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.

Megltinides

nateglinide
repaglinide

Mechanism

binds to K+ channels on β-cells → postprandial insulin release

Clinical use
type 2 diabetes mellitus
may be used as monotherapy, or in combination with metformin

ANTIASTHMATIC AGENTS

 Classification for antiasthmatic drugs.
 
I. Bronchodilators

i. Sympathomimetics (adrenergic receptor agonists)

Adrenaline, ephedrine, isoprenaline, orciprenaline, salbutamol, terbutaline, salmeterol, bambuterol

ii. Methylxanthines (theophylline and its derivatives)

Theophylline 
Hydroxyethyl theophylline 
Theophylline ethanolate of piperazine

iii. Anticholinergics

Atropine methonitrate 
Ipratropium bromide

II. Mast cell stabilizer

Sodium cromoglycate
Ketotifen 

III. Corticosteroids

Beclomethasone dipropionate 
Beclomethasone (200 µg) with salbutamol

IV. Leukotriene pathway inhibitors 

Montelukast 
Zafirlukast

Phenytoin (Dilantin): for tonic-clonic and all partial seizures (not effective against absence seizures)

Mechanism: ↓ reactivation of Na channels (↑ refractory period, blocks high frequency cell firing, ↓ spread of seizure activity from focus)

Side effects: ataxia, vertigo, hirsutism (abnormal hair growth), gingival hyperplasia, osteomalacia (altered vitamin D metabolism and ↓ Ca absorption), blood dyscrasias (rare; megaloblastic anemia, etc)

Drug interactions: induces hepatic microsomal enzymes (can ↓ effectiveness of other drugs); binds tightly to plasma proteins and can displace other drugs

Dextromethorphan  
O-methylated dextrorphan,  Excellent oral antitussive,  No analgesic effect,  No GI effects,  No respiratory depression

Antimania Drugs

MANIC SYMPTOMSMANIC SYMPTOMS

Elevated  or irritable mood
Increased activity or psychomotor agitation
Reduced need for sleep
Inflated self esteem or grandiosity
Increased or pressure of speech
Flight of ideas

These drugs are used to treat manic-depressive illness.

1. Lithium
2. Carbamazepine
3. Valproic acid

Mechanisms of action

1. Lithium works inside the cell to block conversion of inositol phosphate to inositol.
2. Carbamazepine blocks sodium channels 
3. Valproic acid blocks sodium and calcium channels

PHARMACOKINETICS

Absorbed readily and almost completely from the GI tract; peak concentrations in 1-2 hrs

Lithium toxicity

1. Nausea, diarrhea, convulsions, coma, hyperreflexia, cardiac arrhythmias, hypotension.
2. Thyroid enlargement; increases thyroid stimulating hormone (TSH) secretion; may cause hypothyroidism.
3. Polydipsia, polyuria (lithium inhibits the effect of antidiuretic hormone on the kidney).

Clinical applications concerning lithium 

- Patients must be warned against sodium-restricted diets because sodium restriction leads to greater retention of lithium by the kidney.
- Patients must have regular (e.g., monthly) blood checks because the margin of safety is narrow.

Endocrine Effects – Goitre and hypothyroidism commonly

Cardiac Effects:– ECG changes(common) - T-wave flattening/inversion and appearance of U wavesflattening/inversion and appearance of U waves

Li and Pregnancy -1st Trimester:Cardiovascular anomalies of the newborn, especially Ebstein's malformation
- 3rd Trimester: Neonatal goiter, CNS depression, hypotonia ("floppy baby" syndrome)

Drug–drug interactions of lithium
Diuretics and newer nonsteroidal anti-inflammatory drugs (NSAIDs) reduce lithium excretion and may cause lithium toxicity.