1. Anxiolytic, Hypnotic and antiepileptc Drugs
Dr. Hashem Mansour

2. Introduction
Anxiety is an unpleasant state of tension, apprehension, or uneasiness (a fear that arises from either a known or an unknown source).
The physical symptoms of severe anxiety are similar to those of fear (such as tachycardia, sweating, trembling, and palpitations) and involve sympathetic activation.

3. BENZODIAZEPINES
Benzodiazepines are widely used anxiolytic and hypnotic drugs.
Benzodiazepines are generally considered to be safe and effective in treatment acute states.

4. Mechanism of action
The targets for benzodiazepine actions are the γ-aminobutyric acid (GABA) receptors.
Binding of GABA to its receptor triggers an opening chloride channels.
The influx of chloride ions causes hyperpolarization of the neuron inhibiting the formation of action potentials.

6. Pharmacokinetics
1. Absorption and distribution: Completely absorbed after oral administration (lipophilic).
2.Distribute throughout the body and penetrate into the CNS.
3. Duration of action: The half-lives of the benzodiazepines are important clinically, because the duration of action may determine the therapeutic usefulness.
The benzodiazepines can be roughly divided into short-, intermediate-, and long-acting groups

7. Duration of action

8. Pharmacokinetics
Metabolized by the hepatic microsomal system to active compounds.
Excreted: in the urine.
All benzodiazepines cross the placenta and may depress the CNS of the newborn if given before birth.
The benzodiazepines are not recommended for use during pregnancy.
Nursing infants may also be exposed to the drugs in breast milk.

9. Dependence
Psychological and physical dependence on benzodiazepines can develop if high doses of the drugs are given for a prolonged period.
Abrupt discontinuation of the benzodiazepines results in withdrawal symptoms, including confusion, anxiety, agitation, restlessness, insomnia, tension, and (rarely) seizures.

10. Adverse effects
Drowsiness and confusion are the most common side effects.
Ataxia occurs at high doses Cognitive impairment (decreased long-term recall and retention of new knowledge), amnesia.
Benzodiazepines should be used cautiously in patients with liver disease.
These drugs should be avoided in patients with acute angle closure glaucoma.

11. Uses 1. Anxiety disorders. 2.Sleep disorders. 3. Amnesia.
4. Seizures: lorazepam and diazepam are the drugs of choice in terminating status epilepticus
5. Muscular relaxant: Diazepam is useful in muscle strain, and in treating muscle spasm.

12. OTHER ANXIOLYTIC AGENTS
Selective serotonin reuptake inhibitors (SSRIs, such as paroxetine)
It may be used alone or prescribed in combination with a low dose of a benzodiazepine during the first weeks of treatment.
After 4 to 6 weeks, begins to produce an anxiolytic effect, the benzodiazepine dose can be tapered.

13. Mechanism of action

14. Pharmacokinetics Absoption is good orally
All of the SSRIs taken once-daily dosing
In the case of fluoxetine, the combined action of the parent and the demethylated form allow once/ week.
Metabolized by liver (active metabolite)
Excreted by kidney

15. Adverse Effects
Adverse effects result in insomnia, increased anxiety, irritability, and nausea and emesis.
Some patients also report a dullness of intellectual abilities and concentration.
Paroxetine is associated with an increased risk of congenital cardiac malformations when administered in the first trimester of pregnancy

16. Implication in P.T practice
physiotherapist need to be aware about hypnotics and their effects and side effects.
Benzodiazepines associated with drowsy and postural incoordination.
The P.T should be aware from falling during exercise.
Some patients also report a dullness of intellectual abilities and concentration

18. Anti-epileptics

19. Definitions Seizure: the clinical manifestation of
an abnormal, excessive excitation
and synchronization of a population
of cortical neurons
Epilepsy: recurrent seizures (two or
more) which are not provoked by
systemic or acute neurologic insults

20. Etiology Congenital defects, head injuries, trauma, hypoxia
Infection e.g. meningitis, brain abscess, viral encephalitis
Concussion, depressed skull, fractures.
Brain tumors (including tuberculoma), vascular occlusion.
Drug withdrawal, e.g. CNS depressants .
Fever in children (febrile convulsion).
Metabolic abnormalities
Photo epilepsy

21. ILAE Classific-ation of Seizures

22. Classification of siezure

23. Mechanism of action

24. Mechanism of action
Glutamate inhibitor
lamotrigin

25. ANTISEIZURE DRUGS 2. Hydantoins: Phenytoin.
1. Carboxamides: Carbamazepine.
2. Hydantoins: Phenytoin.
3. Barbiturates (Phenobarbital) and their analogues (Primidone – pro drug)

26. ANTISEIZURE DRUGS 5. Benzodiazepines: Clonazepam, Diazepam
4. Valproates: Sodium valproate
5. Benzodiazepines: Clonazepam, Diazepam
6. GABA analogues: Gabapentin.
7. Hetereogenic anticonvulsants: Lamotrigine, Levetiracetam, Pregabalin and Topiramate.

