filename: 11. epilepsy & opioids.docx

7/30/2019 Filename: 11. epilepsy & opioids.docx

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E P I L E P S Y

Epilepsy and antiepileptic drugs:

Epilepsy: is a very common chronic disorder characterized by recurrent

seizures

Seizure: excessive discharge of cortical neuron Convulsion: involuntary contraction of voluntary muscles

** Patients may have epilepsy or seizure disorders without convulsionsInternational classification of seizures

1)Partial "focal": In which the excessive neuronal discharge involves one part of the

cortex

Seizure activity starts in one part of the brain

Main types of partial "focal" seizures:

A.Simple: consciousness is preserved (seizure activity while person isalert)


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B.Complex: consciousness is impaired (seizure activity with change inawareness of surroundings)

2)Generalized: In which the excessive neuronal discharge involves the whole cortex

Seizure activity involves the whole brain

Main types of generalized seizures:

A.Tonic-clonic (Grand-mal seizures):Composed of two phases:

Tonic phase: abrupt loss of consciousness (less than 1 min), epileptic cry,

falling, generalized stiffening of body muscles and limbs are back arched

Clonic phase:alteration of muscle contraction and relaxation(stiffening and

jerking of body & limbs & head muscles) with lip or tongue biting, eyes

blinking, fecal & urinary incontinence

** Usually there's a phase after these two phases known as post-ictal

confusional fatigue phase where the patient is tired, confused, having letharg

and unaware of what has just happened!!


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Absence (petit-mal seizures):

*Onset of this type occurs from ages 3-16 years (mainly in children)

*Characterized by:altering of consciousness lasting for10-30 seconds when the

patient stares and blinks without falling

** After the seizure ends the patient gets back to his/her activity

B.Myoclonic:o Characterized by: single or multiple muscle jerk (jerking

movements of the body)

C.TonicD.Atonic

o Characterized by: loss of body

tone and falling heavily to theground without any convulsions

3)Status epilepticus: It is a life threatening emergency requiring quick treatment


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In which there's series of seizures without recovery of consciousness

between attacks

4)Febrile seizures: Young children (3 months to 5 years) frequently develop seizures

with illness accompanied by high fever

The cause of these seizures is an infection accompanied with high fever

To treat these seizures we should treat the fever (pyrexia)

Treatment of choice is: Diazepam which is given rectally

** Diagnosis of specific seizure type is important for prescribing the most

appropriate anti-seizure drug (because for each type of seizure we have

specific group of drugs)

** Treatment may involve combination of drugs

Aim of treatment:

Complete suppression of seizures "fits, attacks" and if not possible then,

Reduction of seizure frequency "number" as much as possible with minimum

and tolerable adverse drug reactions (ADRs)

** Usually, treatment of epilepsy is highly challenging, first of all we should

carefully diagnose the type of seizure the patient has based on patient's full

description of the seizure type and frequency, then we should select the prope

type of drug based on patient's age, drug to drug interaction, liver and kidney

function tests, and other factors

** The management of patients with epilepsy is focused on 3 main goals:


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o Improve quality of life

o Controlling seizures

o Avoiding side effects of anti-seizure drugs

** Anti-seizure drugs are associated with many adverse drug reactions and

many drug to drug interactions

Etiology of epilepsy:

Primary "idiopathic" seizures:

These seizure have no identifiable cause

** Some seizures arise secondary to other conditions. However, in most cases

the cause of the seizure is unknown

Secondary "symptomatic or acquires" seizures:

These seizures occur secondary to an identifiable cause such as:

a. Intracranial neoplasms

b.Infectious diseases, such as: meningitis, influenza

c. High fever (in children)d.Head traumae.Metabolic disorders, such as: hypoglycemia and hypocalcaemiaf. Alcohol or drug withdrawal (sudden stoppage)

Clinical evaluation of epilepsy:

History includes an evaluation of the seizure, including interviews of the

patients family

Laboratory test may also identify an underlying etiology (CBC, Glucose

level, Calcium level to detect any metabolic disorder)


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Neurological imaging studies may also identify an underlying etiology (MRI, CT

scan to detect any brain neoplasm or injury)

EEG "electro-encephalo-gram" studies measure the electrical activity of thebrain

It is the most important test to diagnose epilepsy (although in some cases it

might not be helpful)

An EEG is useful for classifying the seizure, but the EEG by itself cannot rule

seizures in or out (as there are patients with normal EEGs who have seizure

disorders)

