor sites stimulated by + Edrophonium is used for
acetylcholine, as well as diagnosis of myasthenia gravis
neurons that release only.
acetylcholine ADULTS
• miosis: constriction of the pupil; + Adults should be cautioned
relieves intraocular about the many adverse effects
pressure in some types of that can be anticipated when
glaucoma using a cholinergic agonist.
• myasthenia gravis: autoimmune Flushing, increased sweating,
disease characterized by increased salivation and GI
antibodies to cholinergic receptor upset, and urinary urgency often
sites, leading to occur. The patient also
destruction of the receptor sites needs to be aware that dizziness,
and decreased response at drowsiness, and blurred
the neuromuscular junction; it is vision may occur and that driving
progressive and and operating dangerous
debilitating, leading to paralysis machinery should be avoided.
• nerve gas: irreversible OLDER ADULTS
acetylcholinesterase inhibitor + Older patients are more likely to
used experience the adverse
in warfare to cause paralysis and effects associated with these
death by prolonged drugs—CNS, cardiovascular,
muscle contraction and GI, respiratory, and urinary
parasympathetic crisis effects. Because older patients
• parasympathomimetic: often have renal or hepatic
mimicking the effects of the impairment, they are also more
parasympathetic nervous system, likely to have toxic levels of the
leading to bradycardia, drug related to changes in
hypotension, pupil constriction, metabolism and excretion.
increased gastrointestinal A. DIRECT-ACTING
secretions and activity, increased CHOLINERGIC AGONISTS-
bladder tone, relaxation similar to
of sphincters, and Ach and react directly with
bronchoconstriction receptor sites to cause the same
• Cholinergic agonists act at the reaction as if Ach had stimulated
same site as the the receptor sites. These
neurotransmitter acetylcholine drugs usually stimulate
(ACh) and increase muscarinic receptors within the
the activity of the ACh receptor parasympathetic system. They
sites throughout the are used as systemic agents
body to increase bladder tone, urinary
• Cholinergic agonists work either excretion, and
directly or indirectly gastrointestinal (GI) secretions
DRUG THERAPY ACROSS THE and as ophthalmic agents to
LIFESPAN
induce miosis to relieve the for any patient receiving indirect-
increased intraocular pressure acting cholinergic agonists
of glaucoma. Systemic to treat myasthenia gravis. The
absorption usually does not occur patient and a significant
when these drugs are used other should understand when to
ophthalmically. use the drug and how to
B. INDIRECT ACTING administer it.
CHOLINERGIC AGONISTS- do not • The reversible indirect-acting
react cholinergic agonists fall into
directly with ACh receptor sites; two main categories: (1)agents
instead, they react chemically used to treat myasthenia
with acetylcholinesterase (the gravis and (2) agents used to treat
enzyme responsible for the Alzheimer’s disease.
breakdown of ACh) in the synaptic Agents for Myasthenia Gravis
cleft to prevent it from • Myasthenia gravis is a chronic
breaking down ACh. As a result, muscular disease caused by
the ACh that is released from a defect in neuromuscular
the presynaptic nerve remains in transmission. It is thought to be
the area and accumulates, an autoimmune disease in which
stimulating the ACh receptors for patients make antibodies
a longer period of time than to their ACh receptors. These
normally expected. These drugs antibodies cause gradual
work at all ACh receptors, in the destruction of the ACh receptors,
parasympathetic nervous system, resulting in fewer and
in the central nervous system fewer receptor sites available for
(CNS), and at the neuromuscular stimulation. ACh is
junction. Most of these drugs theneurotransmitter that is used
bind reversibly to at the nerve–muscle
acetylcholinesterase, so their synapse.
effects pass with 6
time when the Alzheimer’s Disease
acetylcholinesterase is released + Alzheimer’s disease is a
and allowed to chronic, progressive disease of
break down ACh. the
Nerve Gas: An Irreversible brain’s cortex. Eventually it results
Indirect-Acting Cholinergic in memory loss so
AgonistDeveloped as a weapon, severe that the patient may not
nerve gas is an irreversible remember how to perform
acetylcholinesterase inhibitor. basic activities of daily living and
The drug is inhaled and quickly may not recognize close
spreads family members. Although
throughout the body, where it Alzheimer’s disease primarily
permanently binds with strikes the elderly, it has a
acetylcholinesterase. tremendous impact on family
Pralidoxime: Antidote for members of all ages. For example,
Irreversible Indirect-Acting adult children of
Cholinergic Alzheimer’s patients, many of
Agonists whom are busy raising
• Pralidoxime (Protopam children of their own, may find
Chloride), the antidote for themselves in the role of
irreversible caregivers—in essence,
acetylcholinesteraseinhibiting becoming parents of their parent.
drugs, or nerve This new role can put tremendous
gas, is given IM or IV to reactivate stress on individuals who
the acetylcholinesterase are trying to struggle with work,
that has been blocked by these family, and issues related to
drugs. Freeing up the their parent’s care.
acetylcholinesterase allows it to + The cause of the disease is not
break down accumulated yet known, but it is known
acetylcholine that has that there is a progressive loss of
overstimulated ACh receptor ACh-producing neurons
sites, and their target neurons in the
causing paralysis. cortex of the brain. These
• Pralidoxime does not readily neurons seem to be related to
cross the blood–brain barrier, memory and associations
and it is most useful for treating between memories that allow
peripheral drug effects. It connections between
reacts within minutes after thoughts and stimuli
injection and should be available Another Treatment for
Alzheimer’s Disease
+ In late 2003 the U.S. Food and Adults
Drug Administration ➢ They should be encouraged to
approved a new drug for treating void before taking the
Alzheimer’s disease. The medication if urinary retention or
drug, memantine hydrochloride hesitancy is a problem.
(Namenda), had been used ➢ They should be encouraged to
in Europe for several years and drink plenty of fluids and to
had been reported to slow avoid hot temperatures because
the memory loss of patients with heat intolerance can occur
moderate to severe and it will be important to
dementia associated with maintain hydration should this
Alzheimer’s disease. Memantine happen.
has a low to moderate affinity for ➢ These drugs should not be
NMDA receptors with no used during pregnancy because
effects on dopamine, gamma- they cross the placenta and could
aminobutyric acid, histamine, cause adverse effects on
glycine, or adrenergic receptor the fetus.
sites. It is thought that Older Adults
persistent activation of the CNS
➢ are more likely to experience
NMDA receptors
the adverse effects
contributes to the symptoms of
associated with these drugs; dose
Alzheimer’s disease. By
should be reduced, and
blocking these sites, it is thought
the patient should be monitored
that the symptoms are
very closely
reduced or delayed.
➢ because older patients are
+ The drug is available in a tablet
more susceptible to heat
form and an oral solution
intolerance owing to decreased
and is started at 5mg/d PO,
body fluid and decreased
increasing by 5 mg/d at weekly
sweating, extreme caution should
intervals. The target dose is 20
be used when an
mg/d given as 10 mg twice
anticholinergic drug is given.
daily. Dose reduction should be
considered in patients with ➢ Older adults may also have
renal impairment. Headache, renal impairment, making them
dizziness, fatigue, confusion, more likely to have problems
and constipation are common excreting these drugs.
adverse effects. The drug These drugs can be used to:
should not be taken with anything ✓ decrease secretions before
that alkalinizes the urine. anesthesia
Patients and family members ✓ treat parkinsonism
need to understand that this ✓ restore cardiac rate and blood
drug is not a cure but may offer pressure after vagal
some extended time with stimulation during surgery
mild symptoms. The long-term ✓ relieve bradycardia
effects of this drug have not ✓ relieve pylorospasm and
been studied in the United States. hyperactive bowel
ANTICHOLINERGICS ✓ signs and symptoms of motion
sickness and vomiting
➢ drug that opposes (block) the
7
effects of
SUMMARY (EXPLAINED)
acetylcholine at acetylcholine
• nervous system divided into:
receptor sites.
