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Questions and Answers
What is the main concept behind the Structure Activity Relationship?
Who presented the Structure Activity Relationship concept in 1868?
What is the purpose of modifying the structure of a molecule in SAR?
What does SAR allow scientists to understand?
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What is the field of study where SAR is a fundamental concept?
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What does SAR stand for?
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Which neurotransmitter is involved in the parasympathetic nervous system at the preganglionic and postganglionic levels?
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Phenoxybenzamine is a nonselective alpha-adrenergic _ that blocks alpha-adrenergic receptors.
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Isoprenaline is a nonselective beta agonist.
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Match the following CNS drug classes with their descriptions:
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Who synthesized heroin in 1898?
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What is the name of the synthetic derivative of morphine that is prepared by catalytic hydrogenation and dehydrogenation under acidic conditions?
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Morphine is the prototype ligand for the kappa-receptor.
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Cocaine is used as a _______ topical anesthetic.
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Match the following: Local Anesthetic with its classification:
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Which functional group is present at the 3-position of the pyridine ring in Zolpidem?
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What is the core structure of Zaleplon?
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Zolpidem has a methyl group at the 5-position of the _ ring.
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Match the NON-BZD or Z-drug with its respective core structure:
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Study Notes
Structure Activity Relationship (SAR)
- Introduced by chemists Alexander Crum Brown and Thomas Richard Fraser in 1868
- Enables scientists to identify specific chemical groups or features responsible for biological effects of a molecule
- Fundamental concept in medicinal chemistry and pharmacology
- Describes the relationship between a molecule's chemical structure and its biological activity
- Modifying a molecule's structure can enhance or alter its potency to achieve desired therapeutic outcomes in drug development
Structure Activity Relationship (SAR)
- SAR is a fundamental concept in medicinal chemistry and pharmacology that refers to the relationship between the chemical structure of a molecule and its biological effects.
- Modifying the structure of a molecule can enhance or alter its potency to achieve desired therapeutic outcomes.
Autonomic Nervous System (ANS)
- The ANS is a division of the nervous system that controls involuntary actions, such as heart rate, blood pressure, and digestion.
- The ANS consists of two branches: sympathetic and parasympathetic nervous systems.
- Sympathetic nervous system (SNS): stimulates the "fight or flight" response, increasing heart rate, blood pressure, and energy levels.
- Parasympathetic nervous system (PNS): promotes relaxation, decreasing heart rate, blood pressure, and energy levels.
Autonomic Nervous System (ANS) Drugs
- Sympatholytic drugs: block the sympathetic nervous system, decreasing heart rate and blood pressure.
- Sympathomimetic drugs: stimulate the sympathetic nervous system, increasing heart rate and blood pressure.
- Cholinergic agonists: mimic the action of acetylcholine, stimulating the parasympathetic nervous system.
- Cholinergic antagonists: block the action of acetylcholine, inhibiting the parasympathetic nervous system.
Parasympathetic Nervous System (PNS) Drugs
- Direct-acting cholinergic agonists: bind directly to muscarinic or nicotinic receptors, stimulating the parasympathetic nervous system.
- Indirect-acting cholinergic agonists: prevent the breakdown of acetylcholine, increasing its effects on the parasympathetic nervous system.
- Cholinergic antagonists: block the action of acetylcholine, inhibiting the parasympathetic nervous system.
Central Nervous System (CNS) Drugs
- Analgesics: drugs that relieve pain, classified into opioid and non-opioid analgesics.
- Anesthetics: drugs that induce anesthesia, classified into local and general anesthetics.
- Hypnotic drugs: drugs that induce sleep.
- CNS stimulants: drugs that increase alertness and energy.
- CNS depressants: drugs that decrease alertness and energy.
- Antipsychotic drugs: drugs that treat psychosis.
Opioid Analgesics
- Opioid receptors: µ, δ, and κ receptors, which are responsible for the effects of opioid analgesics.
- Morphine: a prototype opioid analgesic that binds to µ receptors.
- Codeine: a natural opioid analgesic that occurs in opium.
- Heroin: a synthetic opioid analgesic that is 2-3 times more potent than morphine.
- Hydrocodone and oxycodone: synthetic opioid analgesics that are 5-10 times more potent than morphine.
Mixed Agonist/Antagonist Opioids
- Nalbuphine: a semi-synthetic opioid agonist that binds to κ receptors and is a partial antagonist at µ receptors.
- Butorphanol: a synthetic opioid analgesic that is a partial agonist/antagonist at µ and κ receptors.
Opioid Antagonists
- Naltrexone: a synthetic opioid antagonist that binds to opioid receptors, blocking the effects of opioid analgesics.
- Naloxone: a synthetic opioid antagonist that is used to treat opioid overdose.
- Nalmefene: a synthetic opioid antagonist that is used to treat opioid dependence.
Anesthetic Drugs
- Local anesthetics: drugs that reversibly prevent the transmission of nerve impulses, used to numb a specific area of the body.
- General anesthetics: drugs that induce a state of unconsciousness, used to perform surgery.
Other CNS Drugs
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Antipsychotic drugs: drugs that treat psychosis, such as chlorpromazine and haloperidol.
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CNS stimulants: drugs that increase alertness and energy, such as amphetamine and methylphenidate.
