Prelim Chapter 2 Drug Receptor and Pharmacodynamics Flashcards
the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects
Receptor
describes the actions of a drug on the body and the influence of drug concentrations on the magnitude of the response
Pharmacodynamics
Most receptors are made up of——
Protein
Drugs bind to them and then after binding there will be a series of events physiological events, then there will be effect or response
Receptor
Macromolecular Nature of Drug Receptors
Note: we have alot of receptors inside the body, most of them made up of protein, some are lipids, nucleic acid. But we really have different types of receptors in our body and their effects
Original substance in the body that bind to that specific receptor
Ligands
•Their ligands are presently unknown
•May prove useful targets for the development of new drugs.
ORPHAN RECEPTORS
Receptor that is manufactured itself by our body
Endogenous receptor
•mediate the actions of endogenous chemical signals such as neurotransmitters, autacoids and hormones.
REGULATORY PROTEINS
Once the drug bind sa mga protein na ni, there will be endogenous resposes, physiological responses sa body
Regulatory protein
These are all chemical messengers in the body, they carry certain message inside the body, they carry it going to the different organs , now they reach the certain organs in our body, they will elicit thier pharmacologic action
- neurotransmitter
-autocoids
-hormones
These are produce by pur neurons/nerve cells
Neurotransmitter
Neurotransmitter
Ex.
Norepinephrine
GABA
Acetycholine
Glutamate
Dopamine
…..
Local mediator, produce by our cells after a release, they will produce a response, after release by the cell automatic naa na dayon ilang receptor then mag react na dayon sila
Autocoids
Ex. Histamine
Note: Neurotransmitter and Hormones they will travel all over your body just to cause and effect
…..
These are produce by our glands
Hormones
Ex.
Insulin- pancrease
Epinephrine - adrenal medulla
Oxytocin- love hormones
Serotonin-happy hormones
•also identified as drug receptors
•may be inhibited or activated by binding a drug
•Ex: dihydrofolate reductase for methotrexate
ENZYMES
— its function in the body is to speed up chemical processess/speed up chemical reaction/speed up metabolism
Enzymes
Enzymes example
dihydrofolate reductase for methotrexate
Enzyme: Dihydrofolate reductase(enzyme needed for cell division)
Drug: methotrexate(anti cancer drug)
Moa: Inhibits rhe cell division and ,ultiple of our cancer cells
….
-considered as drug receptor
-its function is to transport of chemical from one part of the body to another
•Ex: Na+/K+ ATPase - membrane receptor for digitalis glycosides
TRANSPORT PROTEINS
Board exam Questions:
Is Na+/K+ ATPase a enzyme or not?
Noo.😝😂,Na+/K+ ATPase is not an enzyme, but a transport protein or a pump
Note: For Heart Failure drug : Digoxin, Brand: Lanoxin
…
- These are protein original function is for cell structure
-they contribute to the formation of certain structure in the body
-they can also be a receptor, target by our drug
•Ex: Tubulin - receptor for colchicine
STRUCTURAL PROTEINS
Drug for gout
Cholchicine
DNA contains Nitrogenous base : in Purine theres a Guanine and adenine, then if they degrade what do you call to that?
Uric Acid
•receptors which are spare for a given pharmacologic response that are able to possibly elicit a maximal biologic response at a concentration of agonist that does not result in occupancy of the full complement of available receptors
SPARE RECEPTORS
Spare meanss…
Extra
Concept of Spare Receptor:
Spare means extra, our receptor in the body is limited, kung unsa lang ang available na receptor, didto lang pud mag bind atung gi inum na tambal, what if na occupy na tanan ang receptor? -spare receptor
Note:
Receptors
90% proteins
10% Lipids and Nucleic Acid
…..
Four Subtypes of Receptors
Class 1
Class 2
Class 3
Class 4
Class 1 is also known as
Ionotropic receptors associated with ligand-gated ion channels
•Ionotropic receptors associated with ligand-gated ion channels
•Features:
Location = cell membrane;
Effect = millisecond
Examples
•Nicotinic Receptor - controls Na+ channels (Ligand-gated) – inhibited by curare and derivatives, ganglionic blockers
•GABAA-receptor complex - controls Cl- channels
inward Cl- conductance = hyperpolarization of cell membranes
stimulate GABAA - benzodiazepines, Barbiturates (GABAmimetic, GABA-ergic)
Class 1
controls Cl- channels
GABAA-receptor complex
- controls Na+ channels (Ligand-gated) – inhibited by curare and derivatives, ganglionic blockers
Nicotinic Receptor
hyperpolarization of cell membranes
inward Cl- conductance
- benzodiazepines, Barbiturates (GABAmimetic, GABA-ergic)
Stimulate GABAA
Note:
Na+ activate the cell
Result:
-more Positibe inside the cell (called Depolarization)
-become more active (CNS Stimulant)
….
Note:
Cl- activate the cell
Result:
-more negative inside the cell (called hyperpolarization)
-become depress (slow down)
Cl- ligand is called
GABAA-receptor complex
Cl- drug that can help bind to the receptor
Benzodiazepines
Diazepam,midazolam and alprazolam is an example of what therapeutic class?