CNS and PNS
➢ BLOCKS THE
• PNS= Somatic and Autonomic
PARASYMPATHETIC. Result :
• Autonomic= Sympathetic,
SYMPATHETIC PREDOMINATES
Parasympathetic,
➢ Atropine is the only widely used and Enteric
anticholinergic • Sympathetic (adrenergic)- fight
drug or flight;
DRUG THERAPY ACROSS THE stimulant; increase activity; aka
LIFESPAN thoracolumbar
Children outflow; neurotransmitter=
➢ If a child is given one of these norepinephrine and
drugs the child should be epinephrine
closely watched and monitored EFFECTS OF EPINEPHRINE
for adverse effects, and 1. lipolysis- dissolution of fats
appropriate supportive measures *fatty acid- product of dissolution
should be instituted. of fats; can be
➢ Dicyclomine must not be used converted to glucose; glucose is
in children younger than 6 energy therefore you have
months old because of the risk of energy to fight or flight
serious side effects.
2. proteolysis- causes protein *cholinergic receptors/
metabolization cholinoceptors- named
*amino acid- product of protein according
metabolism; can be to alkaloids (muscarine and
converted to glucose nicotine) used to determine
3. glycogenolysis- breaking down them
of glycogen to glucose CHOLINERGIC RECEPTORS
from the liver 1. Muscarinic receptors
*THEREFORE INCREASE IN 2. nicotinic receptors
EPINEPHRINE GIVES A LOT ADRENERGIC RECEPTORS
OF ENERGY* 1. alpha-1 receptors- at smooth
EFFECTS OF SYMPATHETIC muscles; stimulation
NERVOUS SYSTEM of this causes contraction of
1. Increased heart rate smooth muscle
2. Increased blood pressure 2. alpha-2 receptors- found in
because of intestinal smooth
vasoconstriction muscles; stimulation of this
*the smaller the lumen of blood causes GI tract relaxation
vessel the greater and no movement
the pressure 3. beta-1 receptors- cause
3. Blood shunted to skeletal increase in cardiac
muscles causing increase contraction; stimulation of heart
of action rate
4. Blood glucose increase 4. beta-2 receptors – causes
NEGATIVE EFFECTS OF relaxation of smooth
SYMPATHETIC muscle
1. GI tract decreased activity *alpha receptor- for
2. Bronchus and bronchioles will excitation/stimulation except
dilate intestinal
3. Pupils dilate smooth muscles
• Parasympathetic (cholinergic) - *beta receptors- inhibitory to all
rest and tissues except heart
digest; decrease activity; aka *alpha-1 and beta-1 –for
craniosacral stimulation
outflow; *alpha-2 and beta-2 – for
neurotransmitter=acetylcholine relaxation
*when acetylcholine will be *beta-2 agonist- cause dilation of
extruded to the synaptic bronchus; treat bronchial
cleft, some of it will be reuptake spasm (bronchial asthma, COPD)
back to the cell *to treat bronchial spasm
*to treat myasthenia gravis, (bronchial asthma, COPD); let
prevent reuptake of bronchus to relax for it to dilate
acetylcholine or prevent *beta blocker- decrease heart
destruction of acetylcholine rate; constriction of bronchus;
• Enteric- unofficial 3rd division of treat hypertension
autonomic *do not use beta blockers to
nervous system because this patients who have hypertension
have a direct and bronchial asthma
control over gastrointestinal *almost all beta-2 antagonists
system generally have slight effect on
STEPS OF NEUROTRANSMITTER beta-1
FUNCTION (ACh) 8
1. Synthesis of ACh DRUG LISTS and MECHANISM OF
2. Storage of ACh at vesicle ACTION
3. Release of ACh UNIT 5: Drugs Acting on the
4. Attachment to receptor site Autonomic Nervous System
5. Termination of action- I. ANDRENERGIC AGONIST-
destruction of ACh by sympathetic
acetylcholinesterase A. ALPHA- SPECIFIC
*every step can be blocked ADRENERGIC AGONIST
*transporters- carries 1. Pheneylephrine (Neo-
neurotransmitters in and out of Synephrine)- Agonist of
membrane ɑ1 – Adrenoceptors
*Norepinephrine Transporter 2. Midodrine (ProAmantine)-
(NET)- transporter of Alpha1- Agonist
norepinephrine 3. Clonidine (Catapres)- alpha-2
*Choline Transporter- transporter adrenergic
of acetylcholine agonist
B. BETA- SPECIFIC ADRENERGIC
AGONISTS
1. Isoproterenol (Isuprel)- Beta 1 1. Phentolamine (Regitine)-
and Beta2 Blocks the
adrenergic receptor agonist postsynaptic alpha1-adrenergic
2. albuterol (Proventil, Ventolin) - receptors;
Also known as blocks presynaptic alpha2-
salbutamol; Acts on beta2 receptors, preventing
adrenergic receptor; the feedback control
Inhibits the release of immediate ofnorepinephrine release.
hypersensitivity C. Alpha1-Selective Adrenergic
mediators from cell, especially Blocking Agentsblock the
mast cell postsynaptic alpha1-receptor
3. arformoterol (Brovana) sites
4. levalbuterol (Xopenex) 1. Alfuzosin (Uroxatral)
*MOA C and D: beta2 adrenergic 2. Doxazosin (Cardura)
receptor agonist which 3. Prazosin (Minipress)
causes stimulation of 4. Tamsulosin (Flomax)
intracellular adenylcyclase, the 5. Terazosin (generic)
enzyme D. Nonselective Beta-Adrenergic
that catalyzes the conversion of Blocking Agents
ATP to cyclic AMP 1. Carteolol (generic)
5. formoterol (Foradil, 2. Metipranolol (OptiPranolol)
Perforomist) 3. Nebivolol (Bystolic)
6. metaproterenol (Alupent) 4. Nadolol (Corgard)
7. pirbuterol (Maxair Autohaler) 5. Propranolol (Inderal,
8. terbutaline (=Brethine) Hemangeol)- prototype of
*MOA E to F: Beta-2 Adrenergic all beta blockers
Receptor 6. Sotalol (Betapace, Betapace
C. BOTH ALPHA AND BETA- AF)
RECEPTOR 7. Timolol (Timoptic)
1. Dopamine (Intropin)- Naturally E. Beta1-Selective Adrenergic
occurring Blocking Agentscannot cause
neurotransmitter and immediate broncho-constriction because
precursor of they
norepinephrine. Major don’t bock beta-2 receptor sites
cardiovascular effects 1. Acebutolol (Sectral)
produced by direct action on 2. Atenolol (Tenormin)
alpha- and betaadrenergic 3. Betaxolol (Betoptic)
receptor. 4. Bisoprolol (Zebeta)
2. dobutamine (Dobutrex)- alpha- 5. Esmolol (Brevibloc)- shortest
1, beta1 and acting beta
beta2 adrenergic receptors. blocker
3. ephedrine (generic)- Direct and 6. Metoprolol (Lopressor, Toprol
indirect XL)
sympathomimetic amine. *alpha blockers can be used for
Thought to act treating BPH (benign
indirectly by releasing tissue prostatic
stores of hypertrophy/hyperplasia) and
norepinephrine and directly by hypertension
stimulation of because they all have the same
alpha- beta1 and beta2 MOA
adrenergic receptors. * BPH- inflammation of prostate
4. epinephrine (Adrenalin, Sus- causing the blockage of urine
Phrine)- Both *all boys’ prostate will enlarge by
alpha-1 and alpha 2 adrenerdic the age of 40 and above
receptors *prostatectomy- removal of
5. norepinephrine (Levophed)- prostate; if men with enlarged
Both alpha-1 and prostate doesn’t want to wear
alpha 2 adrenerdic receptors catheter
II. ANDRENERGIC ANTAGONIST- * Alpha 1- stimulant for smooth
parasympathetic muscles except GI tract
A. Nonselective Adrenergic *if a person have BPH but NOT
Blocking Agents- block hypertensive, can still use
both alpha- and beta-adrenergic alpha blockers
receptors * alpha blockers- causes dilation
1. Amiodarone (Cordarone) of smooth muscles around
2. Carvedilol (Coreg) prostate and vascular system
3. Labetalol (Normodyne, *beta blockers- decreases heart
Trandate) rate; decrease blood
B. Nonselective Alpha-Adrenergic pressure; used for hypertension;
Blocking Agents parasympathetic
*giving beta blockers to patients Dilate pupil, Parlyzes the ciliary
with respiratory problems body, decrease
(like asthma) is ineffective Tremors and Rigidity of muscles
because beta blockers are 9
parasympathetic and in UNIT 6: DRUGS ACTING ON
parasympathetic activity the EDOCRINE SYSTEM
bronchus will constrict. Therefore INTRODUCTION TO THE
you are just increasing the ENDOCRINE SYSTEM
likelihood of asthmatic attack Endocrine system
*beta agonist- sympathetic - A system that provides
*sympathetic- GI decrease communication within the body
activity, pupils and bronchus and helps to regulate growth and
dilate development, reproduction,
*when using beta blocker DO NOT energy use and electrolyte
withdraw it abruptly balance.
because it may cause rebound - works in conjunction to the
hypertension and sudden nervous system to maintain
increase of your activity internal homeostasis and to
III. CHOLINERGIC AGONISTS- integrate the body's response to
parasympathetic the external environment.
