Sedatives and hypnotics drugs ppt by kashikant yadav
Solpadol (zolmitriptan ) 1
1. Pharmaceutical dosage forms .
Medical background .
Product information .
Market analysis .
Competitors .
Doctor specialty
Message to drs .
2.
3. Types of dosage forms:
The need for dosage forms:
1- Accurate dose.
2- Protection e.g. coated tablets .
3- Protection from gastric juice.
4- Masking taste and odor.
5- Placement of drugs within body tissues.
6- Sustained release medication.
7- Controlled release medication.
8- Optimal drug action.
9- Use of desired vehicle for insoluble drugs.
4. Types of dosage forms (Cont.):
They are classified according to:
Route of administration Physical form
Oral Solid
Topical Semisolid
Rectal liquid
Parenteral
Vaginal
Inhaled
Ophthalmic
Otic
6. 1-Tablet (Cont.)
A coating may be applied to:
1- hide the taste of the tablet's components.
2- make the tablet smoother and easier to
swallow .
3- make it more resistant to the environment.
4- extending its shelf life.
7. 3-Effervescent tablet:
Effervescent tablets are uncoated tablets that generally
contain acid substances (citric and tartaric acids) and
carbonates or bicarbonates and which react rapidly in
the presence of water by releasing carbon dioxide.
-They are intended to be dissolved or dispersed in water
before use providing:
A- Very rapid tablet dispersion and dissolution.
B- pleasant tasting carbonated drink.
8. 4- Chewable tablet:
- They are tablets that chewed prior to
swallowing.
- They are designed for administration
to children e.g. vitamin products.
9. 5- Capsule:
Hard gelatin capsule
Soft gelatin capsule
A capsule is a medication in a gelatin container.
- Advantage: mask the unpleasant taste of its contents.
- The two main types of capsules are:
1- hard-shelled capsules, which are normally used for
dry, powdered ingredients,
2- soft-shelled capsules, primarily used for oils and for active
ingredients that are dissolved or suspended in oil.
10. 6- Lozenge:
-It is a solid preparation consisting of sugar and gum, the
latter giving strength and cohesiveness to the lozenge
and facilitating slow release of the medicament.
12. Orodisperible tablets Oral tablets
They are to be placed under the They are to be swallowed
tongue and produce immediate through GIT passage or GIT
systemic effect by enabling the entry .they pass through
drug absorbed directly through liver circulation and
mucosal lining of the mouth metabolism process .
beneath the tongue.
Absorption through oral cavity Absorption through GIT
avoids first-pass metabolism (Stomach –Duodenum –
(does not pass through portal Intestine ) and pass through
circulation & less metabolism ) portal circulation (First pass
effect )
13. Sublingual tablets Oral tablets
-The tablets are small & flat, -The tablet are small & Big .
-compressed lightly to keep them -Durable taste or no
soft. -The tablet not dissolve quickly
-The tablet dissolve quickly to be and take from 1-3 hrs
allowing the Active ingredient to absorbed completely .
be absorbed quickly.
It’s designed to dissolve in small It ‘s designed to dissolve in GIT
quantity of saliva. organs . (Stomach - Duodenum
– Intestine )
-Fast onset of action (the fastest ) -Slow on set of action .
-Rapid absorption -Slow absorption
-Increase B.A. -Decrease B.A.
-Reduction in side effects -More side effects
-Suitable in disease like Migraine -Not Suitable in disease like
also N. & V. nausea & V.
14. Mechanism of transportation (sublingual )
Highly vascular mucosal lining
Sublingual capillaries and veins
Jugular veins
Superior Vena cava
Arterial Circulation
14/20
17. 4 lobes of Brain
Frontal : responsible for
personality characteristics
Parietal :controls PAIN
Occipital : involved with vision
Temporal : responsible for
memory, smell & speech
18. Brain Anatomy and Parts of the Brain
The brain is made up of
three major segments -
forebrain, midbrain and
hindbrain.
Each segment consists of
different parts.
19. 1- Forebrain
The forebrain is the largest segment of the
brain located in the upper most part of
the brain , It consists
A - Cerebrum
B - Thalamus
C - Hypothalamus
20. A- Cerebrum :
- The cerebrum or the cortex is the largest part of the brain
( thinking & remembering) .
- Separated into two hemispheres right & left by
a deep longitudinal groove called the cerebral fissure.