Normal EEG will NOT exclude epilepsy! As patients have normal EEG between

attacks but abnormal EEG during attacks

Principles of drug therapy:

Seizure control

Approximately 50% of epileptics achieve complete seizure control through

drug therapy

In another 25% of epileptics, drugs reduce the frequency of seizures

Epileptics generally require continuous drug therapy for at least 4 seizure-

free years before the drug can be discontinued

Anti-epileptic drugs are indicated when there is two or more seizures

occurred in short interval

One seizure doesn't require anti-epileptic drug treatment

An initial therapeutic aim is to use only one drug (mono-therapy)

Single drug is used initially NOT combination of drugs


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Before any drug treatment is instituted, remedial causes of the seizure

activity should be excluded

A single primary drug that is most appropriate for the seizure type must

be selected

If there is more than one appropriate primary drug, then, age, sex,

and compliance of the patient must be considered

Additional therapy

If seizures recur after the maximal tolerated dose of the primary drug isreached, then, a second drug is added at a low dose

The dose of the second drug is increased gradually until an optimal

therapeutic level is reached

The first drug is maintained until the optimal dose of the second drug is

determined; then the first drug is discontinued gradually to avoid

triggering seizure activity

The sudden withdrawal of drugs should be avoided NOT to trigger

unwanted seizure activity

Withdrawal of anti-seizure drugs may be considered after seizure-free

period of 2-3 or more years

Mechanism of action of anti-epileptic drugs:

In epilepsy, there's excessive neuronal discharge in the central nervoussystem which is either partial or generalized, and drugs used to treat

epilepsy work by one of these mechanisms:

a. Increasing the activity ofinhibitory neurotransmitters in the CNS

Inhibitory tone by facilitation ofGABA-mediated hyperpolarization


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Drugs increasing inhibition include: barbiturates and benzodiazepines

b.Decreasing the activity ofexcitatory neurotransmitters in the CNS

Pre-synaptic Ca influx through type-T channels in thalamic neurons

Drugs decreasing excitation include: ethosuximide and valproic acid

c. Decreasing the neuronal firing in the CNS by blocking the voltage-gatedion channels

Axonal conduction by preventing Na influx through fast Na channels

Drugs decreasing neuronal firing include: Carbamazepine, phenytoin

and also barbiturates and valproic acid(at high doses)

Antiepileptic drugs:

1)Phenytoin: Mechanism of action: blocks voltage-gated sodium channels in

neuronal membrane and thus decreasing axonal conduction and firing

Clinical uses:partial seizures & generalized tonic-clonic seizures

** Phenytoin is used successfully in the treatment of partial seizures

as well as generalized tonic-clonic seizures, but if we use phenytoin in

the management ofabsence seizures then seizures will get worse

Phenytoin has narrow therapeutic index(considered as an un-savedrug)

Phenytoin is metabolized by zero

order kinetics in which the relation

between the dose & plasma

concentration is not linear


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So that small increase in drug dose results in rapid increase in plasma

concentration and this will increase the risk for drug toxicity

Phenytoin has high drug to drug Interactions since it is:

a.Highly protein bound drug so that increasing free drug concentrationmay produce a high toxic effect

b.Hepatic enzyme inducer drug so that it will accelerate the metabolism ofother drugs

** Ifphenytoin is the primary drug used to treat seizures, and it was

proven that this drug isn't effective to stabilize seizures, then asecondary drug should be used to stabilize the condition, let's say it was

Carbamazepine, we should keep in mind that Phenytoin decreases the

effectiveness of Carbamazepine since it induces its metabolism

Side effects:

a.CNS:ataxia, diplopia (double vision), nystagmus (rapid vertical andhorizontal eye movement)

b.Gingival hyperplasia(especially inchildren)

c. Hairsutism (enhance hair growth)d.Teratogenic effects

Phenytoin shouldn't be given during

pregnancy (especially in the first trimester) NOT to induce fetal

malformation (cleft lip and palate)e.Abnormalities of vitamin D catabolism (leading to bone disorders due

to vitamin D deficiency, like: osteomalacia in adults or rickets in children)f. folate levels (leading to megaloblastic anemia)

** Keep in mind that phenytoin side effects are dose related


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2)Carbamazepine:Mechanism of action: blocks voltage-gated sodium channels in neuronal

membrane and thus decreasing axonal conduction and firing (same asphenytoin)

Clinical uses:partial seizures & generalized tonic-clonic seizures

(same as phenytoin)& for non-epileptic disorders such as: Trigeminal

Neuralgia & mania & neuropathic pain

** Trigeminal neuralgia is characterized by facial pain due to problems

in trigeminal nerve** Mania ( ) is characterized by mood changes

** Neuropathic pain is commonly encountered in diabetic patients if

their condition isn't stabilized

Similarities between phenytoin & Carbamazepine:

a.Both are hepatic enzyme inducers (both accelerate the metabolism o

other drugs)b.Both enhance catabolism of vitamin D (both lead to bone disorders)c. Both cause megaloblastic anemia but more with phenytoin (both

decrease folate levels)d.Both are NOT used in treatment of absence seizures

Side effects:

a.CNS:ataxia and diplopia (double vision)b.Abnormalities of vitamin D catabolism (leading to bone disorders

due to vitamin D deficiency, like: osteomalacia in adults or rickets

in children)c. folate levels (leading to megaloblastic anemia)


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3)Valproic acid: Mechanism of action: blocking voltage-gated sodium channels at high

doses OR can potentiate the inhibitory effect of GABA OR blocking T-calcium channel

** Valproic acid is one of the drugs having multiple mechanisms of

action

** Valproic acid is one of the drugs having broad anti-seizure effects

and can be used for any type of epilepsy

Clinical uses: partial seizures & generalized tonic-clonic seizures &

absence seizure & Myoclonic seizures

Side effects:

a.Alopecia (enhance hair loss)

b.TeratogenicityValproic acid shouldn't be given during pregnancy (especially in th

first trimester) NOT to induce fetal malformationc. Liver damage (enhance haptotoxicity)

4)Ethosuximide: Mechanism of action: act by blocking T-calcium channels

Clinical uses: The main drug used to treat absence seizures

5)Phenobarbital: It is one type ofbarbiturates

Mechanism of action: blocking voltage-gated sodium channels at high

doses OR can potentiate the inhibitory effect of GABA


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Clinical use: same as phenytoin for partial seizures & generalized

Tonic-Clonic seizures & maybe used in the treatment ofstatus

epilepticus

6)Benzodiazepinesa.Diazepam: given Intravenously to treat status epilepticusb.Clonazepam: to treat absence seizures & Myoclonic seizures

Drugs used in seizure disorders:

1)Partial seizures and generalized tonic-clonic seizures Carbamazepine,Phenytoin, Valproic acid and Phenobarbital

2)Absence Seizures Ethosuximide, Valproic acid and Clonazepam3)Myoclonic Clonazepam and Valproic acid

** There are adjunct newer drugs which aren't used along but in combinatio

with the old drugs

** Newer drugs are highly expensive and have fewer adverse effects

Management of status epilepticus:

1)Establish airway, oxygenate, recovery position

2)Establish intravenous access and give intravenous lorazepam 2-4 mg OR

intravenous diazepam 5-10 mg OR intravenous midazolam 10 mg

** Lorazepam, Diazepam and Midazolam are Benzodiazepines derivatives

** Don't memorize doses** Lorazepam is our first drug of choice while diazepam and midazolam

are alternatives

3)Check blood for: glucose, urea and electrolytes, Calcium, anticonvulsant

levels, and arterial blood gas and pH


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4)Ifseizures continue, administer intravenous Phenobarbital OR intravenous

phenytoin as second-line treatment

5)In sever status epilepticus especially that doesn't respond to thesemeasures, general anaesthesia and neuromuscular blocker(muscle

relaxant) and artificial respiration are needed

** It is important that we stop seizures in here because their continuation

leads to brain damage


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Opioid Analgesics- Analgesics: are drug that can relieves (reduce) pain without loss of

consciousness , they acting on CNS or peripheral pain mechanism to

suppress pain sensation.

analgesics including opioids (powerful highly effective pain killer) and

NSAIDS(non-steroidal anti-inflammatory drugs) like : aspirin, ibuprofen

and voltaren.- Narcotics: they have an analgesic effect(pain relieve) and sedative

properties(CNS sedation).- Opioids: include natural ,semi synthetic and synthetic alkaloids that

produce a morphine like-effect , their effect can be block by

specific(non-selective) opioids antagonist known as Naloxone.

Opioids highly use illegally(addiction),they induce psychology,

physiology and physical dependence.

- Pain: unpleasant sensory and emotional experience associated with

actual or potential tissue damage.

- Classification of pain by

1) by onset and durationChronic painAcute painpersistant or recurrent.Sudden in onset- often difficult to treat .- usually subsides once treated

2) Types of pain

- Neuropathic pain : the pain due to neuronal damage(nerve

damage) in the peripheral tissue or in CNS.


