3. UNITS
Unit I:Antibiotcs
Unit II: anthelmintic drugs
Unit III: antiprotozoal drugs
Unit IV: Antifungal drugs
Unit V: Antiviral drugs
4.
5.
6. UNIT 1: MEDICATIONS FOR PAIN, FEVER, SEIZURES AND
INFLAMATION
• Key Unit competence: Provide appropriate medications for pain, fever,
Inflammation, and seizures.
• 1.1. Overview on pathophysiology of fever
Thermoregulation is interceded by the hypothalamus. Peripheral
thermoreceptors located in different body parts as skin, abdominal organs, as
well as central thermoreceptors found in the spinal cord and other central
locations offer the hypothalamus with information about skin and core
temperatures. If these temperatures are abnormally high, the hypothalamus
responds by triggering or heat loss mechanisms. While, when the temperatures
are abnormally low the hypothalamus responds by triggering heat production,
heat conservation.
7. 1.1. Overview on pathophysiology of fever Cont’
• Body temperature is determined by the balance between heat production by
tissues, particularly the liver and muscles, and heat loss from the periphery.
Normally, the hypothalamic thermoregulatory center maintains the internal
temperature between 37° and 38° C.
• Fever results when something raises the hypothalamic set point, triggering
vasoconstriction and shunting of blood from the periphery to decrease heat
loss; sometimes shivering, which increases heat production, is induced.
• These processes continue until the temperature of the blood bathing the
hypothalamus reaches the new set point. Resetting the hypothalamic set
point downward for example, when antipyretic drugs are given, initiates heat
loss through sweating and vasodilation. The capacity to generate a fever is
reduced in certain patients like alcoholics, the very old, the very young
8. 1.1. Overview on pathophysiology of fever Cont’
• Pyrogens are substances that cause fever. Exogenous pyrogens are usually
microbes or their products. The best studied are the lipopolysaccharides of
gram negative bacteria, commonly called endotoxins and Staphylococcus
aureus toxin, which cause toxic shock syndrome.
• Fever is a natural defense mechanism for neutralizing foreigner organisms.
High body temperature or fever destroys and kills many species of bacteria;
but when it remain high it destroy even some normal cells of human body.
Medications used to treat fever are known as antipyretics.
9. • Fever is diagnosed by measuring body temperature using thermomether , The
use of thermometer to measure body temperature is the most accurate way of
diagnosing fever. Sites for fever mesearument include
oral,axillary,tympanic,anal depending on available materials, age, status and
preferance of the patient.
• A nurse should consider as fever the temperture above 37.50 c, if the
thermometer is not available touching the skin is an other alternative even
though,it is less acurate and can expose to any other health related problems
such as infection desease transmission.
• This is especially the case if you’re self-diagnosing. When using touch to
diagnose a fever in someone else, touch your own skin first, then touch the
other person to compare the two temperatures. If the other person is a lot
hotter than you, they may have a fever. You can also try pinching the skin on
the back of your hand to check for signs of dehydration. If the skin doesn’t snap
back quickly, you might be dehydrated. Dehydration may be a sign of a fever.
10.
11. 1.2 Medications for fever
• Fever is treated by different medications including Acetaminophen or
Paracetamol which is a commonly used antipyretic. It is classified in
antipyretic analgesic drugs. Paracetamol is a chief of group of medication used
to reduce fever by direct action at the level of the hypothalamus and dilation
of peripheral blood vessels, which enables sweating and dissipation of heat.
• DIFFERENT FORMS OF PCT
12. • Adverse effects associated with acetaminophen use include
• headache,
• hemolytic anemia,
• renal dysfunction,
• skin rash, and fever.
• Hepatotoxicity is a potentially fatal adverse effects that is usually associated
with chronic use and overdose and is related to direct toxic effects on the liver.
The dose that could prove toxic varies with the age of the patient, other drugs
that the patient might be taking, and the underlying hepatic function of that
patient.
• When overdose occurs, acetylcysteine can be used as an antidote.
14. • Pain is a displeasing sensory and emotional experience related to real or
potential tissue impairment. It arises with many disorders, diagnostic tests, and
treatments. It incapacitates and distresses more people than any single
disease. It is the most common reason for consultation in health care facilities.
Sensory experience of pain depends on the interaction between the nervous
system and the environment.
• The processing of noxious stimuli and the resulting perception of pain implicate
the peripheral and central nervous systems. Among the nerve mechanisms and
structures involved in the transmission of pain perceptions to and from the
area of the brain that interprets pain are nociceptors, or pain receptors, and
chemical mediators.
• Nociceptors are receptors that are preferentially sensitive to a noxious
stimulus. Nociceptors are also called pain receptors; Nociceptors are part of
complex multidirectional pathways. These nerve fibers branch very near their
origin in the skin and send fibers to local blood vessels, mast cells, hair follicles,
and sweat glands. When these fibers are stimulated, histamine is released from
the mast cells, causing vasodilation. Nociceptors answer to high-intensity
mechanical, thermal, and chemical stimuli.
15. • Physiologically, pain occurs when sensory nerve endings called nociceptors
(also referred to as pain receptors) come into contact with a painful or noxious
stimulus. The resulting nerve impulse travels from the sensory nerve ending to
the spinal cord, where the impulse is rapidly shunted to the brain via nerve
tracts in the spinal cord and brainstem. The brain processes the pain sensation
and quickly responds with a motor response in an attempt to cease the action
causing the pain.
• Pain can be caused by a mechanical, chemical or inflammatory, or thermal
mechanism. Pain of mechanical origin can be caused by acute trauma, injury,
or overuse. It may be constant, variable, or intermittent in nature and is
affected by movement and position. Pain of chemical or inflammatory origin is
associated with arthritis and other inflammatory disorders. It is often constant
but responds to positioning, therapy, rest, and gentle movement. Pain of
thermal origin is the result of excessive heat or cold.
16.
17. • Factors influencing the pain response include past experiences to pain, anxiety,
culture, age, gender, and expectations about pain relief. These factors may
increase or decrease the person’s perception of pain, upswing or reduced
tolerance for pain, and affect the responses to pain.
Types of pain
18. Types of pain
• Types of pain include nociceptive pain or Physiological pain (figure A)
which is a stimulation of sensory receptors for body and feels like aching,
throbbing and sharp such us stubbing of toe or case of damage or disease. It
can be Superficial when Skin and mucous membranes are involved, deep
somatic when Muscles and joints are involved or visceral when Organs are
involved.
• Neuropathic pain (figure B) is an abnormal reaction to stimuli caused by
damaged nerves. It can occur as a result of injury or infection. It can also
flare up any time without an obvious pain inducing event or factor. It is
mostly a burning pain.
• Sympathetic pain (figure C) is due to damage to sympathetic nerves. It is a
bburning pain with vasomotor instability and most of the time it is
associated with rregional sympathetic blocks.
19. Pain assessment
• The pain assessment begins by observing the patient carefully; noting the
patient’s overall posture and presence or absence of overt pain behaviors
and asking the person to describe, in his or her own words, the specifics of
the pain the words used to define the pain may point toward the etiologic.
The features to consider in a whole pain assessment are the intensity, timing,
location, quality, personal meaning, aggravating and alleviating factors, and
pain behaviors. Pain is a subjective phenomenon.
• The highly subjective nature of pain Contests its assessment and
management for every health care provider. The report of pain is a social
deal; thus, assessment and management of pain require a good rapport with
the person in hurt. In pain assessment, the health care provider reviews the
patient’s report of the pain and other factors that may impact pain as well as
the person’s response to pain liberation strategies. Documentation of the
pain level as graded on a pain scale becomes part of the patient’s medical
record, as does a record of the pain relief obtained from interventions
20. • Pain assessment includes defining what level of pain relief the acutely ill
patient, believes is needed to recover quickly or improve utility, or what level
of relief the chronically or terminally ill patient requires to maintain wellbeing.
Many scales were designed to assess the extent of pain at different levels.
• The most commonly used scale is numeric scale that uses number to rate
pain for people aged 9years and above. By numerical scale, the patient rate
verbally his/her client from 0 to 10 depending of his/her feeling of pain then
the health care provider classify to no pain, mild pain, moderate pain, severe
pain depending on the number the client has indicated and considering the
figure below.
21. 1.4 Medication for pain management
• Analgesia is defined as insensibility of pain. Medications used to relive pain are
analgesic or painkiller.
• Analgesics are classified as
Opioid analgesics (strong opioid: morphine, fentanyl and weak opioid: Tramador,
codeine) and
non-opioid analgesics that include salicylates (example aspirin),
non-steroidal ant inflammatory drugs like ibuprofen and acetaminophen.
Morphine is indicated to relieve acute or chronic moderate to severe and to
complement general, local, or regional anesthesia.
All forms of morphine are contraindicated in case of asthma, hypersensitivity to
morphine or its components, labor with premature delivery and respiratory
depression or upper airway obstruction.
Morphine is available in various forms like capsules, Tablets, Oral Solution, Syrup,
infusion.
22. Morphine
• The dosage of morphine varies considering the form, intensity of pain, route of
administration, indications and age of the patient.
• Tablets of morphine are administered as initial dose of 15 to 30 mg orally every
4 hours as needed to manage pain. For oral solution initial dose is 10 to 20 ml
orally every 4 hours as needed. For maintenance dose individually titrate to a
dose that provides an appropriate balance between pain management and
opioid-related adverse reactions.