*adverse effect- parasympathetic (Neuroendocrine)
over stimulation Glands
*there will be flushing and - endocrine glands are collection
sweating when taking these drugs of specialized cells that produce
because in parasympathetic hormones. Table 34.1 Endocrine
there will be dilation of blood glands with associated hormones
vessels causing blood to appear and
clear on skin clinical effects
A. DIRECT-ACTING *melatonin- causes sleep; sleep
CHOLINERGIC AGONISTS inducing hormone; stimulated in
1. Bethanecol (Duvoid, dark
Urecholine) environment that’s why when you
2. Carbachol (Miostat) want to sleep turn off the lights
3. Cevimeline (Evoxac) *serotonin- another sleep
4. Pilocarpine(Salagen) inducing hormone; from
B. INDIRECT ACTING tryptophan
CHOLINERGIC *milk is source of tryptophan
AGONISTSdestroys *parathyroid
acetylcholinesterase to promote hormone/parathormone can
production increase serum calcium
of acetylcholine levels by destroying the bone/
1. Nerve Gas- Irreversible lyses the bone because the bone
Indirect-Acting is the
Cholinergic Agonist number 1 source of calcium for
• Pralidoxime: Antidote for blood (serum calcium)
Irreversible *when serum calcium level is low,
Indirect-Acting Cholinergic stimulate parathyroid hormone
Agonists *when serum calcium level is
2. Agents for Myasthenia Gravis high, stimulate thyroid hormone
a. Endophronium (Enlon) * parathyroid hormone- release of
b. Neostigmine calcium from bone to blood;
c. Pyridostigmine (Mestinon) osteoclastic hormone
3. Agents for Alzheimer’s Disease * calcitonin- release of calcium
a. Donepezil (Aricept)- reversible from blood to bone; osteoblastic
cholinesterase inhibitor hormone
b. Galantamine (Razadyne) *osteoblast- immature bone;
c. Rivastigmine (Exelon) bone formation
IV. ANTICHOLINERGICS/ *osteoclast- bone destroyer
CHOLINERGIC ANTAGONIST/ * bone is the number one source
Parasymphatolytics- Muscarinic of calcium in serum
blocker; sympathetic * milk- number one source of
A. ATROPINE- Muscarinic blocker dietary calcium
:Reduce Salivation, * calcium tablets intake is not
Increase heart rate, Mydriasis, necessary because it may cause
BLOCKS calcium stones at kidney
acetylcholine, Decrease Hormones
peristalsis, decrease - are chemicals that are produced
secretions, increase constriction in the body
of detrussor muscle, All hormones:
1. Are produced in very small 3. Gonadotropin - releasing
amounts hormone
2. Are secreted directly into the 4. Corticotropin - releasing
bloodstream hormone
3. Travel though the blood to 5. Prolactin - releasing hormone
specific receptor sites throughout Has two inhibiting factors that act
the body as regulators:
4. Act to increase or decrease the 1. (GH) Growth hormone release -
normal metabolic cellular inhibiting factors
processes when they react with (somatostatin)
their specific receptor sites 2. (PRL) Prolactin inhibiting factor
5. Are immediately broken down (PIF)
Hormones may act in two Two networks:
different ways: 1. Vascular capillary network -
1. Some hormones react with carries the hypothalamic -
specific reactor sites on a cell releasing factors directly to the
membrane to cause an effect. anterior pituitary
They alter enzymes to produce an 2. Neurologic network - delivers
immediate effect. two other hypothalamic
Example: hormone such as hormones (anti diuretic hormone
insulin that react with specific and oxytocin) to posterior
receptor sites on the cell pituitary
membrane act very quickly, often Pituitary gland
within - divided into 3 lobes:
seconds to produce an effect. 1. Anterior lobe
2. Other hormones actually enter 2. Posterior lobe
the cell and react with a 3. Intermediate lobe
receptor site inside the cell to 1. Anterior pituitary gland
change mRNA which enters the -produces 6 major hormones: -
cell stimulating in nature
nucleus to affect cellular DNA, • Growth hormone (GH)
and thereby alters the cell's • Adrenocorticotropic hormone
function. (ACTH)- stimulate adrenal
These hormones take a while to glands to release these hormones
produce an effect. • Follicle stimulating hormone
Example: The estrogen hormone (FSH)-
which full effects may not be • Prolactin (PRL)- stimulates
seen for months or years, as breast to produce milk
evidenced by the changes that • Thyroid stimulating hormone
occur at (TSH)- stimulate thyroid gland
puberty. to produce thyroid hormone and
Hypothalamus calcitonin
- the master gland of the - these hormones are essential for
neuroendocrine system the regulation of growth,
- main endocrine hormone reproduction, and some
- receive signal from different metabolic processes.
parts of body if there is a * prolactinoma- very common
decrease or increase of their benign lesion of anterior pituitary
functional hormones causing increase production of
- does not act directly to the organ prolactin
thus send signal to anterior * increase in prolactin in men will
pituitary cause gynecomastia(breast
- controlling organ secondary to enlargement), decrease in libido,
CNS and infertility
- the coordinating center for the * Human Chorionic Gonadotropin
nervous and endocrine (HCG)- once tested positive in the
responses to internal and external urine it indicates pregnancy
stimuli * increase in HCG indicates
- secretes and produce numbers pregnancy or hydatidiform mole
of releasing hormones (H mole)
- releases vasopressin – anti- “uray”
diuretic hormone and oxytocin * H mole is considered pregnancy.
which are stored in the posterior * increase in Thyrotropin-
pituitary releasing Hormone (TRH)
- hypothalamic hormones are indicates
releasing in nature hypothyroidism
1. Growth hormone - releasing Table 34.2 Hypothalamic
hormone hormones, associated anterior
2. Thyrotropin - releasing pituitary
hormone (TRH)
hormones, and target organ of available hormone level
response DRUGS AFFECTING
• Once hypothalamus releases HYPOTHALAMIC HORMONES
releasing hormone, it acts on Factors that stimulate the release
the pituitary gland. Pituitary gland of hormones
release stimulating • growth hormone–releasing
hormone. Stimulating hormone hormone
will act on the target organ. • thyrotropin-releasing hormone
Target organ will secrete specific • gonadotropin-releasing
hormones for action. hormone (GnRH)
• TRH is also called the • corticotropin-releasing
thyrotropin-releasing hormone hormone
• Target organ for growth hormone • Prolactin-releasing hormone.
is all organs Factors that inhibit the release of
2 hormones
• LH and FSH acts on the ovary • somatostatin (growth hormone–
and testes to release inhibiting factor
estrogen and progesterone • prolactin-inhibiting factor
(female) and testosterone (male) Drugs Affecting Anterior Pituitary
• FSH- cause maturation of Hormones
follicle inside ovary, stimulates ➢ Agents that affect pituitary
ovarian follicle(female); function are used mainly to mimic
spermatogenesis, stimulaes or antagonize the effects of
conversion of testosterone to specific pituitary hormones.
estrogen (male) ➢ They may be used either as
• LH- cause ovulation and replacement therapy for
formation of female hormone, conditions resulting from a
stimulates androgen production, hypoactive pituitary or for
production of estrogen in diagnostic purposes.
ovary (female); testosterone ➢ Antagonists are also available
production (male) that may be used to block the
• FSH and LH given for infertility effects of the anterior pituitary
reasons hormones
• Melanin- gives skin color Growth Hormone Agonist
• Dopamine- prolactin-inhibiting • The anterior pituitary hormone
factor that is most commonly used
2. Posterior Pituitary gland- pharmacologically is GH.
generally does not release any • GH is responsible for linear
hormone; skeletal growth, the growth of
also receives or restores hormone internal organs, protein synthesis,
from hypothalamus and the stimulation of
- stores two hormones: many other processes that are
1. ADH required for normal growth.
- also referred to as vasopressin • Hypopituitarism is often seen as
- is directly release in response to GH deficiency before any
increase plasma osmolarity other signs and symptoms occur.
or decrease blood volume Hypopituitarism may occur
2. Oxytocin as a result of developmental
- stimulates uterine smooth abnormalities or congenital
muscle contraction in late phases defects of the pituitary,
of circulatory disturbances (e.g.,
pregnancy and cause milk release hemorrhage, infarction), acute or
3. Intermediate lobe chronic inflammation of the
- produces endorphins and pituitary, and pituitary tumors.
enkephalins • GH deficiency in children results
- they are released in response to in short stature (dwarfism).
overactivity of pain nerves, Adults with somatotropin
sympathetic stimulation, deficiency syndrome (SDS) may
transcutaneous stimulation, have hypopituitarism as a result
guided of pituitary tumors or trauma,
imagery, and vigorous exercise. or they may have been treated for
Hypothalamic - Pituitary axis- GH deficiency as children,
pathway between hypothalamus resulting in a shutdown of the
to pituitary production of
pituitary somatotropin.