- The right hemisphere controls the left side of the body and
vice versa..
22. 2- Midbrain
The upper section of the
brainstem which is the
lower part of the brain
adjoining the spinal cord
23. 3- Hindbrain
- Located at the upper part of
the spinal cord .
- Responsible for the vital functions :
Respiration & heart beat.
consists of
Cerebellum, Pons ,Medulla oblongata
25. Pons & medulla
are parts of the brainstem
that connects the brain with spinal cord.
Pons
- Contain control centers of face & eye movements.
- origins of 5th, 6th, 7th and 8th Cranial nerves.
Medulla
- Contains control centers of heart & lungs.
- The cranial nerves 9th, 10th, 11th, and 12th
26. The meninges
Are 3 membranous envelopes:
1- The pia mater,
2- The arachnoids
3- Dura mater
that surround the brain and spinal cord.
27. Migraine
The term migraine is Greek word hemikrania.
Migraine headache is a complex, recurrent headache disorder .
In the United States, more than 30 million people have 1 or more
migraine headaches per year.
Approximately 75% of all persons who experience migraines
are women .
28. The classic migraine episode is characterized by:
“unilateral head pain preceded by various visual, sensory,
motor symptoms, collectively known as an aura”.
The aura consists of visual manifestations such
as scotomas, photophobia . (e.g., bright zigzag lines)
29. However, migraine headaches may be unilateral or
bilateral and may occur with or without an aura.
In the current International Headache Society (IHS)
categorization, the headache previously described as
classic migraine is now known as migraine with aura,
and that described as common migraine is now
termed migraine without aura.
Migraines without aura are the most common,
accounting for more than 80% of all migraines.
30. Migraine Headache Classification :
“The International Headache Society (IHS)
• Migraine without aura, or common migraine
• Migraine with aura or classic migraine.
31. Pathophysiology
The mechanisms of migraine remain not completely understood.
Migraine is associated with a neuronal network excitability, with
activation and sensitization of
the trigeminovascular system.
32.
33.
34. Signs & symptoms
Migraines present with recurrent severe headache
associated with autonomic symptoms.
An aura only occurs in a small % of people. it is variable
Severity of the pain .
Duration of the headache.
Frequency of attacks
35. The prodrome The aura The pain The postdrome
which occurs
which immediately also known as The effects of
hours or days
precedes the headache phase, migraine may
before the
headache usually in 1/2 of persist for some
headache.
the head days after the
Incidence accompanied by main headache
Incidence
20–30% nausea, vomiting.. has ended.
40–60%
They appear
gradually over 5 It increases gradually
to 20 minutes and lasts from
generally last less 4 - 72 hours.
than 60 minutes.
36. The prodrome The aura The pain The postdrome
Symptoms include :
• Symptoms include :
1-altered Symptoms include
1- a sore feeling in
mood, irritability, depr 1-photophobia
Symptoms the area where the
ession or euphoria, foggy vision ,
include : migraine was, mood
2- colored vision, changes .
fatigue, yawning, exces bright lines in 1- mood • some report
sive sleepiness, front of eyes, changes, impaired thinking
3-craving for certain 2- sensation of pins depression, for a few days after
food (e.g. chocolate), or numbness on tiredness, the headache has
body . passed.
4-stiff ms (sp.in 2- loss of The pt. may feel
neck), hot ears, 3- vertigo, loss of appetite etc gastrointestinal
smelling power,
5- constipation or symptoms, mood
diarrhea, increased
nausea/vomiting and weakness.
37. Migraine Headache Cause:
The cause of migraines is unknown.
Migraine Headache Triggers:
A trigger is any stimulus that initiates an episode of migraine.
A migraine episode can be precipitated by exposure or withdrawal of triggers
• Emotions and stress: Emotional disturbances like grief, anger, stressful
life, mental over exertion can precipitate an attack.
• Alcohol : Intake of alcohol or withdrawal of alcohol might trigger an attack.
• Environmental factors (e.g., weather, attitude, time zone changes)
38. Migraine Headache Triggers:
• Foods that contain caffeine
• coffee, chocolate),
• monosodium glutamate (found in Chinese food),
• light aggravates headaches in some.
• Hormonal changes in women: Many women complain of headaches either
before or during menstrual periods while others have during pregnancy or
menopause.