• It is important to note that oral solution is available in 3 concentrations 2
mg/mL, 4 mg/mL, and 20 mg/mL; reserve use of 20 mg/mL concentration for
patients who are opioid-tolerant. For the parenteral use, intravenous dosage is
0.1 mg to 0.2 mg/kg via slow IV injection every 4 hours, intramuscular
administration is 10 mg IM every 4 hours alternatively, 2 to 10 mg IV as needed
to manage pain (based on 70 kg adult).
• The dose of morphine is adjusted for pediatric patients .morphine is classified
in pregnancy category c
23. Tramadol
• Tramadol is among the commonly used weak opioid. It is used to relieve
moderate pain.
• It binds to the receptors and inhibits the reuptake of norepinephrine and
serotonin this enhance tramadol analgesic effect.
• In adults and adolescents over age 16, it is administered 50 to 100 mg every 4 to
6 hr. as needed to manage pain without exceeding 400mg daily. It is reduced in
hepatic and renal conditions.
• The maximum for patient aged 75 and above is reduced to 300 mg daily.
Tramadol should not be used for patient with history of addictions. Tramadol is
contraindicated for persons with alcohol intoxication; excessive use of central
acting analgesics, hypnotics, opioids, or other psychotropic drugs;
hypersensitivity to tramadol or its components.
• Tramadol is a pregnancy category C drug. Tramadol is available in different forms:
capsules (a), tablet (b), caplets(c) and injectable(d).
24. 1.5 World health organization (WHO) pain management
ladder
• The optimal pain control is multimodal and individualized. This does not
contradict the value of the generalized WHO pain ladder, but clinicians should
feel free to modify it, as needed, for individual patients, reflecting modern pain
practice.
• The WHO pain ladder describes pain in terms of intensity and recommends that
analgesics be prescribed starting at Step 1 using non opioid analgesics, such as
acetaminophen or non-steroidal anti-inflammatory drugs such as ibuprofen If
the pain persists or worsens, the clinician prescribes pain relievers from Step 2,
described as “weak opioids,” such us tramadol with or without a non-opioid. At
this point, if pain persists or worsens, the patient is administered a “strong
opioid,” at Step 3.
• Thus, pain therapy is based on pain intensity and patients progress through the
steps one by one, from lowest to highest, until pain relief is obtained.
26. Myths about Pain
• There is myth that pain medications always lead to addiction this belief
prevent some clients and health care provider to use painkillers
frequently.
• There is belief that Pain medications always cause heavy sedation,
some clients and professional refuse to administer prescribed dose
thinking that there may be sedation. Again, there is belief that some
kinds of pain cannot be relieved.
• These affect the client physically, emotionally when health care
providers do not give painkillers thinking that the pain may not be
relieved. Pain and suffering are character-building.
• Narcotic analgesics in older patients should be avoided. This is not
true, older person respond well on the effect of narcotic drugs if it has
been administered with considerations for each patient specificity.
27. 1.6. Anaesthetics
• Anesthetic is a drug used to cause complete or partial loss of sensation. It is called
local anesthesia when it blocks nerve preventing depolarization of nerve
membranes, blocking the transmission of pain stimuli and, in some cases, motor
activity and it is general when it causes induction of loss of consciousness, amnesia
(loss of memory), analgesia and loss of reflexes to allow surgical procedure
performance.
• Induction is the time from the beginning of anesthesia until achievement of surgical
anesthesia. Use of anesthetic agents suspends the sensation in parts of the body
they exist.
• The anesthetics can be subdivided into general and local anesthetics, depending on
their site of action.
• General anesthetics are central nervous system (CNS) depressants used to produce
loss of pain sensation and consciousness.
• Sedatives are agents given prior to induction of an anesthetic agent if indicated it
leads on loss of conscious and muscle relaxation to easier other procedures such us
intubation. Typically, the experience is smooth one and the patient has no recall of
the events.
28. 3 Stages of sedation
• a) Minimal Sedation, the minimal sedation level is a drug-induced state
during which the patient can respond normally to verbal commands.
Cognitive function and coordination may be impaired, but respiratory and
cardiovascular functions are not affected.
• b) Moderate sedation is a form of anesthesia that may be produced
intravenously. It is defined as a depressed level of consciousness that does
not impair the patient’s ability to maintain a patent airway. And to respond
appropriately to physical stimulation and verbal command.
• c) Deep Sedation is a drug-induced state during which a patient cannot be
easily aroused but can respond purposefully after repeated stimulation The
difference between deep sedation and anesthesia is that the anesthetized
patient is not arousal. Deep sedation and anesthesia are achieved when an
anesthetic agent is inhaled or administered intravenously.
29. • Local anesthesia is the injection or application of a solution containing the local
anesthetic into/to the tissues at the planned incision site. Often it is combined with
a local regional block by injecting the nerves immediately supplying the area.
• The advantages of local anesthesia are as follows:
– It is simple, economical, and no expensive.
– Equipment needed is minimal.
– Postoperative recovery is brief.
– Undesirable effects of general anesthesia are avoided.
– It is ideal for short and superficial surgical procedures
Local anesthesia is often administered in combination with epinephrine. Epinephrine
constricts blood vessels, which prevents rapid absorption of the anesthetic agent and
thus prolongs its local action. Rapid absorption of the anesthetic agent into the
bloodstream, which could cause seizures, is also prevented.
Local anesthesia is the anesthesia of choice in any surgical procedure in which it can
be used.
30. Local anesthetics
• Bupivacaine (marcaine), etidocaine (duranest) those anesthetics are administered by
infiltration peripheral nerve block the duration is 2–3 times longer it is used cautiously in
patients with known drug allergies or sensitivities. While using bupivacaine should consider
a period of analgesia persists after return of sensation; therefore, need for strong
analgesics.
• Procaine (novocaine) is administered subcutaneously, intramuscularly, intravenously, or
spinal.it has low toxicity; inexpensive it can cause some idiosyncrasies skin rash poor
stability. There is a need to observe for reaction such us hypotension, bradycardia, weak
pulse. Usually administered with epinephrine, causing vasoconstriction, thereby slowing
absorption and prolonging nerve deadening effect .
• Tetracaine (pontocaine) is administered to topical infiltration nerve block it causes topical
infiltration nerve block but can cause some idiosyncrasies skin rash poor stability, as potent
as procaine usually administered with epinephrine.
• Lidocaine (xylocaine) and mepivacaine (carbocaine); Lidocaine can be administered in
topical or injection, it is Rapid Longer duration of action, while administer Lidocaine they
should consider, Useful topically for cystoscopy Injected for use in dental work and surgery,
Observe for untoward reaction, drowsiness, depressed respiration. Lidocaine is currently
widely used local anaesthesia; it acts by blocking neuronal pain impulses. It may be injected
as a nerve block for spinal and epidural anesthesia. It blocks sodium channels located
within the membranes of neurons
31. Lidocaine is available in injectable forms(A), Cream for topical use( B),spray (C)
and patches (D). Their use will depend on the client, procedure to be performed
and the desired effect.
33. • In case the body get exposed to various stimuli like physical injury,
exposure to toxic chemicals, extreme heat, invading microorganism or cell
death, it reacts by defense mechanism called inflammation.
• The latter is considered nonspecific defense mechanism as it proceds in
the same way regardless of the cause that triggered it. The main purpose
of infammation is to recover the body from injury or destroy
microrganism. By neutralizing the foreign agent and removing cellular
debris and dead cells, repair of the injured area is able to proceed at a
faster pace. Whether the damage is due to pathogens, chemicals, or
physical trauma, the damaged tissue releases a number of chemical
mediators that act as an alarms to notify the surrounding area of the
injury.
34. • Chemical mediators of inflammation include histamine, leukotrienes,
bradykinin, complement, and prostaglandins. Some of these
inflammatory mediators are important targets for anti-inflammatory
drugs.
• Signs of inflammation include swelling, pain, warmth, and redness of
the affected area. Inflammation may be classified as acute or chronic.
Acute inflammation has an immediate onset and 8 to 10 days are
normally needed for the symptoms to resolve and for repair to begin.
If the body cannot contain or neutralize the damaging agent,
inflammation may continue for long periods and become chronic.
35. 1.8 Anti-Inflammatory Drugs
• Anti-inflammatory agents are drugs that block the effects of the inflammation. The
inflammatory response is the body’s nonspecific response to cell injury, resulting in
pain, swelling, heat, and redness in the affected area. Anti inflammatory drugs have
antipyretic effect by blocking fever, often by direct effects on the thermoregulatory
center in the hypothalamus or by blockade of prostaglandin mediators.
Antinflammatory drugs include nonsteroidal anti-inflammatory drugs (NSAIDs),
salicylates, acetic acid classes.
• Nonsteroidalanti-inflammatory drugs are that widely used. They act by blocking
prostaglandin synthesis and acting as anti-infl ammatory, antipyretic, and analgesic
agents. The NSAIDs are rapidly absorbed from the GI tract, reaching peak levels in 1
to 3 hours. They are metabolized in the liver and excreted in the urine. NSAIDs cross
the placenta and cross into breast milk. Therefore, they are not recommended
during pregnancy and lactation because of the potential adverse effects on the fetus
or neonate.the general side effects of NSAD include :Bleeding ,Gastric abset and
reduced kidney function . There are two main classes of antinflammatory drugs
including propionic acids and acetic acids.Among the propionic acid drug; ibuprofen
is the mostly used drug to treat inflammation.
