Neuron Basic Structure (How brain cells communicate)

• Synapse:A junction between the terminal button of an axon and the membrane of another neuron
• Terminal button(orbouton):The bud at the end of a branch of an axon; forms synapses with another neuron; sends information to that neuron.
• Neurotransmitter:A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron.

Different types of Synapses
1-Axo-denrdritic 
2-Axo-axonal 
3-Axo-somatic

Chemical transmission in the CNS 

The CNS controls the main functions of the body through the action endogenous chemical substances known as “neurotransmitters”.
These neurotransmitters are stored in and secreted by neurons to “transmit”information to the postsynaptic sites producing either excitatoryor inhibitory responses.
Most centrally acting drugs exert their actions at the synaptic junctions by either affecting neurotransmitter synthesis, release, uptake, or by exerting direct agonistor antagonistaction on postsynaptic sites.

Sulfonylureas

1st generation
tolbutamide
chlorpropamide

2nd generation

glyburide
glimepiride
glipizide

Mechanism

glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP
→ closes K+ channels → depolarization → ↑ Ca2+ influx → insulin release

sulfonylureas mimic action of glucose by closing K+ channels in pancreatic β cells 
→ depolarization → ↑ Ca2+ influx → insulin release

its use results in

↓ glucagon release
↑ insulin sensitivity in muscle and liver

Clinical use

type II DM

stimulates release of endogenous insulin 
cannot be used in type I DM due to complete lack of islet function

Toxicity

first generation

disulfiram-like effects
especially chlorpropamide

second generation

hypoglycemia
weight gain

Factors affecting onset and duration of action of local anesthetics

pH of tissue

pKa of drug

Time of diffusion from needle tip to nerve

Time of diffusion away from nerve

Nerve morphology

Concentration of drug

Lipid solubility of drug

Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)

Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i.    Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)

Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia

Local anesthetic selection

Local anesthetics are typically divided into 3 main categories:

short, intermediate and long acting local anesthetics.

Based on duration of the procedure and the duration of the individual agents

Short acting agents

1. Mepivacaine 3 %

2. Lidocaine 2%

Intermediate acting agents

1. Lidocaine 2% 1:100000 epi

2. Lidocaine 2% 1:50000 epi

3. Mepivacaine 2% 1:20000 neocobefrin

4. Prilocaine 4%

5. Articaine 4% 1:100000 epi

Long acting agents

1. Bupivacaine 0.5% 1:200000 epi

Pharmacodynamics

Pharmacodynamics is the study of what drugs do to the body and how they do it.

Dose-Response Relationships

- Basic Features of the Dose-Response Relationship:  The dose-response relationship is graded instead of all-or-nothing (as dose increases, response becomes progressively larger).

- Maximal Efficacy and Relative Potency

- Maximal Efficacy: the largest effects that a drug can produce

- Relative Potency:  Potency refers to the amount of drug that must be given to elicit an effect.

- Potency is rarely an important characteristic of a drug.

- Potency of a drug implies nothing about its maximal efficacy.