Mayra Pagan

PHARMACOLOGY- NURSING

Antiepileptic Drugs
(antiseizure)

EPILEPSY affects 510 of the general population.

It is due to sudden, excessive or prolonged
depolarization of some or all cerebral neurons.
*The main Goal of Antiepileptic Drugs is to
restore normal patterns of electrical activity in
the brain*

Changes in
Electroencephalogram (seizure)

HISTORY
Bromides (1857)
Phenobarbital (1912)
Phenytoin (1938)
Later: Ethosiximide, Carbmazepine
New anticonvulsants (in the last 1520 years):
vigabatrin, gabapentin, lamotrigine, topiramate,
oxcarbazepine, levetiracetam, pregabalin etc.

ANTISEIZURE DRUGS

1. Carboxamides : Carbamazepine, Oxcarbazepine

2. Hydantoins: Phenytoin, used in digitalis

intoxication too
3. Barbiturates Phenobarbital and their
analogues, Primidone prodrug
4. Succinimides: Ethosuximide
5. Valproates (enzyme inhibitors): Sodium valproate (Depakin)
6. Benzodiazepines: Clonazepam, Clorazepate, Diazepam,
Lorazepam, Nitrazepam
7. GABA analogues: Gabapentin, Tiagabine
8. Hetereogenic anticonvulsants: Lamotrigine, Levetiracetam,
Pregabalin (partial seizures, peripheral neuropathic pain),
Topiramate, Vigabatrin

MECHANISM OF ACTION OF ANTIEPILEPTIC

DRUGS
1. Enhancing GABA synaptic transmission: barbiturates, benzodiazepines, gabapentin, levetiracetam, tiagabine, vigabatrin, topiramate, valproate; the result is increased permeability to chloride ion,
which reduces neuronal excitability. Valproate and topiramate block
GABA transaminase and tiagabine blocks reuptake of GABA.
2. Reducing cell membrane permeability to voltage-dependent
sodium channels: carbamazepine, lamotrigine, oxcarbazepine,
phenytoin, topiramate, valproate.
3. Reducing cell membrane permeability to calcium T-channels:
valproate, ethosuximide; the result is diminishing of the generation
of action potential.
4. Inhibiting excitory neurotransmitter glutamate: lamotrigine.

GABA
GABA
Barbiturates
Benzodiazepines
Gabapentin
Levetiracetam
Tiagabine
Topiramate
Valproate
Vigabatrin

Na++
Na
Carbamazepine
Lamotrigine
Oxcarbazepine
Phenytoin
Topiramate
Valproate

Ca2+2+
Ca
Ethosuximide
Levetiracetam
Pregabalin
Valproate

INDIVIDUAL ANTIEPILEPTICS
CARBAMAZEPINE: including adrenal corticosteroids, hormonal
contraceptives, theophylline and warfarin.
Dose: Standard tablets are taken twice a day. Carbamazepine is a
drug of first choice for focal and secondary generalized epilepsy
but aggravates myoclonic and absence seizure.
Used: It is useful for the treatment of trigeminal neuralgia,
postherpetic pains, etc.
Adverse reactions (ARs): reversible blurring of vision, diplopia,
dizziness, ataxia, depression of AV conduction, skin rashes, liver, and
kidney dysfunction.

PHENYTOIN (DILANTIN)
Potent inducer of hepatic metabolizing enzymes affecting itself and
other drugs (carbamazepine, war-farin, adrenal and gonadal steroids,
thyroxine, tricyclic antidepressant, doxycycline, vitamin D, folate).
Precautions: Drugs that inhibit phenytoin metabolism include:
valproic acid, cimetidine, co-trimoxazole, isoniazid, chloram-phenicol,
some NSAIDs, disulfiram.
Used: It is used to prevent all types of partial seizure, generalized
seizure,and St. epilepticus. It is not used for absence attacks.
Adverse Reactions: impairment of cognitive function (which has led
many physicians to prefer carbamazepine and valproate), sedation,
hirsutism, skin rashes, gum hyperplasia (due to the inhibition of
collagen metabolism),hyperglycemia, anaemia, osteomalacia.

