Pharmacodynamics- theory and checmicals Flashcards
What is the action of competitive antagonists?
Competitive antagonists reversibly block receptors without activation and their effects are surmountable by increasing the dose of an agonist.
What is physiological antagonism?
Physiological antagonism occurs when two drugs produce opposing physiological effects via different biochemical pathways.
Selective Serotonin Reuptake Inhibitors (SSRIs) like fluoxetine are used to treat depression, and loop diuretics like furosemide are used for the treatment of oedema. These are examples of drugs inhibiting ???
are examples of drugs inhibiting transporters
For what conditions are Alpha 1-adrenoceptor agonists prescribed? Eg phenylephrine
Alpha 1-adrenoceptor agonists are used as nasal decongestants due to their vasoconstrictor effect.
Drugs like nitroglycerine and isosorbide dinitrate activate guanylate cyclase to relax vascular smooth muscle for angina relief. these are examples of drugs that ACTIVATE ???
examples of drugs that activate enzymes
Angiotensin II receptor blockers like losartan and β-adrenoceptor antagonists like propranolol are used to treat conditions such as high blood pressure and heart failure. These are examples of drugs inhibiting ???
examples of drugs inhibiting cell surface receptors
What are irreversible antagonists?
Irreversible antagonists have reactive chemical groups that form covalent linkages with receptors and their effects are not surmountable by increasing the dose of an agonist.
Kinase linked receptors, such as tyrosine kinase receptors, are activated following dimerization and their kinase domain is activated via ???
phosphorylation.
What is the use of enzyme activators? HINT: think of disease process driven by lack of …
Enzyme activators are used when the disease process is driven by too limited or lack of enzyme activity.
What determines a drug’s pharmacological activity? the combination of a drug’s ??? and distribution of its target receptor in cells and tissues
A combination of a drug’s specificity and the distribution of its target receptor in cells and tissues
What is the therapeutic use of GABAA chloride channel openers?
GABAA chloride channel openers like benzodiazepines are used for treating anxiety.
Cyclooxygenase inhibitors like aspirin and ACE inhibitors like captopril are used for pain relief and to treat high blood pressure, respectively. These are enzyme INHIBITORS or ACTIVATORS?
INHIBITORS
a medicine is a drug in a formulation that allows appropriate delivery. May involve improving:
* ???
* Stability
* Taste
* Physical form
Absorption
TRUE or FALSE: A drug is any substance or product that is used or intended to be used to modify or
explore physiological systems or pathological states for the benefit of the recipient
TRUE
drugs interact with biomolecules to exert chemical influence on ???
cellular function
Most drug targets are proteins such as
- Receptors, enzymes, carrier molecules (i.e. transporters) and ??? channels.
ion channels
TRUE or FALSE: drugs include endogenous substances such as hormones, neurotransmitters, ions, antibodies
TRUE
The interaction between drug molecules and drug targets impacts
??? function
physiological function
Agonists occupy receptors and activate or deactivate (?) cell processes
activate
A combination of a drug’s specificity
and the distribution of its target receptor in cells and tissues determines its ???
pharmacological activity
Antagonists occupy receptors but do not elicit a tissue response, hence also referred to as “inhibitors” as they inhibit a ??? response
physiological
response
Drug specificity refers to the relative
selectivity that a drug exhibits for a ???
receptor
Small changes in a drug’s chemical structure can cause loss OR gain (?) of activity because it no longer binds to its receptor. Alternatively, structure can also be manipulated to increase activity (whether agonistic or antagonistic)
loss only
TRUE or FALSE: No drug is completely specific for its target receptor
TRUE
Drug potency refers to the ??? of drug required to produce an effect
concentration
One drug is more potent than another if it acts on the same target (receptor) but elicits the same effect (i.e. EC50) at a lower OR higher (?) concentration
lower concentration
Drug affinity is a thermodynamic property reflecting the strength with which a drug binds to its target. Often measured as the equilibrium dissociation constant, ???
Kd
Drug efficacy is the tendency of the drug to activate a tissue response once bound to its ???. Measured by differences in maximal response
receptor
Competitive antagonists REVERSIBLY or IRREVERSIBLY (?) block receptors without activation. Effects surmountable by increasing agonist dose e.g. pseudoephedrine (adrenergic receptor agonist) vs propranolol (competitive adrenergic antagonist). Must have same receptor binding site
REVERSIBLY
what type of antagonist has reactive chemical groups that form covalent linkages with receptors? HINT: Rarely used clinically, more useful in in vitro research
irreversible antagonists
what type of antagonist doesn’t bind the same binding site on a receptor as the agonist?
non-competitive antagonists
what type of antagonist binds an allosteric site causing a conformational change in the receptor that reduces the binding and response to an agonist AND effects are NOT surmountable?
non-competitive antagonists
??? antagonism describes the binding of one drug to another, covalently or otherwise
chemical
Antagonist effects the rate of absorption, excretion or metabolic degradation of another drug. what type of antagonism is this?
Pharmacokinetic Antagonism
Histamine induces gastric acid secretion from parietal cells (stomach) whereas omeprazole blocks acid secretion by a totally different pathway - Omeprazole is a physiological antagonist of histamine. This is an example of what type of antaognism?
physiological antagonism
Warfarin (anticoagulant) hepatic metabolism (inactivation) is accelerated by phenobarbital (induces liver enzymes), which reduces its anticoagulant effects. this is an example of what type of antagonism?
pharmacokinetic antagonism
example of ion channels:
IP3 receptors
nicotinic acetylcholine receptors
P???
