Pharmacodynamics Flashcards
Pharmacodynamics meaning
Pharmacodynamics describes the effect of the drug on the body
Components of pharmacodynamics
Drug Action: invisible changes
Drug effect: visible changes
Drug response
Drug effect definition
Physiology changes brought about by a drug
Types of drug effects
1). Desired effects
2) Side effects
3) adverse effects
What is desired effect
Refers to the physiology changes that are expected and desired
Occurs at the normal therapeutic dose of the drug
What are side effects
Refers to physiology changes that are expected but undesired
Occurs at normal therapeutic dose of the drug
Adverse effects meaning
Refers to physiological changes that are unexpected and undesired
Can occur at any dose
Can be life threatening
List the use, side effects and adverse effects of aspirin
Used to treat clotting problems
Side effect is bleeding
Adverse effects= Reye syndrome that presents as hepatic encephalopathy ie leads to liver and brain damage
Septrin: Desired effect, side effect, adverse effect
Desired effects: Used to treat infections
Side effects: Coloration of the urine
Adverse effect: Steven Johnson syndrome (peeling of the skin)
The body responds to a drug in two ways
Effectively or lethally
Factors that determine drug effect
1) Dose
2) Drug interaction
3) weight
4) Age
5) Genetics
6) Disease
7) Diet
What curve shows the relationship between the dose and drug response
LDR curve
Log Drug Response curve
Important things to know about the dose response relationship
Dose of a drug is directly proportional to the response
Meaning an increase in the dose= an increase in the response
Features of LDR curve
1) It is sigmoid shaped
2) Log dose on the X-axis (abscissa)
3) Response on the Y-axis( ordinate)
4) possess an Emax
5) About 20-80% of the curve is a straight line used for statistical analysis
6) Drugs with similar mechanism of action have parallel curves
List the two experiments used for dose response
1) Graded response
2) Quantal response
Characteristics of the graded response experiment
1) It Is done on only one subject
2) it is to identify the relationship between the dose and the intensity of effect
3) Used to identify the potency and the Efficacy Emax
Major Parameters gotten from the log dose response graded experiment
Potency/ Effective concentration EC50
Efficacy/ Emax
Define potency of a drug/ effective concentration EC50
Potency is measured as the dose required to produce 50% of the maximal response
Define efficacy/ E max
The maximum drug response that can be achieved
The smaller the dose the __________the potency
The higher the dose the ___________ the potency
1). The higher the potency
2) The smaller the potency
Characteristics of quantal experiment
1) it is carried out on a population
2) it is also known as All or none response
3) it’s target is to know the frequency of effect
4) outcome: DR- Quantal curve
Parameters for Dose response Quantal curve
1) Effective dose ED50
2) Lethal dose LD50
3) Therapeutic Index TI
4) Margin of safety MS
Define Effective Dose 50
This refers to the dose required to cause an effect in 50% of the population
Lethal dose 50 meaning
This can be defined as the dose required to cause death in 50% of the population
Define therapeutic index
This refers to the ratio of the lethal dose in 50% of the population divided by the effective dose for 50% of the population
TI: LD50/ED50
Why is the TI a measure of a drugs safety
Because the larger the value of TI indicates a larger LD50 meaning that a large amount of the drug has to be given to cause death
True or false
Large Therapeutic index= toxic drug
F
Large therapeutic index means that the lethality is high so it would take a large dose of the drug for it to be toxic
Define margin of safety
Refers to the ratio of the lethal dose of 1% of the population divided by the ration of the effective dose for 99% of the population
M.I= LD1/ED99
What is drug interaction
Effects of two drugs being used concurrently on each other’s drug effect
