Mechanism of Action

When a local anesthetic is injected, it is the ionized [cation] form of the local anesthetic that actually binds to anionic channel receptors in the sodium channel, thus blocking the influx of sodium ions which are responsible for lowering the -70mv resting potential towards the firing threshold of -55mv which then results in depolarization of the nerve membrane. However, only the lipid soluble nonionized [base] form of the local anesthetic can penetrate the various barriers [e.g., nerve membrane, fibrous tissue] between the site of injection and the targeted destination which is the sodium channel.

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)

Pramlintide -Amylin mimetics

Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying

Clinical use

type I and II DM

Diphenoxylate (present in Lomotil)

• A meperidine congener
• Not absorbed very well at recommended doses.
• Very useful in the treatment of diarrhea.

Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin

Indications:

infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)

SYMPATHOMIMETICS 

β2 -agonists are invariably used in the symptomatic treatment of asthma. 

Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system 

Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants 

SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.

TERBUTALINE
It is highly selective β2  agonist similar to salbutamol, useful by oral as well as inhalational route.

SALMETEROL

Salmeterol is long-acting analogue of salbutamol 

BAMBUTEROL

It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.

METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)

THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects). 

ANTICHOLINERGICS

Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.

MAST CELL STABILIZERS

SODIUM CROMOGLYCATE

It inhibits degranulation of mast cells by trigger stimuli. 
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell 

KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1  antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. 
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.

LEUKOTRIENE PATHWAY INHIBITORS

MONTELUKAST

It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma.