Drugs Affecting Mediators & Transmitters of Cell Communication PDF

27 Drugs Affecting Mediators & Transmitters of Communication ILOs By the end of this lecture, students will be able to 1. Deduce the therapeutic utility of drugs modulating some mediators. 2. Predict how modulation of transmitters can serve in control of many diseases From previous...

27 Drugs Affecting Mediators & Transmitters of Communication ILOs By the end of this lecture, students will be able to 1. Deduce the therapeutic utility of drugs modulating some mediators. 2. Predict how modulation of transmitters can serve in control of many diseases From previous lectures, it was clear that signals of communication can PASS LOCALLY from the signaling cell to the target cell by Direct Contact, or by acting in an Autocrine or Paracrine manner. When that Paracrine Communication occurs between a. Neurons, i.e., then their action occurs via the synapse at the SYNAPTIC CLEFT. b. A nerve and a skeletal muscle, i.e., then their action occurs via MOTOR END PLATE The mediator then is considered a NEUROTRANSMITTERS. N.B. Some of these local mediators can still find access and exert also systemic effects. If a signal of communication passes directly to blood and is CONVEYED SYSTEMICALLY to distant targets via the circulation, then that signal is considered a HORMONE and its signaling cell belongs to an endocrine gland. Examples of different NON-ENDOCRINE MEDIATORS are shown in figure 1: Fig. 1: Different types of non-endocrine mediators ATP & ADP; Adenosine tri- & di-phosphate - NO; Nitric Oxide - AT; Angiotensin - ET; Endothelin - NPY; Neuropeptide Y - ANP; Atrial natriuretic peptide - VIP; Vaso-active intestinal peptide In many disease states, such mediators may be upregulated/increased, downregulated/ suppressed or malfunctioning. That is why we use DRUGS accordingly to reverse the situation and set balance back to normal. N.B. DRUG EXAMPLES ONLY WRITTEN IN PURPLE MUST BE KNOWN BY THEIR NAMES Example of such drugs and their modality of action in some diseases will be stated. ____________________ Page 1 of 3  DRUGS that suppress mediators or block their action, if found in excess, in some diseases is achieved by: ▪ Inhibiting their synthesis ▪ Blocking their receptor interaction by receptor antagonists ▪ Increasing their degradation ▪ Inhibiting their Synthesis as: Using Angiotensin Converting Enzyme Inhibitors [Ramipril] to suppress increased Angiotensin-II [AgII] level to lower the blood pressure when treating hypertension or manifestations of heart failure. ▪ Blocking their Receptors by Receptor Antagonists as: Using the Angiotensin-1 Receptor Blockers [Valsartan] to block the effect of Angiotensin-II; thus, helping in treatment of hypertension and heart failure. ▪ Increase their degradation: Using the Cholinesterase Reactivators [Oximes] to set the enzyme Acetylcholinesterase [Ach-E] active again in order to degrade excess Acetylcholine (ACh) at the synaptic cleft during insecticide (organophosphorus) poisoning. ____________________ DRUGS that increase mediators or mimic their action if found suppressed or malfunctioning in some diseases by: ▪ Giving the mediator itself or its analogues ▪ Giving a drug that can mimic the mediator’s action ▪ Stimulating mediator synthesis ▪ Increasing mediator release from stores ▪ Decreasing mediator breakdown ▪ Inhibiting the uptake of the mediator ▪ Activating the receptors’ interaction by a receptor agonist: ▪ Giving the mediator itself or its analogues: Using an Insulin Analogue to overcome the existing reduction in insulin release & action in cases of diabetes. ▪ Giving a drug that can mimic the mediator’s action: Using Nitric Oxide [NO] donners as organic nitrates [Nitroglycerine], which can cause venous and arterial dilatation that is demanded for treatment of angina pectoris and relieving symptoms of heart failure. ▪ Stimulating mediator synthesis: Using the beta 2-adrenoreceptor [2-ADR] blocker [Nebivolol] to activate Nitric Oxide Synthase that will increase NO production and lower the blood pressure when treating hypertension or manifestations of heart failure. Page 2 of 3  ▪ Increasing mediator release from stores: Using the Dual Acting Sympathomimetics [Pseudoephedrine] that (beyond its direct action) can indirectly release catecholamines as epinephrine (adrenaline) from stores to activate alpha 1-adrenoreceptor [1-ADR] causing vasoconstriction, thus used as nasal drops in flue remedy. ▪ Decreasing mediator breakdown: Using a Reversible Anticholinesterase Inhibitor [Ach-E Is] [Neostigmine] that will prevent degradation; so, will increase ACh at the motor end plate to increase skeletal muscle contraction in cases of myasthenia gravis. ▪ Inhibiting the uptake of the mediator: Using Selective Serotonin Reuptake Inhibitors [SSRIs] [Fluoxetine] to prevent 5-HT presynaptic re-uptake; so, increases 5-HT within the synaptic cleft that is needed to elevate mood and treat depression. ▪ Activating the receptors’ interaction by a receptor agonist: Using the beta 1-adrenoreceptor [1-ADR] Agonist [Dobutamine] to activate the cardiac muscle; like that induced by epinephrine (adrenaline) to treat cardiogenic shock. Page 3 of 3