Four major drug interaction
1) additive
2) synergism
3) potentiation
4) antagonism
Define additive interaction
Enhancement of the effect by combining two already effective drugs
1+1=2
E.g paracetamol and ibuprofen
Define Potentiation
Enhancement of the effect of one drug by another that has no effect by itself, when combined
1+0=2
E.g Levodopa +Carbidopa
Used for treating pakinstons disease
Or
Amoxicillin+ Clavulanic acid( augumentin) for treating infections
Define synergism
Enhancement of the effect of one drug by another which has the same effect, than when used individually
1+1>2
E.g penicillin + aminoglycoside
Prednisolone + NSAIDS
Define antagonistic drug interaction
Attenuation/ decrease of the effect of one drug by another which has the opposite effect
1+1<= 1
Propranolol + salbutamol
Pilocarpine + Atropine
Types of antagonism
1) chemical antagonism
2) physiological antagonism
3) pharmacological antagonism
Amlodipine and atenolol is for treating what and what type of drug interaction is it
Additive drug interactions
Anti hypertensive drug
List an additive analgesic drug combination
Aspirin and paracetamol
Nitric oxide and halothane is used for treating what and is what type of interaction
Additive drug interaction
Used as a general anasthetic
List an example of hypoglycaemic drugs that are additive
Glibenclamide + metformin
Ephedrine + theophyline is used for treating what and is what type of interaction
An additive interaction
As a bronchodilator
Fentanyl
Highly potent drug used as pain medication
Low potent drug also used for pain relief
Meperidine
Types of drugs that undergo chemical antagonism
Dimercaprol and mercuric ion
Deferoxamine and iron
Histamine and adrenaline undergo what type of antagonism
Physiological
Types of drugs that undergo stimulation
Pilocarpine on salivary glands , adrenaline on heart muscle
Types of drugs that undergo depression
Barbiturates on CNS, quinidine on heart, omeprazol on gastric secretion
Types of drugs that undergo replacement
Levodopa in Parkinson’s disease
Insulin in diabetes mellitus
Types of drug that undergo cytotoxic action
Cyclophosphamide, zidovudine, penicillin
Examples of drugs that use physical mechanisms of drug action: when the drug does not produce any chemical reaction or change in the cells of the body and the effect is only physical
Activated charcoal binding with poisons in the stomach
Mannitol used as an osmotic diuretic
Bulk laxative e.g ispaghula
Examples of chemical mechanisms of drug action
1) sodium bicarbonate as an antacid
2) dimercaprol, deferoxamine, pennicillamine (copper poisoning) as chelating agents
3) pralidoxamine: organophosphate poisoning
4) cholestyramine
Examples of competitive inhibitors
Angiotensin converting enzymes e.g Captopril
Reversible Anticholinesterases e.g neostigmine, physostigmine
Alloprinol to inhibit xanthine oxidase
Examples of non competitive inhibitors
Irreversible anticholinesterases e.g organophosphorous compounds
Aspirin inhibits cyclooxygenase enzymes
Monoamine oxidase inhibitors used to treat depression e.g imipramine
Proton pump inhibitors e.g omeprazole inhibits the H+/k+/ATpase in parietal cells of the stomach
List the sodium channel drugs
Quinidine, procainamide, local anaesthetics
Define chemical antagonism
Caused by combination of agonists with antagonist with resulting inactivation of the agonist e.g dimercarpol and mercuric ion
Define physiological antagonism
Caused by agonist and antagonists acting at two independent sites and inducing independent but opposite effects e.g histamine and adrenaline
Define pharmacological antagonism
In this case the term competitive and non competitive antagonism are used
T or F in competitive antagonism
The Emax is unchanged
The potency or km is decreased
T
Competitive the potency is decreased
Emax remains the same
T or F in non-competitive antagonism
The Emax is unchanged
The potency or km is decreased
F
Emax is decreased
Potency remains the same
Are Acetylcholine and atropine types of competitive or non competitive antagonists