Negative feedback system * increasing amount of estrogen
- responsible for secretion of progesterone can cause sodium
hormones reabsorption and lead to fluid
- release of hormones dependent retention
on the highness or lowness
* using these before puberty will - Compresses blood vessel
cause precocious puberty – early decreasing its lumen
puberty (vasoconstrictor)
* once organ senses that you have 2. Oxytocin – stimulates milk
a lot of hormone, it will stop ejection or “let down” in lactating
manufacturing such hormone women. In pharmacological
example: most body builders doses, it can be used to initiate or
injecting themselves steroid improve uterine contractions in
hormone labor. Used after giving birth
(androgenic hormone, because it causes contraction of
testosterone) because it will uterus to prevent bleeding.
develop muscle Uterine contraction can prevent
mass, the testicle will stop bleeding because it can block
producing testosterone because small blood vessel openings.
of a lot og • Diabetes insipidus- lack of ADH;
injected hormone. don’t have inhibitor for
Growth Hormone Antagonist urination; can cause death after
✓ GH hypersecretion is usually couple of hours if not
caused by pituitary tumors and corrected
can occur at any time of life. This * body only have 6 liters of blood
is often referred to as * kidney strains 180 liters of blood
hyperpituitarism. per day (7.5 liters per hour); 6
✓ If hyperpituitarism occurs liters
before the epiphyseal plates of per hour (men) therefore person
the may die after an hour if without
long bones fuse, it causes an ADH
acceleration in linear skeletal because of frequent urinating
growth, producing gigantism of 7 blood fluid contents without
to 8 feet in height with fairly reabsorption
normal body proportions. • Syndrome of Inappropriate
✓ In adults, after epiphyseal Antidiuretic Hormone
closure, linear growth is Secretion (SIADH) - if there is a lot
impossible. Instead, of ADH; common side
hypersecretion of GH causes effect of head injury; retention of
enlar32gement in the peripheral water causes decrease of
parts of the body, such as the concentration of sodium inside
hands and feet, and the internal the body, amount of sodium
organs, especially the heart. remains the same but because of
✓ Acromegaly is the term used to increase in water content
describe the onset of due to not urinating as a cause of
excessive GH secretion that SIADH, the sodium in the
occurs after puberty and body is diluted. Diluted sodium
epiphyseal plate closure indicates hyponatremia
• Used for BPH (benign prostatic (Dilutional Hyponatremia)
hypertrophy) and prostatic Adrenocortical Agents
cancer because these occurs Indications for Use of Adrenal
because of testosterone Agents
stimulation. Therefore • Widely used to suppress the
suppressing testosterone immune system
stimulation • Short-term use to relieve
can treat BPH inflammation during acute stages
• Breast cancer may occur due to of
increase on duration of illness – Do not cure any
exposure to estrogen like early inflammatory disorders
menarche and late Anatomy of the Adrenal Glands
menopause • Location – Flattened bodies
• Gigantism- increase release of which sit on top of each kidney
growth hormone happens • Composition – Adrenal medulla:
before closure of epiphysis. An inner core; part of the
• Acromegaly- increase release of SNS – Adrenal cortex: An outer
growth hormone happens shell; produces hormones
after closure of epiphysis. Not called corticosteroids
grow taller but instead, bones Controls and Actions of the
will be prominent Adrenal Glands
Posterior Pituitary Hormones 1. Hypothalamus secretes
1. Antidiuretic hormone (ADH, releasing hormone CRH
also known as vasopressin) 2. CHR stimulates anterior
- Decreases urination; used if pituitary
dehydrated 3. anterior pituitary releases
ACTH
4. ACTH stimulated adrenal disorders
cortex to produce different – To relieve discomfort
hormones – To give the body a chance to heal
Types of Corticosteroids from the effects
• Androgens – Male and female of inflammation
sex hormones • Pharmacokinetics
• Glucocorticoids – Stimulate an – Well absorbed from many sites
increase in glucose levels for – Metabolized by natural systems;
energy; can cause hypocalcemia mostly within the
• Mineralocorticoids – Affect liver
electrolyte levels and – Excreted in the urine
homeostasis • Contraindications
3 – Known allergy
*Aldosterone- regulate Na and K – Acute infection
in kidnets; once sodium is – Lactation
reabsorbed, water goes with it; • Caution
wherever sodium goes water will – Diabetes because
follow glucocorticoids increases
Site of Action of the glucose
Adrenocortical Agents – Acute peptic ulcer
Actions of Adrenocortical • Adverse Reactions
Hormones – Related to route of
• Increase blood volume administration
(aldosterone effect) because – Systemic use is associated with
aldosterone increases sodium endocrine
reabsorption and once sodium disorders
is reabsorbed water goes with it • Drug-to-Drug Interaction
• Cause the release of glucose for – Increase in drug when given with
energy erythromycin,
• Slow rate of protein production ketoconazole, or troleandomycin
(reserves energy) – Decrease in drug when given
• Block activities of the with salicylates,
inflammatory and immune barbiturates, phenytoin, or
systems rifampin
(reserves a great deal of energy) Mineralocorticoids (Aldosterone
Causes of Adrenal Insufficiency Hormone)
• A patient does not produce • Actions
enough ACTH – Holds sodium, and with it, water
• Adrenal glands are not able to in the body
respond to ACTH – Causes the excretion of
• Adrenal gland is damaged potassium by acting on the
• Secondary to surgical removal renal tubule
of the gland • Indications
• Prolonged use of corticosteroid – Replacement therapy in primary
hormones and secondary
Adrenal Crisis adrenal insufficiency
• Signs • Pharmacokinetics
– Physiological exhaustion – Absorbed slowly and distributed
– Hypotension throughout the
– Fluid shift body
– Shock and even death – Hepatic metabolism
• Treatment • Contraindications
– Massive infusion of replacement – Known allergy
steroids – Hypertension because
– Constant monitoring and life aldosterone causes
support procedures elevation of blood fluid
Glucocorticoids – CHF
• Actions – Cardiac disease
– Enter target cells and bind to • Caution
cytoplasmic receptors – Pregnancy
– Initiate many complex reactions – Presence of any infection
responsible for – High sodium intake
anti-inflammatory and • Adverse Reactions
immunosuppressive effects – Increase fluid volumes
– Hydrocortisone, cortisone, and – Allergic reactions
prednisone have • Drug-to-Drug Interaction
some mineralocorticoid activity – Decrease effectiveness with
• Indications salicylates,
– Short-term treatment of many barbiturates, hydantoins,
inflammatory rifampin, and
anticholinesterases Thyroid Glands
Thyroid and parathyroid Agents • The thyroid gland is located in
Key Terms the middle of the neck, where it
• bisphosphonates: drugs used to surrounds the trachea like a
block bone resorption and shield. Its name comes from the
lower serum calcium levels in Greek words thyros (shield) and
several conditions eidos (gland).
• calcitonin: hormone produced • It produces two hormones—
by the parafollicular cells of thyroid hormone and calcitonin.
the thyroid; counteracts the • The thyroid is a vascular gland
effects of parathyroid hormone to with two lobes—one on each
maintain calcium levels side of the trachea—and a small
• cretinism: lack of thyroid isthmus connecting the
hormone in an infant; if untreated, lobes. The gland is made up of
leads to mental retardation cells arranged in circular
• follicles: structural unit of the follicles. The center of each
thyroid gland; cells arranged in follicle is composed of colloid
a circle tissue in which the thyroid
• hypercalcemia: excessive hormones produced by the gland
calcium levels in the blood are stored. Cells found around the
• hyperparathyroidism: excessive follicle of the thyroid gland
parathormone are called parafollicular cells
• hyperthyroidism: excessive which produces the hormone
levels of thyroid hormone calcitonin.
