Pharmacology Flashcards
ß1 Receptor
- Sympathetic
- Heart
ß2 Receptor
- Sympathetic
- Bronchi in the lungs
α1 Receptor
- Sympathetic
- Smooth muscle, periphery
α2 Receptor
- Sympathetic
- autoreceptors
M1 Receptor
- Parasympathetic
- Brain
M2 Receptor
- Parasympathetic
- Heart and autoreceptors
M3 Receptor
- Parasympathetic
- Airways and exocrine glands
Nicotinic Receptor
- Parasympathetic
- brain and neuromuscular junction
Adverse effect of drugs may be :
- An extension of the desired effect: dose related
2. Unrelated to the desired effect: surprise toxicity
What are the criterias to be CEPA toxic?
CEPA toxic = persistence + bioaccumulation + toxic
What’s the approach of treatment of poisoning?
- Maintain vital functions: ABCD
- Identify poison
- Decontaminate – prevent further absorption
- Enhance elimination (like use of activated charcoal)
- Antidote: chelating agents, antivenins, receptor antagonists
Distinguish first order and zero order DRUG and KINETICS
DRUG:
First order drugs always follow first order kinetics (proportional to the concentration) while 0 order drug follows 0 order kinetics when saturated and then 1st order kinetic when below threshold of saturation. YOU CAN PREDICT THE CLEARANCE OF FIRST ORDER DRUGS
KINETICS:
1. First order kinetics (elimination): amount eliminated/unit time depends on the amount in the compartment and thus can be predicted.
2. In a 0 order kinetic, you can’t predict the T1/2.
(Half life T1/2 = time to decrease 50%)
What are factors of the drugs that influence its absorption?
o Lipid solubility (more hydrophobic, faster) o pH (depends on the tissue that absorbs it and f the drug is ionized or not) o Blood flow to tissue (more blood flow = faster but stay less longer) o Bioavailability (depends on the route)
What are the 2 phases of drug metabolism?
Phase 1: drug metabolite with modified activity (lipophilic)
Phase 2: Inactive drug metabolite (hydrophilic)
What are the different receptor superfamilies ?
Receptors: recognizes a transmitter or hormone, triggers cellular response
Types:
1. Nuclear receptors
2. Catalytic receptors (they recruit proteins to do stuff, like RTK)
3. Cytokine receptors
4. Ligand-gated ion channels
5. Receptors coupled to G proteins (most targeted receptors by drugs)
Define the types of agonist/antagonist.
Categories:
- Full agonist (high efficacy)
- Partial agonist (medium efficacy)
- Antagonist (0 efficacy)
- Inverse agonist (negative efficacy)
True or false: The higher is a therapeutic index, the safer the drug is.
True !
List some of the factors that contribute to inter-patient variability.
Age Gender Renal and hepatic function Concurrent drugs Concurrent diseases Adverse/allergic reactions Pharmacogenetic (phenotype, pharmacokinetics, pharmacodynamics)
Non-compliance is a big contributor to therapeutic failure. What are its causes ?
Denial Forgetfulness Stubbornness Embarrassment Side effects/interaction with other drugs
Explain pharmacokinetics and pharmacodynamics.
Pharmacokinetics: how it gets to the site, how it is distributed (ADME: absorption, distribution, metabolism, excretion)
Pharmacodynamics: pharmacologic effect, clinical response, how it acts (toxicity/effectiveness). WHAT DRUGS DO IN THE BODY
*Distinction: pharmacology includes ALL substances and effects on living cells (properties, effects, mechanism, pharmacokinetics, therapeutic use)
what’s a drug potency ?
is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity (based on EC50)
i.e. the dose that give 50% of the expected effect
What’s the therapeutic index ? what does it mean if high?
- TI (therapeutic index) = LD50 / ED50 = lethal dose for 50% of the person / dose that does an effect on 50% of the person
- the higher the TI, the safer the drug (increased margin of safety)
define compliance
sometimes called adherence, it’s the extent to which a patients follow treatment instruction
what are the 4 types of non-compliance ?
- patient fails to obtain the medication
- patient fails to take the medication as prescribed
- patient prematurely discontinues the medication
- patient (or another person) takes the medication innaproprietely
does a patient prefer to take more drugs less often in a day of less drugs more often ?
more drugs less often (the number of drugs doesn’t appear to be as important as the number of times a day doses must be remembered)
what’s a endogenous ligand ? What else can be ligand in the body ?
- a substance that the body makes (neurotransmitter, hormone or other mediator)
- drugs can also be ligands of the body’s receptor
what are the receptor that most drugs target ?
GPCR (récepteurs couplé aux protéines G)
do all drugs act on receptors ?
No.
what does a low dissociation constant (Kd) means ?
Kd = k2/k1. It reflects the affinity of a drug to a receptor.
the lower the Kd, the higher the affinity to a receptor
what are spare receptors ?
receptors where maximal effect occurs without all receptors occupied by agonist
what does constitutive receptor activity mean ?
that even without receptor activity, some receptors can be activated (do something)
in order for a inverse agonist to work, what does the receptors need to do when unbond ?
unbound receptors produce a detectable basal signal (constitutive receptor).
The response is then lower than the basal response when there’s a inverse agonist.
on what is based efficacy ?
on the maximal effect. If 2 drugs reach a 100% maximal effect, they have the same efficacy even if one takes longer to reach it.
on what is based potency ?