36. • Ibuprofen is available as tablets (A, B, C) either 200mg or 400mg per tablet
and oral solution (D, E) In adults, ibuprofen dose is 400 mg tid or qid with
the maximum of 1,200 mg/day and for pediatric clients the dosage is 5 -
10mg/kg 6-8hrly the maximum being 30mg/kg/day. Ibuprofen has a half-
life of 1.8 to 2.5 hours. It is metabolized in the liver and excreted in the
urine.The commonly adverse effect of ibuprofen includes headache,
dizziness, somnolence, fatigue, rash, nausea, dyspepsia, bleeding, drug-
induced peptic ulcer, constipation. Ibuprofen is a pregnancy category C
before the first 30weeks of gestation and D from 30 weeks.
• Diclofenac and indomethacin are acetic acid derivative Nonsteroidal anti
inflammatory drugs.
37. • Diclofenac is indicated for the treatment of acute and chronic pain associated with
inflammatory conditions in adults. In adults, diclofenac is prescribed as 50 mg t.i.d.,
p.r.n or bid–qid with the maximum of 200 mg per day, 100 mg for first dose only. The
half-life is 2hours. The dose is reduced, if needed, for elderly patients and those with
serious renal dysfunction. For injectable, the dosage is 2mg/kg/day resulting
approximately in 1ampoule bid the half-life being 1.15 hours for suppositories 100mg
bid is prescribed and the half is 3 to 6 hours. Patches for topical application, one patch
is applied bid to the most painful area 12 hours.
• Diclofenac is contraindicated for persons with active GI bleeding or ulcers; asthma
attacks, rhinitis, or urticarial from aspirin or other NSAIDs, hypersensitivity to
diclofenac or NSAIDs; treatment of perioperative pain after coronary artery bypass
grafting. It is a Pregnancy category B drug.
• Indomethacin Relief of moderate to severe pain in PO 25 to 50 mg b.i.d. to q.i.d.,
increased by 25 or 50 mg daily every week, if needed the maximum being 200 mg
daily. Diclofenac comes as an oral capsule (A, B), oral tablet (C), injectable (D, E) topical
gel(G), suppository(H), transdermal patch (I), topical solution, and powder packets for
oral solution.
38. • Salicylates are salicylic acid compounds used as anti-infl ammatory, antipyretic, and
analgesic agents.They inhibit the synthesis of prostaglandin, which is an important
prostaglandin mediator of pyrogens at the thermoregulatory center of the
hypothalamus.They are most popular and oldest anti-inflamamtory drugs with
antipyretic and analgesic properties. They are generallyavailable without prescription
and are relatively nontoxic when used as directed. Salicylates are readily absorbed
directly from the stomach, reaching peak levels within 5 to 30 minutes. They are
metabolized in the liver and excreted in the urine. The half-life of 15 minutes to 12
hours, depending on the salicylate.
• Salicylates cross the placenta and enter breast milk; they are not indicated for use
during pregnancy or lactation because of the potential adverse effects on the
neonate and associated bleeding risks for the mother. Salicylates should not be used
by people with known allergy to salicylates or other nonsteroidal anti-inflammatory
drugs and those with active bleeding. It is the same for patients presenting nasal
polyps, those hostory of asthma, chiken pox or influenza,surgery or othe invasive
procedures within 1 week as this may lead to bleeding . They are not used by pregnant
and lactating mothers and persons with reanl impairement.
39. • Aspirin is the most commonly used salicylate
• Aspirin is available in oral tablet of 75mg,100mg and 500mg.
• In adults the dose is 350–650 mg every 4 h with the maximum of 4 gr per day.
For children ages 2 to 14, 10 to 15 mg/kg/dose every 4 hr, p.r.n., up to 80
mg/kg daily. Pregnancy category: D. The adverse effects of aspirin include
nausea, vomiting, heartburn, epigastric discomfort, occult blood loss,
dizziness, tinnitus, acidosis.
40.
41. • The treatment of common cold consists of antihistamines, anti-
inflammatories and decongestant drugs. The signs and
symptoms of allergic rhinitis resemble those of the common cold.
They include tearing eyes, sneezing, nasal congestion, postnasal
drip, and itching of the throat. The Goal of treating rhinitis aims at
preventing its occurance and relieve the present symptoms.The
drugs used to treat rhinitis are categorized into two groups.
• The Preventers which drugs used as prophylaxis include
antihistamines, intranasal corticosteroids, and mast cell
stabilizers.
42.
43. • The Relievers are used to provide immediate, though temporary, relief for
acute allergy symptoms once they have occurred. Relievers include the oral
and intranasal decongestants, usually drugs from the sympathomimetic
class. In addition to treating allergic rhinitis with drugs, nurses should help
patients identify sources of the allergies and recommend appropriate
interventions.
• These may include removing pets from the home environment, cleaning
moldy surfaces, using microfilters on air conditioning units, and cleaning dust
mites out of bedding, carpet, or couches. The histamine receptors
responsible for allergic symptoms are called H1 receptors. The other major
histamine receptor, H2, is found in the gastric mucosa and is responsible for
peptic ulcers .Antihistamines are drugs that selectively block histamine from
reaching its H1 receptors, there by alleviating allergic symptoms. Because the
term antihistamine is nonspecific and does not indicate which of the two
histamine receptors are affected, H1-receptor antagonist is a more accurate
name.
44. • Antihistamines are drugs that block the release or action of histamine, a
chemical released during inflammation that increases secretions and narrows
airways in antihistamines drugs. Antihistamines are found in multiple out of
the counter preparations that are designed to relieve respiratory symptoms
and to treat allergies. When choosing an antihistamine, the individual
patient’s reaction to the drug is usually the governing factor. Because first-
generation antihistamines have greater anticholinergic effects with resultant
drowsiness, a person who needs to be alert should be given one of the
second-generation, less-sedating antihistamines. Because of their out of the
counter availability, these drugs are often misused to treat colds and
influenza.
• Chlorpheniramine is a commonly used drug in adults to treat simple common
cold and rinitis while in moderate and chronic cases,desloratidin is preferred.
45. •Decongestants are drugs that decrease the blood flow to
the upper respiratory tract and decrease the
overproduction of secretions. Decongestants decrease the
overproduction of secretions by causing local
vasoconstriction to the upper respiratory tract .This
vasoconstriction leads to a shrinking of swollen mucous
membranes and tends to open clogged nasal passages,
providing relief from the discomfort of a blocked nose and
promoting drainage of secretions and improved airflow.
57. Medications for seizures
• Medications for the management of seizure disorders are called antiseizures.
Most anti-seizures have specific uses; that is, they are of value only in the
treatment of certain types of seizure disorders. There are four categories of
drugs used as anticonvulsants: barbiturates, benzodiazepines, hydantoins,
and the succinimides.
• 1. Barbiturates medications
Phenobarbital
2. . Benzodiazepine antiseizures
Diazepam (Valium )
Lorazepam ((Ativan)
Clonazepam (Klonopin)
59. UNIT 2: DRUGS ACTING ON GASTROINTESTINAL TRACT
• KEY UNIT COMPETENCE: To provide appropriate medications for common
gastrointestinal medical conditions management.
• 2.1. Definition and classification of drugs acting on gastrointestinal tract:
• The anatomic structures of GI include the oral cavity, pharynx, oesophagus,
stomach, small intestine, and large intestine the digestive tract plays a role of
bringing life sustaining elements into the body, and taking waste products out
of it, accessory organs (e.g., liver, gall bladder, salivary glands, and pancreas).
Regulation of these actions is controlled by many mechanisms.
• One control mechanism of the GI tract is the autonomic nervous system
(ANS), which consists of the sympathetic branch (fight-or flight response) and
the parasympathetic branch (homeostatic response)
60. • Gastrointestinal drugs can be administered for a variety of reasons. Some
gastrointestinal drugs encourage peristalsis, suppress it, or reduce its
undesirable by-products. Other GI drugs decrease the flow of saliva, control
vomiting and diarrhoea, loosen stool, cause vomiting, protect the GI tract,
decrease acid production, or re-establish GI normal flora.
• These medications can be classified into the following categories based on
their use:
• – Drugs for gastritis and peptic ulcer diseases
• – Antiemetic drugs
• – Oral rehydration salts (ORS)
• – Intravenous fluids
• – Antispasmodic drugs
• – Laxative drugs
61. • Drugs that are used for gastritis and peptic ulcer disease management
usually include proton pump inhibitors, H2 receptor antagonists,
antacids, and others such antibiotics or miscellaneous drugs.
Antiemetic drugs are the medications used for management of nausea
and vomiting. Dehydration can be prevented or managed using either
oral rehydration salts which are prepared solutions administered orally
or intravenous fluids. Antispasmodic drugs are medications used in the
management of different categories of visceral pain, including the pain of
gastrointestinal tract such as the pain in intestines or stomach. Finally,
laxatives are used to stimulate or facilitate evacuation of the bowels, for
example in a case of constipation.
62. 2.2. Introduction to drugs for gastritis and peptic ulcer disease
• An ulcer is an erosion of the gastrointestinal mucosa. It is always associated with
inflammation of the affected part. Although ulcers may occur in any portion of the
alimentary canal, the duodenum is the most common site. The term peptic ulcer is
specific to the lesion located in either the stomach that is named gastric ulcer or
small intestine which is the duodenal ulcer.
• The risk factors for developing peptic ulcers (PUD) are many and include close
family history of PUD, blood group (persons with blood group O were found at higher
risk), smoking tobacco because it leads to an increase of gastric acid secretion,
consuming the beverages and food that contain caffeine and or other irritant like
spices. Consuming some drugs expose to peptic ulcer diseases.
