epinephrine binds to alpha receptor --> activation of phospholipase C --> breakdown membrane to inositol triphosphate --> IP3 causes release of intracellular calcium --> calcium acts through calmodulin to contract arteriolar smooth mm. --> increase BP
Describe the mechanism of phospholipase A2.
phospholipase A2 converts membrane phospholipids to arachadonic acid --> arachadonic acid is converted to leukotrienes and prostaglandins --> inflammation and pain (BLOCKED BY GLUCOCORTICOID)
What is LC50?
concentration in air or water at which half the population dies
What is LD50?
dose at which half the population dies
What is TD50?
dose at which half the population experiences adverse effects
What is LOAEL?
lowest dose at which there was an adverse or toxic effect observed.
What is NOAEL?
highest dose at which there was no observed adverse effects
What are chromaffin cells?
neuroendocrine cells in close proximity to pre-synaptic sympathetic ganglia; release catecholamines, ie. epinephrine and NE
Diuretics acts by what cellular mechanism?
osmotic pull through ion pump inhibition
Describe a nicotinic ganglionic receptor as describes by SAR studies.
quaternary nitrogen with 3 methyl groups (ie positive charge) separated from a carbonyl oxygen by 5.9A (molecule must have positive charge and carbonyl; extra C or replacing CH3 with C2H2 will prevent or decrease binding to receptor)
Potency is a measure of ________ at the site of action.
An agonist has both __(2)__ for the receptor.
affinity and intrinsic activity
As BP increases, _________ are stimulated and deliver a higher rate of impulses to the vasomotor of the brain; this causes... (3)
baroreceptors; decreased HR, decreased contractility, and vasodilation of blood vessels
Assessment of the relative safety of a drug derived from the extremes of the quantal-dose effect curves of the effects being compared.
certain safety factor (CSF)
All motor nerves of the somatic NS, all pre-ganglionic fibers of the autonomic NS, and all post-ganglionic fibers of the parasympathetic division of the ANS.
A quantal relationship measures __________ responses.
Relationship in which the number or percent of individuals responding increases as the dose increases.
In the presence of an alpha blocker, epinephrine can only activate beta receptors, causing... (2)
an increase in HR and a decrease in BP (without alpha blocker, it increases both)
Excitatory Post-Synaptic Potential (EPSP) is a graded __________ of a post-synaptic membrane in response to stimulation by a neurotransmitter.
Inhibitory Post-Synaptic Potential (IPSP) is a graded ____________ of a post-synaptic membrane in response to stimulation by a neurotransmitter.
Agonists possess __________, but antagonists do not.
Margin of safety is aka ____________.
ED50 can only be determined from data involving _________ responses.
For quantal response data, _______ and _______ cannot be determined.
Junction b/w an autonomic neuron and and effector organ or cell.
A partial agonist has less ________ than a full agonist and therefore, it may act as a(n) _________ to the full agonist.
intrinsic activity; competitive antagonist
When the antagonist combines reversibly with the same binding sites as the agonist and can be displaced from these sites by an excess of agonist.
competitive/ surmountable antagonism
When the antagonist binds irreversibly and the effects of the antagonist cannot be overcome by increasing the concentration of agonist.
non-competitive/ insurmountable antagonism
If two drugs are not both capable of producing the same maximum efficacy, they cannot be compared with respect to ________.
Capacity of a drug to manifest its effects by a singe mechanism of action at a single receptor type; all effects are produced due to a single receptor mechanism.
A drug's capacity to produce one particular effect in preference to others.
With ___________, the total number of available receptors does not change, only the sensitivity of the individual receptors changes.
desensitization (depolarizing block)
With ___________, the ability to alter the number of receptors available to interact with an agonist, either causing an increase or decrease in a drug response.
up- or down-regulation
Lidocaine is a __________ that blocks the opening of ______________.
weak base; cholinergic nicotinic sodium channels of skeletal muscle