27. INDIVIDUAL ANTIEPILEPTICS
CARBAMAZEPINE : is a drug of first choice for focal and secondary generalized epilepsy.
It is useful for the treatment of trigeminal neuralgia, postherpetic pains.

28. VALPROIC ACID (Sodium valproate)
Valproic acid is effective for the treatment of generalized and partial epilepsy, febrile convulsion.
ARs can be troublesome: 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 2–12 weeks).

29. Phenytoin
It is used to prevent all types of partial seizure, generalized seizure, and st. epilepticus. It is not used for absence attacks.
Phenytoin is 90% bound to plasma albumin and small changes in binding will result in a higher concentration of free active drug.

30. BARBITURATES
Antiepilepsy members include phenobarbital and primidone (which is largely metabolized to phenobarbital, i.e. it is a prodrug).
They are still used for generalized seizures; sedation is usual.

31. Hetereogenic anticonvulsants
LAMOTRIGINE: is effective for the treatment of partial and secondarily generalized tonic-clonic seizure.
TOPIRAMATE is used as adjunctive treatment for partial seizure, with or without secondary generalization.

32. Adverse Effects of AEDs
Dizziness , Fatigue , Ataxia, Diplopia :all AEDs
Irritability: levetiracetam
Word-finding difficulty: topiramate
Weight loss/anorexia: topiramate.
Weight gain: valproate (also associated with polycystic ovarian syndrome )carbamazepine, gabapentin, pregabalin

33. Typically Idiosyncratic
Renal stones: topiramate.
Anhydrosis, heat stroke: topiramate
Acute closed-angle glaucoma: topiramate
Hyponatremia: carbamazepine.
Aplastic anemia: valproate, carbamazepine
Hepatic Failure: valproate, lamotrigine, phenobarbital
Rash: phenytoin, lamotrigine, carbamazepine

34. Gabapentin and Pregabalin
Gabapentin and pregabalin are absorbed after oral administration.
Excreted unchanged, mainly in the urine.
These compounds have no known interactions with other ASDs.

35. Therapeutic use
Gabapentin and pregabalin are effective for focal onset seizures.
It is the best drugs for the management of fibromyalgia and the neuropathic pain associated diabetic peripheral neuropathy, postherpetic neuralgia, or spinal cord injury.

36. Adverse Effects
The most common adverse effects of somnolence, dizziness, ataxia, and fatigue.
These effects resolve within 2 weeks of onset during continued treatment.
Gabapentin and pregabalin are both listed in pregnancy category C.

38. Implication in physiotherapy
The physical therapist may play a vital role in this process by monitoring patient response to medication and in forming the medical team of any abnormal findings.
In some cases , the drug regimen may be insufficient to control seizure activity and may cause serious adverse effects .

39. Implication in physiotherapy
Some of these adverse effects may impact rehabilitation procedures directly; via sedation, dizziness, ataxia, and gastric disturbances .
In cases of ataxia, coordinational exercises may need to be added to the rehabilitation program to combat this problem

40. Implication in physiotherapy
Some patients extremely sensitive to environmental stimuli like light, sound and so on.
Physiotherapist should be alert of any change in behavior or functional status which may increase seizure episodes and adverse events.

41. CLINICAL RELEVANCE FOR RE HABILITATION
Adverse Drug Reactions
Sedation
Dizziness
Ataxia; postural imbalance
Gastrointestinal distress
Fit during therapy

42. Effects Interfering with Rehabilitation
Decreased arousal and alertness
Postural imbalance due to ataxia
Uncontrolled seizure activity

43. Possible Therapy Solutions
Explore options with physicians regarding the risks versus benefits of the medication as they relate to functional outcomes
Understand that outcomes may be affected at all levels : body function, structure, activity, and participation