• Hunger
• Lack of sleep
• Certain Medications
• Perfume & other strong odors
39. Simplified Diagnostic Criteria for Migraine
The International Headache Society elaborated diagnostic criteria for migraine.
These are as follows:
• Repeated attacks of headache lasting 4–72 h in pts with a normal physical
examination (no other reasonable cause for the headache) and:
Plus at least 1 of the following
At least 2 of the following features:
features:
Unilateral pain Nausea or vomiting
Throbbing pain Photophobia & phonophobia
Aggravation by movement
Moderate or severe intensity
40. neuronal network excitability
activation and sensitization of the
trigeminovascular system.
Trigeminal nerves with
their cell bodies in the
trigeminal ganglion higher brain centers are
transmit sensory impulse Sensory impulse from
activated in the thalamus &
caused by distension of the trigeminal nerves is
cerebral cortex, resulting in
the blood vessels of the carried from the
the perception of headache
Dura and meninges. The trigeminal ganglia to
pain
peripheral terminals of the brainstem
these neurons also release trigeminal nucleus
potent neuropeptide caudalis (TNC),
vasodilators,
41. 1 .Trigeminal nerves with their cell bodies in the
trigeminal ganglion transmit noxious sensory input caused by
distension of the blood vessels of the dura and meninges.
The peripheral terminals of these neurons also release potent
neuropeptide vasodilators, Substance P and Calcitonin Gene Related
Peptide (CGRP), causing dilation of dural blood vessels
42. 2 .Sensory input from the trigeminal nerves is conveyed
from the trigeminal ganglia to the brainstem trigeminal
nucleus caudalis (TNC).
3. From the TNC, higher brain centers are activated in
the thalamus and cerebral cortex, resulting in the
perception of headache pain.
43. The serotonin receptor (5-hydroxytryptamine [5-HT]) is
believed to be the most important receptor in the headache
pathway.
Stimulation of the trigeminal nerve releases substance P (SP),
calcitonin gene-related peptide (CGRP), and neurokinin A (NKA).
These substances produce neurogenic inflammation that then
interacts with the blood vessel wall, producing dilatation, plasma
extravasation, and sterile inflammation.
44. Plasma extravasation is blocked by ergots, sumatriptan,
the newer 5-HT1B/D agonists, indomethacin,
acetylsalicylic acid, gamma amino butyric acid (GABA)
agonists such as valproic acid and benzodiazepines
45. These findings suggest that sumatriptan and selective
5-HT1 agonists decrease headache by abolishing
neuropeptide release in the periphery and blocking
neurotransmission by acting on second-order
neurons in the trigeminal-cervical complex.
46. Management of Migraine :
Management
There are three main aspects of treatment:
1. Trigger avoidance.
2. Acute symptomatic control.
3. And pharmacological prevention.
Medications are more effective if used earlier in an
attack.
47. Trigger avoidance
A headache diary may help determine what triggers a persons migraines
and therefore help them avoid these triggers. A trigger may occur up to 24
hours prior to the onset of symptoms. The majority of migraines are not
however caused by triggers.
Migraine treatment
Pharmacologic agents used for the treatment of migraine can be
classified as abortive (i.e., for alleviating the acute phase) or
prophylactic (i.e., preventive).
51. Solpadol 5mg
Oro- Dispersible Tablet
DESCRIPTION
Solpadol Orally Disintegrating Tablets contain
zolmitriptan, which is a selective 5-
hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist.
52. Mechanism of Action
Migraine headache symptoms are suggested to be due to local cranial
vasodilatation &/or to the release of sensory neuropeptide through nerve
endings in the trigeminal system.
Zolmitriptan (and its N-desmethyl metabolite) has high affinity to 5-HT1D
and 5-HT1B receptor & low affinity for 5-HT1A receptors.
Zolmitriptan has an agonist effect at the 5-HT1D/1B receptor on intracranial
blood vessels and sensory nerves of the trigeminal system, causing local
cranial v.c & inhib. of pro-inflammatory neuropeptide release.
53. Pharmacokinetics:
Absorption:
• Zolmitriptan display linear pharmacokinetics after oral
administration.
• Food has no significant effect on the bioavailability of
zolmitriptan.
• No accumulation occurred on multiple dosing.
