CNS stimulants

Question 1

Convulsants and respiratory Stimulants

Answer 1

Doxapram

• K+channel antagonist, inducing action potentials in chemorecepters in carotid bodies
• short acting respiratory stimulant used in post-op respiratory depression; acute respiratory failure; neonatal apnoea

Strychnine

• Inhibiting glycine receptor
• low doses cause improvement in visual and auditory activity, used in athletes for endurance performance.
• High doses as convulsant poison, extensor spasm triggered by minor sensory stimuli - strychnine smile

Question 2

Amphetamines

Answer 2

MOA

• CNS: stimulate dopamine transmission
• PNS: stimulate NA transmission/sympathomimetics

1. competitive inhibitor of monoamine uptake
2. displace monoamine from synaptic vesicles
3. inhibit MAO at high concentrations to reduce breakdown of monoamines.

All leading to increased release of Dopamine or NA

• Methy-amphetamine/Meth—Locomotor stimulants - excessive movement, twitching excitement/euphoria insomnia anorexia but diminshed with continuous use
• Methylphenidate/ “Methylin” “Ritalin”
• 3,4 MDMA aka Ecstacy, clinically used to treat ADHD

Amphetamine psychosis - symptoms almost indistinguishable from schizophrenia after taking repeatedly for a few days.

Tolerance quickly develops for euphoria and anorexia.

Desiring euphoria leads to dependance

Question 3

Cocaine

Answer 3

MAO:

MARI (esp dopamine) - enhance adrenergic effect of sympathetic system

Effect:

CNS: euphoria, increased sociability, pleasure magnification, increased motor activity

Peripherally: Tachycardia/disarrhythmias, vasoconstriction, BP, increased risk of MI and CVA

Excessive doses can cause tremors, convulsions followed by dysphoria (emotional depression) and cardiovascular respiratory depression

No evidence of physical dependance but marked psychological dependance as withdraw leading to deterioration of motor performance and learned behaviour, restored after retaking.

Question 4

Methylxanthines(caffine, Theophyline)

Answer 4

MAO:

1. inhibit cAMP/cGMP phosphodiesterases - increased activation of protein kinases - increased activtion of ryanadine receptor
2. Block adenosine receptor A1/2 - aggressive and agitated behaviour
3. Vasodilation of afferent glomerular artery, GFR, diuresis

Effects

CNS: mild stimulants

Peripherally:

• CVS: cardiac muscles stimulants due to activation of ryanadine receptors, increased intracellular calcium release, increased contractility;
• Respiratory: bronchial/ smooth muscle relaxant - theohyline used to treat asthma very rarely

Question 5

Psychotomimetics/Hallucigenic/Psychedelic

Answer 5

MAO

5HT receptor agonist - LSD, Psylocybin, Mescaline

5HT uptake inhibitor - MDMA (ECSTACY)

NMDA glutamate receptor antagonist - phencycldine -angel dust; ketamine - dessociative anasthesia

Effect:

distorted thought and perception

hallucinations/bad trip - paranoid delusions/flashbacks

Tolerance develops quickly but no physical withdrawl symptoms