P2X receptors
example of G-protein coupled receptors:
- P??? receptors
P2Y receptors
7 transmembrane domaine G-protein coupled receptor and G protein interact at the interface of the membrane and ???
cytoplasm
G-coupled protein receptors can be triggered by neurotransmitters which also activates ???
ligand-gated ion channels
Kinase linked receptors (catalytic receptors): tyrosine kinase receptors are activated following ???
dimerisation
Kinase linked receptors:
Kinase domain is activated via
???. Downstream signalling molecules signal via ??? reactions
phosphorylation
examples of Kinase linked receptors (catalytic receptors):
- cytokine receptors
- integrins
- tyrosine ???
tyrosine kinase
what type of receptors are typically activated by steroidal or non-steroidal hormones. Agonists diffuse across membrane (or via transporter). Bind to receptor in cytoplasm or nucleus and alter transcription in the nucleus (long-term changes)
nuclear receptors
Drugs activating cell surface receptors:
Alpha 1-adrenoceptor agonists
constrict arterioles (vasoconstrictor)
e.g. phenylephrine, oxymetazoline
For use as nasal decongestants
agonist or antagonist?
agonist
GABAA chloride channel openers for treating anxiety includes: benzodiazepines - Valium
This is an agonist or antagonist for ion channel opening?
agonist
Potassium channel openers for vasodilation include: Minoxidil
This is an agonist or antagonist for ion channel opening?
agonist
mu (μ)-opioid receptor agonists for
analgesia e.g. morphine. Endogenous ligand of μ-opioid receptor is endomorphin.
agonist or antagonist?
agonist
Drugs activating nuclear receptors:
Oestrogen receptor agonists for hormone replacement therapy in post-menopausal women e.g. ???
estradiol
what is an example of the drug molecule being the same structure as the native ligand? Hint: drug that activates nuclear receptors
estradiol
Glucocorticoid receptor agonists for treatment of inflammation
* Hydrocortisone = endogenous
* Dexamethasone = non-endogenous
these agonists activate ??? receptors
activating nuclear receptors
Activators of guanylate cyclase to relax
vascular smooth muscle for angina relief e.g. nitric oxide (NO)-generating organic nitrates
* Nitroglycerin
* Isosorbide dinitrate
agonists drugs that activate ???
enzymes
Reactivators of cholinesterase after
poisoning with nerve agent or
organophosphate pesticides. e.g. ??? is an antidote which can cross
the BBB. An agonist that activates enzymes
Pralidoxime
Calcium channel blockers for angina and high blood pressure
e.g. ???
Antagonist
Amlodipine
Sodium channel blockers to prevent
propagation of nerve signals. e.g. ??? used as local anaesthetic
antagonist
Lidocaine
Angiotensin II receptor (type1) blockers (AT1 antagonists) for treating high BP, heart failure, chronic renal insufficiency. e.g. ??? and ??? the sartans
(inhibit cell surface receptors)
losartan, valsartan
β-Adrenoceptor antagonists for treating angina, myocardial infarction, high BP include: ???, metoprolol, atenolol
(inhibit cell surface receptors)
propanolol
Mineralocorticoid receptor
antagonists for oedema due to liver
cirrhosis and heart failure. Is an aldosterone antagonist. (Drugs inhibiting nuclear receptors)
spironolactone
Oestrogen receptor antagonists for the treatment of breast cancer. ??? can be used but efficacy is limited due to the risk of drug resistance
(Drugs inhibiting nuclear receptors)
tamoxifen
Cyclooxygenase inhibitors inhibit
prostaglandin (inflammatory mediator) synthesis to provide pain relief. Known as non-steroidal anti-inflammatory drugs (NSAIDS).
e.g. ibuprofen, ???
(Drugs inhibiting enzymes)
aspirin
Angiotensin Converting Enzyme (ACE) Inhibitors for high blood pressure, heart failure, and chronic renal insufficiency.
e.g. captopril, ???
(Drugs inhibiting enzymes)
ramipril
Transporters bind to and shuttle membrane impermeable ligands across the cell membrane
e.g. ??? transporter, Serotonin transporter (SERT)
Noradrenaline
TRUE or FALSE: Some drugs bind to transporters and cause changes that prevent proper functioning of transporters e.g. cocaine binding to noradrenaline transporter. Changes in the concentration of specific solutes (e.g. noradrenaline in synapses) mediate the effects of inhibitors of transporters.
TRUE
Selective Serotonin Reuptake
Inhibitors (SSRIs) for the treatment of depression and anxiety are agonists inhibiting ???
e.g. Fluoxetine, paroxetine, citalopram
transporters
Inhibitors of Na-2Cl-K symporter (loop diuretics) in renal epithelial cells to increase urine and sodium output for the treatment of oedema
e.g. ???, bumetanide
(Drugs inhibiting transporters)
Furosemide
Drug potency refers to the ??? of drug required to produce an effect. One drug is more potent than another if it acts on the same
target (receptor) but elicits the same effect (i.e. EC50) at a lower
???
concentration
concentration