Competitive
List types of non competitive agonists
Epinephrine and dibenamine
What type of drug action does eosinopril give
Depression
Reduces blood pressure
What type of drug action does methylsalicitic acid give
Irritation
Calcium channel drugs
Nifedipine, verapamil, diltiazem
Block the voltage gated calcium channels useful in hypertension and arrhthmias
List potassium channel drugs
Amiodarone, sulfonylureas
List chloride channel drug
Benzodiazepines
What drug inhibits choline carrier
Hemicholinium
Inhibition of noradrenaline vesicular uptake is by _________
Reserpine
Examples of agonist drugs
Acetylcholine, adrenaline, noradrenaline, benzodiazepines( for gaba receptors)
Examples of antagonistic drugs
Atropine, scopolamine ( both inhibit acetylcholine receptors)
Phenylbenzamine ( inhibit adrenergic receptors)
Flumazenil
Examples of inverse agonist drugs
Beta carbolines inverse agonists of gaba receptors
Inhibition of neuronal reuptake of noradrenaline is by ________
Desipramine
Inhibition of neuronal reuptake of serotonin is by ________
Fluoxetine
Inhibition of weak acid carrier by drugs ________
Probenecid
Antagonists of gaba receptors
Flumazenil
Carbolines are inverse agonists of what receptors
Gaba receptors
Most drugs produce their effects by interacting with a discrete target bio molecule list them
RICE
1) Enzymes
2) carrier molecules
3) ion channels
4) receptors
What are ligands
Ligands are substances that interact at the receptor binding site
Could be endogenous or exogenous
List characteristics of receptors
1) sensitivity
2) specificity
3) selectivity
4) saturability
Define specificity of a receptor
A drug only binds to one single type of receptor and causes one single effect
Define selectivity of a receptor
A drug binds to one or a few types of receptors with higher affinity than other receptors
Define saturability of a receptor
A receptor has a limited number of binding sites and is therefore saturated at high ligand concentrations
List the molecules serving as receptors
1) Enzyme
2) membrane proteins (glycoproteins, lipoproteins)
3) Nucleic acid
4) complex polysaccharide
Define an agonist
An agent which activates a receptor to produce an effect similar to the physiological signal molecule
Define antagonist
An agent which prevents the action of an agonist on a receptor but does not have an effect on its own
Define partial agonist
An agent that activates a receptor to produce submaximal effect, but antagonizes the effect of a full agonist
T or F grapefruit inhibits cyp450 enzymes
T
T or F
Garlic causes increased bleeding when used with anticoagulant
T
T or F tyramine containing foods should be taken with monoamine oxidase inihibitors
F
Is phenobarbital an enzyme inhibitor or inducer
It is an enzyme inducer
Inhibitors of cyp450 enzymes include (CIG POKER)
Cimetidine
Isoniazid
Grapefruit juice
Phenelzine (Mao inhibitor)
Omeprazole
Ketoconazole
Erythromycin
Retonavir
Criteria for classifying receptors
Pharmacological criteria
Tissue distribution
Ligand binding
Transducer pathway
Molecular cloning
Define inverse agonists
An agent which activates a receptor to produce an effect to the opposite direction to that of the agonist
List drugs that have covalent bonds
Several anti cancer drugs
Organophosphate anticholinesterases
Examples of ligands
Drugs, hormones, neurotransmitters
List all the receptor theories
1) Occupancy theory
2) Rate theory
3) Stephenson theory
4) Ariens theory
5) The induced fit theory
6) Macromolecular perturbation theory
What type of receptors does acetylcholine have
Nicotinic and muscarinic receptors
M1, M2, M3 etc
Nm and Nn
List the criteria for classifying receptors
1) pharmacological criteria: Muscarinic, nicotinic, alpha and beta adrenergic
2) Tissue distribution: the cardiac beta adrenergic receptor as beta 1 and bronchial as beta 2
3) ligand binding
4) Transducer pathway
5) Molecular cloning
What are silent receptors
These are sites which bind specific drugs but no pharmacological response is elicited