• Those drugs are corticosteroids, nonsteroidal anti-inflammatory drugs ibuprofen for
example that causes direct cellular damage to GI mucosal cells and a reduced
secretion of protective mucus and bicarbonate ion, platelet inhibitors such as aspirin
also increase risk to PUD. In addition to that, excessive psychological stress, as well as
infection with Helicobacter pylori are the risk factors to peptic ulcer diseases.
63. • The primary cause of PUD is infection by the gram-negative bacterium
Helicobacter pylori. Different clinical studies and research have revealed that,
approximately 50% of the population has H. pylori present in their stomach and
proximal small intestine. The NSAIDs and H. pylori infection act synergistically
to promote ulcers. Their combination poses a 3.5 times greater risk of ulcers
than either factor alone.
• The characteristic symptoms of duodenal ulcer are an aggravating or burning
upper abdominal pain that occurs 1 to3 hours after a meal. The pain is worse
when the stomach is empty and often disappears on ingestion of food. Night-
time pain, nausea, and vomiting are uncommon.
• The nonsteroidal anti-inflammatory drugs related ulcers are more likely to
produce gastric ulcers, whereas H. pylori associated ulcers are more likely to be
duodenal. Ulceration in the distal small intestine is known as Crohn’s disease,
and erosions in the large intestine are called ulcerative colitis. These diseases,
together categorized as inflammatory bowel disease.
64. • For patients with PUD who are infected with H. pylori, elimination of the
bacteria using anti-infective therapy is the primary goal of pharmacotherapy. If
the treatment includes only antiulcer drugs without eradicating H. pylori, a very
high recurrence rate of PUD is observed.
• The goals of drug therapy for PUD pharmacotherapy are to provide immediate
relief from symptoms, promote healing of the ulcer, and prevent future
recurrence of the disease. Drugs for PUD are available both as on prescription
and OTC drugs are available.
The primary classes of drugs used to treat peptic ulcer diseases are:
• – Proton pump inhibitors.
• – H2-receptor antagonists.
• – Antacids.
• – Miscellaneous drugs.
• – Antibiotics.
65. Brief description on mechanism of action for main drugs for gastritis and peptic ulcer disease
66. 2.3. Proton pump inhibitors and H2-receptor antagonists
• The proton pump inhibitors (PPIs) are the commonly drugs used to treat peptic
ulcer diseases. They act by blocking the enzyme responsible for secreting
hydrochloric acid in the stomach. They are drugs of choice for the short-term
therapy of PUD.
• Proton pump inhibitors (PPIs) reduce acid secretion in the stomach by binding
irreversibly to H+, ATPase, the enzyme that acts as a pump to release acid (also
called H+, or protons) onto the surface of the GI mucosa. The PPIs reduce acid
secretion to a greater extent than the H2-receptor antagonists and have a
longer duration of action. PPIs heal more than 90% of duodenal ulcers within 4
weeks and about 90% of gastric ulcers in 6 to 8 weeks.
67. • Several days of PPI therapy may be needed before patients gain relief from
ulcer pain. Beneficial effects continue for 3 to 5 days after the drugs have been
stopped. These drugs are used only for the short-term control of peptic ulcers.
The typical length of therapy is 4 weeks.
• Among them we have Omeprazole and lansoprazole that are used concurrently
with antibiotics to eradicate H. pylori. Esomeprazole (Nexium) and
pantoprazole (protonix) offer the convenience of once-a-day dosing.
Omeprazole is a widely used proton pump inhibitor.
• It is pregnancy category C drug.
70. H2-RECEPTOR ANTAGONISTS:
• The discovery of the H2-receptor antagonists in the 1970s marked a major
breakthrough in the treatment of PUD. Since their discovery, they are available as
OTC and are widely used in the treatment of hyperacidity disorders of the GI tract.
Histamine has two typesof receptors, H1 and H2. Activation of H1 receptors
produces the classic symptoms of inflammation and allergy, whereas the H2
receptors are responsible for increasing acid secretion in the stomach.
• The H2-receptor antagonists are effective at suppressing the volume and acidity of
parietal cell secretions. Duodenal ulcers usually heal in 6 to 8 weeks, and gastric
ulcers may require up to 12 weeks of therapy. All of the H2-receptor antagonists are
available the outer of the counter for the short-term 2 weeks treatment of gastro
esophageal reflux (GERD).
• All H2-receptor antagonists have similar safety profiles: Adverse effects are minor
and rarely cause discontinuation of therapy. Patients, who are taking high doses, or
those with renal or hepatic disease, may experience confusion, restlessness,
hallucinations, or depression.
71. MEDICATIONS BELONGS TO H2 RECEPTOR ANTAGONIST
• : Famotidine (Pepcid): PO (Active ulcers); 20 mg bid or 40 mg at
bedtime for 4–8 week PO (GERD); PO: 20 mg bid for 6 week
• Nizatidine (Axid): PO; 150–300 mg at bedtime
• Ranitidine (Zantac): PO; 100–150 mg bid or 300 mg at bedtime IV/IM;
50 mg every 6-8 h
72. Cimetidine (Tagamet)
• Cimetidine (Tagamet) is used less frequently than other H2-receptor
antagonists because of numerous drug–drug interactions that commonly lead
to inhibition of hepatic drug-metabolizing enzymes and because it must be
taken up to four times a day. Antacids should not be taken at the same time
because the absorption of the H2-receptor antagonist will be diminished. All
H2-receptor antagonists have similar safety profiles.
• Cimetidine is indicated for the treatment and prevention of recurrence of
duodenal ulcer, the treatment of active and benign gastric ulcer.
• It is also used to manage gastroesophageal reflux disease, to treat
pathological hypersecretory conditions, such as Zollinger-Ellison syndrome and
to prevent stress-related upper GI bleeding during hospitalization.
73. Ranitidine or zantac
• Ranitidine or zantac is a commonly used H2-Receptor antagonist. Ranitidine
acts by blocking H2 receptors in the stomach to decrease acid production. It
has a higher potency than cimetidine, which allows it to be administered
once daily, usually at bedtime. Adequate healing of the ulcer takes
approximately 4 to 8 weeks, although those at high risk for PUD may
continue on drug maintenance for prolonged periods to prevent recurrence.
Gastric ulcers require longer therapy for healing to occur.
• Intravenous (IV) and intramuscular (IM) forms are available for the treatment
of acute, stress-induced bleeding ulcers. Tritec is a combination drug with
ranitidine and bismuth citrate.
• Ranitidine is available in a dissolving tablet form (EFFER dose) for treating
GERD in children and infants older than 1 month of age.
• Administer after meals and monitor liver and renal function.
74. Ranitidine
• Ranitidine does not cross the blood–brain barrier to any appreciable extent, so it
does not cause the confusion and CNS depression observed with cimetidine.
Although rare, severe reductions in the number of red and white blood cells and
platelets are possible; thus, periodic blood counts may be performed. High doses
may result in impotence or loss of libido in men. It is a pregnancy category B drug.
• Contraindications include hypersensitivity to H2-receptor antagonists, acute
porphyria, and OTC administration in children less than 12 years of age.
• Drug–Drug Interactions: Ranitidine has fewer drug–drug interactions than
cimetidine. Ranitidine may reduce the absorption of cefpodoxime, ketoconazole, and
itraconazole.
• Antacids should not be given within 1 hour of H2-receptor antagonists because the
effectiveness may be decreased due to reduced absorption.
• Smoking decreases the effectiveness of ranitidine. For the laboratory tests,
ranitidine may increase the values of serum creatinine, AST, ALT, LDH, alkaline
phosphatase and bilirubin. It may produce false positives for urine protein. With
herbal and food absorption of vitamin B12 depends on an acidic environment; thus,
deficiency may occur. Iron is also better absorbed in an acidic environment
79. 2.4. ANTACID DRUGS
• Antacids are alkaline substances that are used to neutralize
stomach acid. They provide temporary relief from heartburn or
indigestion and for this they are sometimes also called anti-
heartburn drugs, but they do not promote healing of the ulcer, nor
do they help to eradicate H. pylori.
• The anti-acid drugs are alkaline, inorganic compounds of
aluminum, magnesium, sodium, or calcium. Combinations of
aluminum hydroxide and magnesium hydroxide, the most common
type, are capable of rapidly neutralizing stomach acid.
• Chewable tablets and liquid formulations are available.
80. Aluminium hydroxide
• Aluminium hydroxide is an inorganic agent used alone or in combination with
other antacids. Combining aluminium compounds with magnesium (Gaviscon,
Maalox, and Mylanta) increases their effectiveness and reduces the potential
for constipation. Unlike calcium-based antacids that can be absorbed and
cause systemic effects, aluminium compounds are minimally absorbed. Their
primary action is to neutralize stomach acid by raising the pH of the stomach
contents.
• Unlike H2-receptor antagonists and PPIs, aluminium antacids do not reduce
the volume of acid secretion. They are most effectively used in combination
with other antiulcer drugs for the symptomatic relief of heartburn due to PUD
or GERD. A second aluminium salt, aluminium carbonate (Basaljel), is also
available to treat heartburn.
81. • Aluminium compounds should not be taken at the same time as other
medications, because they may interfere with absorption. Use with sodium
polystyrene sulfonate may cause systemic alkalosis. When this drug is
administered some lab tests may vary. For example, the values for serum
gastrin and urinary pH may increase. Serum phosphate values may decrease.
About food and herbal interaction, aluminium antacids may inhibit the
absorption of dietary iron. There is no specific treatment for overdose for
hydroxide aluminium.
