Drugs 7

• ED50 


  median effective dose (in 50% population)
• TD50


  median toxic dose (50% population)
• Therapeutic index calculation


  TD50 / ED50
• therapeutic index is a 


  measure of drug safety, ration between dose producing toxicity and dose producing therapeutic effects
• larger TI


  greater margin of drug safety
• low TI drug 


  monitor plasma conc levels (risk of adverse reaction)
• drug potency 


  the amount of a drug required to produce a defined effect
• more portent drug 


  less to produce effects
• atenolol and metoprolol potency

  atenolol more potent than metoprolol
• drug effectiveness 


  how well achieves its purpose in a clinical sense, more effective has greater max level of effect
• atenolol and metoprolol effectiveness

  both achieve similar max level of anti-anginal effects (max effect same, but different dose)
• differences in max effect of drug are more important than differences in potency
• why are some drugs more effective than others

  drugs act via different pathways, different capacity to produce desired effect and drugs have different capacity to modulate the activity of common target
• morphine pathway action


  activate u opioid receptor and increase descending pathway (suppress pain signal) and decrease ascending pathway (inhibit pain signal being relayed to brain), is a full agonist and effective
• ibuprofen pathway


  decrease production of prostaglandins to decrease pain sensitisation
• drug selectivity 


  is the ability of drug to discriminate between targets, due to difference in affinity of drugs for targets, is not absolute is lost as drug conc increases
• selective drug 


  high affinity for target, less adverse effects as lower affinity for other target
• non selective drugs 


  similar affinity for multiple receptors, risk of adverse effects
• structure activity relationship drugs

  relationship between structural characteristics of a drug and its binding site and resultant effect
• what does adrenaline stimulate

  all 5 adrenoreceptors
• metoprolol selectivity 


  high affinity B1 receptors (decrease heart work) low affinity B2 (airway smooth muscle relaxation)
• risk of high conc of metoprolol

  selectivity lost and antagonise the B2 receptor also which inhibits airways smooth muscle relaxation = risk for asthmatics
• tramadol 


  a u opioid receptor antagonist and a serotonin-NA re-uptake inhibitor for pain relief
• 2 drugs used in combination for pre-exposure prophylaxis HIV prevention

  TDF - 300 mg daily and TAF 25 mg daily
• why give TAF and TDF together

  TAF is converted in lymphocytes to tenofovir, toxicity is associated with TDF as covered to tenofovir in plasma = systemic exposure as is hydrophilic and hangs around can lead to renal toxicity
• buprenorphine 


  a u opioid receptor partial agonist, relief withdrawal symptoms of opioid use disorder (given sublingually)
• naloxone (and why given with buprenorphine)

  a u opioid receptor antagonist, poorly absorbed sublingually but if i.v injected with antagonist the effects of buprenorphine, used to discourage misuse
• drug tolerance 


  the diminished response to a drug following repeated or prolonged exposure
• causes of drug tolerance

  change in receptors, active extrusion of drug from cell, translocation of receptors, extrusion of mediators, increased metabolic degradation of drug, physiological adaptation
• GABA 


  primary inhibitory nt in the CNS
• example of ligand gated ion channel

  GABAa receptor
• GABAa activation


  Cl- influx and hyperpolarisation, decreases neuronal excitability
• example of enzyme linked receptor

  insulin receptor
• example of nuclear receptor

  glucocorticoid receptor
• what do synthetic glucocorticoids do

  treat asthma, suppress pro inflammatory gene expression
• insulin stimulated translocation of GLUT4


  signal transduction creates sites for GSVs at cell membrane promotes translocation and exocytosis of GSVs = more GLUT4 at cell membrane for glucose uptake