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-Nociceptive pain : result of activation of

sensory(afferent)receptors(nociceptors) by mechanical, thermal or

chemical stimuli.

Functional, physiologic or normal pain.Opioids peptide : are used exogenous but they presented as

endogenous opioids, synthesize by nerve cell and adrenal

medullary cells and interact with opioid receptors. They can be

released to regulate pain sensation and stressful situation or

anticipation of pain .

Endogenous opoids: endorphins, dynorphines and enkephalines .

Opioids receptors :

Beginning with their class, usually effector opioids receptor are G-

protein coupled receptor .

But the other mechanism that the opioids act on neuron byvoltage gated channel, in which they will cause closing of ca

2+

channel on presynaptic neuron to inhibit neuronal firing to initiate

action potential, on the same time they will cause open K+

channel

on postsynaptic neuron .


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You know from the physiology that entrance of Ca is important to

enhance neurotransmitters in presynaptic neuron. Opioids can lock

through opioid receptor interance of Ca by closing Ca channel in

presynaptic neuron, no Ca entrance no releasing of

neurotransmitter(excitation).

On the same time opioid receptor affect on postsynaptic neuron, they

inhance K efflux its mean neuronal inhibition (repolarizing or

hypopolarized or neuronal initial) so we can suppressing pain sensation by

inhibit formation (propagation) of action potential.

Receptor stimulation :

Mu * P hysical dependence

E uphoria


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A nalgesiaR espiratory depression

*kappa

S edation

A nalgesia (spinal)

M iosis

*Delta

A nalgesia

(mu), (delta), (kappa) stimulation lead to analgesia.

Opioid overdose will depress respiratory system(death).

- Classification of opioids :1) Natural : morphine - codeine thebaine.

2) Semi synthetic : heroin(diacetylmorphine) it's lipid solubility highr

than morphine , heroin rapidly penetrate CNS so rapidly get the ipiod

effect (that need by addicted individual).

3) Synthetic : meperidine-methadone-dextromethorphan-fentanyl-

pentazocin.

- Classification : (exam Q)

1) Strong agonists :

Ex: morphine methadone fentanyl- meperidine.

2) Moderate agonist:


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Ex: codeine.

3) Mixed agonists-antagonist :

Ex : pentazocin.(it can act as agonist and as antagonist

depending in which receptor it bind)

4)Antagonist :

Ex: Naloxone, used to treat overdose(toxicity)very very imp.

*slide 13: the figure isn't to memorize..

To get a powerful analgesic effect we use strong

agonist(fentanyl), as much we stimulated receptors as much get

analgesic effect .

Morphine : morphine and other opioid act through binding to

opioid receptors. These receptors distributed in the CNS at

regions involved in transmission and modulation of pain.

Pharmacological actions :

-Strong agonsits

- acute effect :

1) Analgesia : can suppress pain sensation without loss of

consciousness.


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Visceral pain relieve better than somatic pain.

Nociceptive pain is better relieve than neuropathic pain.

Degree of analgesia is dose dependent(increase the dose

increase the analgesics effect)

2) Euphoria : morphine produces a powerful sense of contiment

and well-bieng.(cause of addiction)

3) Sedation, drowsiness and hypnosis .

We can get active CNS depressant effect if it's used with CNSdepressant.

4) Respiratory depression : inhibits respiratory center in the

medulla and decreasing its sensitivity to CO2 (Co2 retention) . it

is dose-related .

Death from morphine overdose is usually due to respiratory

failure.

5) Antitussive : opioid(drug) suppress the dry cough by suppress

the cough central in the medulla which control cough reflex .

Two types of cough : unproductive(dry or irritant) should be

suppressed while productive(sputum and respiratory secretion)

cough shouldn't be suppress .

Dextromethorphan is one component of low cough , can be

used as antitissive , it is safe(very low CNS addiction effect) it

can used public (no restriction) .

Codeine is a potent inhibitor of the cough reflex.


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Meperidine has a week effect .

6)Miosis : opioid act on (mu)and(kappa) receptors to stimulate

oculomotor nucleus to constrict pupil . pin point pupils(verydense smaller pupil-) are characteristics of morphine over dose

(opioid addiction)

7) Nausea and vomiting: Stimulation of CTZ.

Because it stimulate chemoreceptor trigger zone,and once it stimulated

,its stimulation may initiate vomiting.

8) GIT effects They found that morphine and other opioids can reduce

GI motility ,Increases GI tone , by that they reduce gastrointestinal

secretion so Produces constipation.

