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PHARMACOLOGY 1 - Coggle Diagram

- - - - Lipid soluble drugs, Vd HIGH
        Lipid insoluble drugs, Vd LOW
  - - - COMPARTMENT
        
        1
        
        1 COMPARTMENT - 1-COM assumes the body as one homogenous volume (rapid mixture) eg. aminoglycosides
        
        2
        
        2 COMP - 2-COM assumes all processes are first order
        (slow mixture) eg. vancomycin
      - TYPE
        
        1ST ORDER MODEL
        
        The pharmacokinetics of MOST drugs is 1 at therapeutic doses:
        
        A fraction dose of drug is absorbed per unit time
        
        A fraction of amount of drug in body is eliminated per unit time. ↑ or ↓ dose will produce a proportional
        
        ↑ or ↓ in plasma concentration and in drug effect.
        
        A SS will be achieved for ANY rate of drug administration.
        
        Steady State, SS
        
        Dosage regimens :
        – to give sufficient amounts that the required therapeutic effect arises, but not a toxic dose.
        
        Maintenance dose is = rate of elimination at SS
        (i.e. at SS, rate of elimination = rate of administration):
        – Dosing rate = CL x desired [drug in plasma]
        – A loading dose is an initial dose of drug given to shorten the time to reach the SS concentrations.
        – Loading dose = Vd x desired concentration (i.e. [drug at SS])
        
        0 ORDER
        
        Zero order (special dose forms, high concentrations of some drugs). A
        
        constant amount of drug is absorbed per unit time (or) A constant amount of drug is eliminated per unit time
        
        Drug may accumulate infinitely
        
        There is no "half-life"
  - - - Therapeutic Window
        
        Cmax : short-term side effects.
        
        Cmax : safe and tolerable level.
        
        Cmin : control of the disease.
        
        t1/2 : how often you have to take it.
        
        AUC : total exposure to the drug.
- - - - RISK- the probability or likelihood that harm will
        occur under specified conditions.
      - HAZARD - the potential to cause harm.
      - SAFETY - the probability that harm will not occur
        under specified conditions.
  - - - ADDIVITY - overall effect of two toxins is the direct addition of the
        individual toxicities of the doses given.
      - SYNERGISM - toxicity of the doses of two toxins is greater than the sum of the toxicities of these two doses. Synergy >additive toxicities.
      - POTENTIATION ~ synergism, but the toxins have different effects but here, one substance leads to a greater effect by a second toxic substance.
      - ANTAGONISM - one substance reduces the toxicity of another.
      - TOLERANCE- subsequent exposure to toxic dose levels prove to be less toxic than normal.
  - - - ED50
        
        effective dose.
        
        Generally used for drugs - the dose required to have a therapeutic or other effect in 50% of sample population.
      - TD50
        
        toxic dose.
        
        The dose required to elicit a defined toxic effect (e.g. fatty liver, fever, etc.) in 50% of the sample population.
      - LD50
        
        lethal dose.
        
        The dose required for lethality in 50% of the sample population.
  - - - A dosage range of a drug to produce its therapeutic effect
        • Between the minimum therapeutic dosage and the minimum toxic dosage
        
        • E.g. min. therapeutic dose for drug A is 10mg/L, toxic dose is 25mg/L → Therapeutic window is 10-25mg/L
  - - - No Observed Adverse Effect Level, NOAEL
      - Zero Equivalent point, ZEP (same as control)
      - Low Observed Adverse Effect Level, LOAEL (Hormesis)
    - - Threshold Limit Value-Time Weighted Average (TLV-TWA, USA):
        workers’ dose exposure after 8 hr mean every day without adverse effects.
        