• hypocalcemia: calcium Thyroid Hormone
deficiency • The thyroid gland produces two
• hypoparathyroidism: rare thyroid hormone using iodine.
condition of absence of • Thyroxine or tetraiodothyronine
parathormone; may be seen after (T4) contains four iodine
thyroidectomy atoms, which is given
• hypothyroidism: lack of therapeutically in the synthetic
sufficient thyroid hormone to form
maintain metabolism levothyroxine.
• iodine: important dietary 4
element used by the thyroid gland • Triiodothyronine (T3) which
to contains three iodine atoms,
produce thyroid hormone which is given in the synthetic
• levothyroxine: a synthetic salt of form liothyronine.
thyroxine (T4), a thyroid • Triiodothyronine (T3) is more
hormone; the most frequently active than Thyroxine or
used replacement hormone for tetraiodothyronine (T4)
treating thyroid disease • In hyperthyroidism, do not allow
• Liothyronine: the l-isomer of the conversion of T4 to T3
triiodothyronine (T3), and the (T4 – 1 iodine = T3)
most potent thyroid hormone, • The thyroid cells remove iodine
with a short half-lif of 12 hours from the blood, concentrate it,
• metabolism: rate at which the and prepare it for attachment to
cells burn energy tyrosine, an amino acid which
• myxedema: severe lack of would result into thyroid
thyroid hormone in adults hormone.
• Paget’s disease: a genetically • The thyroid hormone regulates
linked disorder of overactive the rate of metabolism (rate at
osteoclasts that are eventually which energy is burned) in almost
replaced by enlarged and all the cells of the body.
softened bony structures • Thyroid hormones affect:
• parathormone: hormone –heat production and body
produced by the parathyroid temperature
glands; responsible for –oxygen consumption and
maintaining calcium levels in cardiac output
conjunction with calcitonin –blood volume
• postmenopausal osteoporosis: –enzyme system activity
condition in which dropping –metabolism of carbohydrates,
levels of estrogen allow calcium fats, and proteins
to be pulled out of the bone, • Thyroid hormone production
resulting in a weakened and and release are regulated by the
honeycombed bone structure anterior pituitary hormone called
• thioamides: drugs used to thyroid-stimulating hormone
prevent the formation of thyroid (TSH). The secretion of TSH is
hormone in the thyroid cells, regulated by thyrotropinreleasing
lowering thyroid hormone levels
hormone (TRH), a hypothalamic increasing levels of TSH.
regulating factor. • Hyperthyroidism is treated with
• To keep the level of thyroid thioamides or iodines
hormone within narrow range of • Both hypothyroidism and
normal, a negative feedback hyperthyroidism causes goiter
mechanism happens. • Effect of thyroid hormone is
• An increased in thyroid hormone general increase (increase
levels in response to an heart rate, etc.). thyroid hormone
increased TSH will send a is a stimulant
negative feedback to the pituitary • Cardiac problem - most
gland and hypothalamus to common cause of death of
decrease TSH release and TRH hyperthyroid patients because
release. A drop in TRH levels will constant increase of heart rate
lead to a drop in TSH levels will cause weakness; frequent
which in turn drops thyroid usage of heart causes it to
hormone levels. increase in size (Cardiomegaly
Thyroid Dysfunction with hyperthyroidism)
• Thyroid dysfunction involves • In hyperthyroidism you eat a lot
either underactivity bur don’t get fat, because
(hypothyroidism) or overactivity you eat a lot, digest a lot, absorb a
(hyperthyroidism). This lot, BUT use a lot of
dysfunction can affect any age energy also.
group. • Since metabolism product is
Hypothyroidism heat, then your temperature will
• Hypothyroidism is the most be very high
common type of thyroid THYROID AGENTS
dysfunction. Thyroid Hormone
• Hypothyroidism is a lack of • Thyroid hormone products
sufficient levels of thyroid replace the low or absent levels of
hormones to maintain a normal natural thyroid hormone and
metabolism. This condition suppress the overproduction of
occurs in a number of TSH by the pituitary. These
pathophysiological states: products can contain both natural
–Absence of the thyroid gland and synthetic thyroid hormone.
–Lack of sufficient iodine in the • Giving thyroid hormone is to
diet to produce the needed treat hypothyroidism
level of thyroid hormone Antithyroid Agents- block
–Lack of sufficient functioning production of thyroid hormone;
thyroid tissue due to tumor or treat
autoimmune disorders hyperthyroidism using
–Lack of TSH due to pituitary thioamides and iodide solutions.
disease Parathyroid Glands
–Lack of TRH related to a tumor or • The parathyroid glands are four
disorder of the very small groups of
hypothalamus glandular tissue located on the
• Hypothyroidism is treated with back of the thyroid gland. The
replacement thyroid hormone. parathyroid glands produce PTH
• Hashimoto’ s Thyroiditis – most (parathyroid hormone), an
common cause of important regulator of serum
hypothyroidism calcium levels.
• Iodine deficiency – most • PTH is the most important
common cause of endemic goiter regulator of serum calcium levels
Hyperthyroidism in the body. PTH has many actions
• Hyperthyroidism occurs when including the following:
excessive amounts of thyroid –Stimulation of osteoclasts or
hormones are produced and bone cells to release calcium
released into the circulation. from the bone
• Graves’ disease is the most –Increased intestinal absorption
common cause of of calcium
hyperthyroidism. –Increased calcium reabsorption
• Goiter (enlargement of the from the kidneys
thyroid gland) –Stimulation of cells in the kidney
• This can happen if the thyroid to produce calcitriol, the
gland does not make sufficient active form of vitamin D, which
thyroid hormones to turn off the stimulates intestinal transport
hypothalamus and anterior of calcium into the blood
pituitary; in the body’s attempt to • Calcium is an electrolyte that is
produce the needed amount used in many of the body’s
of thyroid hormone the thyroid is metabolic processes. These
continually stimulated by processes include membrane
transport systems, conduction of • Primary hyperparathyroidism
nerve impulses, muscle occurs more often
contraction, and blood clotting. in women between 60 and 70
To achieve all of these effects, years of age. Secondary
the serum levels of calcium must hyperparathyroidism occurs most
be maintained between 9 frequently in patients with
and 11 mg/dL. This is achieved chronic renal failure.
through regulation of serum Signs and symptoms of calcium
calcium by PTH and calcitonin. imbalance
• Calcitonin is released when Parathyroid Agents
serum calcium levels rise. - The drugs used to treat disorders
Calcitonin works to reduce associated with parathyroid
calcium levels by blocking bone function are drugs that affect
resorption and enhancing bone serum calcium levels. There are
formation. This action pulls two parathyroid replacement
calcium out of the serum for hormones available and one
deposit into the bone. When form of calcitonin; other drugs
serum calcium levels are low, PTH affect calcium levels in different
release is stimulated. ways.
When serum calcium levels are Antihypocalcemic Agents
high, PTH release is blocked. • Deficient levels of PTH result in
Parathyroid Dysfunction and hypocalcemia (calcium
Related Disorders deficiency). Vitamin D stimulates
• Parathyroid dysfunction involves calcium absorption from the
either absence of PTH intestine and restores the serum
(hypoparathyroidism) or calcium to a normal level.
overproduction of PTH • Hypoparathyroidism is treated
(hyperparathyroidism). This primarily with vitamin D and, if
dysfunction can affect any age necessary, dietary supplements
group. of calcium.