• When taken regularly or in high doses, aluminium antacids cause constipation.
At high doses, aluminium products bind with phosphate in the GI tract and
longterm use can result in phosphate depletion. Those at risk include those
who are malnourished, alcoholics, and those with renal disease.
• This drug is not indicated for patients with suspected bowel obstruction.
Precaution should be taken while administering antacid. Administer aluminium
antacids at least 2 hours before or after other drugs because absorption could
be affected. They are pregnancy category C.
82. ANTACID DRUGS:
• Aluminium hydroxide (AlternaGEL, others); 600 mg tid–qid Per os
• Calcium carbonate (Titralac, Tums)
• Calcium carbonate with magnesium hydroxide(Mylanta, Rolaids):
1–2 g bid–tid Per os 2–4 capsules or tablets prn (max: 12 tablets/day) per os
. Magnesium hydroxide (Milk of Magnesia: 5–15 mL or 2–4 tablets as
needed up to four times daily Per os
. Sodium bicarbonate (Alka-Seltzer, baking soda): 325 mg–2 g one to four
times/day Per os
85. MISCELLANEOUS DRUGS FOR PUD
• Prostaglandin Analogues
• Misoprostol is a synthetic analogue of prostaglandin E1 which inhibits gastric acid
secretion, causes vasodilatation in the submucosa and stimulates the production of
protective mucus.
• Indications
• Even though it is used some times to terminate the pregnancy, misoprostol
(Cytotec) inhibits gastric acid secretion and stimulates the production of protective
mucus. Its primary use is for the prevention of peptic ulcers in patients who are
taking high doses of NSAIDS or corticosteroids.
• The purpose of its use is to enhance the healing of duodenal ulcer and gastric ulcer,
including those induced by NSAIDs and as prophylaxis of gastric and duodenal
ulceration in patients on NSAID therapy.
• Side effects
• The side effects of cytotec are diarrhea, abdominal pain, nausea and vomiting,
dyspepsia, flatulence, abnormal vaginal bleeding, rashes and dizziness. It is a
pregnancy X drug. Misoprostol is available in tablet forms.
87. Bismuth Chelate
• Mechanism of action
• Bismuth chelate is a colloidal tripotassium dicitratobismuthate that precipitates at
acid PH to form a layer over the mucosal surface and ulcer base, where it combines
with the proteins of the ulcer exudate. This coat is protective against acid and pepsin
digestion. It also stimulates mucus production and may chelate with pepsin, thus
speeding ulcer healing. Several studies have shown it to be as active as cimetidine in
the healing o duodenal and gastric ulcers after four to eight weeks of treatment. It
has a direct toxic effect on H. pylori.
• Indications
• It is used as part of triple therapy in the treatment of peptic ulcer diseases
associated with helicobacter pylori.
• Bismuth chelate elixir is given diluted with water 30 minutes before meals and two
hours after the last meal of the day. This liquid has an ammoniacal, metallic taste
and odour which is unacceptable to some patients and chewable tablets can be used
instead.
• Antacids or milk should not be taken concurrently. Ranitidine bismuth citrate tablets
are also available for the treatment of peptic ulcers and for use in H. pylori
eradication regimes.
88. • Adverse effects The adverse effects include blackening of the tongue, teeth
and stools causing potential confusion with melaena and nausea. Bismuth is
potentially neurotoxic. Urine bismuth levels rise with increasing oral dosage,
indicating some intestinal absorption. Although with normal doses the blood
concentration remains well below the toxic threshold.
• Contraindication: It should not be used in renal failure
89. Antibiotics Used to Treat PUD
• Peptic ulcer diseases have many risk factors and cause. Helicobacter pylori; a gram-
negative bacterium is associate with duodenal ulcer in 80% of patient and 70% of
patients with gastric ulcer. If not well eradicated, it is strongly associated with
gastric cancer.
• A combination of antibiotics is used concurrently to eradicate H. pylori. Once
eliminated from the stomach, reinfection with H. pylori is uncommon. Those with
peptic ulcers who are not infected with H. pylori should not receive antibiotics
because it has been shown that these patients have a worse outcome if they
receive H. pylori treatment. Thus, patients should be tested for H. pylori before
initiating treatment for infection.
• Two or more antibiotics are given concurrently to increase the effectiveness of
therapy and to lower the potential for bacterial resistance. The antibiotics are also
combined with a PPI or an H2-receptor antagonist. Bismuth compounds (Pepto
Bismol, Tritec) are sometimes added to the antibiotic regimen. Although technically
not antibiotics, bismuth compounds inhibit bacterial growth and prevent H. pylori
from adhering to the gastric mucosa. Antibiotic therapy generally continues for 7 to
14 days.
90. Drugs used to eradicate helicobacter pylori
• The presence of the bacterium helicobacter pylori is a major causative factor
in the aetiology of peptic ulcer disease. The incidence of H. pylori infection in
patients with gastric ulcer approaches 100%. The strongest evidence of a
causal relationship between H. pylori and peptic ulcer disease is the marked
reduction in ulcer recurrence and complications following successful
eradication of the organism.
• It has been shown that the speed of ulcer healing obtained with acid
suppressing agents is accelerated if H. pylori eradication is achieved
concomitantly. Eradication of H. pylori infection prior to the commencement
of NSAID therapy reduces the occurrence of gastro- duodenal ulcers in
patients who have not had previous exposure to NSAIDs.
• H. pylori appears to be associated with increased risk of gastric cancer of the
corpus. For these reasons, it is very important to eradicate that pathogen.
91. • In eradication of that pathogen, Amoxicillin, clarithromycin are the commons
antibiotics used in combination for tritherapy or Quadritherapy.
A combination of 3 drugs called tritherapy or 4 drugs known as Quadritherapy is
necessary.
• The Following are possible combination:
• First line: Tri-therapy
• PPI+ clarithromycin+ metronidazole
• PPI+ amoxicillin+ Tinidazole
• Anti H2+ Clarithromycin +amoxicillin
• Anti H2+ Amoxicillin+ metronidazole
• Examples:
• 1. Bismuth + metronidazole+ amoxicillin for two weeks. This combination has a
success rate of 70-80%.
• 2. Omeprazole 20mg bid (on empty stomach) + metronidazole 500mg at the end of
the meal+ clarithromycin 500mg for one week. This combination has a success rate
of 95-100%.
92. • Second line: Quadritherapy
• Tritherapy + misoprostol (cytotec) or add bismuth to tritherapy
• Note: For persons with penicillin intolerance, tetracycline should be used in
place of tetracycline.
• Non pharmacological management:
• In addition to pharmacological management, it is important to educate the
patient about hygienodietetic measures of ulcer prevention and enhancement
for healing.
• It is recommended to consume milk as it contains calcium and avoid some
food like cabbages, sombe, and spicy foods as well as quit smoking and avoid
alcohol consumption.
93. 2.6. Antiemetic drugs
• Antiemetic are drugs for treating or preventing nausea and vomiting.
Their mechanism of action is of inhibiting dopamine or serotonin
receptors in the brain.
• The classes of antiemetics include antagonists of dopamine, serotonin,
neurokinin, histamine and acetylcholine,
• Differents classes of antiemetics
• Dopamine antagonists: Metoclopramide Domperidone Prochlorperazine
Chlorpromazine Butyrophenones Droperidol, Haloperidol.
• Serotonin Antagonists: Ondansetron Granisetron Palonosetron
Tropisetron
• Anticholinergics/Antihistamines: Doxylamine Cyclizine Pheniramine
Promethazine
• Neurokinin receptor antagonist: aprepitant, rolapitant, casopitant,etc
Are effective to treat post surgical noussea and vomiting and cancer
therapy.
94. 2.7. Laxative drugs
• Laxatives are drugs that promote bowel movements. Laxatives promote the
evacuation of the bowel, or defecation, and are widely used to prevent and
treat constipation. Indications for laxative include either the prophylaxis of
constipation or treatment of chronic constipation.
• The main classes are chemical stimulants, bulk stimulants and lubricants.
• chemical stimulants: These are a group of medications that stimulate the
normal gastrointestinal reflexes by chemically irritating the lining of the
gastrointestinal wall, leading to increasing of its activity.
• The drugs found in this group are bisacodyl (Dulcolax), cascara (generic), castor
oil (Neoloid), and senna (Senokot).
95. • The bulk stimulants are also called mechanical stimulants. Bulk
stimulant laxatives increase the bulk by osmotic pull of fluid into the
feces. That increase the increased bulk stretches the gastro-intestinal
wall, leading to the stimulation and increased GI movement. The
commonly used bulk stimulants include magnesium sulfate (Epsom salts),
magnesium citrate (Citrate of Magnesia), magnesium hydroxide (Milk of
Magnesia), lactulose (Chronulac), polycarbophil (FiberCon), psyllium
(Metamucil), and polyethylene glycol-electrolyte solution (GoLYTELY,
MiraLAX).
• LUBRICANT DRUGS: For some persons, there may be a need to make
defecation easier without using drugs designed to stimulate the
gastrointestinal tract, in this case they benefit from lubricants usage.
Patients with hemorrhoids and those who have recently had rectal
surgery may need lubrication of the stool.
• Lubricating laxatives include docusate (Colace), glycerin (Sani-Supp), and
mineral oil (Agoral Plain).
96. 2.8. Body fluid compartments
• In human body, the fluids travel between compartments that are separated by
semipermeable membranes. Control of water balance in the various
compartments is indispensable to homeostasis. The imbalances of body fluids
are frequent and require the treatment most of the times using drugs.