Anti seizure drug
Slow down the firing of neurons
Anti seizure drugs
Note: class 1 or Ionotropic Receptors
…..
aka: Metabotropic 7 transmembrane-spanning G-protein-linked
Class 2
•aka: Metabotropic 7 transmembrane-spanning G-protein-linked
•Features:
Location = cell membrane;
Effect= in seconds
Class II
Other involved in chemical messenger in Class 2
G protein-coupled receptor
Receptor Tyrosine kinase
3 types of G-proteins
•Gs - activates adenylyl cyclase which produces the second messenger cyclic adenosine monophosphate (cAMP)
•Gi - inhibits adenylyl cyclase
•Gq - activates phospholipase C generating two secondary messengers: 1,4,5-triphosphate (IP3) & diacylglycerol (DAG)
- activates adenylyl cyclase which produces the second messenger cyclic adenosine monophosphate (cAMP)
Gs
- inhibits adenylyl cyclase
Gi
- activates phospholipase C generating two secondary messengers: 1,4,5-triphosphate (IP3) & diacylglycerol (DAG)
Gq
Notes
Class 1 Ionotropic Receptor
Class 2 Metabotropic Receptor
….
Note:
- Both are ligand-gated Transmembrane protein
Metabotropic receptors do not have … channels
Ionotropic Receptor change its shape to create a channel
….
•Enzyme-linked receptors
•Features:
Effect = minutes to hours;
posesses tyrosine kinase activity as part of their structure
Examples: (endogenous Drug)
•Epidermal growth factor
•Atrial natriuretic peptide
•Insulin
Class III
•Intracellular receptors
•Features: Effect = hours to days
Examples
•Tubulin is the target of antineoplastic agents such as paclitaxel
Class 4
Notes
Class 1 Ionotropic Receptor
Class 2 Metabotropic Receptor
Class 3 Enzyme-linked receptors
Class 4 Intracellular receptors
….
•the total number of cell-surface receptors is reduced, and the cell’s responsiveness to ligand is correspondingly diminished because of the rapid degredation those receptors due to accelerated endocytosis
Down Regulation
- pharmacologic potency and maximal efficacy
– As the concentration of drug increases, its pharmacologic effect also gradually increases until all the receptors are occupied
•Graded Dose-Response Relations
•Refers to the concentration or dose of a drug required to produce 50% of that drug’s maximal effect.
•Example: Candesartan (4-32 mg) is more potent than Irbesartan (75-300 mg)
Example
•If ED50 of two drugs for producing a specified quantal effect are 5 and 500mg, respectively, then the first drug can be said to be 100 times more potent than the second drug for that particular effect.
POTENCY
•is the magnitude of response a drug causes when it interacts with a receptor
•dependent on the number of drug-receptor complexes formed and the intrinsic activity of the drug
EFFICACY
•crucial for making clinical decisions when a large response is needed
•may be determined by the drug’s mode of interaction with receptors
Ex: Diuretics that act on one portion of the nephron may produce much greater excretion of fluid and electrolytes than diuretics that act elsewhere
•Efficacy may be limited due to possible toxicity
Maximal Efficacy
- determining the dose of the drug required to produce a specified magnitude of effect in a large number of individual patients or experimental animals
Quantal Dose-Effect Curves
•ED50
•the dose at which 50% of individuals exhibit the specified quantal effect
Median Effective Dose
•TD50
•the dose required to produce a particular toxic effect in 50% of the population
Median Toxic Dose
•LD50
•If the toxic effect is death of the animal
Median Lethal Dose
•the ratio of TD50 to the ED50 for some therapeutically relevant effect
Therapeutic Index
•determines the drug’s ability to fully or partially activate the receptors
INTRINSIC ACTIVITY
•a drug that binds to a receptor and produces a maximal biologic response that mimics the response of the endogenous ligand
Full Agonists
•have intrinsic activities greater than zero but less than one
•cannot produce the same maximal efficacy as a full agonist even if all the receptors are occupied
•becomes an antagonist if taken concomitantly with a full agonist
Partial Agonists
•have an intrinsic activity less than zero, reverse the activity of receptors, and exert the opposite pharmacological effect of agonist
Inverse Agonists
•bind to a receptor with high affinity but possess zero intrinsic activity
•Antagonism - may occur by either blocking the drug’s ability to bind to the receptor or by blocking its ability to activate the receptor
Antagonists
- may occur by either blocking the drug’s ability to bind to the receptor or by blocking its ability to activate the receptor
•Antagonism
•prevents an agonist from binding to its receptor and maintains the receptor in its inactive state
•Ex: Terazosin (Norepinephrine)
Competitive Antagonists
•bind covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist
Irreversible Antagonists
•also causes a downward shift of the Emax, with no change in the EC50 value of an agonist
•binds to a site (allosteric site) and prevents the receptor from being activated by the agonist
•Ex: Picrotoxin in GABA receptors
Allosteric Antagonists
•an antagonist that may act at a completely separate receptor, initiating effects that are functionally opposite with the agonists
Functional Antagonism
•usually caused by genetic differences in metabolism of the drug or by immunologic mechanisms, including allergic reactions
IDIOSYNCRASY
•usually refers to allergic or other immunologic responses to drugs
Hypersensitivity
•a state of decreased responsiveness to the drug’s effect as a consequence of continued drug administration
Tolerance
•a response in which responsiveness diminishes rapidly after administration of a drug
Tachyphylaxis
Classification of Drugs
•Functional Modifiers - alter normal physiological functions
Tachycardia associated with anxiety - Beta blockers
Fever (response to endogenous pyrogen IL-1) - antipyretics
Naproxen - fever due to cancer
..
•supplement or replace endogenous substance that are lacking or insufficient
Ex: T1DM - absolute insulin deficiency - INSULIN
Replenishers
•diagnosis of certain conditions
Ex: Myasthenia Gravis = Tensilon test (Edrophonium)
Diagnostic Agents
•drugs used to kill/ inhibit growth/ multiplication of cells or nucleic acids considered as foreign to the body
a. Anti-infectives
b. Antineoplastics
Chemotherapeutic Agents