VALPROIC ACID (Sodium valproate)

It is a nonspecific inhibitor of metabolism, and inhibits its own
metabolism, and that of lamotrigine, phenobarbital, phenytoin and
carbamazepine.
Use: Valproic acid is effective for treatment of generalized and partial
epilepsy, febrile convulsion and post-traumatic epilepsy.
Adverse Effect : weight gain, teratogenicity, polycystic ovary
syndrome, and loss of hair which grows back curly. Nausea can be
a problem, rarely, liver failure (risk maximal at 212 weeks). Ketone
metabolites may cause confusion in urine testing in diabetes mellitus.

BENZODIAZEPINES

Diazepam given intravenously or rectally is highly effective for

stopping continuous seizure activity, especially generalized tonicclonic status epilepticus. The drug is occasionally given orally on
a long-term basis, although it is not considered very effective in
this application, probably because of the rapid development of
tolerance. A rectal gel is available for refractory patients who need
acute control of bouts of seizure activity.
Lorazepam appears in some studies to be more effective and
longer-acting than diazepam in the treatment of status epilepticus
and is preferred by some experts.
Clonazepam is a benzodiazepine used as a second line drug for
treatment of primary generalized epilepsy and status epilepticus.

Clonazepam, Clorazepate,
Diazepam, Lorazepam,
Nitrazepam

GABAAbenzodiazepine
receptor
complex

s
Z
BD te
si

GABA

GABAAsite
+

Cl
+ Barbitu-

rate sate

Barbiturates

 LAMOTRIGINE: inhibits excitory neurotransmitter

glutamate. Lamotrigine is effective for the treatment of partial and
secondarily generalized tonic-clonic seizure. It is generally well
tolerated but may cause serious
Adverse Reations: of the skin, including StevensJohnson syndrome
and toxic epidermal necrolysis.
TOPIRAMATE: is used as adjunctive treatment for
partial seizure, with or without secondary generalization.
Adverse Reactions: sedation, weight loss, acute myopia, raised
intraocular pressure.
ETHOSUXIMIDE: blocks T-type calcium ion
channels. It is active in absence seizures (petit mal).
Adverse Reactions: gastric upset, CNS effects and allergic reactions.

StevensJohnson syndrome

MAIN INDICATIONS OF ANTIEPILEPTIC

DRUGS

Treatment of status epilepticus in adults

Patient in opisthotonus (grand mal)

Parkinsonism Drugs

Parkinsons Disease
Parkinsons disease (PD) is a progressive
disorder of movement that occurs mainly in
the elderly.
The chief symptoms are:
Tremor at rest, usually starting in the hands (pillrollingtremor), which tend to diminish during voluntary
activity.
Muscle rigidity, detectable as an increased resistance in
passive limb movement
Bradykinesia
Suppression of voluntary movements (hypo kinesis), due
partly to an inherent inertia of the motor system, which
means that motor activity is difficult to stop as well as to
initiate.

Parkinsons Disease
Associated with marked loss of dopamine
from basal ganglia.
Can be induced by MPTP, a neurotoxin
affecting dopamine neurons in the corpus
striatum.

Factors contributing to degeneration of

nigrostrial

Belladonna roots have been empirically

used for
treatment of PD in 1920s in Bulgaria by
healer
Ivan Raev (Sopot: 18761938).

Atropa belladonna
L.
(Deadly night shade)

Radix Belladonnae:

(cura bulgara)atropine

Drugs Treatment of Parkinsons

Disease
Drugs that replace dopamine (e.g. levodopa, usually
used concomitantly with peripherally acting dopa
decarboxylase inhibitor, e.g. carbidopa)
Drugs that mimic the action of dopamine (e.g.
bromocriptine, pergolide and others in development)
MAO-B inhibitors (e.g. selegiline)
Drugs that release dopamine (e.g. amantadine)
Acetylcholine antagonists (e.g. artane)

Levodopa

Mechanism:
(1) Because dopamine does not cross the blood-brain barrier
levodopa, the precursor of dopamine, is given instead.
(2) Levodopa is formed L-tyrosine and is an intermediate in the
synthesis of catecholamines.
(3) Levodopa itself has minimal pharmacologic activity, in
contrast to its decarboxylated product, dopamine.
(4) Levodopa is rapidly decarboxylated in the gastrointestinal
tract. Prior to the advent of decarboxylase inhibitors
(carbidopa), large oral doses of levodopa were required; thus,
toxicity from dopamine was a limiting factor.

