pharmacodynamics mbbs 2013-class-1.pptx
TRANSCRIPT
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
1/24
PharmacodynamicsDr.U.P.Rathnakar
MD.DIH.PGDHM
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
2/24
Pharmaco dynamics
Principles & mechanism of drug action
Receptor & Non- rec. mediated drug action
Dose response relationships
Therapeutic Index-Drug potency and efficacy
Factors modifying drug action
Drug interactions
Adverse drug reactions- Bioassay-
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
3/24
Pharmaceutical process
Drug reaches the patient
Pharmacokinetic process What body does to the drug
Pharmacodynamic process
What drug does to the body Pharmacotherapeutic process
Therapeutic effect on the patient
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
4/24
PRINCIPLES [Types] OF
DRUG ACTION
1. Stimulation
Adrenaline
Pilocarpine
2. Depression Quinidine
Morphine
Barbiturates
3. Irritation Bitters
Counter irritants
4. Replacement
Insulin
Iron
Levodopa
5. Cytotoxic action
Penicillin,
Chloroquine
cyclophosphamide
6. Modification of
immune status
Vaccines
Sera
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
5/24
Mechanism of Drug Action
Non-receptor mediated
Physical
Chemical
Enzymes
Ion channels
Transporters
Immune status
Receptor mediated
Receptors on the cell
membrane
Receptors inside the cell
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
6/24
Mechanism of Drug Action
Non-receptor Mediated
Osmosis
Adsorption
Demulcent
Radioactivity
Examples
20% Mannitol in Glaucoma
Activated charcoal inpoisoning
Soothing effect of cough
lozenges
I131 in Hyperthyroidism
Physical
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
7/24
Mechanism of Drug Action
Non-receptor Mediated
Antacids
Chelation
Enzymes
Enzyme inhibition
[Specific or non specific]
Enzyme Stimulation-
Activation
Induction
Examples
Neutralize acid in stomach
BAL in Arsenic poisoning
ACE inhibitors in HTN
[specific]
Phenol, formaldehyde[non
specific]- [no therapeutic value]
Pralidoxime in OP
poisoning
Enzyme inducers[Rifampicin]
Chemical
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
8/24
Mechanism of Drug Action - Non-
receptor Mediated
Stimulation of AB
production in body
Ion channels
Na channels
Ca channelsTransporters
Serotonin transporter
GABA transporter
Examples
BCG against TB, Polio
vaccine against Polio
Quinidine in heart
Nifedipine
Blocked by Fluoxitine
Blocked by Tiagabine
Antibody production
[Immune]
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
9/24
Mechanism of Drug Action
Non-receptor mediated
Physical
Chemical
Enzymes
Ion channels
Transporters
Immune status
Receptor mediated
Receptors on the cell
membrane
Receptors inside the cell
M h i f D A i R
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
10/24
Mechanism of Drug Action - Receptor
Mediated [Eg.Adrenergic Receptors, Muscarinicreceptors]
Receptor:
Protein macromolecules
Present on cell wall or Inside the cell
To which drug binds, interacts, produces
action Drug[D] + Receptor[R] D-R-Complex Action
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
11/24
Receptor Mediated drug action
Terms
Affinity: Ability of the drug to bind to receptor
Intrinsic activity: Ability of drug to produce pharmacological activity
after binding
Agonist: Drug which binds and Affinity + Intrinsic activity
produces pharmacological action Eg. Morphine, Adrenaline
Antagonist: Binds but no action. Affinity + NO Intrinsic activity
[But blocks receptors] Eg. Naloxone, AtropinePartial agonist: Binds BUT Affinity + LESS intrinsic
less Action activity-Pindolol
Inverse agonist:Binds BUT Affinity + opp. Activity to agonist
Produces action opp.of agonist [b-carboline & GABA Rec]
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
12/24
Receptor super families
Minutes to
Hours to Days
Intracellular
receptors
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
13/24
Receptor Super Families
MEMBRANE BOUND RECEPTORS
GPCR: Eg. Muscarinic, Adrenergic receptors
Ligand gated Ion channel: Eg. Nicotinic receptors
Enzymatic: Eg. Insulin receptor
INTRACELLULAR RECEPTORS Nuclear Receptors: Eg. Steroid, Thyroid hormone
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
14/24
Second Messengers[Effectors]
Binding of a hormone or drug to its receptor does not
instantly produce clinical effects. Instead, a series of
rapid biochemical events couples receptor binding to
ultimate clinical effects. These biochemical events arecalled second messengers.
cAMP
Ca++
Second messengers
Amplify signal
Binding
Biochemical events
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
15/24
Functions of receptors
To carry signal into the cell
To amplify signal
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
16/24
CONCEPT OF SPARE
RECEPTORS
Some agonists could elicit maximal
physiological effects by occupying only a
small fraction of the total receptor population
suggested that there were "spare receptors.
Quick response for low concn of drug and fast
dissociation [100% effect is produced when less than 100% of receptorsare occupied]
Eg.Neurotransmission EC50=Kd50-No spare receptors
EC50
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
17/24
Receptor Regulation
Down regulation
Prolonged use of agonists
[salbutamol 2]
Receptor no.
[ 2 receptors]
Decreased efficacy
Up regulation
Prolonged use of antagonists
[Propranolol]
Receptor no. [ receptors]
[Sudden withdrawal
Increased sensitivity of
adreno-receptorsAngina
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
18/24
Drug potency & Efficacy
Potency- Amount of drug required to obtain a
particular response[More potent less dose]
Efficacy-The ability of a drug to elicit a maximal
response Aspirin is less potent[300mg] & less efficacious than
morphine[10mg]
Pethidine is less potent[100mg]equally efficacious
as morphine[10mg]
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
19/24
Dose-response curves determine how much of
a drug (X-axis) causes a particular effect, or a
side effect, in the body (Y-axis).
Dose-response [potency & effect]curve[DRC]
100%
50%
EC50
E max
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
20/24
Graded dose response curves[Single subject- Continuous]
Advantages of Log-dose curve
Large no.of doses can be plotted on a small graph paper
Comparison of two or more drugs easier as middle portion is
straight line
Linear [Simple]dose response curve Log dose response curve
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
21/24
Quantal dose response curve
Quantal or all or none: frequency with which any drug evokesa all or none response in a population
LD50
&
ED50
35% 35%
12%
3%
11%
4%
4%
15%
50%
85%
97% 100%
1
0
0
2
0
0
3
0
0
4
0
0
5
0
0
6
0
0
Cumulative DRC
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
22/24
Therapeutic index [TI]
LD50=Dose which kills 50% of sample population
ED50=Dose which produces desired effect in 50% of
sample
TI= Median lethal dose[LD50]or Toxic Dose50]Median effective dose[ED50]
Wider the TI-More safe the drug
Eg.Penicillin -wide TI , Digoxin narrow TI
Certain safety factor = LD1/ED99
LD1=Lethal dose for 1% population
ED99=Effective dose for 99% of population
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
23/24
Therapeutic range
Therapeutic range: Range between dose which
produces minimal Th.effect and Max.acceptable
adverse effect
Therapeutic range
Max.ADE
Acceptable-ADE
Min.Th.Effect
-
8/22/2019 Pharmacodynamics MBBS 2013-Class-1.pptx
24/24
Combined effect of drugs
When 2 drugs are administered together:-
1. They may be Indifferent to each other
2. One may increase the action of the other-
Synergism
3. Action may be decreased or abolished
Antagonism