        Short Term Exposure Limit (TLV-STEL): mean exposure time15 min
        
        Ceiling, (TLV-C): max conc that should not be exceeded Maximum Exposure Limit (MEL, UK)
- - - - D = drug; R = receptor; k1 = association constant;
        K-1 = dissociation constant; k2 = activation constant
    - - TYPE:
        
        Ligand-gated ion channels - cholinergic nicotinic receptors
        
        G-protein-coupled receptors - alpha & beta adrenoceptors
        
        enzyme-linked receptors - insulin receptors
        
        intracellular receptors - steroid receptors
        
        Ligand-gated ion channel
        
        Ionotropic receptor
        • Fast synaptic transmission (tissue response in milliseconds)
        • Ionotropic-ligand binding → conformational change in receptor → rapid opening of intrinsic ion channel → ions flow down electrochemical gradient
        
        G protein-coupled receptor
        
        Metabotropic receptor
        • Membrane receptor which is coupled to effector system via G- protein
        • For many hormones & slow transmitters
        • Metabotropic-ligand binding → conformational change in receptor → G protein binding & production of 2nd messenger via enzymatic processes
    - - Covalent bond: 50 - 150 kcal/mol ( irreversible )
      - Hydrophobic interaction: 0.5 - 1 kcal/mol ( reversible)
      - Hydrogen bond 2 - 5 kcal/mol (reversible)
      - Ionic bond 5 - 10 kcal/mol (reversible)
    - - Signal transduction: process where the binding of a drug to its receptor initiates a series of biochemical events that produce the pharmacological response
      - Signalling can be local or distance: PARACRINE / ENDOCRINE
    - - Receptor Occupancy theory
        
        Law of Mass Action
        • Magnitude of response is directly proportional to the number of receptor occupied
        • Max response: ALL receptors are fully occupied
        • Reversible binding
      - Spare Receptor theory
        
        Max response: NOT ALL receptors need to be occupied
        • Safety margin
      - Rate theory
        
        Depends on the RATE of receptor to be occupied by the drug/ligand
        • MORE ligand-receptor interactions occur per unit time, STRONGER the response
  - - - AFFINITY - Ability of a drug to bind to the receptor
      - EFFICACY
        
        Ability of a drug-receptor complex to activate & produce response
        
        Emax = max response produced
      - POTENCY
        
        Amount of drug is required to produce a response
        
        EC50 or ED50 = concentration or dose of a drug that gives 50% of the Emax
    - - AGONIST
        
        Binds to a receptor and activates the cell to produce response
        
        TYPE
        
        FULL leading gto induce changes in a maximal effect
        
        can induce a corformational change in the receptor leading to a maximal effect
        
        the ability to induce changes in the receptor conformation leading to activation is a measure of intrinsic activity
        
        PARTIAL
        
        induce some degree of receptor activation but not of sufficient magnitude response
        
        A partial agonist may be more potent, less potent or equally potent;
        [potency is an independent factor.]
      - ANTAGONIST
        
        • Binds to a receptor
        • BLOCKS the action of agonist
        
        TYPE
        
        a. Chemical antagonism
        
        Counter the effect of agonist by binding directly/chelating – no receptor involvement (non-specific)
        • To form insoluble & inactive complex
        • E.g. protamine (+ve) neutralises the action of heparin (-ve)
        
        b. Physiological/functional antagonism
        
        Counter the effect of agonist by binding to a different receptor and causing opposing effect
        • E.g. Histamine (histamine receptor), Adrenaline (adrenergic receptor)
        
        c. Pharmacological antagonism
        
        Competitive (reversible)
        
        Effect of antagonist can be overcome by adding the dose of agonist (surmountable)
        
        Antagonist binds to the same active site on receptor, agonist can displace it (reversible)
        
        ED50: ↑ ; Emax: same
        
        Non-competitive (irreversible)
        
        Cannot be overcome by increasing the dose of agonist (non-surmountable)
        
        Antagonist binds to the same active site (covalent bond), or binds to a different site (allosteric site) on receptor (irreversible)
        
        ED50: no change; Emax: ↓
    - - Dose-response relationship: the intensity of the response elicited by a drug is proportional to the dose administered
      - TYPE
        
        Graded dose-response curve – Emax, ED50
        
        Quantitative
        • Response is measured on a continuous scale
        • E.g. BP, HR
        • % response (y-axis) against log dose (x-axis)
        • Response is determined using ONE single biological unit (human/animal/cell/tissue culture)
        
        Quantal dose-response curve – ED50, TD50, LD50
        
        All-or-none pharmacological effect
        • Calculation for therapeutic index
        • E.g. pain, death
        • Individual in population responding (y-axis) against log dose (x-axis)
        • Response is determined using a GROUP of subjects