Pharmacokinetics:
Levodopa is well absorbed from the small bowel; however, 95% is rapidly
decarboxylated in periphery.
Peripheral dopamine is metabolized in the liver to dihydroxyphenylacetic acid
(DOPAC) and homovanillic acid (HVA), which are then excreted in urine.

Drug interactions:
Vit B6 reduces the beneficial effects of Levodopa by enhancing its
extracerebral metabolism.
Therapy with MAO inhibitors must be stopped 14 days prior to the initiation of
levodopa therapy.
Phenothiazines, reserpine, and butyrophenones antagonize the effects of
levodopa because they lead to a junctional blockade of dopamine action.

Pharmacologic effects:

The effects on bradykinesia and rigidity are more rapid and complete than the
effects on tremor. Other motor defects in PD improve. The psychological well-being
of patient is also improved.
Tolerance to both beneficial and adverse effects occurs with time. Levodopa is
most effective in the first 2-5 years of treatment. After 5 years of therapy, patients
have dose-related dyskinesia, inadequate response, or toxicity.

Adverse effect:
Principal adverse effects include:

Anorexia, nausea, and vomiting upon initial administration, which often limit the
initial dosage.

Cardiovascular effects, including tachycardia, arrhythmias, and orthostatic

hypotension.

Mental disturbances, including vivid dreams, delusions, and hallucination.

Hyperkinesia

On-off phenomena

Sudden discontinuation can result in fever, rigidity,

and confusion. The drug should be withdrawn

Carbidopa
Carbidopa is an inhibitor of dopa
decarboxylase. Because it is unable to
penetrate the blood-brain barrier, it acts to
reduce the peripheral conversion of levodopa
to dopamine. As a result, when carbidopa and
levodopa are given concomitantly.
Virtue:
a. It can decrease the dosage of levodopa.
b. It can reduce toxic side effects of levodopa.
c. A shorter latency period precedes the
occurrence of beneficial effects.

Selegiline
A selective inhibitor of MAO-B, which predominates
in DA-containing regions of the CNS and lacks
unwanted peripheral effects of non-selective MAO
inhibitors.
It enhances and prolongs the antiparkinsonism effect
of levodopa.
It may reduce mild on-off or wearing-off phenomena.
*Long-term trials showed that the combination of
selegiline and levodopa was more effective than
levodopa along in relieving symptoms and prolonging
life*

Amantadine
Therapeutic uses and
mechanism of action
Amantadine is an antiviral agent used in the
prophylaxis of influenza A2 . It was found to improve
parkinsonian symptoms by stimulating the release of
dopamine from dopaminergic nerve terminals in the
nigrostriatum and delaying its reuptake.
Amantadine may be more efficacious in Parkinsonism
than the anticholinergic atropine derivatives but is less
effective than levodopa. It has been used alone to
treat early PD and as an adjunct in later stages.

Anticholinergic agents:
Artane
Mechanism:
Since the deficiency of dopamine in the triatum augments the excitatory
cholinergic system in the striatum, the blockade of this system by
anticholinergic agents, such as artane, helps to alleviate the motor
dysfunction.
Improvement in the parkinsonian tremor is more pronounced than
improvement in bradykinesia and rigidity.
Therapeutic uses:
Although not as effectives as levodopa or bromocriptine, it may have an
additive therapeutic effect at any stage of the disease when taken
concurrently.
Adverse effects:
Mental confusion and hallucinations.
It can occur as can peripheral atropine-like toxicity (e.g. cycloplegia, urinary
retention, constipation)

Cholinergic
Drugs

Cholinergic drugs are medications that produce the

same effects as the parasympathetic nervous system.

