Week 2 Flashcards
Metabolism of drugs occur primarily in the ____ and usually makes the drug more _______.
In some cases the more polar the drug metabolite may be excreted in the ____ into the small intestine and then stool
liver
polar
bile
What are the two phases of drug metabolism and what is the major in phase 1 ______ and what is the primary enzyme in phase 2______ and what is there biological function
cytochrome P-450
Glucuronyl transferase
function is to ad more polar groups to make it more water soluble
cytochrome P-450 is actually a family closely related enzymes called _____ or ____
isozymes or isoforms
where is cytochrome P-450 found in the body
in the ER inside liver cells
in phase II gluucuronyl transferase adds a molecule of ______ however this molecule can also be sometimes added ______
glucuronic acid
ionic sulfate
codeine and heroin are both metabolized into the ______ drug ______
active
morphine
_____ and ____ are cholesterol drugs and these forms become active
simvastatin
atorvastatin
______(—–) an otc antihistamine is actives into prescription _____(—-)
Loratidine(claritin)
Desloratidine(clarinex)
the in active form of a drug can then become active by metabolism is called ______
pro-drugs
in how many half lives does the drug have no clinical potency
4-5 half-lives
Two drugs that can increase their half life by storage in lipids are ____ and ____
THC
sodium pentothal
the rate of drug excretion front he body depends on what two factors
- rate of drug metabolism (mostly by liver)
2. rate of excretion by kidneys or in intestinal bile.
relatively non-polar drugs are reabsorbed in _
nephrons
most drugs are inactivated on the first pass of the blood through the liver and this is refereed to as the ____ _____ _____
first pass effect
drugs with half lives of ___-____ usual provide once a day dosing
10-24 hours
sedatives with narrow therapeutic range
barbiturates
sedatives with large therapeutic range:
benzodiazepines (valium, xanax)
the reason new borns should be given a lower does than normal is because x4
- lower level of liver enzymes
- less renal function
3,lower serum albumen - less developed BBB
patients with _____ disease will have a decreased excretion of the drug and the potentially increased drug activity
liver
______(especially older than 80) have decreased _____ and ____ function resulting in slower drug excretion.
liver & renal
LD50
lethal does for 50% of the population
ED50
effective does for 50% of the population
LD50/ED50
therapeutic index (TI) (the bigger the number the safer)
what are 3 drugs with small TI
coumadin digoxin (TI=2) phenytoin (Dilantin) (TI=3)
how many half lives may it take for a drug to reach equilibrium blood level
4 half-lives
bioavailabilty in pill form may be influenced by X5
- empty stomach or with food
- whether the drug is taken with +2 or +3 ions
- gelatin capsule or tablet form
- size of drug crystals
- presence of constipation or diarrhea in the patient
_________ are the details of processes by which a drug produces its effect.
pharmacodynamics
a drug usually binds to a receptor and the receptor may be a ____ and ______
channel protein
enzyme
if the drug activates the receptor it is referred to as a
agonist
if the drugs prevents activation of the receptor it is referred to as an ______ or _______
antagonist or blocker
in some cases a drug may bind tot he receptor and gives partial activation, it is referred to as a
partial agonist
_____ (—–) is a partial agonist which binds to the nicotine receptor but doesn’t give the strong effect of nicotine and helps taper a person off
Varenicline(Chantix)
ibuprofen and aleve inhibit ____ ______ the enzyme that make inflammatory molecules
prostaglandin cyclooxygenase
_______ is an opiate antagonists to help people get off the addiction
Buprenorphine
drug may bind on the ____ of a membrane protein and activate the protein to catalyze a reaction on the ___ (second messenger). thus the drug never enters the cell
outside
inside
a drug may bind to a membrane ____ and wither open or close the channel
protein
drug may bind to a membrane protein which then activates a __ protein in the inside which then activates a second protein membrane bound protein
G
Drugs may pass through membrane, pass into the ___ and activate synthesis of new proteins
nucleus
EX. steroids
what occurs in phase 1
phase 2
phase 3
phase 1-drug may be metabolized faster than it can bind to receptors
phase 2-the physiological response increases in proportion to the number of receptors bound by the drug
phase 3-reduced effects are obtained until no further increase in effect and this is refereed to as the PLATEAU EFFECT
some drugs may inherently activate the receptor more effective than other drugs and these drugs are more ___
oxycodone is more ____ than _____
efficacious
efficacious than codeine
morphine is more potent than ______-
just because is more potent does not mean that it is more efficacious
meperidine (demerol)
_______ _______ occurs when the number of drug receptors decreases with time upon repeated stimulation thus decreasing the effect of the drug.
