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.

Midazolam -Intravenous Anesthetics
 Midazolam is a benzodiazepine used for preoperative sedation, induction of anesthesia, or maintenance of anesthesia in short procedures.

Classification Based on

a. Chemical structure

I. Sulphonamidcs.and others - c.g.. sulphadiazine. etc.

2. Beta-lactum ring - e.g.. penicillin

3. Tetracycline - e.g.. Oxytetracycline,.doxycycline.etc.

b. Mechanism of action

1. Inhibits cell-wall synthesis - penicillin. cephalosporin..cycloserine. etc.

2. Cause leakage from cell-membrane – polypeptides (polymyxin,  Bacitracin), polyenes (Nystatin)

3. Inhibit protein synthesis - tetracyclines. chloramphenicols. erythromycin.

4. Cause mis-reading of mRNA code - aminoglycosides

5. Interfere with DNA function - refampicin.. metronidazole

6. Interfere with intermediary metabolism - sulphonamides. ethambutole

c. Type of organism against which it is primarily activate

I. Antibacterial - penicillin.

2. Antifungal - nystatin.

d. Spectrum of activity

1. Broad spectrum - tetracylines .

2. Narrow spectrum - penicillin G (penG). streptomycin.erythromycin

e. Type of action

I. Bacteriostatic - sulphonamides, erythromycin.tertracyclines

2. Bacteriocidal - penicillin. aminoglycoside

f. Source

I. Fungi - penicillin. cephalosporins

2. Bacteria - Polymyxin B

Aspirin

Mechanism of Action

ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding

Uses of Aspirin

Dose-Dependent Effects:

Low: < 300mg blocks platelet aggregation

Intermediate: 300-2400mg/day antipyretic and analgesic effects

High: 2400-4000mg/day anti-inflammatory effects

Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks

Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks

Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.

Distal (Potassium Sparing) Diuretics

Agents:

spironolactone
triamterene

Mechanism of action

Inhibition of Na/K exchange at aldosterone dependent distal tubular site

Spironolactone - competes with aldosterone for regulatory site

Triamterene - decreases activity of pump directly
•    Either mechanism decreases potassium wasting
•    Either mechanism produces poor diuresis (when used alone)
o    relatively unimportant Na recovery site

Diurectic activity increased if:

•    sodium load (body) is high 
•    aldosterone concentrations are high 
•    sodium load (tubule) is high - secondary to diuresis

Other electrolytes unaffected

Toxicity

•    spironolactone may produce adrenal and sex hormone effects with LONG-TERM use
•    Both drugs may produce electrolyte imbalance
 

Seizure classification:

based on degree of CNS involvement, involves simple ( Jacksonian; sensory or motor cortex) or complex symptoms (involves temporal lobe)

1.    Generalized (whole brain involved): 

a.    Tonic-clonic:

Grand Mal; ~30% incidence; unconsiousness, tonic contractions (sustained contraction of muscle groups) followed by clonic contractions (alternating contraction/relaxation); happens for ~ 2-3 minutes and people don’t breathe during this time

Drugs: phenytoin, carbamazepine, Phenobarbital, lamotrigine, valproic acid

Status epilepticus: continuous seizures; use diazepam (short duration) or diazepam + phenytoin

b.    Absence:

Petit Mal; common in children; frequent, brief lapses of consciousness with or without clonic motor activity; see spike and wave EEg at 3 Hz (probably relates to thalamocorticoreverburating circuit)

Drugs: ethosuximide, lamotrigine, valproic acid

c.    Myoclonic: uncommon; isolated clinic jerks associated with bursts of EEG spikes; 

Drugs: lamotrigine, valproic acid

d.    Atonic/akinetic: drop seizures; uncommon; sudden, brief loss of postural muscle tone
Drugs: valproic acid and lamotrigine

2.    Partial:  focal

a.    Simple:  Jacksonian; remain conscious; involves motor or sensory seizures (hot, cold, tingling common)

Drugs: carbamazepine, phenytoin, Phenobarbital, lamotrigine, valproic acid, gabapentin

b.    Complex: temporal lobe or psychomotor; produced by abnormal electrical activity in temporal lobe (involves emotional functions)

Symptoms: abnormal psychic, cognitive, and behavioral function; seizures consist of confused/altered behavior with impaired consciousness (may be confused with psychoses like schizophrenia or dementia)

Drugs: carbamazepine, phenytoin, laotrigine, valproic acid, gabapentin

Generalizations: most seizures can’t be cured but can be controlled by regular administration of anticonvulsants (many types require treatment for years to decades); drug treatment can effectively control seizures in ~ 80% of patients