Anticonvulsant Drugs

A.    Anticonvulsants: drugs to control seizures or convulsions in susceptible people

B.    Seizures: abnormal neuronal discharges in the nervous system produced by focal or generalized brain disturbances

Manifestations: depend on location of seizure activity (motor cortex → motor convulsions, sensory cortex → abnormal sensations, temporal cortex → emotional disturbances)

Causes: many brain disorders such as head injury (glial scars, pH changes), anoxia (changes in pH or CSF pressure), infections (tissue damage, high T), drug withdrawal (barbiturates, ethanol, etc.), epilepsy (chronic state with repeated seizures)

C.    Epilepsy: most common chronic seizure disorder, characterized by recurrent seizures of a particular pattern,  many types (depending on location of dysfunction)

Characteristics: chronic CNS disorders (years to decades), involve sudden and transitory seizures (abnormal motor, autonomic, sensory, emotional, or cognitive function and abnormal EEG activity)

Etiology: hyperexcitable neurons; often originate at a site of damage (epileptogenic focus), often found at scar tissue from tumors, strokes, or trauma; abnormal discharge spreads to normal brain regions = seizure

Idiopathic (70%; may have genetic abnormalities) and symptomatic epilepsy (30%; obvious CNS trauma, neoplasm, infection, developmental abnormalities or drugs)

Neuropathophysiology: anticonvulsants act at each stage but most drugs not effective for all types of epilepsy (need specific drugs for specific types)

Seizure mechanism: enhanced excitation (glutamate) or ↓ inhibition (GABA) of epileptic focus → fire more quickly → ↑ release of K and glutamate → ↑ depolarization of surrounding neurons (=neuronal synchronization) → propagation (normal neurons activated)

Class III Potassium Channel Blockers

Prolong effective refractory period by prolonging Action Potential

Treatment: ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to  sinus rhythm, maintenance of sinus rhythm
– Amiodarone (Cordarone) – maintenance of sinus rhythm
– Bretylium (Bretylol) 
– Ibutilide (Corvert) 
– Dofetilide (Tykosyn) 
– Sotalol (Betapace) 

 Amiodarone 
- Has characteristics of sodium channel blockers, beta blockers, and calcium channel blockers 
- Has vasodilating effects and decreases systemic vascular resistance 
- Prolongs conduction in all cardiac tissue 
- Decreases heart rate 
- Decreases contractility of the left ventricles 

Class III - Adverse Effects 
- GI- Nausea vomiting and GI distress 
- CNS- Weakness and dizziness
- CV-Hypotension, CHF, and arrhythmias are common. 
- Amiodarone associated with potentially fatal Hepatic toxicity, ocular abnormalities and serious cardiac arrhythmias. 

Drug – Drug Interactions
These drugs can cause serious toxic effects if combined with digoxin or quinidine. 
 

Estimation of the risk of anesthesia (American Society of Anesthesiologists scale)

• ASA 1: healthy patient.

• ASA 2: patient with stable, treated illness like arterial hypertension, diabetes melitus, asthma bronchiale, obesity

• ASA 3: patient with systemic illness decreasing sufficiency like heart illness, late infarct

• ASA 4: patient with serious illness influencing his state like renal insuficiency, unstable hypertension, circulatory insuficiency

• ASA 5: patient in life treatening illness

• ASA 6: brain death- potential organ donor

Ciprofloxacin : Ciprofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase

Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and  Gram-negative bacteria.

Enterobacteriaceae, Vibrio,  Hemophilus influenzae, Neisseria gonorrhoeae

 Neisseria menigitidis,  Moraxella catarrhalis,  Brucella, Campylobacter,

 Mycobacterium intracellulare, Legionella sp., Pseudomonas aeruginosa,

Bacillus anthracis - that causes anthrax

Weak activity against: Streptococcus pneumoniae,

No activity against:  Bacteroides,  Enterococcus faecium, Ureaplasma urealyticum  and others

It is contraindicated in children, pregnancy, and epilepsy.

Ciprofloxacin can cause photosensitivity reactions and can elevate plasma

theophylline levels to toxic values. It can also cause  constipation and sensitivity to caffeine.

Dosage in respiratory infections is 500-1500 mg a day in 2 doses.

Topical Anesthetics

Benzocaine

Benzocaine is a derivative of procaine, an ester type local anesthetic, and is poorly soluble in water and is

available only as a topical anesthetic.

-  Localized allergic reactions are sometimes encountered    

-  Overdosing is unlikely as benzocaine is poorly absorbed into the blood, which decreases the likelihood of systemic toxicity.

- The onset of surface anesthesia is rapid requiring less than one minute.

Tetracaine

- Tetracaine is an ester type local anesthetic

-  Topically applied tetracaine as opposed to benzocaine has a prolonged duration of action.

Cocaine

- Cocaine is a ester type anesthetic that is used exclusively as a topical agent.

- Cocaine is unique among topical and injectable anesthetics in that it has vasoconstrictive as well as anesthetic properties. It is used sparingly because of its abuse potential but is still used when hemostasis of mucous membranes is essential.

- Cocaine is generally available in concentrations of 2-10 % solution.

Lidocaine

- Lidocaine is an amide local anesthetic that is available in injectable and topical formulations.

- It is available in gel, viscous solution, ointment and aerosol preparations in concentrations ranging from 2-10 %.

- The onset of anesthesia is slower relative to benzocaine but, the duration is about the same.

- Absorption into the bloodstream is greater than benzocaine providing a greater risk of systemic toxicity.

OXYMETAZOLINE
 

It is a directly acting sympathomimetic amine used in symptomatic relief in nasal congestion which increases mucosal secretion.

It is used:
- As a nasal decongestant in allergic rhinitis, with or without the addition of antazoline or sodium chromoglycate. 
- As an ocular decongestant in allergic conjunctivitis.

Compounds like naphazoline and xylometazoline are relatively selective α2 agonists, which on topical application produce local vasoconstriction.