9) Urinary retention: Due to contraction of sphincter, inhibition of reflex

of urination and increase ADH release >>>urinary retention.

By that we considered morphine and other opioids should not be usedin patient with benign prostatic hyperplasia, in which this patient who

already complain from urinary retention,so if this patient used opioids

the risk will be more.

10) Biliary tract: Morphine is contraindicated in biliary colic because

Contraction of biliary muscle and sphincter of Odi Biliary tract spasm

Opioidscan exacerbate biliary colic .

by that opioids will lead excessive pain in colic except morphine.

11) UTERUS: they found that morphine can decrease uterine tone,by

that they will be prolong labor >>>so morphine has multiple effect.


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12) SEDATION and have anxiolytic effects.

13) CARDIOVASCULAR SYSTEM :

( no prominent effects).

*They found that if the morphine used in a high dose lead to Peripheral

vasodilation , most prominent effect due to histamine release and

decreased adrenergic tone.

*Very high doses of morphine may produce bradycardia .

14) Histamine release: Morphine releases histamine from mast cells,histamine is a neurotransmitter,once the histamine release, will

induce bronchoconstriction , vasodilation,(the vasodilation associated

with urticaria, sweating, redness).

Because it can cause bronchoconstriction, so morphine is

contraindicated in patient with bronchial asthma or patient with chronic

obstructive pulmonary disease.

*** there is something very important about morphine:

Morphine suppress respiratory center, increase CO2 retention >>> this

will induce cerebral vasodilation >>> this will increase intra cranial

pressure(ICP) or cerebrospinal fluid pressure>>>therefore morphine

and other opioids is usually contraindicated in patient

with acute head injury .

Suppose that there is patient with RTA (renal tubular acidosis),come this

patient with this injury, he need an analgestic,they found that morphine

can increase ICP,so If this patient with head injury(that already has


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increase in ICP) and receive morphine this will increase ICP more and

more,by that this will increase the risk of hemorrhage .

actions of Morphine (CNS) contd.

*Depression:

1. respiratory centre depression Both rate and depth of respiration are

diminished-( Dangerous in Head injury and asthmatics).

2. suppress Cough Centre

3.supress Vasomotor centre, so they can lead to bradycardia.

In high doses can reduce the BP.

*stimulation:

1.CTZ sensitize CTZ to vestibular and other impulses.

Why it stimulate the chemo receptor trigger zone ? this will initiate

vomiting it stimulate :

2.Edinger Westphal Nucleus (stimulate occulomator nerve will

cause miosis ).

3.Vagal centre(if stimulate vagal nereve,this will lead to Bradycardia ).

*chronic effects :


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1. Tolerance : Tolerance and physical dependence are manifestations of

chronic toxicity .

What does we mean by toleranc :Chronic(long) use there will be a

reduction in drug efficiency (+pharmacodynamic in nature in which

there is adaptation of central nervous system of usual doses of

morphine)..

**Tolerance develops To:

1)Analgesia 2)Euphoria 3) Sedation

**While the Tolerance DOES NOT develop to:

1) Miosis 2)Constipation

**Crosstolerance develops to other opioids ,forexamples :

For ex: Patient used morphine to control pain due to cancer,continuousused will lead to tolerance, if this patient switch to other opioids, the

similar drug also become not effective because this drug is cross

tolerance to other opioids.

The most other problem with chronic use is dependence :

2. Dependence : characterized by physiological dependence and

psychological dependence.

Physical or physiological, sudden Abnormal physical state in which the

drug must be administered to maintain normal function.


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Psychological dependence is addiction, while physical dependence is

seen in which continuous drug used become essential to overcome

withdrawal symptoms,in which this symptoms are highle severe.

Physical dependence is a powerful reinforcement for continued drug

taking behavior.

They found thay withdrawal symptomscan be more severe if the

patient use an antagonist.

Withdrawal syndrome can be induced by naloxone(antagonist).

withdrawal symptomsare highly severe if the patient suddenly stop

the drug.

Methadone:Produces very mild withdrawal or abstinence syndrome.

If we have an addict we need to treat this addict, how he/she can be

treated ? for ex: individual who become addict to heroin, how we

can treat this addiction ?