Distribution:
The mean absolute bioavailability is approximately 40%. Plasma
protein binding is 25%
54. Metabolism:
• Zolmitriptan is converted to an active
N-desmethyl metabolite .
Elimination:
• Total elimination in urine and feaces are 65% and 30%
respectively.
• About 8% of the dose was recovered in the urine as
unchanged zolmitriptan.
55. SPECIAL POPULATIONS:
Age: Zolmitriptan pharmacokinetics in healthy elderly non-migraineur
volunteers (age 65−76 yrs) were similar to those in younger non-migraineur
volunteers (age 18 - 39 yrs).
Gender: Mean plasma concentrations of zolmitriptan were
up to 1.5-fold higher in females than males.
Renal Impairment:
Severe renal impairment :Clearance was reduced by 25%
Moderate renal impairment :no significant change in clearance
56. Hepatic Impairment:
Zolmitriptan should be administered with caution in subjects with liver
disease, generally using doses less than 2.5 mg
Hypertensive Patients:
No differences in the pharmacokinetics of zolmitriptan or its effects on
blood pressure were seen in mild to moderate hypertensive
volunteers compared to normotensive controls.
57. DRUG INTERACTIONS:
• Fluoxetine, the pharmacokinetics of zolmitriptan were unaffected by
4 weeks of pretreatment of oral fluoxetine.
• MAO-A inhibitors (following one week of administration), lead to a
great increase in the conc. of zolmitriptan & its active metabolites.
But a selective MAO-B inhibitor has no effect on the pharmaco-
kinetics of zolmitriptan & its metabolite.
• Cimetidine half-life of zolmitriptan & its active metabolite were
approximately doubled following cimitidine administration.
58. • Oral contraceptives, plasma concentration of zolmitriptan were
generally higher in female taking oral contraceptives compared to
those not taking oral contraceptives, zolmitriptan mean Cmax is
increased and Tmax was delayed.
• Propranolol the Cmax of zolmitriptan increased 1.5 fold after one
week of dosing with propranolol .
• Acetaminophen has no effect on zolmitriptan but zolmitriptan
delays the time of maximum concentration in the blood of
acetaminophen by one hour.
• Metoclopramide, a single 10 mg dose of metoclopramide had no
effect on the pharmacokinetics of zolmitriptan or its metabolites.
59. INDICATIONS AND USAGE:
•Solpadol is indicated for the treatment of
acute migraine with or without aura in adults.
•It's not intended for the prophylactic therapy of
migraine
60. CONTRAINDICATIONS:
• Hypersensitivity to the active substances or to any of its excipients.
• Ischemic heart disease patients
• Uncontrolled hypertension.
• Not be given within 24 hours of treatment with another 5-ht agonist, or
an ergot-containing or ergot-type medication.
61. WARNING AND PRECAUTION:
-Solpadol should not be given to patients in whom unrecognized coronary
artery disease (CAD) is predicted by the presence of risk factors (e.g.
hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong
family history of CAD).
-Its recommended that patients who are intermittent long term users of
Solpadol and who have or acquire risk factors predictive of CAD, undergo
periodic interval cardiovascular evaluation as they continue to use
Solpadol.
62. SIDE EFFECTS:
Some patients may experience pain or tightness in the chest or throat, shortness
of breath, wheeziness, heart throbbing, swelling of eyelids, face, or lips, or a skin
rash may happens rarely.
Rare side effects: tingling, heat, drowsy, dizzy, tired, or sick.
PREGNANCY AND LACTATION:
This product is not to be used in pregnancy or lactation except when the
potential benefit justifies the potential risk.
63. DOSAGE AND ADMINISTRATION:
The recommended dose is 2.5 mg to 5 mg of Solpadol tablets for
treatment of acute migraines in adults.
If migraine returns, a second dose may be taken not less than 2 hours
after the first dose.
(The maximum dose of Solpadol in 24 hours is 10 mg).
OVERDOSAGE:
There is no experience with clinical overdose. Volunteers receiving single
50 mg oral doses of zolmitriptan commonly experienced sedation.
64. INSTRUCTIONS TO PATIENTS:
Patient should be instructed not to remove the tablet from the
blister until just prior to dosing.
PACKING AND PRICE :
A pack of 3 strips, each containing 2 tablets of 16 L.E.
STORAGE:
Store at controlled room temperature not exceeding 30 Cº
. Protect from light and moisture and keep out of reach of
children.