Hypoparathyroidism Antihypercalcemic Agents
• The absence of PTH results in a • Suppress parathyroid hormone
low calcium level and calcium
(hypocalcemia) and a relatively Agents to Control blood glucose
rare condition called levels
hypoparathyroidism. This is most Key Terms
likely to occur with the • Adinopectin- hormone
accidental removal of the produced by adipocytes that acts
parathyroid glands during thyroid to
surgery. increase the release of glucose
• Treatment consists of calcium from liver and protect the
and vitamin D therapy to blood vessels from inflammatory
increase serum calcium levels. changes
• Vitamin D is a treatment • diabetes mellitus: a metabolic
because this is necessary for the disorder characterized by
absorption of calcium in the high blood glucose levels and
intestine. Vitamin D is acquired altered metabolism of proteins
from the cholesterol of skin with and fats; associated with
the help of sunlight. Sunlight thickening of the basement
5 membrane, leading to numerous
acts on the skin cholesterol for complications
this to be transformed to • dipeptidyl peptidase-4 (DDP-4):
Vitamin D. Vitamin D will be enzyme that quickly
brought to the kidneys to be metabolizes glucagon-like
activated. Only the activated form polypeptide-1
of Vitamin D helps in the • endocannabinoid receptors:
absorption of calcium is the receptors found in the adipose
intestine. tissue, muscles, liver, satiety
Hyperparathyroidism center, and gastrointestinal (GI)
• The excessive production of PTH tract that are part of a signaling
leads to an elevated system within the body to
calcium level (hypercalcemia) keep the body in a state of energy
and a condition called gain
hyperparathyroidism. This can • cannabinoid- substance found
occur as a result of parathyroid in cannabis sativa(marijuana)
tumor or certain genetic • glucagon-like polypeptide-1
disorders. The patient presents (GLP-1): a peptide produced in
with the GI tract in response to
signs of high calcium levels. carbohydrates that increases
insulin release, decreases Diabetes is a complicated
glucagon release, slows GI disorder that alters the
emptying, and stimulates the metabolism of
satiety center in the brain glucose, fats, and proteins,
• glycogen: storage form of affecting many end organs and
glucose; in the liver; can be causing
broken down for rapid glucose numerous clinical complications.
level increases during times of It is part of the metabolic
stress syndrome, a
• glycosuria: presence of glucose collection of conditions that
in the urine predispose to cardiovascular (CV)
• glycosylated hemoglobin: a disease.
blood glucose marker that Treatment of diabetes is aimed at
provides a 3-month average of regulating the blood glucose level
blood glucose levels through the use of insulin or other
• hyperglycemia: elevated blood glucose-lowering drugs.
glucose levels (>106 mg/dL) Maintaining the level of serum
leading to multiple signs and glucose within a certain range is
symptoms and abnormal very
metabolic pathways important to the nervous system.
• hypoglycemia: lower-than- The nerves in the central nervous
normal blood sugar (<40 mg/dL); system (CNS) receive glucose by
often results from imbalance diffusion; they do not have insulin
between insulin or oral agents receptor sites like all other cells.
and patient’s eating, activity, and Maintaining the appropriate
stress glucose level is a complicated
• incretins: peptides that are process that
produced in the GI tract in involves diet, exercise, and drug
response to food that help to management. At times, the blood
modulate insulin and glucagon glucose level is lowered too
activity much, producing a state of
• insulin: hormone produced by hypoglycemia.
the beta cells in the pancreas; When this occurs, glucose-
stimulates insulin receptor sites elevating agents need to be used
to move glucose into the to quickly
cells; promotes storage of fat and return the serum glucose levels to
glucose in the body a normal level.
• ketosis: breakdown of fats for • Hypoglycemia- most common
energy, resulting in an complication of Antidiabetic
increase in ketones to be excreted agents
from the body ❑ Glucose Regulation
• polydipsia: increased thirst; Glucose is the leading energy
seen in diabetes when loss of source for the human body.
fluid and increased tonicity of the Glucose is stored in the body for
blood lead the hypothalamic rapid release in times of stress. As
thirst center to make the patient a
feel thirsty result, blood glucose levels can
• polyphagia: increased hunger; be readily maintained so that the
sign of diabetes when cells neurons always receive a
cannot use glucose for energy and constant supply of glucose to
feel that they are starving, function.
causing hunger The body’s control of glucose is
• sulfonylureas: oral antidiabetic intricately related to fat and
agents used to stimulate the protein
pancreas to release more insulin metabolism, balancing energy
❑ Antidiabetic agents, as the conservation with energy
name implies, are used to treat consumption to
diabetes mellitus, the most maintain homeostasis in a variety
common of all metabolic of situations.
disorders. Many factors have an impact on
• Increase in stress must also this balance and the body’s ability
increase need for antidiabetic to
agents because with stress adapt and to maintain
epinephrine is released metabolism
• Epinephrine – increases blood Pancreas Gland (Function) –
glucose organ responsible for glucose
• Stress is insulinopenic – control
decreased insulin production 1. Endocrine Glands (ductless
gland) – secretions directly to
bloodstream not passing any gastrointestinal (GI) tract in
ducts; produce hormones called response to food.
islet of Langerhans which contain ▪ Insulin circulates through the
endocrine cells that body and reacts with specific
produce specific hormones. insulin receptor sites to stimulate
These hormones work together the transport of glucose into
to maintain blood glucose with in the cells to be used for energy, a
normal limits: process called facilitated
alpha cells - release glucagon in diffusion. Insulin also stimulates
direct response to the synthesis of glycogen
low blood glucose levels (glucose stored for immediate
beta cells - release insulin in release during times of stress
direct response to high or low glucose), the conversion of
blood glucose levels and when lipids into fat sored in the
stimulated by incretins form of adipose tissue, and
delta cells - produce synthesis of needed proteins from
somatostatin (growth amino acids
hormoneinhibiting factor) in ❑ Glucagon- when destroyed
response to very low blood byproduct is glucose; once
glucose level; somastostatin also released/
blocks the secretion stimulated will affect the liver
of insulin and glucagon: because this stores glycogen,
somastostasin is universal glycogen broken down to glucose,
inhibitor of the secretory cells, glucose given to the blood;
inhibits insulin and correcting hypoglycemia;
glucagon secretion, generally it opposite of insulin
inhibits secretion from Glucagon is released from the
the cell alpha cells in the islets of
• Beta cells – produces insulin; Langerhans in
glucagon secreted by alpha response to low blood glucose
cells (BIGA) levels. Glucagon causes an
• Somastostatin- universal immediate
inhibitor of secretory cells mobilization of glycogen stored in
2. Exocrine Gland – follows the liver and raises blood glucose
through a duct; releases sodium levels
bicarbonate and pancreatic Breakdown of glycogen will
enzymes in the common bile duct produce glucose, the glucagon
to be released in the small once
intestine, where they neutralize stimulated, once released, will
the affect the liver because the liver
acid chyme from the stomach and stores
aid digestion. your glycogen and the glycogen
• Pancreatic secretions are very will now be broken down to
basic in nature which can become
cause lysis of tissues once found glucose so that the glucose will
outside pancreas leading to now be given to the blood
burns of internal organs • When a person is too full (e.g.
• Saponification – lyses/ burns of from fiesta) there will be
internal organs increase in insulin while when
• Pancreatic polypeptide (PP starved there is relase of
cells/ F cells) – secretes glucagon
Pancreatic polypeptide; for ❑ Other Affecting Glucose
protein digestion Control
• G cells- secrets gastrin Other factors in the body have
Insulin been found to have an impact on
▪ hormone produced by beta cells glucose, fat, and protein
of the islets of Langerhans, metabolism. These factors play a
without insulin your glucose role in the
cannot enter the cell overall energy balance in the
▪ stimulated by an increase in body.
blood glucose; stimulus is Adipocytes, or fat cells, were once
hyperglycemia thought to just store fat
▪ allows entry of glucose to cell for energy. However, they have
▪ The hormone is released into been found to have a major
circulation when the levels of impact on
glucose around these cells rise. It glucose and fat metabolism
is also released in throughout the body through the
7 secretion
response to incretins, peptides
that are produced in the
of adiponectin. This hormone because growth hormone will use
acts to increase insulin energy for growth, increase of
sensitivity, FFAs,
decrease the release of glucose and increase in protein building.
from the liver, and protect the Fluctuating levels of growth
blood hormone
vessels from inflammatory can upset metabolic
changes. When adiponectin homeostasis. Box 38.2
levels are high, summarizes the effects of
it exerts a protective effect on the various factors on blood glucose
body. When adiponectin levels levels
are Glucose Control Mechanisms
low, as in cases of intraabdominal ➢ Insulin
fat accumulation, glucose levels -decreases blood glucose;
rise glycogen storage; adipose tissue
and blood vessel injury increases. deposit; synthesis of proteins to
Endocannabinoid receptors have form amino acids
been identified in adipose ➢ Glucagon
tissue, muscles, liver, the satiety - increases blood glucose
center, and the GI tract. These ➢ Somastostasin
receptors seem to be part of a - decreases insulin release;
signaling system within the body decreases glucagon
to keep release ; slows GI emptying
the body in a state of energy gain,
➢ Growth Hormone
to prepare for stressful situations.