Sudden withdrawal induce severe sudden abrupt discontinuation

will induce severe withdrawal syndrome .

we cant make gradual reduce in heroin,we use another drug which

known as methadone ,this drug is used in program for the treatmentof opiods addiction,in which methadone can produce euphorietic

effect is less than that euphoria produce by heroin or morphine,the

patient will get the euphorietic effect, which is lesser , and with time

we can reduce methadone dose.This mean there is addicted,if this


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addicted receive the antagonist ,the antagonist will initially give

excessive pain withdrawal symptoms , because the antagonist make

longer symptoms,by that is like making sudden withdrawal drug,this

will lead excessive withdrawal symptoms , the patient is switch to

methadone and with time we reduce the dose of methadone, in

which methadone is used orally for reduce euphoria , but is less than

that of morphine and heroin and othersby that you will see

methadone will reduce a mild withdrawal symptoms comparing

with heroin.

Therapeutic uses of morphine

1)Analgesic postoperative pain

Cancer pain.

Renal colic

Therapeutic uses in the treatment of pain as an analgesia,chronic pain

due to cancer ,pain of renal colic and to control postoperative pain.

2)for the treatment of Acute pulmonary edema due to left ventricular

failure(LVF). To decrease anxiety and because of the vasodilation it

will reduce the pre load and the after loads.

3)Antitussive in severe and refractory cough. codeine has greater

antitussive effect than morphine.

Morphine can be used as antitussive, it is effector,this is theory but in

practical NO,because of the high risk of addiction.


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It is impossible to find morphine in antitussive cooperation , it is

impossible because the high risk of dependence ,we can use other opiods

derivatives With loss or no CNS addiction like dextramethrophan or

As ,has powerful antitussive effect with low or no addiction

effect.

4)Preanesthetic medication:

When we talk about anesthetia we talk about group of drug taken

before administration anesthetic known as Preanesthetic

medication.

Each drug has specific aim :

opidis can be used as Preanesthetic medication,to control postoperative

pain, to sedate the pain , to relieve anxiety .

5)In the treatment of diarrhea , morphine is effective,but it seen it is

impossible to find morphine tablets for control diarrhea,or morphine

can be used voluntary morphine for diarrhea because of high risk ofaddiction, we will talk later on about another drug.

Contraindications

Contraindications and cautions in therapy of morphine :

1)Bronchial asthma : and chronic respiratory diseases. Due to :Respiratory center depression , bronchoconstriction and histamine

release.

2)In patient with acute head injury : because it increase ICP by that

increase the risk of hemorrhage

3)Urinary retention: like-benign prostatic hyperplasia


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4)During pregnancy : they found to control labor pain in part, they

found that morphine can penetrate placenta and induce respiratory

depression in babies and withdrawal syndrome.

5)Impaired renal and hepatic functions, it is important because you

know in liver as well as the kidney has a role in drug irritation.

6)Use of pure agonists with weak partial agonists.

Vomising of pure agonist with drug that has a weak or partial

agonist effect, drug that has mix agonist antagonist.

Pure agonist it is used with the drug that has partial agonist

effect or mixed agonist antagonist .

Pure antagonist is used with drug that has partial agonist or

mixed agonist antagonist .

Now if mixed agonist antagonist used the a it will act >>> as

an agonist >>>good for pain relieving.

But if this drug used in combination with full agonist , like

morphine, this drug will act >>> as an antagonist.

The mixed agonist antagonist if it used with strong agonist it

act as >>>antagonist ,this is mean it block the opioids receptor ,

by that is it ineffective control pain , ineffective in preanesthetic

medication or

Other opioids

* Meperidine :(the other name is Pethidine).

it is strong agonist


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less potent than morphine

in high doses produce CNS excitation(because of its metabolites)and

convulsions

they found that Meperidine produce less smooth muscle spasm

and less miosis, respiratory depressant effects. less antitussive

effect comparint with morphine.

because of that Meperidine is effective for relieving biliary colic ,

because of less miosis , in opising to other opioids lead to

meperidine to produce mydriasis (not miosis), because of lessmuscle spasm, it is effective to control pain, it it the best opioids to

control biliary colic

uses :

1)Analgesic as substitute of Morphine

2)Preanaesthetic medication

3)As analgesic during labor(during labor we need a powerful

analgesic, because it is a painful) ,less fetal respiratory depression.

So the best selective opioids during labor is :

Meperidine or pethidine ,it is the same name, because it has

Heroin

Has no medical used(not used clinically), commonly used between

adults , highly addictive, because of high

Methadone

It is strong agonist.


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Oral less addictive than morphine, with no or mild withdrawal

syndrome.

Therapeutic uses: Used in the treatment of addiction.

Methadone is used as an analgesic as well as in the controlled

withdrawal of dependent abusers from heroin and morphine.

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