• The body fluids are mostly consisted with water, which serves as the universal
solvent in which most nutrients, electrolytes, and minerals are dissolved.
Water alone is responsible for about 60% of the total body weight in a middle-
age adult. A new-born may contain approximately 80% water, whereas an
older adult may contain only 40%.
• In a simple model, water in the body can be located in one of two places, or
compartments. The intracellular fluid (ICF) compartment, which contains
water that is inside cells, accounts for about two thirds of the total body
water.
98. • The remaining one third of body fluid resides outside cells in the extracellular
fluid (ECF) compartment.
• The ECF compartment is further divided into two parts:
Fluid in the plasma, or intravascular space, and
Fluid in the interstitial spaces between cells.
• The extracellular fluid is divided into:
1. Plasma
2. Interstitial fluid and lymph
3. Bone and dense connective tissue water
4. Transcellular (cerebrospinal, pleural, peritoneal, synovial, and digestive
secretions)
99. • The plasma and interstitial fluids are the two most important because of constant
exchange of fluid and electrolytes between them. Plasma and interstitial fluid are
separated by the capillary endothelium. Plasma circulates in the blood vessels,
whereas the interstitial fluid bathes all tissue cells except for the formed elements of
blood. For this reason, Claude Bernard, the French physiologist, called the interstitium
“the true environment of the body”. For fluids movement, the osmolality, tonicity
and osmolarity are key.
• The osmolality is a fluid is a measure of the number of dissolved particles, or solutes,
in 1 kg (1 L) of water. In most body fluids sodium, glucose, and urea, determine the
osmolality. Sodium is the greatest contributor to osmolality due to its abundance in
most body fluids. The normal osmolality of body fluids ranges from 275 to295 milli-
osmols per kilogram (mOsm/kg). Tonicity is the ability of a solution to cause a change
in water movement across a membrane due to osmotic forces. Whereas osmolality is
a laboratory value that can be precisely measured, tonicity is a general term used to
describe the relative concentration of IV fluids.
NOTE: Normally there should be a balance between fluid input and output. When the
output is greater than fluid intake, body fluid deficit may result and the person has
dehydration, electrolytes imbalances and / or shock that may be fatal depending on the
severity.
100. Fluid requirements
• In human, body fluid requirement varies according across the life span and its
calculation is based on weight and there is a need to adjust up or down based
on specific medical conditions.
• In general, infants, children and adolescents have higher ml/kg requirement
than adults.
• Table 2.8.1: In adults, the fluid requirements are as follows:
101. Table 2.8.2.Fluid requirements in children
• In pediatric population, fluid requirements are calculated considering
the child weight
102. 2.9. Intravenous fluids and calculation of drop rate
• In human, there must be a balance between fluid input and fluid output. The
latter should not exceed the intake, if this is the case then, there will be
manifestations of fluid volumes deficits if the opposite edema is the result. In
general, fluid is lost through gastrointestinal tract when a person vomits, has
diarrhea, with chronic laxative use, gastric suctioning but also with excessive
sweating, athletic activity, prolonged fever, severe burns, hemorrhage, excessive
diuresis, complications of diabetes like diabetic ketoacidosis etc.
• In clinical practice, restoring and maintaining proper fluid volume, composition,
and distribution is a significant problem in the treatment of seriously ill patients
and those with or at risk of fluid and electrolytes imbalance.
• Nurses are in good position for the intravenous fluid administration and
monitoring.
103. • Fluids are administered
to refill total body water,
restore blood volume and pressure and/or shift water from one fluid
compartment to another,
restore and maintain electrolyte and acid–base balance.
Classification of intravenous fluids
According to their tonicity, intravenous fluids are classified as:
isotonic, hypertonic and hypotonic.
According to their viscosity, there are:
colloids and crystalloids.
104. • Isotonic solutions have the same concentration of solutes (same osmolality) as
plasma.
• Hypertonic solutions contain a greater concentration of solutes than plasma
• Hypotonic solutions have a lesser concentration of solutes than plasma.
• If hypertonic solution is administered, the plasma gains more solutes than the
interstitial fluid. Water will move, by osmosis, from the interstitial fluid
compartment to the plasma compartment. This type of fluid shift removes water
from cells and can result in dehydration.
• Water will move in the opposite direction, from plasma to interstitial fluid, if a
hypotonic solution is administered. This type of fluid shift could result in
hypotension due to movement of water out of the vascular system. Isotonic
solutions will produce no net fluid shift
105. Crystalloid and colloidal IV fluids
• Crystalloids are IV solutions that contain electrolytes and other substances
that closely mimic the body’s ECF. They are used to replace depleted fluids and
to promote urine output. Crystalloid solutions are capable of quickly diffusing
across membranes, leaving the plasma and entering the interstitial fluid and
ICF. It is estimated that two thirds of infused crystalloids will distribute in the
interstitial space. Isotonic, hypotonic, and hypertonic solutions are available.
• COLLOIDS IV FLUID contain large molecules like proteins that remain in the
blood for a long time because they are too large to easily cross the capillary
membranes. When they are circulating, they have the same effect as
hypertonic solutions. They pull water molecules from the cells and tissues into
the plasma through their ability to increase plasma osmolality and osmotic
pressure. They are plasma volume expanders that are used in treatment of
hypovolemic shock due to burns, haemorrhage or after surgery.
110. DROP RATE CALCULATION
• In all health facilities across health care system, many different types of
medications are delivered as continuous IV infusions in acute, ambulatory, long-
term and critical care settings.
• With poor attention before during even after IV drug medications, Medication
error arise. These errors, which may be having serious negative consequences,
can be eliminated or kept to a minimum by knowing the standard to medication
errors.
• The drop rate calculation is very important for all continuous or intermittent IV
infusion Continuous IV infusions are often used when the medication needs to
be greatly diluted, the drug level in the blood must be tightly controlled, or
large volumes of fluids need to be infused.
111. The drop rate calculation requires to have the following
information
• 1. Amount of infusion/medication to be given(volume)
• 2. Ordered dose
• 3. Time or length of administration in minutes
• 4. Drop factor: the number of the drops in the iv chamber
that is equivalent to 1ml Having all this information the drop
rate or flow rate is calculated as follow:
112.
113. • For IV infusion, tubing varies in size. The macrodrip tubing delivers 10 to 20
gtts/ mL and is used to infuse large volumes or to infuse fluids quickly.
• Microdrip tubing delivers 60 gtts/mL and is used for small or very precise
amounts of fluid, as with neonates or pediatric patients.
114. • In general, the drop factor is considered as 20 but may change
depending on the manufacturer of the infusion set. Before
administering IV fluid a nurse must verify it on the available set.
• An IV drip rate is a way of describing the rate of an intravenous infusion
based on the number of drops (gtt) that are administered to the patient
per minute. This is influenced by
The type of the tubing (microdrip or macrodrip),
The total volume that is required to be infused, and
The time over which the infusion is ordered to run.
115. NURSING CONSIDERATONS FOR IV INFUSIONS ADMINISTRATION
1. Assess baseline assessment prior to administration:
• It is the responsibility of a nurse to take a complete health history prior to IV
fluid administration. This may include but not limited to cardiovascular
conditions like hypertension, neurologic conditions, and endocrine, hepatic,
renal….
• Also obtain a drug history including allergies, current prescription and over
the-counter (OTC) drugs, and herbal preparations.
• Obtain baseline weight and vital signs, level of consciousness (LOC), breath
sounds, and urinary output as appropriate.
• Evaluate appropriate laboratory findings like electrolytes, full blood count, if
possible, urine specific gravity and urinalysis, blood urea nitrogen [BUN] and
creatinine, total protein and albumin levels, renal and liver function studies
• Assess for desired therapeutic effect
• Double check doses with another nurse before giving any IV fluids
116. NURSING CONSIDERATONS FOR IV INFUSIONS ADMINISTRATION cont’
• . 2. After administration, a nurse should continue the monitoring
• Continue frequent assessments for therapeutic effects.
• Monitoring of vital signs, urinary output, and the level of consciousness.
• Assess for and promptly report adverse effects: tachycardia, HTN, dysrhythmias, decreasing LOC,
increasing dyspnea, lung congestion, decreased urinary output, muscle weakness or cramping, or
allergic reactions.
• Monitor for signs of fluid volume excess or deficit like increasing or decreasing BP , tachycardia,
changes in quality of pulse
• Monitor for signs of potential electrolyte imbalance including nausea, vomiting, GI cramping,
diarrhea, muscle weakness, cramping or twitching, paresthesias, and irritability
• Weigh the patient daily and report a weight gain or loss of 1 kg ormore in a 24-hour period
• Assist the patient with obtaining fluids and with eating as needed.
• Closely monitor for signs and symptoms of allergy if colloids are used.
• Closely monitor IV sites when infusing potassium or ammonium.
• Monitor nutritional status and encourage appropriate fluid intake toprevent electrolyte imbalances
as electrolyte imbalances may occur due to inadequate nutrition or fluid intake as well as from drug
therapy-like diuretics.
117. NURSING CONSIDERATONS FOR IV INFUSIONS ADMINISTRATION cont’
3. Teaching
• Instruct the patient to immediately report dyspnea, itching, feelings of Throat
tightness, palpitations, chest pain or tightening, or headache.
• Instruct the patient to report any irritation, pain, redness, or swelling at the IV site
or in the arm where the drug is infusing.
