Pharmacodynamics Flashcards
what is the definition of pharmacodynamics?
the study of a drugs effect at its site of action *mechanism of action
what is drug half-life dependent on?
the volume of distribution and the clearance of the drug
what is steady state?
the rate of drug accumulation is equal to the amount being eliminated
what is an accumulation factor and when must it be considered?
when drugs are given repeatedly and accumulate to reach a steady-state level
- Accumulation factor must be considered when calculating a loading or maintenance dose.
what are acute, short-term or immediate effects?
drug effects that occur within minutes to hours where the effect is proportional to concentration
what are delayed effects?
drug effects that occur after days or weeks
how might a drug have delayed effects?
- a delay in distribution (high VD)
- turnover of the enzyme/receptor that is involved in the effect
- the accumulation factor needed to reach a steady state
what are cumulative effects?
irreversible drug effects that can produce higher drug peak concentrations and saturate an uptake mechanism
whats an example of cumulative effects?
the use of chemotherapeutic drugs on DNA binding which will result in a cytotoxic effect
drugs that have very large therapeutic windows would be considered?
safe drugs
what are steady-state plasma concentrations utilized to calculate?
loading and maintenance doses
what is the formula for loading dose?
volume of distribution (VD) x target concentration (TC or P c) / bioavailability
A large VD can indicate a high loading dose but what must you consider when administering the drug?
drugs must be initially be given slowly over a longer period of time to make sure that a toxic effect is not achieved
what is the maintenance dose formula?
drug clearance (CL) x target concentration (TC or Pc) x dosing interval / bioavailability
what does maintenance dose provide?
helps to keep the steady-state drug concentration over a long period of time
what are agonists?
a chemical that upon binding to a receptor triggers a response
what does receptor occupancy indicate?
that the magnitude of the effect depends on the affinity and intrinsic activity of the drug
what is the formula for effect size?
Effect size = f (e x B)
e = intrinsic activity
B = number of bound receptors
most drug antagonists are? why?
competitive antagonists, due to the reversibility
what are inverse agonsits?
drug that induce a response opposite of the agonist by binding with constitutively active receptors and stabilizing them which will reduce the receptor’s activity
what is an example of a drug that can augment an agonist response?
diazepam (Valium®) with the endogenous agonist, GABA
- Diazepam helps to further lower the negative potential inside of neurons thus decreasing the chances of firing.
what is Therapeutic Index (TI)?
- the ratio of LD50 (lethal dose) to ED50 (effective dose) for a given drug and is a measure of drug safety
TI = LD50/ED50
a safe drug will always have a ?
large therapeutic index
how do adjunctive drugs work and what does it allow?
- work through different receptor mechanisms to enhance the therapeutic effect of a primary drug.
- This allows clinicians to use lower doses of the primary drug, which is especially useful if that drug has a high risk of toxicity.
(e.g., use of immunosuppressive agents with glucocorticoids to treat inflammatory disorders)
how can the selectivity of a drug action increase?
controlling how and where the drug is delivered, ensuring that it reaches the desired target while minimizing effects on other parts of the body and by manipulating the concentration of drug available to receptors in different parts of the body
(e.g., giving aerosol administration of a glucocorticoid to a patient that has asthma)
what is a graded dose response curve?
describes a drug effect which increase in proportion to increasing drug dose.
what is a quantal dose response curve?
plots the rate of an outcome occurrence in a population against the drug dose (all-or-none response)
what are 5 types of receptors found in the human body?
- intracellular receptors
- tyrosine kinase receptors
- insulin receptor
- ion channel receptors
- adrenergic receptors
what are examples of lipophilic agonists and what do they do?
- estradiol
- testosterone
- progesterone
- aldosterone
can activate nuclear receptors to influence intracellular signaling and gene transcription
what are examples of receptors that can have both ligand binding sites and enzymatic sites ?
recetor tyrosine kinases
- epidermal growth factor (EGF)
- platelet derived growth factor (PDGF)
- insulin
- cytokines
what are some examples of ion channel receptors and what do they do?
cause depolarization or hyperpolarization of excitable cells
- glutamate
- GABA
- acetylcholine receptors (nicotinic)
- 5-HT receptor 3 (serotonin)
what are the GPCR signaling pathways?
- production of IP3 and DAG causes release of calcium and activation of protein kinase C (PKC)
- activation of adenylate cyclase (AC) and increases cAMP levels to activate Protein Kinase A (PKA)
what are examples of endogenous ligands that work through the GPCR PKC pathway?
- Angiotensin II (target vascular smooth muscle, causes vasoconstriction/increases blood pressure)
- Acetylcholine (target salivary gland, increases saliva production)
- Epinephrine (target heart, increases heart rate)
what are antagonists that can block the GPCR PKC pathway?
- Valsartan (AT1R blocker)
- Atropine (Parasympatholytic drug)
- Propranolol (Beta-blocker)
what are examples of endogenous ligands that work through the GPCR PKA pathway?
- Epinephrine (target adipose tissue, increases lipolysis)
- Histamine (parietal cells of gastric mucosa, causes acid secretion)
- Dopamine (brain, activates reward system)
what are antagonists that can block the GPCR PKA pathway?
- Haloperidol (dopamine receptor blocker)
- Cimetidine (histamine receptor 2 blocker)
what are phosphodiesterase enzyme inhibitors and what are examples?
enzymes that block PDE from regulating the pathway of recycling cAMP back into AMP which ultimately increasing the amount of intracellular cAMP
- theophylline (bronchodilator)
- caffeine
what is desensitization ?
the absence of a cell signal in the presence of agonist and over time this would develop into tolerance
for a drug or a agonist
what is physiological antagonism?
endogenous ligands can exert different physiological responses depending on the receptor and drugs that block these receptors could cause for some ligands to bind to other receptors countering a particular response
what is indirect antagonism?
when a substance reduces or inhibits the effect of another without directly interacting with the receptor that the agonist targets
what are pharmacological antagonists?
when two drugs block each other (ex: heparin directly binding to protamine sulfate)
how can a partial agonist “act” like an inhibitor?
when it competes with a full agonist for the same receptor.
- This happens because a partial agonist, even when it fully occupies the receptor, produces a weaker response than a full agonist would.
what are examples of partial agonists and what are they used for?
- buprenorphine: used to help with withdraw symptoms for patients with opioid addictions
- Aripiprazole: a partial dopamine 2 receptor agonist used to treat psychosis, can block the effects of high dopamine in the mesolimbic tract