- decreases insulin sensitivity;
When stimulated, these
increases protein
receptors promote food intake,
building; increases FFA formation
decrease
➢ Incretins
adiponectin release, increase fat
• - increases insulin release;
breakdown, decrease insulin
decreases glucagon release;
sensitivity, increase fat storage,
stimulates satiety center; slows
and alter gastric emptying to
GI emptying
promote
greater nutrient absorption. ➢ Adinopectin
Patients who are obese have been - increases insulin sensitivity;
shown decreases glucose output from
to have increased stimulation of liver; protects vessels from
these receptors. inflammatory reactions
The sympathetic nervous system ➢ Catecholamines
(SNS), through - decreases insulin release;
norepinephrine and epinephrine increase glucose output from liver
effects, directly causes a and muscles; increases
decrease in breakdown of fat to FFAs
insulin release, an increase in the Examples: norepinephrine,
release of stored glucose, and an epinephrine, dopamine,
increase in fat breakdown. A serotonin
person under stress will have ➢ Corticosteroids
increased - increases glucose output;
glucose levels and increased free decreases insulin sensitivity
fatty acid (FFA) levels, which will - competes with calcium
provide the energy needed for the ➢ Endocannabinoid System
immediate “fight or flight”, - increases food intake by
associated blocking satiety signals;
with a stress reaction. Prolonged decreases
stress can alter the con trol of adiponectin release; decreases
metabolism that regulates the insulin sensitivity; increases
body’s energy balance. fat synthesis; alters gastric
Corticosteroids, which are motility
released diurnally but also during Loss of Blood Glucose Control
a stress reaction, decrease When an insufficient amount of
insulin sensitivity, increase insulin is released or insulin
glucose release, receptors
and decrease protein building. All are no longer responding, several
of these actions conserve energy metabolic changes occur,
and beginning
provide immediate glucose for with hyperglycemia, or increased
any stressful situation. blood sugar.
Growth hormone causes Hyperglycemia results in
decreased insulin sensitivity glycosuria: Sugar is spilled into
the urine because the enter the cell because there is no
concentration of glucose in the insulin
blood is too high • Patients with diabetes will be
for complete re-absorption. very thin because as cells
Because this sugar-rich urine is demand for glucose, first it will
an ideal ask liver to lyse glycogen
environment for bacteria, cystitis causing glycogenolysis, the blood
is a common finding. have a lot of glucose BUT
The patient experiences fatigue cannot enter the cell
because the body’s cells cannot • Lipolysis produces a lot of
use acetoacetic acid(acetone which
the glucose that is there; they is
need insulin to facilitate transport a ketone) which causes ketosis
of the which is the cause of fruity
glucose into the cells. breath
• Cystitis- inflammation of the Effect of blood glucose increase:
urinary bladder • Kidneys: renal blood vessels are
Lipolysis, or fat breakdown, destroyed causing renal
occurs as the body breaks down nephropathy
stored fat into FFAs for energy • Eyes: diabetic retinopathy,
because glucose is not usable. causes blindness
The patient experiences ketosis • Because of the decrease of
as metabolism shifts to the use of oxygen supply to nerves, it will
fat cause diabetic neuropathy.
for energy. Ketones are produced • diabetic neuropathy: cannot feel
that cannot be removed the area supplied by the
effectively. nerve the main reason why
Acidosis also occurs because the diabetic patients will not know if
liver cannot remove all of the they already have wound
waste • dehydration: because of
products (acid being a primary increase of glucose amount in
waste product) that result from blood, water intake must also be
the increased
breakdown of glucose, fat, and • Kussmaul’s Breathing: because
proteins. of metabolic acidosis
• Muscles break down because • Blood vessel: increase in
proteins are being broken deposition of plaques at tunica
down for their essential amino intima of the small and medium
acids. The breakdown of sized blood vessels
proteins results in an increase in • Tunica intima- innermost lining
nitrogen wastes, which is of blood vessel
manifested by an elevated blood Characteristics:
urea nitrogen concentration - complex disturbances in
and sometimes by protein in the metabolism
urine. - affects carbohydrates, proteins,
• Patients with hyperglycemia do and fat metabolism
not heal quickly, because of Clinical signs:
this protein breakdown, as well as • Hyperglycemia ( fasting blood
the lack of a stimulus to sugar level greater than 126
initiate protein building. mg/dL
• All of these actions eventually • Glycosuria ( the presence of
contribute to development of sugar in the urine
the complications associated 8
with chronic hyperglycemia or The alteration in the body’s ability
diabetes. to effectively deal with
Diabetes Mellitus - “honey urine” carbohydrate, fat, and protein
TRIAD: (effects) metabolism over the long-term
1. Polydipsia –increase thirst results in a thickening of the
2. Polyphagia – increase hunger basement membrane (a thin
3. Polyuria – increase urination layer of collagen filament that lies
• Increase blood glucose = just below the endothelial
increase osmolality (viscosity) of lining of blood vessels) in large
blood and small blood vessels.
• increase osmolality (viscosity) • This thickening leads to changes
of blood – stimulus for thirst in oxygenation of the vessel
• mannitol- sugar used to treat lining; damage to the vessel
edema lining, which leads to narrowing,
• Polyphagia: the cell is just vessel remodeling, and
floating in food but food cannot decreased blood flow through the
vessel; and an inability of oxygen ketoacidosis and CNS changes
to rapidly diffuse across the that can progress to coma.
membrane to the tissues. ▪ This level of hyperglycemia
These changes result in an needs to be treated immediately
increased incidence of a number with
of insulin.
disorders, including the following: Hypoglycemia- commonly
Atherosclerosis: Heart attacks caused by imbalance in glucose
and strokes related to the levels while
development of atherosclerotic taking insulins or oral agents
plaques in the vessel lining Patients need to be carefully
Retinopathy: Resultant loss of monitored to determine
vision as tiny vessels in the effectiveness of therapy with
eye are narrowed and closed these drugs to prevent
Neuropathies: Motor and inadvertent
sensory changes in the feet and overdose
legs and progressive changes in ❖ Blood sugar concentration
other nerves as the oxygen lower than 60mg/dL
supply to these nerves is slowly Occurrence:
cut off - starvation
Nephropathy: Renal dysfunction - lowering the blood sugar too far
related to changes in the with treatment of
basement membrane of the hyperglycemia
glomerulus - The initial reaction to falling
• Type 1- insulin dependent blood glucose level is
;autoimmune disease; juvenile parasympathetic stimulation—
diabetes – already diabetic at increased GI activity to
birth increase digestion and
• Type 2 – non-insulin dependent; absorption. Rathe12r
all cells are insensitive to 1 rapidly, the SNS
insulin; adult onset; generally responds with a “fight-or-flight”
caused by the food we eat. reaction that increases blood
• Type 3 – caused by damage to glucose levels by initiating the
pancreas breakdown of fat and glycogen
• Type 4 – gestational diabetes; to release glucose for rapid
occurs only in pregnancy energy.
Hyperglycemia, or high blood Signs and Symptoms of
sugar, results when there is an Hypoglycemia and
increase Hyperglycemia
in glucose in the blood. Recent UNIT 6: DRUGS ACTING ON
guidelines suggest a fasting EDOCRINE SYSTEM
glucose DRUGS AND MECHANISMS OF
level of 130 or above is indicative ACTION
of hyperglycemia. I. HYPOTHALAMIC AND
Clinical Signs and Symptoms of PITUITARY AGENTS
Hyperglycemia: A. Drugs Affecting Hypothalamic
• Fatigue Hormones- most are
• Lethargy releasing hormones and do not
• Irritation have direct effect on the
• Glycosuria gland
• Polyphagia 1. Agonists
• Polydipsia a. goserelin(Zoladex)
• Itchy skin b. histrelin(Vantas)
Signs of Impending Dangerous c. leuprolide(Lupron)
Complications of Hyperglycemia: d. nafarelin(Synarel)
• Fruity breath as the ketones e. tesamorelin (Egrifta)-
build up in the system and are stimulates the release
excreted through the lungs. of GH from the pituitary
• Dehydration as fluid and MOA a-d:
important electrolytes are lost Inhibit pituitary gonadotropin
through the kidneys secretion,with
• Slow, deep respirations a resultant drop in the production
(Kussmaul's respirations) as the of sex
body tries to rid itself of high acid hormones.
levels •GnRH analogues
• Loss of orientation and coma •GnRH agonist that occupies
▪ If the hyperglycemia goes pituitary
unchecked the patient will GnRH receptors and desensitizes
experience them;
causes an initial increase and thyroid cancer and who do not
then profound have evidence of
decrease in LH and FSH levels. metastatic thyroid cancer.