EC50. The drugs that reach the faster its EC50 is the more potent.
what does potency reflect ?
recognition of a drug to a receptor
what does efficacy reflect ?
transduction of the signal
what do surmountable antagonism reflects V?
competitive reversible antagonism
what do INSURMONTABLE antagonism could reflect ?
- competitive irreversible antagonism
- non competitive antagonism
when you talk about a antagonist, what does insurmontable mean ?
that the antagonist is not surmountable by high agonist concentration
allosterism is an other word for ?
noncompetitive antagonism
It is true ? The more hydrophobic a drug is, the faster it’s gonna get absorb ?
Yes and no – CUT-OFF PHENOMENON : after a certain oil/water partition, the absorption rate goes down.
how can the fact that the drug is ionized or not change the absorption of a drug ?
- NONIONIZED ACIDS get absorbs more in low PH (stomach)
- NONIONIZED BASES get absorbs more in high PH (intestines)
what happens if a drug is bounded to a protein carrier ?
if they stay bounded, they’ll never have an effect !
what is the main goal of metabolisation ?
to get a drug more hydrophilic and get into the pipi (hihihi pipi caca)
how can a drug have a bioavaibility of 100% ?
by intravenous dose (bypass the portal circulation)
what is the main actor in phase 1 of metabolisation ?
CYP (like p450)
what are the phase 2 reactions ?
conjugaison (+= h20)
what can happen if the acetaminophen intake exceeds therapeutic doses ?
both normal pathways are saturated and the p450-dependant pathway becomes increasingly important. As long as there’s GSH, it’s not toxic but when none is available, it causes LIVER FAILURE.
what do p450 inducer mean ?
that’ll accélère la metabolisation = speed up drug inactivation
what do p450 inhibitors do ?
inhibits metabolisation = drugs stays longer.
example of inducers :
- etanol (alcohol)
- rifampin
- smoking
example of inhibitors
- grapefruit juice
- quinidine
how can the urine pH play on elimination ?
if the urine is more acidic, it’ll clear out more the basic substances and vice versa
what’s the apparent volume of distribution (V) ?
a physical propriety of a drug : a certain drug has a higher or lower tendency to be distributed more broadly in a person’s body.
Vd = amount of drug in the body/concentration in the blood
what’s the clearance ?
rate of drug elimination.
= amount of blood cleared of drug/unit of time
how can you calculate the t1/2 of a drug ?
(0,693 x apparent volume of distribution) / clearance
what’s the 2 compartment model ?
When you give a drug, there’s a time it’ll increase in the plasma, but then it’s start distributing = fast drop in plasma concentration. The second drop (slower) represent the elimination
what’s a loading dose ?
a first higher dose because you want the steady state to be achieved faster than the 4 half live (normally it takes that time)
what’s the LOAEL ?
: lowest observed adverse effect level
NOAEL
No observed adverse effect concentration (looks like it has an effect, but it’s not significant)
substances are deemed to be toxic if they enter, or may enter, the environnement in amounts that :
- have an immediate or long-term effect on the environment or its biological diversity
- endanger the environment upon which life depends
- endanger human life or health
If exposure and hazard of a drug don’t overlap, is it CEPA toxic ?
No (of the exposure is too low to cause hazard, it’s not toxic)
what post-ganglionnaire neurotransmitter is an exception in the sympathetic system ?
Ach in the sweat glands
MUSCARINIC Ach receptor are mostly ?
parasympathetic (and sweat glands)
NE and E receptors (adrenoreceptors) are 100%
sympathetic
where can a therapeutic drug act in the CHOLINERGIC junction ?
- on the release of the vesicule containing Ach
- on the presynaptic receptors (feedback control)
- on the postsynaptic receptors
- on Ach esterase (AchE inhibitors)
Ach esterase (AchE)
elimine l’acéthylcholine
what’s the main difference between muscarinic and nicotinic receptor ?
MUSCARINIC - act through G-protein - take minute or second for effect NICOTINIC - act through ligand-gated ion channels (conformational change) - takes milliseconds to produce effect
name a kind of AchE inhibitor
nerve gases
where can a therapeutic drug act in the ADRENERGIC junction ?
- transmitter synthesis
- transmitter storage
- transmitter release
- pre or post synaptic receptors
- transmitter reuptake
- enzymatic inactivation
What’s a autoreceptor ? name an example ?
it’s a presynaptic receptor that modulate the transmitter release
- a2 adrenergic receptor
how does the parasympathetic slows down the heart ?
Ach is released from the vagus nerve onto mAChR (M2) in the sino-artrial node of the heart
is beta2 stimulated by both epinephrine and norepinephrine ?
No, not by norepinephrine
clonidine
a2 agonist.
-Leads to decrease in NE secretion and BP.
prazosin
a1 antagonist
- inhibits peripheral vasoconstriction
what is pheochromocytoma ? how do you treat it ?
a tumor secreting excessive (nor)adrenaline.
- best treated with an irreversible antagonist like phenoxybenzamine
albuterol
beta1 and 2 agonist (aka HR and airways +++)
nicotine
nicotinic receptor (parasympa) agonist
atropine
muscarinic receptor (parasympa) antagonist
propanolol
beta blocker