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CNS depressants: drugs that decrease alertness and energy, such as benzodiazepines and barbiturates.### Ester Local Anesthetics
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Cocaine is a topical ester local anesthetic
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Procaine has low lipid solubility and is unstable in basic solutions, acting by inhibiting Na+ influx through voltage-gated sodium channels
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Chloroprocaine has a 2 chloride substitution and is used for cutaneous or mucous membrane filtration for surgical procedures, epidural anesthesia, and peripheral conduction block
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Tetracaine has an added butyl group, increasing lipid solubility and topical potency, used for infiltration anesthesia, spinal anesthesia, or topical use
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Benzocaine is used for endoscopy, bronchoscopy, and topical anesthesia, with toxicity risks of methemoglobinemia (infants and children)
Amino Amide Local Anesthetics
- Lidocaine is the most widely used local anesthetic, used for infiltration, peripheral nerve and plexus blockade, and epidural anesthesia, with cardiac toxicity risks of bradycardia, hypotension, and cardiovascular collapse (arrest and death)
- Mepivacaine is indicated for infiltration anesthesia, dental procedures, peripheral nerve block, or epidural block, and is a safer alternative to lidocaine
- Prilocaine HCl is a water-soluble salt for nerve block or infiltration in dental procedures, with a 4% solution that should be protected from light
- Etidocaine is the most potent amino amide local anesthetic, used for epidural anesthesia, topical anesthesia, and peripheral nerve or plexus block, with an added alkyl chain and one ethyl group on the tertiary amine to a butyl group, giving it a quicker onset, longer half-life, and increased potency
- Bupivacaine has a butyl group that increases lipophilicity, potency, and duration of action, is highly bound (95%), and has cardiotoxicity risks, especially with the R isomer or racemic mixture
- Levobupivacaine is the pure S enantiomer, available in solution for epidural administration, peripheral nerve block administration, and infiltration anesthesia
General Anesthesia
Stages of General Anesthesia
- Stage I (Analgesia): onset of drowsiness to loss of eyelash reflex
- Stage II (Excitement): agitation and delirium
- Stage III (Surgical anesthesia): painful stimuli will not elicit a somatic reflex or deleterious autonomic response
- Stage IV (Impending death): onset of apnea to failure of circulation and respiration, ending in death
Classification of General Anesthesia
- Inhaled
- Injected
Inhaled General Anesthesia
- MAC (minimum alveolar concentration) measures inhaled anesthetic potency
- Blood:gas partition coefficient measures anesthetic solubility, with low solubility desirable
- SAR of volatile general anesthetics involves hydrophobicity and lipid solubility, molecular size and shape, functional groups and electronic properties, and stereochemistry
SAR of Volatile General Anesthetics
- Nitrous oxide (laughing gas) is a dissociative anesthetic, causing euphoria and hallucinations
- Halothane is a nonflammable, nonpungent, volatile liquid halogenated ethane, increasing HR, cardiac arrhythmias, cerebral blood flow, and ICP, with risk of malignant hyperthermia (MH) and succinylcholine interaction
- Methoxyflurane is a volatile liquid with high blood:gas partition coefficient and slow induction and prolonged recovery, metabolized to dichloroacetate, difluoromethoxyacetate, oxalate, and fluoride ions
- Enflurane is a volatile liquid with blood:gas PC of 1.8 and MAC of 1.68%
- Isoflurane is a volatile liquid with MAC of 1.15 and blood:gas PC of 1.43
- Desflurane is a nonflammable, colorless, very volatile liquid packaged in amber-colored vials, with blood:gas PC of 0.42, MAC of 7.3%, and oil:gas PC of 18.7
- Sevoflurane is a volatile, nonpungent, nonflammable, and nonexplosive liquid, with blood:gas PC of 0.65, oil:gas PC of 50, and MAC of 2.1%
Injectable General Anesthesia
- Propofol is an injectable sedative-hypnotic for induction and maintenance of anesthesia or sedation, with alterations to the phenol ring or isopropyl groups impacting anesthetic potency and duration
- Etomidate is a carboxylated imidazole for induction of general anesthesia, exerting its effect via GABAA receptor, rapidly metabolized in the plasma and liver, and achiral: cyclopropyl and dihydrogen
- Ketamine is a rapid-acting agent for induction of general anesthesia, acting as a noncompetitive antagonist at the glutamate and NMDA receptor, causing transient increase in BP, and binding to mu, delta, kappa, and sigma opioid receptors
Hypnotic Drugs (Sleeping Pills or Sedatives)
- Benzodiazepines enhance the effect of GABA, having a calming effect on the brain, examples include diazepam and lorazepam
- SAR of benzodiazepines involves 7-nitro or halogen substitution, 5-phenyl substitution, 3-hydroxy or 3-oxo substitution, 1,2-positions, and ring A substitution
- Non-benzodiazepines (Z-drugs) include zolpidem, zaleplon, and eszopiclone, acting on GABA, with a lower risk of dependence and shorter half-lives
- Core structures of non-benzodiazepines include imidazopyridine (zolpidem), pyrazolopyrimidine (zaleplon), and cyclopyrrolone (eszopiclone)
- Functional groups of non-benzodiazepines include the imidazopyridine ring, methyl group at the 5-position, phenyl group at the 3-position, and ethyl substituent on the imidazo nitrogen (zolpidem), isopropyl group at the 5-position and phenyl ring at the 3-position (zaleplon), and fluorinated phenyl group (eszopiclone)
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Description
This quiz tests understanding of the concept of Structure-Activity Relationship, presented by Alexander Crum Brown and Thomas Richard Fraser. It examines the relationship between a molecule's chemical structure and its biological effects.