Silent receptors are better called
Drug acceptors or sites of loss e.g plasma proteins
What are spare receptors
A drug can produce the maximal response when even less that 1% of the receptor is occupied, the remaining unoccupied receptors are just serving as receptor reserve and are called spare receptors
List dieases linked to receptor malfunction
1) myasthenia gravis : autoantibodies that inactivate nicotinic acetylcholine receptors
2) hypoparathyroidism: mutation of genes encoding GPCR’s
3) cancers: mutation of genes encoding GPCR’s
4) insulin resistant diabetes
5) Testicular feminisation
6) Familial Hypercholesterolaemia
Ligand binding and channel binding opening occur on a millisecond timescale so they are confined to excitable tissues such as:
CNS, NMJ, autonomic ganglia
G proteins are heterotrimeric molecules having 3 subunits ____, ____, _____
Galpha Gbeta Ggamma
CAMP regulates many aspects of cellular functions such as
Cell division, cell replication, ion channels, ion transport
Results of IP3-DAG pathway
1) Mediates/ modulates contraction
2) Secretion/ transmitter release
3) Neuronal excitability
4) Intracellular movements
5) eicosanoid synthesis
6) cell proliferation
Examples of drugs that use enzyme linked receptors
Insulin receptors
Cytokine receptors
Examples of drugs that use intracellular receptors
Steriod drugs
Examples of drugs that use ligand gated receptors
GABA receptors
Nicotinic cholinergic receptors
Examples of drugs that use G protein coupled receptors
Adrenergic receptors
Muscarinic cholinergic receptors
List the types of receptors based on transduction pathway
Ligand gated ion channels
G protein coupled receptors
Intracellular receptors
Enzyme linked receptors
List the 4 biomolecular structures that drugs can interact with in the biochemical way
RICE
Receptors
Ion channels
Carrier proteins
Enzymes
List the classification of receptors
Pharmacological
Ligand binding
Transducer pathway
Tissue distribution
Molecular cloning
What experiment is also called all or none rule
Quantal experiment
If the drug binds to the same recognition site as the endogenous agonist it is called what
Primary agonist/ orthosteric
If the drug binds to a different recognition site as the endogenous agonist it is called what
Allostetic agonists
T or F adrenaline antagonizes histamine
T because the both bind to different sites on the lungs adrenaline and adrenaline causes bronchodilation by binding to beta 2 receptors which is opposite to bronconstriction caused by histamine through H1 receptors
What is tachyphylaxis
Is a type of tolerance which occurs very rapidly
What is desensitization
Decreased response to the agonist after it’s repeated injection in small doses
Example of competitive antagonists
Atropine- acetylcholine
Morphine- Naloxone
Adrenaline- histamine
Example of non competitive antagonists
Diazepam- Bicuculline
Repeated administrations of a drug results in
Diminished effect (tolerance)
Which type of tolerance occurs very rapidly
Tachyphylaxis
What is desensitization
Decreased response to the agonist after it’s repeated injection in small doses
Tolerance may be due to
1) masking or internalization of the receptors
2) loss of receptors (down regulation)- decreased synthesis increased destruction
3) exhaustion of mediators( depletion of catecholamine)
Examples of competitive antagonism
Acetylcholine and atropine
Morphine and naloxone
Examples of non competitive antagonists
Diazepam and bicuculline
Examples of ion channel physiological Ligands
Acetylcholine(M2), GABA
Example of ion channel ligand gated drugs
Nicotine, gabapentin
Example of ion channel voltage gated drugs
Lidocaine and verapamil
List the functional families of GPCR
Beta adrenergic receptors
Muscarinic cholinergic receptors
Eicosanoid receptors
Example of GPCR beta adrenergic receptor drugs
Dobutamine
Example of GPCR muscarinic cholinergic receptor drugs
Atropine
Example of GPCR eicosanoid receptor drugs
Misoprostol
Monteluskat