Cholinergic Drugs
Purpose
Cholinergic drugs produce the same effects as acetylcholine. Acetylcholine is the
most common neurohormone of the parasympathetic nervous system, the part of
the peripheral nervous system responsible for the every day work of the body.
While the sympathetic nervous system acts during times of excitation, the
parasympathetic system deals with everyday activities such as salivation,
digestion, and muscle relaxation.
The cholinergic drugs may be used in several ways. The cholinergic muscle
stimulants are used to diagnose and treat myasthenia gravis, a disease that
causes severe muscle weakness. This class of drugs includes ambenonium
chloride (Mytelase), edrophonium chloride (Tensilon), neostigmine (Prostigmine),
and piridogstimina (Mestinn). These drugs are also widely used in surgery, both
to reduce the risk of urinary retention, and to reverse the effects of the
muscle relaxant drugs that are used in surgery.
Cholinergic drugs are also used in control of glaucoma, a disease that is caused
by increased pressure inside the eye. The most common drugs used for this
purpose are demecarium (Humorsol) and echthiophate (Phospholine iodide).

Cholinergic Drugs CONT.

Description
Cholinergic drugs usually act in one of two ways. Some directly mimic the
effect of acetylcholine, while others block the effects of
acetylcholinesterase. Acetylcholinesterase is an enzyme that destroys
naturally occurring acetylcholine. By blocking the enzyme, the naturally
occurring acetylcholine has a longer action.

Recommended dosage
Cholinergic drugs are available only by prescription. They may be
available as eye drops, capsules, tablets, or injections.

Side effects
When used properly, cholinergic drugs will increase muscle strength in
patients with myasthenia gravis. In eye drop form, they can reduce the
intraocular pressure in glaucoma.

Cholinergic Drugs CONT.

Precautions
Cholinergic drugs should be avoided when the patient has any sort of
obstruction in the urinary or digestive tracts, such a a tumor, or severe
inflammation which is causing blockage.
They should be used with caution in patients with asthma, epilepsy,
slow heart beat, hyperthyroidism, or gastric ulcers.
The effects of the cholinergic drugs are to produce the same effects as
stimulation of the parasympathetic nervous system. These effects
include slowing of the heartbeat, increases in normal secretions
including the digestive acids of the stomach, saliva and tears. For this
reason, patients who already have a problem in one of these areas,
such as a slow heartbeat or stomach ulcers, should use these drugs
with great caution, since the medication will make their conditions
worse.

C
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CHOLI
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Cholinergic Drugs CONT.

The possible adverse effects of cholinergic drugs
are:
slow heart beat, possibly leading to cardiac arrest.
muscle weakness, muscle cramps, and muscle pain
convulsions
weak breathing, inability to breath
increased stomach acid and saliva
nausea and vomiting
dizziness, drowsiness, and headache

Anticholinergic Drugs
Anticholinergics are a class of medications that inhibit
parasympathetic nerve impulses by selectively blocking the
binding of the neurotransmitter acetylcholine to its receptor in
nerve cells. The nerve fibers of the parasympathetic system are
responsible for the involuntary movements of smooth muscles
present in the gastrointestinal tract, urinary tract, lungs, etc.
Anticholinergics are divided into three categories in accordance
with their specific targets in the central and/or peripheral
nervous system : antimuscarinic agents, ganglionic blockers,
and neuromuscular blockers .

Anticholinergic Drugs
Purpose
Anticholinergic drugs are used to treat a variety of disorders such as
gastrointestinal cramps, urinary bladder spasm, asthma, motion sickness,
muscular spasms, poisoning with certain toxic compounds, and as an aid to
anesthesia
Precautions
Atropine should be avoided by persons suffering from hepatitis, glaucoma,
gastrointestinal obstruction, decreased liver or kidney function, and allergy to
anticholinergic agents. Scopolamine is not indicated in cases of glaucoma,
asthma, severe colitis, genitourinary or gastrointestinal obstruction, and
myasthenia gravis , as well as people with hypersensitivity to cholinergic
blockers.
The prescription of ganglionic blockers to patients with kidney insufficiency, or
coronary or cerebrovascular disorders requires special caution and should only be
a choice when other agents cannot be used instead