• Teach the patient to continue to consume enough liquids to remain adequately, but
not overly, hydrated. Drinking when thirsty, avoiding alcoholic beverages, maintaining
a healthy diet, and ensuring adequate but not excessive salt intake will assist in
maintaining normal fluid and electrolyte balance.
• Teach the patient to rise from lying or sitting to standing slowly to avoid dizziness or
falls.
• Instruct the patient to call for assistance prior to getting out of bed or attempting to
walk alone,
• Teach the patient that excessive heat conditions contribute to excessive sweating
that leads to fluid and electrolyte loss, and extra caution is warranted in these
conditions.
118. 2.10. Oral Rehydration Salts (ORS) and homemade rehydration solution
• The oral rehydration solution (ORS) is an oral powder that contains mixture of
glucose, sodium chloride, potassium chloride, and sodium citrate. It is
dissolvable in water and after being dissolved in the requisite volume of
water they are intended to be used for the prevention and treatment of
dehydration due to diarrhea. It is always combined with zinc are
recommended by the WHO and UNICEF to be used collectively to ensure
the effective treatment of diarrhea.
• ORS replaces the essential fluids and salts lost through diarrhea.
• Zinc decreases the duration and severity of an episode and reduces the risk
of recurrence in the immediate short term.
• ORS and zinc are highly effective and affordable products for treatment of
childhood diarrhea that could prevent deaths in up to 93% of diarrhea cases.
119. • ORS is a powder for dilution in 200ml, 500ml and 1L and they are hermetically
sealed, laminated sachets made of multiply laminations with aluminium foil or
polyethylene foil.
• They are two types of ORS;
• High osmolality rehydration salt that has the osmolality of 311molm/L,
• Low osmolality oral rehydration solution that has 245molm/L.
• The latter,being very effective, it is recommended by WHO for use due to its great
pharmacological and therapeutic effect. It is available as low osmolarity 20.5g/1L
and low osmolarity 10.2g/0.5L.
• ORS has contributed to life saving due to the pharmacokinetics and therapeutic
values of its components.
• Glucose facilitates the absorption of sodium and hence water in small intestine.
• Sodium and potassium are important in replacement of losses of the essential ions
during diarrhea and vomiting.
• Citrate corrects the acidosis that occurs as a result of diarrhea and dehydration.
121. • In clinical practice, ORS is indicated for the treatment of fluid losses especially
in case of diarrhea in infants, children and adults with mild to moderate
dehydration.
• The amount to be given is determined on basis of weight and the amount of
solution require depend largely on child status. For child with marked signs of
dehydration or who combines to pass frequently watery stools will require
more solution than those with less marked signs or who are not passing
frequent stools.
• The approximate amount of ORS solution to give in the first 4 hours:
• Below 4 months / less than 5 kg: 200–400 mL
• 4–11 months / 5–7.9 kg: 400–600 mL
• 12–23 months / 8–10.9 kg: 600–800 mL
• To 4 years / 11–15.9 kg: 800–1,200 mL
• To 14 years / 16–29.9 kg: 1,200–2,200 mL
• 15 years or older / 30 kg or more: 2,200–4,000 mL
122. • If a child wants more than the estimated amount of ORS solution, and there
are no signs of overhydration, give more.
• In case the child’s weight is unknown, use patient’s age and if the weight is
known the amount of ORS is estimated by multiplying the child’s weight in kg
times 75ml.
• During the initial stages of therapy, while still dehydrated, adults can consume
up to 750 mL per hour, if necessary, and children up to 20 mL/kg body weight
per hour.
• Normal feeding can continue after the initial fluid deficit has been corrected.
Breastfeeding should continue between administrations of ORS.
• Edematous (puffy) eyelids are a sign of overhydration. If this occurs, stop giving
ORS solution, but give breast milk or plain water, and food. Do not give a
diuretic. When the edema has gone, resume giving ORS solution or home
fluids according to Treatment Plan A. After 4 hours, reassess the child fully.
Then decide what treatment to give next: If signs of severe dehydration have
appeared, IV therapy should be started following WHO Treatment Plan C
123. • If the patient still has signs indicating some dehydration, continue oral
rehydration therapy by repeating the treatment described above. At the same
time, start to offer food, milk and other fluids, as described in WHO Treatment
Plan A. If there are no signs of dehydration, the patient should be considered
fully rehydrated.
• NOTE: ORS should not be taken when a patient has cirrhosis of liver, congestive
heart cardiac failure, nephrotic syndrome acute and renal failure, ischemic
heart diseases ,adrenocortical insufficiency, hyperkalemic periodic paralysis,
hyperkalemia, hypoventilatory states, chloride depletion due to continuous
gastric fluid loss, metabolic or respiratory alkalosis, hypocalcaemia,
hyperosmolar states in anuria or oliguria, edematous sodium retaining
conditions, hypertension, peripheral or pulmonary edema or toxaemia of
pregnancy, severe vomiting, diarrhea and dehydration requiring fluid therapy,
dextrose malabsorption, diabetes mellitus, thiamine deficiency, severe under
nutrition as another specific solution ’’ReSoMal’’ is appropriate, hemodilution,
hypophosphatemia, sepsis, and trauma.
124. ORS CONTRAINDICATION
• ORS is also contraindicated for use in patients undergoing treatment with the
following:
• sodium-retaining drugs such as corticosteroids, NSAIDs, carbenoxolone, or diuretics
known to produce hypochloremic alkalosis.
• It is very important to note that, ORS is administered with care in cases of acute
dehydration, heat cramps, extensive tissue destruction, or if patients are receiving
potassium-sparing diuretics. Concurrent use with other potassium-containing drugs
may precipitate hyperkalemia.
• It is very important to dissolve ORS in water of the correct volume. A weak solution
will not contain optimum glucose and electrolyte concentration and a strong solution
may give rise to electrolyte imbalance. Diarrhea can have very serious consequences
in children under 3 years old. Immediate medical advice should be sought. In other
age groups, if symptoms persist for more than 24–48 hours, consult a doctor.
• If nausea and vomiting are present with the diarrhea, small and frequent amounts of
ORS should be drunk first. In infants, immediate medical assistance should be
obtained. Use within 1 hour of reconstitution, or within 24 hours if stored in a
refrigerator.
125. ORS INTERACTIONS
• ORS interact with other medicinal products
• It increases excretion of lithium, resulting in a reduced plasma-lithium
concentration.
• Potassium chloride ACE inhibitors (hyperkalemia); cyclosporine leads to
increased risk of hyperkalemia; potassium-sparing diuretics where
hyperkalemia may result. No known interactions to other actives.
Undesirable effects
• Adverse effects are not very common but in case of excessive amount,
hypernatremia, edema, nausea, vomiting, diarrhea, abdominal cramps, thirst,
reduced salivation, lachrymation, sweating, fever, tachycardia, renal failure,
respiratory arrest, headache, dizziness, restlessness,etc.
• In case of overdose, sodium, potassium restriction, and water intake plus
measures to increase renal sodium, potassium and water output by using loop
diuretics for example are recommended.
126. HOMEMADE ORAL REHYDRATION SALT
• Homemade oral rehydration solution is a rehydration solution prepared at
home using sugar, salt and water locally available at home. It less expensive
most effective but require attention in preparation as in case of error in
preparation it may worsen diarrhoea or cause imbalances.
Materials
Teaspoon
Salt Sugar
Clean or boiled water
Container 1 L OR above
129. 2.11. Anti-spasmodic drugs
• Gastrointestinal antispasmodics are medications used to treat spasms of the
gastrointestinal tract muscles, which can occur in diseases like irritable bowel
syndrome, or IBS for short, biliary colic, and pancreatitis it relieves some of the
symptoms of Irritable Bowel Syndrome (IBS) , prevents, or lowers the incidence of
muscle spasms(colic), bloating and tummy (abdominal) pain, especially those of
smooth muscle such as in the bowel wall, and it reduce the movement (motility) of
the gut (intestines).
Antispasmodics are also used in some other conditions such as:
• Diverticular disease.
• Prevention of nausea, vomiting, and dizziness associated with motion sickness.
• Adjunctive therapy for treatment of GI ulcers
• Decrease secretions before anesthesia or intubation
• Maintenance treatment of bronchospasm associated with COPD.
• Treatment of irritable or hyperactive bowel in adults.
130. • The most common antispasmodic contain anticholinergic properties, which is
helpful in relieving symptoms, such as abdominal pain. They are classified into
two main types: smooth muscle relaxant such as alveline and mebeverine,
and anticholinergics such as hyoscin. However not everybody with IBS finds
that antispasmodics work well, but they are worth trying, as they work well in
a good number of cases.
• There are two main types antispasmodic drugs: Antimuscarinics drugs and
Smooth muscle relaxants
• Smooth muscle relaxants work directly on the smooth muscle in the wall of the
gut. Here they help to relax the muscle and relieve the pain associated with a
contraction of the gut.
131. A. Antimuscarinic drugs
• Antimuscarinic medications are a group of anticholinergic agents, specifically
known for blocking the activity of muscarinic receptors. These receptors play an
important role in mediating the functions of the parasympathetic nervous
system, which controls many involuntary functions to conserve energy, including
the contraction of smooth muscle, dilation of blood vessels, increased bodily
secretions, gastrointestinal activity, and heart rate.
• Because muscarinic receptors are also found in other parts of the body, taking
an antimuscarinic can have other effects. For example, muscarinic receptors also
help to control the production of saliva in the mouth.
