pharmacodynamics for bph
TRANSCRIPT
PharmacodynamicsFor BPH 1st Year
Dr. Pravin Prasad
2nd Year Resident, MD Clinical Pharmacology
Maharajgunj Medical Campus, Institute of Medicine
22nd December, 2016 (Poush 7, 2073), Thursday
Introduction
“Pharmacodynamics is the study of the biochemical and physiological effects of drugs and
their mechanisms of action”- Bluementhal DK, Garrison JC. Pharmacodynamics: Molecular Mechanisms of Drug Action. In:
Bruton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. China: Mc Graw Hill Education; 2011. p 41-72
Pharmacodynamics is the study of drug effects• What & How
Introduction
Action-Effect sequence
Dose-Effect relationship
Pharmacodynamics
Modification of action of one drug
by another drug
Principles of Drug Action
Stimulation:• Selective enhancement of the
level of activity of specialized cells
Replacement:• Use of natural metabolites, hormones, or their congeners in
deficiency states
Irritation:• Non-selective, often noxious
effect on less specialized cells
Depression:• Selective diminution of the level
of activity of specialized cells
Cytotoxic Action:• Selective cytotoxic action on
invading microbes or cancer cells
• Physical interaction
• Chemical interaction
• Binding to proteins
• Binding to Nucleic acids
• Drug Targets
• Receptors
• Ion channels
• Carriers (transporters)
• Enzymes
Mechanism of Drug Action
RICE
Drug Target- Enzymes
• Enzyme stimulation• Pyridoxine
decarboxylase
• Enzyme inhibition• Competitive (equilibrium
type)• Competitive (non-
equilibrium type)• Non-competitive
Non-competitive
Drug Target- Enzymes
Enzyme Endogenoussubstrate
Inhibitor Type
Bacterial folate synthase
Para-amino benzoic acid
SulfadiazineCompetitive (equilibrium)
Cholinesterase Acetylcholine Physostigmine
Malathion, OPs Competitive (non-
equilibrium)Dihydrofolate reductase
DHF Methotrexate
Drug Target- Enzymes
Enzyme Endogenoussubstrate
Inhibitor Type
Carbonicanhydrase
H2O and CO2 Acetazolamide
Non-competitive
H+-K+ ATPase H+ and K+ Omeprazole
Cyclooxygenase
Arachidonic acid
Aspirin
Drug Targets- Ion Channels
•Types:• Ligand gated
• Nicotinic receptors
•G-protein regulated channels• β1 adrenergic receptor activated Ca++ channels
•Voltage operated• Local anaesthetics, phenytoin, Nifedipine
• Stretch sensitive
Drug Targets- Ion Channels
Drug Targets- Transporters (Carriers)
Drug Targets- Transporters (Carriers)
Carrier Transports Blockers
Norepinephrine transporters
Noradrenaline (Norepinephrine)
Desipramine, Cocaine
Gamma butyric acid transporter (GAT1)
GABA Tiagabine
Na+ - K+ - 2Cl- co-transporter
Na+, K+, Cl- Furosemide
Serotonin Transporter
Serotonin Fluoxetine
PharmacodynamicsFor BPH 1st Year
Dr. Pravin Prasad
2nd Year Resident, MD Clinical Pharmacology
Maharajgunj Medical Campus, Institute of Medicine
9th February, 2017 (Magh 27, 2073), Thursday
Drug Targets- Receptors
• Are the macromolecule or binding site located on the surface or inside the effector cell that serves to recognise the signal molecule/drug and initiate a response to it, but itself has no other function-Tripathi KD. Pharmacodynamics: Mechanism of Drug Action; Receptor Pharmacology. In: Essential
of Medical Pharmacology. 7th ed. India: Jaypee Brothers Medical Publishers (P) Ltd; 2014. p 40.
Receptors
Recognise
Response Drug Action
Drug Effect
Drug Targets- Receptors
Receptor Type Examples
G-protein coupled receptors Muscarinic receptors, adrenergic receptors
Ion channels receptors Nicotinic cholinergic, GABAA, glycine
Enzyme-linked Insulin, Epidermal Growth factor, Nerve Growth Factor
Transmembrane JAK-STAT binding receptors
Cytokines, growth hormone, prolactin,interferons
Receptors regulating gene expression Steroids, Vitamin A/D
Drug-Receptor Interaction
• Agonist:• Agent which activates a receptor to
produce an effect similar to that of the physiological signal molecule
• Partial agonist:• Agent which activates a receptor to
produce submaximal effect
• Inverse agonist:• Agent which activates a receptor to
produce an effect in the opposite direction to that of the agonist
Drug-Receptor Interaction
•Antagonist:• Agent which prevents the
action of an agonist on a receptor or the subsequent response, but does not have any effect on its own
Dose Response Curve
Dose Response Curve: Drug Potency
•Amount of drug needed to produce a certain response
•Position of DRC on the dose axis
•Dictates dose of drug
Drug Response Curve: Drug Efficacy
•Maximal response that can be elicited by the drug
•Upper limit of DRC
•Dictates choice of drug
Therapeutic Efficacy/Clinical Effectiveness
Drug Potency Drug Efficacy
Pharmacokinetic variables
Pathophysiological variables
Therapeutic Efficacy / Clinical Effectiveness
Therapeutic Efficacy/Clinical Effectiveness
• Expressed in terms of:
• Degree of benefit/relief afforded by the drug (in the recommended dose range)
OR• Success rate in achieving a defined therapeutic end point
Therapeutic window
Combined Effect of Drugs
Synergism
•Additive• Metformin +
Glibenclamide
• Supra-additive• Sulfamethoxazole +
trimethoprim
Antagonism• Physical antagonism
• Charcoal + alkaloids
• Chemical antagonism• KMnO4 + alkaloids
• Physiological antagonism• Glucagon & insulin on blood
sugar level
• Receptor antagonism
Combined Effects of Drugs- Receptor Antagonism
• Competitive equilibrium:• Acetylcholine & Atropine
• Competitive non-equilibrium:• Phenoxybenzamine +
adrenaline (α receptors)
• Diazepam & Bicuculline