2. Antagonist- GnRH receptor D. Drugs Affecting Posterior
antagonists: binds Pituitary Hormones
reversibly to the pituitary GnRH 1. Conivaptan (Vaprisol) - ADH
receptors, thereby reducing blocker; selectively
the release of gonadotropins and block vasopressin or ADH
consequently testosterone. receptors
a. Degarelix (Firmagon) 2. desmopressin (DDVAP,
b. Ganirelix (Antagon) Stimate) – a vasopressin;
B. Drugs Affecting Anterior has pressor and antidiuretic
Pituitary Hormones effects; increases
1. Growth Hormone Agonists- levels of clotting factor VIII
used purely as a 3. tolvaptan (Samsca)- ADH
replacement of Growth Hormone; blocker; selectively
stimulates skeletal growth, block vasopressin or ADH
growth of internal organs, and receptors
protein synthesis. II. Adrenocortical Agents
a. somatropin (Nutropin, Saizen, A.Glucocorticoids
Humatrope) 1. beclomethasone
b. sumatropin rDNA (Zorbtive) 2. betamethasone
2. Growth Hormone Antagonists 3. budesonide
a. bromocriptine mesylate 4. cortisone
(Parlodel)- inhibit 5. dexamethasone
GH secretion in some patients 6. flunisolide
with acromegaly; acts directly 7. hydrocortisone
on post synaptic dopamine 8. methylprednisolone
receptors in the brain; dopamine 9. prednisolone
agonist; suppress lactation 10. prednisone
❑ dopamine- only prominent 11. triamcinolone
inhibitory B.Mineralocorticoids
substance for prolactin release 1. Cortisone
b. lanreotide(Somatuline Depot)- 2. Fludrocortison
acts like 3. hydrocortisone
somatostatin; affects insulin III.Thyroid and parathyroid Agents
growth factor levels A.Thyroid Agents
c. octreotide(Sandostatin) 1. Thyroid Hormones
d. pegvisomant(Somavert)- binds a. Levothyroxine- replacement to
to GH hormone thyroxine (T4)
receptors on cells, inhibiting GH b. Liothyronine
effects c. Liotrix
C. Drugs Affecting Other Anterior d. Thyroid desiccated
Pituitary Hormones 2. Antithyroid Agents
1. Chorionic gonadotropin a. Thioamides- iodine
(Chorex, others)- acts organification inhibitor; thyroidal
like LH and stimulates the peroxidase inhibitor; thyroid
production of hormone synthesis inhibitor
testosterone and progesterone Organification - function of
2. Chorionic gonadotropin alpha thyroidal peroxidase,
(Ovidrel)- used as addition of iodine to thyroid
a fertility drug to induce ovulation hormone, catalyzed by
in women treated thyroidal peroxidase
with FSH i. Methimazole- thyroid hormone
3. Cosyntropin (Cortrosyn)- used synthesis inhibitor;
in diagnostic thyroid peroxidase inhibitor
purposes to test adrenal ii. Propylthiouracil (PTU)-
functions and thyroxine synthesis inhibitor;
responsiveness; not used for inhibits peripheral conversion of
therapeutic purposes thyroxine to triiodothyronine;
4. Thyrotropin alpha (Thyrogen)- thyroid peroxidase inhibitor;
used as adjunctive common
treatment for radioiodine ablation effect: Hepatotoxic
of thyroid tissue *Saturated Solution of Potassium
9 Iodide (SSKI) – usually given to
remnants in patients who have people living in the mountainous
undergone a near areas due to lack of source of
total to total thyroidectomy for iodine
well-differentiated
(shellfish, etc.) which is the insulin release from beta cells in
reason why there a lot of the pancreas, decreasing
hypothyroid goiter insulin resistance, or altering
cases are in these areas. glucose absorption from GI tract
b. Iodine solutions and release of glucose by liver
i. Radioactive iodine(Sodium B. Sulfonylureas and other
iodide I131)- destroys antidiabetic agents
thyrodal tissue by beta emission 1. Sulfonylureas- insulin
ii. Strong iodine solution secretagogue; increase insulin
iii. Potassium iodide secretion; stimulate beta cells to
❑ Iodide same MOA with produce insulin
thioamide drugs a. 1st generation
MOA ii and iii: thyroid hormone i. Chlorpropamide
synthesis inhibitor; inhibits ii. Tolazamide
release of hormones to iii. Tolbutamide
circulation b. 2nd generation
c. Calcitonins- secreted by i. Glimepiride
thyroid gland; inhibits bone ii. Glipizide
resorption; osteoclastic(deposits iii. Glyburide
calcium to bone) 2. other antidiabetic agents
i. Calcitonin salmon- reduces a. Alpha-Glucosidase Inhibitors-
calcium level by blocking prevent digestion
bone resorption and enhancing of carbohydrates and starches;
bone formation. taken with meal
This action pulls calcium out of ❑ Alpha- glucosidase – prevent
the serum for conversion of complex sugar
deposit into the bone. Affects to simple sugar
mineralization ❑ Only simple sugars are
B.Parathyroid Agents absorbed in the intestine
1. Antihypocalcemic Agents i. Acarbose
a. Calcitriol- vitamin d; increase ii. Miglitol
calcium absorption at b. Biguanide- decrease
intestine production of hepatic
b. Parathyroid hormone- raises glucose; prevents glycogenolysis;
calcium by increasing increase uptake
renal tubular calcium of glucose
reabsorption, increasing i. Metformin
intestinal c. Dipeptidyl Peptidase-4
calcium absorption by increasing Inhibitors
bone turn over which ❑ Dipeptidyl Peptidase-4-
releases calcium to circulation. increases glucagon
Affects mineralization i. Alogliptin
c. Teriparatide- stimulates new ii. Linagliptin
bone formation, leading to iii. Saxagliptin
an increase in skeletal mass iv. Sitagliptin
2. Antihypercalcemic Agents d. Glucagon-like Polypeptide
a. Biphosphonates- does not Receptor Agonist
affect the bone ONLY the (GLP 1 agonist)- stimulate insulin
calcium; promotes osteoclastic release; inhibit
activity, causes glucagon release
deposition of calcium in bone i. Abiglutide
❑ Increase level of phosphate ii. Dulaglutide
decreases calcium level iii. Liraglutide
❑ Phosphate and calcium bind to iv. Teduglutide
each other e. Human Amylins- regulate blood
i. Alendronate glucose by
ii. Etidronate slowing gastric emptying
iii. Ibandronate ❑ Amylin- is a product of beta cell
iv. Pamidronate i. Pramlintide
v. Residronate f. Incretin Mimetic- mimics GLP 1
vi. Zoledronic acid effect/ GLP
IV. Agents to Control blood agonist
glucose levels i. Exenatide
❖ Anti-diabetic Agents g. Meglitinides – insulin
A. Insulin- causes entry of secretagogue; stimulate
glucose to cell; affects insulin release by binding to
glycogenesis; sulfonylurea or SUR 1
usually for treatment of type 1 receptor on beta cell
diabetes mellitus; stimulate i. Nateglinide
ii. Repaglinide
h. Sodium-Glucose
Cotransporter-2 Inhibitors
(SGLT-2 Inhibitors) – the glucose
are urinated
❑ Sodium-Glucose
Cotransporter-2 – cause
reabsorption of
glucose in the kidney
i. Canagliflozin
ii. Dapagliflozin
iii. Empagliflozin
i. Thiazolidinediones- decrease
insulin resitance or
increases cellular sensitivity to
insulin; bind to
peroxisome proliferator-activated
receptor-gamma
(PPAR) in adipocytes to promote
adipogenesis
i. Pioglitazone
10
ii. Rosiglitazone
❖ Glucose- Elevating agents
1. Diazoxide- potassium channel
activator
Glucagon- stimulate
glycogenolysis and release of
glucose