what is an example of this
Pharmacodynamic tolerance
ex. morphine and other opiates
_____ ______ results from the increases synthesis of cytochrome p-450 and /or glucuronyl transferase what is an example of this
metabolic tolerance
barbiturates, tegretol (anti-seizure med and mood stabilizer used for bipolar)
______ dependence is when the a user experiences physical observable withdraw symptoms such as ______ ____ (DT’s) during alcohol withdraw. Symptoms include _____, ____ and uncontrollable _____
physical delirium tremens hallucinations confusion shaking
_____ dependence is when no physically observed symptoms are evident, but compulsion to obtain the drug still exists
phsychological
if two drugs are taken together and there effects add up together then this is referred to as a ______ effect
additive
if two drugs are taken together and the effect is greater than the sum of the two drugs then this effect is referred to as a
synergistic effect
codeine, prozac, and metoprolol (lopressor) are all inactivated by the same isozyme of _____. Thus is a patent is given more than one one of these drugs the isozyme may become saturated thus the effects of both drugs is increased and prolonged
cytochrome P-450 (2D6)
_______ juice acts to inhibit CYP3A4
grapefruit
the production of more cytochrome P-450 by the liver is refereed to as ____ ______
enzyme induction
regular use of alcohol can cause induction of ____ _____ isozymes which can result in faster drug metabolism, on the other hand excessive consumption of alcohol can cause cirrhosis of the _____ resulting in ______ and ______. Thus a slower metabolism of the drug
cytochrome P-450
liver
liver tissue death
liver enzyme levels drop
the most commonly used drugs that exist primarily bound to serum albumen include ______, ______, _____ and _______
coumadin, sulfonamides, digoxin, and Dilantin
drugs act on the autonomic nervous system by……..
inhibition of the electrical conduction down the axon produces ______ either local or general
acting on the electrical conduction in the axon itself.
anesthesia
What are three general inhalation anesthetics
ether
chloroform
sevoflurane
ether
-very flammable, post-op vomitting, lung damage. Not used in the US
Chloroform
non-flammable, but heart arrhytmias. prolonged exposure can cause liver damage. Not used in the US
Sevoflurane
fluorinated ether. non-flammable, very low incidence of liver damage.
modifying neurotransmisssions at synapses. this can produce a much more specific pharmacological action.
a. ) stimulate receptors at the synapse-1.
b. )inhibit synapse receptor-2.
c. ) stimulate and inhibit 3.
d. )increase or decrease the life of the neurotransmitter in the synapse
- agonist
- antagonsit, blocker
- mixed agonist/antagonist
_______ is the neurotransmitter at the ganglia of both the sympathetic and parasympathetic.
acetylcholine (ACh)
the receptors at the ganglia are called _____ ____. these receptors are activated by the binding of ____ and _____
nicotinic receptors
nicotine and ACh
ACh is also the neurotransmitter released by the __-_____ parasympathetic neuron. It binds to receptors called ____ receptors
post-ganglionic
muscarinic receptors
Drugs which activate the post-ganlionic parasympathetic are referred to as ____ _____
cholinergic agonists
Drugs which inactivate the post-ganlionic parasympathetic are referred to as ____
cholinergic antagonists or anticholinergics
the action of acetylcholine is terminated by the enzyme
acetylcholinesterase.
the post ganglionic sympathetic neurotransmitter is
norepinephrine (NE)
what are the 4 types of adrenergic receptors
a1, a2,b1,b2
how is the activity of NE commonly terminated
reabsorption into the afferent neuron
what are the two enzymes that inactivate NE in the afferent neuron.
monoamine oxidase (MAO) and catechol orthomethyl transferase (COMT)
the second important sympathetic neurotransmitter is _________
epinephrine (adrenaline)
what is epinephrine released by in the body.
adrenal medulla
the receptors that epinephrine bind to is _____ however epinephrine can be inactivated by _____
adrenergic Monoamine oxidase (MAO)
what are in B1 x2
heart rate
kidneys
what are in B2 x4
- Bronchi
- uterus
- blood glucose,
- arterioles in heart, lung, skeletal muscle
what are in a1 x5
- peripheral arterioles (skin)
- eye
- genitals
- veins
- visercal arterioles (Gi tract)
epinephrine can act on how many receptors
all 4
norepinephrine can act on how many receptors
all except B2
_____(——) is used after post partum or post-op to stimulate contraction of the detrusor muscle and relaxation of the bladder sphincter to help one go pee
Bethanecol (Urecholine)
______ ______ increase acetylcholine activity by blocking inactivation of ACh. Several types of insecticides and nerve gas act as ______ _____. Continued stimulation of ACh receptors can cause profuse salivation, dedication, urination, bronchoconstriction. Ach is also the transmitter at the neuromuscular junction and continuous stimulation of those receptors can cause muscular and respiratory paralysis which can be fatal
Cholinesterase inhibitors
Cholinesterase inhibitors