Anticholinergic Drugs
CONT.
Side effects

Atropine may cause severe adverse effects with dosedependent degrees of severity. Overdoses of atropine, for
instance, may induce delirium , hallucinations, coma,
circulatory and respiratory collapse, and death. Rapid heart
rate, dilation of pupils and blurred vision, restlessness, burning
pain in the throat, marked mouth dryness, and urinary
retention are observed with higher doses, while lower dosages
may result in decreased salivary, respiratory, and perspiration
secretions. Sometimes surgeons administer atropine prior to
surgery due to this antisecretory property. Scopolamine's main
side effects are similar to those observed with atropine.
The adverse effects of ganglionic blockers include paralysis of
gastrointestinal movements, nausea, gastritis, urinary
retention, and blurred vision.
Neuromuscular blockers'adverse effects may include apnea
(failure in breathing) due to paralysis of the diaphragm,
hypotension (low blood pressure), tachycardia, post-surgery
muscle pain, increased intraocular pressure, and malignant
hyperthermia (uncontrolled high fever).

Description
Antimuscarinic agents are so called because they block muscarine, a
poisonous substance found in the Amanita muscaria, a nonedible
mushroom species. Muscarine is a toxic compound that competes
with acetylcholine for the same cholinoreceptors.Atropine and
scopolamine are alkaloids naturally occurring in Atropa belladonna
and Datura stramonium plants, whereas ipratropium bromide is a
derivative of atropine used to treat asthma.
Under the form of atropine sulfate, atropine is used in the treatment
of gastrointestinal and bladder spasm, cardiac arrhythmias, and
poisoning by cholinergic toxins such as organophosphates or
muscarine. Atropine is used in ophthalmology as well when the
measurement of eye refractive errors is required, due to its papillary
dilation properties. Scopolamine shows an effect in the peripheral
nervous system similar to those of atropine. However, scopolamine is
a central nervous system (CNS) depressant and constitutes a highly
effective treatment to prevent motion sickness, although at high
doses it causes CNS excitement with side effects similar to those
caused by high doses of atropine. Its use in ophthalmology is identical
in purpose to that of atropine. The main use of ipratropium is for
asthma treatment. Ipratropium is also administered to patients with

Benapryzine, benzhexol, orphenadrine, and bornaprine are other

examples of anticholinergic drugs used alone or in combination with
other medications in Parkinson's disease to improve motor function.
Disturbances in dopaminergic transmissions are associated with the
symptoms observed in Parkinson's disease. The beneficial effects of
anticholinergics in this disease are due to the resulting imbalance
between dopamine and acetylcholine ratio in neurons. These
anticholinergic agents may interfere with mood and also decrease
gastrointestinal movements, causing constipation; and the positive
effects on motor functions vary among patients. Other classes of
drugs available today that act on the pathways of dopamine and its
receptors to treat Parkinson's disease, such as levodopa, tolcapone,
and pramipexol, effectively increase the levels of dopamine at
dopaminergic receptors in neurons.
Ganglionic blockers are anticholinergic agents that target nicotinic
receptors in nerve cells of either sympathetic or parasympathetic
systems. The most used ganglionic blockers are trimethaphan and
mecamylamine. Trimethaphan is administered by intravenous
infusion for the emergency short-term control of extreme high blood
pressure caused by pulmonary edema, or in surgeries that require a
controlled lower blood pressure, such as the repair of an aortic

Neuromuscular anticholinergic agents prevent the transmission of

signals from motor nerves to neuromuscular structures of the
skeletal muscle.
Neuromuscular blockers are very useful as muscle relaxants in
several surgical procedures, either as an adjuvant to anesthesia or as
a pre-anesthetic.
Their main therapeutic use is in surgical procedures.
Examples of the first group are mivacurium, tubocurarine,
metocurine, doxacurium, and atracurium; the second group consists
of rocuronium, vecuronium, pipercuronion, and pancuronium.