Comparing and Contrasting the Drug Targets for Cocaine and Nicotine Flashcards
Explain how cocaine can influence catecholamine reuptake proteins & establish changes in drug receptor interactions Utilise HH equation to predict localisation of cocaine at lipid membranes and explain how this relates to local anaesthetic effects Identify nicotine's drug target and distinguish between its autonomic and somatic NS actions Compare and contrast the stimulating ability of cocaine and nicotine Compare and contrast the cardiovascular toxicity of cocaine and nicotine
What are the drug targets for cocaine and nicotine?
Nicotine has generally one target, the nicotinic acetylcholine receptor. Cocaine’s main targets are catecholamine reuptake proteins and Na channels. At low dose, cocaine is more likely to bind to the reuptake proteins. High dose –> Na channels
How does the structure of cocaine allow it to interact with catecholamine reuptake proteins and how does it produce its effects?
Cocaine and catecholamines all posses a lipophilic ring structure, an intermediate linking bond, and an amine group. Cocaine is a substrate for the receptor, but is reuptaken much more slowly. This means it doesn’t remove the dopamine in the synapse, so there are more dopamine-receptor interactions for a longer period of time, leading to euphoria.
How does cocaine interact with Na channels?
The cocaine binding site on the Na channel is on the intracellular side - cocaine has to cross. Cocaine’s benzene ring and uncharged amine –> lipid soluble. Ionised cocaine less able to cross. Cocaine is a weak base. Unionised cocaine can cross more easily but ionised cocaine has a better affinity as the polar side chains anchor it down.
How does the pH partition hypothesis affect the ability of cocaine to interact with Na channels?
Ionised cocaine present more in extracellular fluid. However, there’s sufficient unionised cocaine to cross membranes. The pH drop inside the tissues leads to a larger degree of ionisation, allowing it to bind to the Na channel binding site - blocking it. This has an anaesthetic effect.
How does Nicotine interact with its drug target and what effect does this produce?
The nicotinic acetycholine receptor is an Na ion channel linked receptor. When acetycholine/nicotine binds the receptor, it opens the channel and allows Na to flow through.
In the autonomic NS the receptor is located at the ganglion so it propagates the action potential.
In the somatic NS, the receptor is on the muscle itself, prompting contraction.
How is the stimulating “high” effect created by both nicotine and cocaine?
The stimulation of dopaminergic neurons in the reward pathway from VTA –> Nucleus Accumbens. Activation of the nicotinic receptor by nicotine leads to depolarisation of the nerve and dopamine release. Cocaine slows dopmaine reuptake so dopamine is around longer in the synapse and more D1 receptor-dopamine interactions.
How do cocaine and nicotine peripherally stimulate the sympathetic NS? What effects do they have?
Post-ganglionic neurons have nicotinic receptors which get activated and stimulate the release of noradrenaline, stimulating the tissues. Cocaine can block the reuptake of noradrenaline as it is a catecholamine. A stimulated NS leads to an increased heart rate, and an increase in vasoconstriction. These lead to a high blood pressure.
Describe the major toxic effects of both nicotine and cocaine`
Cardiovascular side effects. Heart rate can be used as a biomarker for toxicity. Cocaine increases HR by about 50%, nicotine <20%. Cocaine is much more dangerous acutely, and it accounts for 25% of heart attacks in people under 40.
LOOK ON PHAR 4 FOR THE DIAGRAM
COCAINE AND NICOTINE EFFECTS SHARED AND ALONE
