Types of Neurons (Function)

•There are 3 general types of neurons (nerve cells): 

1-Sensory (Afferent ) neuron:A neuron that detects changes in the external or internal environment and sends information about these changes to the CNS. (e.g: rods and cones, touch receptors). They usually have long dendrites and relatively short axons. 

2-Motor (Efferent) neuron:A neuron located within the CNS that controls the contraction of    a muscle or the secretion of a gland. They usually have short dendrites and long axons. 

2-Interneuron or association neurons: A neuron located entirely within the CNS in which they form the connecting link between the afferent and efferent neurons. They have short dendrites and may have either a short or long axon.

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.

Methyl salicylate

also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs

Anti-Parkinson Drugs
The disease involves degeneration of dopaminergic neurons in the nigral-striatal pathway in the basal ganglia. The cause is usually unknown. Sometimes it is associated with hypoxia, toxic chemicals, or cerebral infections.

Strategy
1. Increase dopamine in basal ganglia.
2. Block muscarinic receptors in the basal ganglia, since cholinergic function opposes the action of dopamine in the basal ganglia.
3. Newer therapies, such as the use of β-adrenergic receptor blockers.

Drugs
a. L-dopa plus carbidopa (Sinemet).
b. Bromocriptine, pergolide, pramipexole, ropinirole.
c. Benztropine, trihexyphenidyl, biperiden, procyclidine.
d. Diphenhydramine.
e. Amantadine.
f. Tolcapone and entacapone.
g. Selegiline.

Mechanisms of action of three drugs affecting DOPA

1. L-dopa plus carbidopa:
L-dopa is able to penetrate the blood–brain barrier and is then converted into dopamine. Carbidopa inhibits dopa decarboxylase, which catalyzes the formation of dopamine.
Carbidopa does not penetrate the blood–brain barrier; it therefore prevents the conversion of L-dopa to dopamine outside the CNS but allows
the conversion of L-dopa to dopamine inside the CNS.

2. Bromocriptine, pergolide, pramipexole, and ropinirole are direct dopamine receptor agonists.
3. Benztropine, trihexyphenidyl, biperiden, and procyclidine are antimuscarinic drugs.
4. Diphenhydramine is an antihistamine that has antimuscarinic action.
5. Amantadine releases dopamine and inhibits neuronal uptake of dopamine.
6. Selegiline is an irreversible inhibitor of monoamine oxidase B (MAO-B), which metabolizes dopamine. Selegiline therefore increases the level of dopamine.
7. Tolcapone is an inhibitor of catechol-O-methyl transferase (COMT), another enzyme that metabolizes dopamine.
8. Entacapone is another COMT inhibitor.

Dopamine and acetylcholine.
 Loss of dopaminergic neurons in Parkinsonism leads to unopposed action by cholinergic neurons. Inhibiting muscarinic receptors can help alleviate symptoms of Parkinsonism

Adverse effects

1. L-dopa 
-  The therapeutic effects of the drug decrease with time.
- Oscillating levels of clinical efficacy of the drug (“on-off” effect).
- Mental changes—psychosis.
- Tachycardia and orthostatic hypotension.
- Nausea.
- Abnormal muscle movements (dyskinesias).

2. Tolcapone, entacapone (similar to L-dopa).

3. Direct dopamine receptor agonists (similar to L-dopa).

4. Antimuscarinic drugs
-  Typical antimuscarinic adverse effects such as dry mouth.

b. Sedation.

5. Diphenhydramine (see antimuscarinic drugs).

6. Amantadine
-  Nausea.
- Dizziness.
- Edema.
- Sweating.

7. Selegiline
- Nausea.
- Dry mouth.
- Dizziness.
- Insomnia.
- Although selegiline is selective for MAO-B, it still can cause excessive toxicity in the presence of tricyclic antidepressants, SSRIs, and meperidine.

Indications

Parkinson’s disease is the obvious major use of the above drugs. Parkinson-like symptoms can occur with many antipsychotic drugs. These symptoms are often treated with antimuscarinic drugs or diphenhydramine.

Dental implications of anti-Parkinson drugs
1. Dyskinesia caused by drugs can present a challenge for dental treatment.
2. Orthostatic hypotension poses a risk when changing from a reclining to a standing position.
3. The dentist should schedule appointments at a time of day at which the best control of the disease occurs.
4. Dry mouth occurs with several of the drugs.
 

Rofecoxib

Inhibit prostacyclin(PGI2) in vascular  endothelium , letting TXA2 act freely and  promote platelet aggregation. 

used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhea

Higher incidence of cardiovascular thrombotic  events.

Not used due to increase risk of heart attack, stroke

Fluconazole: an antifungal used orally,  intravenously or vaginally to treat yeast and fungal infections. Side-effects of systemic administration include hepatotoxicity (liver damage).

• For vaginal candidiasis (vaginal thrush), a once-only oral dose is often sufficient.