• Therefore, antimuscarinics work by inhibiting the functions of the
parasympathetic nervous system. The two most commonly prescribed
antimuscarinics are atropine and scopolamine(Hyoscine), derived from the
Atroppa belladonna plant.
132. 1. Hyoscine (Buscopan 10 mg Tablets)
• Hyoscine butylbromide are indicated for the relief of spasm, by helps dismiss lower tummy
(abdominal) muscle cramp and pain, it one of antispasmodic medicine which is indicated to
treat cramps in the stomach, the genito-urinary tract or gastrointestinal tract and for the
symptomatic relief of Irritable Bowel Syndrome or bladder(urinary system).
• In gastro- intestinal tract, specificaly it helps to ease bloating and the spasm-type pain that
can be associated with irritable bowel syndrome and diverticular disease. It works by
relaxing some of the muscles in your gastrointestinal and urinary systems. Each tablet
contains hyoscine butylbromide 10 mg.
Posology and method of administration
• Buscopan 10 mg tablets are for oral administration only.
• Buscopan 10 mg tablets should be swallowed whole with adequate water.
• Adults: 2 tablets four times daily. For the symptomatic relief of Irritable Bowel Syndrome,
the recommended starting dose is 1 tablet three times daily, this can be increased up to 2
tablets four times daily if necessary.
• Children: 6 - 12 years: 1 tablet three times daily.
Contraindications
Buscopan 10 mg Tablets are contraindicated in: patients who have demonstrated prior
hypersensitivity to hyoscine butylbromide.
133. • Special Precautions: Buscopan 10 mg Tablets should not be taken on a
continuous daily basis or for extended periods without investigating the
cause of abdominal pain.
• Interaction with other medicinal products and other forms of
interaction
• The anticholinergic effect of drugs such as tri- and tetracyclic
antidepressants, antihistamines, quinidine, amantadine, antipsychotics
(e.g. butyrophenones, phenothiazines), disopyramide and other
anticholinergics (e.g. tiotropium, ipratropium, atropine-like compounds)
may be intensified by Buscopan.
• Concomitant treatment with dopamine antagonists such as
metoclopramide may result in diminution of the effects of both drugs on
the gastrointestinal tract. The tachycardic effects of beta-adrenergic
agents may be enhanced by Buscopan.
134. Adverse Reactions
• Many of the listed undesirable effects can be assigned to the anticholinergic
properties of buscopan
• Immune system disorders: anaphylactic shock, anaphylactic reactions, dyspnoea,
other hypersensitivity
• Cardiac disorders: tachycardia
• Gastrointestinal disorders: dry mouth
• Skin and subcutaneous tissue disorders: skin reactions (e.g. urticaria, pruritus),
abnormal sweating
• Renal and urinary disorders urinary retention (Rare)
135. 2. Atropine
• Atropine is a type of medicine called an antimuscarinic (or sometimes called
an anticholinergic). It works by relaxing the involuntary muscle that is found in
the walls of the stomach and intestines (gastrointestinal tract). Atropine is also
used in case of hypersalvation, bronchial secretions, or bradycardia. This drug
can be used also before anesthesia to prevent the mucus secretion.
• Indication
Relieving stomach cramps or colicky-type abdominal pain, for example
associated with conditions such as irritable bowel syndrome (IBS).
Therapeutic action
Atropine is a type of medicine called an antimuscarinic (or sometimes called an
anticholinergic). It works by relaxing the involuntary muscle that is found in the
walls of the stomach and intestines (gastrointestinal tract). Atropine works by
blocking receptors called muscarinic (sometimes called cholinergic) receptors
that are found on the surface of the muscle cells in the walls of the gut.
136. • This prevents a natural body chemical called acetylcholine from acting on these
receptors. Normally when acetylcholine acts on these receptors it causes the muscle
in the gut to contract. By preventing this, atropine helps the muscle in the gut to
relax. This reduces involuntary contractions and spasms of the muscle. Spasms in the
muscle of the gut wall can cause colicky abdominal pain, cramps, bloating, wind and
discomfort. Atropine relieves these symptoms by relaxing the muscle.
• Administration
Atropine tablets should be swallowed whole with a glass of water. They can be taken
either with or without food. The usual dose is one or two tablets to be taken at night.
Follow the instructions given by your doctor or pharmacist.
• Use with caution in:
• Elderly people, Children, People with Down’s syndrome. Gastroesophageal reflux
disease (GORD). Inflammation of the bowel and back passage (ulcerative colitis),
Diarrhea, People with a high temperature (fever). People with disorders of the
involuntary nervous system that controls body functions such as blood pressure,
heart rate, sweating, bowel and bladder emptying, and digestion (autonomic
neuropathy), People with an overactive thyroid gland (hyperthyroidism), High blood
pressure (hypertension), Heart attack (myocardial infarction) and Glaucoma.
137. • Pregnancy and breastfeeding
This medicine should be used with caution during pregnancy, and only if the expected
benefit to the mother is greater than any possible risk to the developing baby, it passes
into breast milk in small amounts. It should be used with caution by breastfeeding
mothers, and only if the expected benefit to the mother is greater than any possible
risk to the nursing infant.
• Side effects
Medicines and their possible side effects can affect individual people in different ways.
The following are some of the side effects that are known to be associated with
Atropine. Just because a side effect is stated here, it does not mean that all people
using this medicine will experience that or any side effect.
Constipation, dry mouth, flushing and dryness of the skin, increased body temperature,
blurred vision, dilated pupils and dislike of bright light, faster than normal heartbeat
(tachycardia), awareness of your heartbeat (palpitations), irregular heartbeats
(arrhythmias), difficulty passing urine (urinary retention), confusion (especially in
elderly people), feeling or being sick, closed angle glaucoma.
138. Drug interactions
• This medicine may reduce the effects of the following medicines:
Cisapride, domperidone, ketoconazole, metoclopramide. If you
experience a dry mouth as a side effect of this medicine you may find
that medicines that are designed to dissolve and be absorbed from
under the tongue, e.g. sublingual glyceryl trinitrate (GTN) tablets,
become less effective. This is because the tablets do not dissolve
properly in a dry mouth. To resolve this, drink a mouthful of water before
taking sublingual tablets
139. B. Smooth muscle relaxants
• Smooth muscle relaxants work directly on the smooth muscle in the wall of the gut.
Here they help to relax the muscle and relieve the pain associated with a contraction of
the gut. A muscle relaxant is a drug that affects skeletal muscle function and decreases
the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain,
and hyperreflexia.
• The term “muscle relaxant” is used to refer to two major therapeutic groups:
neuromuscular blockers and spasmolytic. Neuromuscular blockers act by interfering
with transmission at the neuromuscular end plate and have no central nervous system
(CNS) activity. They are often used during surgical procedures and in intensive care and
emergency medicine to cause temporary paralysis.
• Spasmolytics, also known as “centrally acting” muscle relaxant, are used to alleviate
musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological
conditions. While both neuromuscular blockers and spasmolytics are often grouped
together as muscle relaxant, the term is commonly used to refer to spasmolytics only.
• The most common Smooth muscle relaxant prototype are alverine, mebeverine,
peppermint oil (colpermin ) and papaverine
140. UNIT 3. MEDICATIONS USED FOR NON-COMMUNICABLE DISEASES
• Key Unit Competence: At the end of this unit, the learner will be able to provide
appropriate medications for hypertension, diabetes mellitus and asthma.
• 3.1. Introduction to antihypertensive drugs
• The cardiovascular system is a closed system of blood vessels that is responsible for
delivering oxygenated blood to the tissues and removing waste products from the tissues.
• Blood pressure is the force exerted by circulating blood against the walls of the body’s
arteries, the major blood vessels in the body. A Blood pressure is written as two numbers.
The first (systolic) number represents the pressure in blood vessels when the heart
contracts or beats. The second (diastolic) number represents the pressure in the vessels
when the heart rests between beats.
• Hypertension is defined as a high blood pressure. It is diagnosed if, when it is measured on
two different days, the systolic blood pressure readings on both days is ≥140 mmHg and/or
the diastolic blood pressure readings on both days is ≥90 mmHg.
• As blood pressure increases, it is more difficult to control it at the target level through
lifestyle modifications alone, and treatment with antihypertensive drugs becomes
necessary. The occurrence of cardiovascular disease can be prevented by reducing the blood
pressure with antihypertensive drugs.
142. Antihypertensive drugs
• Anti-hypertensive drugs are a class of drugs that are used to treat hypertension.
Antihypertensive therapy seeks to prevent the complications of high blood pressure,
such as stroke and myocardial infarction. Appropriate antihypertensive drugs should be
selected considering compelling indications, contraindications and conditions that
require the careful use of drugs and the presence or absence of complications.
• Antihypertensive drugs are administered once a day, in principle, but as it is more
important to control the blood pressure over 24h splitting the dose into twice a day is
desirable in some situations. A gradual reduction in blood pressure is desirable in
hypertensive patients in general, but the target control level should be achieved within
several weeks in high-risk patients, such as those with grade III hypertension and
multiple risk factors.
• The use of two or three drugs in combination is often necessary to achieve the target
of blood pressure control Simplification of the prescription using fixed-combination
drugs is useful for improving adherence and controlling blood pressure.
143. The major classes of antihypertensive drugs
• The major classes of antihypertensive drugs are:
• Diuretics
• Calcium channel blockers
• Angiotensin converting enzyme inhibitors
• Angiotensin II receptor antagonists/blockers,
• Adrenergic blockers, centrally and peripherally acting blockers (sympatholytics),
• Peripheral vasodilators
