cards i couldn't learn from anki Flashcards
What do opioids induce
segmental contractions
what does seratonin do to gut motility?
increases motility
what do D2 blockers do?
promote motility and stop vomiting
what are the three main modulators that regulate gut motility
opioids
dopamine
seratonin
What are the main factors of noradrenergic transmission
VMOA (vesicular monoamine transporter) = NA into synaptic vesicles
MOA (monoamine oxidase) breaks down NA and inibits Ca2+
NAT = noradrenaline transporter = reuptakes NA
what are the two ways adrenaline can be used as a drug
- treatment of anaphylaxis
- local anaesthetic - limits diffusion of local anaesthetic
How do drugs indirectly cause innervation?
indirect innervation is caused when a drug inhibits uptake/ breaks down enzymes that are responsible for the removal of neurotransmitters
What is a drug that induces indirect sympathetic innervation>
amphetamines
Whats the difference between adrenaline and noradrenaline
adrenaline is a hormone, noradrenaline is the neurotransmitter
name an adrenergic agonist
noradrenaline
name the four main types of adrenergic receptors and what they do. where are beta 3 receptors usually found?
The four main types of adrenergic receptors are :
alpha 1 - smooth muscle contraction
alpha 2 - mainly presynaptic
beta 1 - heart frequency and cardiac contractility
beta 2 - smooth muscle relaxation
beta 3 receptors are predominantly found in adipose tissue
explain the difference in nicotinic antagonist effects in the somatic system and in the ANS
nicotinic antagonist in the somatic system are muscle relaxers, as blocking the binding of Ach prevents muscles from contracting. Nicotinic antagonists in the ANS are called ganglionic blockers, due to them blocking Ach binding onto the nAchR receptors on the ganglion
name a nicotinic agonist
nicotine
what do ACHE-inhibitors de at the neuromuscular junction
ACHE-inhibitors cause agonistic effects at the neuromuscular junction
What is ACHE (acetylcholinersterase)
an enzyme that breaks down acetylcholine that is left in the synaptic cleft
name two muscarinic agonists
carbachol, pilocarpine
what type of receptor are muscarinic receptors?
G-protein coupled
name all five muscarinic receptors and what they do
M1, M3, M5 = increase IP 3
M2, M4 = decrease cAMP
What are the effects of the parasympathetic innervation?
DUMBBBELS
Defecation
Urination
Miosis
Bronchorrea - excess pulminory fluid
Bronchospasm - difficulty breathing
Bradycardia - slowed heart rate
Emesis
Lacrimation
Salivation
What is the adrenergic (sympathetic) pathway starting from the spinal chord?
- Preganglionic neuron released Ach
- Ganglionic nAchr binds to Ach
- post ganglionic neuron releases noradrenaline
- adrenergic receptors bind NA
- effect
What is the muscarinic (parasympathetic) pathway starting from the spinal cord?
- Preganglionic neuron released Ach
- Ganglionic nAchr binds to Ach
- post ganglionic neuron releases Ach
- mAchR binds Ach
- effect
What do normal and non-normal distribution curves mean for genetic variability?
normal - gene is NOT SUSCEPTIBLE to polymorphisms
non-normal - gene is SUSCEPTIBLE to polymorphisms
what factors affect renal excretion
- drug size
- amount of free drug
- competition for active secretory pathway
- passive absorption
- renal failure
What is an inverse agonist
inverse agonists promote an opposite response to an agonist
What can drugs bind to
receptors
enzymes
transporters
ion channels
what are the three main subunits that make up a g-protein? what type of energy does it use and what subunits bind to GDP?
the three subunits that make up a heterotrimeric G protein are:
alpha, beta, gamma (Y)
subunit alpha binds to GDP
What are the main features of a kinase-linked receptor?
Single transmembrane protein activated by a range of protein mediators
usually involved with growth
What is the typical pathway for a kinase-linked receptor
Agonists binds to 2 receptors - two receptors dimerise - phosphorylation - effect
What hormones are associated with nuclear receptors
steroid hormones
What is the typical pathway of a nuclear receptor
agonist binds to receptor - receptor binds to another agonist-bound receptor - dimerises - dimer translocates - binds to DNA - transcription - effect
in phase 1 metabolism, induction and inhibition effect cytochrome P450 activity. explain both of these factors
induction = several drugs/carcinogens increase p450 activity. Results in more rapid metabolism of substrates and lower plasma drug levels = decrease in drug effect
E.g. tobacco
inhibition = occurs when two drugs are metabolised by same p450 enzyme. Consequence can be toxicity of the drug with less metabolism
E.g. caffeine
What are the two phases of metabolism? What do they aim to do?
Phase 1 - functionalisation
liver
catabolic reaction
e.g. oxidation, reduction, hydrolysis
Phase 2 - conjugation
liver, lungs, kidneys
anabolic reaction
Adds water soluble parts to the drug
What are the aims of metabolism
to increase the rate of excretion
reduce toxicity
Why do drugs accumulate in adipose (fat) tissue?
site of accumulation since its very lipophilic
can act as a reservoir for slow release
What is needed from a drug to be able to cross the blood brain barrier?
- small mw
- very lipohilic
- must be a substrate for specific transporters
- not substrates for MDRs
what is ion trapping
acid drugs accumulate in basic areas
basic drugs accumulate in acidic areas
Name three body fluid compartments and what they are made of
body comprtments dictate volume of distribution
plasma compartment - large drugs
extracellular compartment - plasma and interstitial
total body water - plasma, interstitial, intracellular
Why is plasma-protein binding important?
- acts as a reservoir
- change in plasma proteins
- change in blood volume
- species dependence
What is the rate of diffusion into the blood affected by
blood flow/tissue volume
Drug characteristics
PLasma/tissue barriers
What is the equation that represents distribution?
k1 x C plasma = k2 x C tissue
remember c - concentration of unbound/ free drug
what is atropine used to treat
asthma
what are five important things to remember when it comes to plasma-protein binding
- only unbound drugs can diffuse into peripheral tissue
- albumin is the most important and most abundant protein for drug binding
- albumin mostly binds to acidic drugs
- plasma-protein binding can be saturable for some drugs
- drugs can compete for plasma protein binding
give an example of a ligand gated ion channel
nicotinic acetylcholine receptors
how do amphetamines work
by being uptaken into the presynaptic terminal by NAT - they then inhibit MOA by inhibiting Ca2+ channels, uptake of VMAT, displacement of NA, Na leaks out
What are the effects of nicotine?
can activate parasympathetic and sympathetic pathways
MTWThF
Mydriasis
Tachycardia
Weakness
hypoTHermia
Fasciculation - muscle twitches
What adrenergic receptor regulates feedback
alpha 2
Give an example of a ganglionic blocker. what are the effects?
Trimethapan
it increases constipation and heart rate, it decreases blood pressure and vasodilation
Name two muscarinic antagonists
atropine and scopolomine
What are the effects of sympathetic innervation
Dry mouth
Mydriasis
Urinary retention
Constipation
Increased breathing
Hypertension
What are beta-blockers and what are they used to treat?
beta-blockers are adrenergic antagonists that treat disrhythmia and hypertension
what does botox do
inhibits released of Ach via exocytosis and causes flaccid paralysis in muscles
what is constitutive receptor activation
the phenomenon which describes how some receptors are in an equilibrium state of activity and inactivity. according to what binds to these receptors, this equilibrium can be shifted.
what are the three lasting effects of drug use on receptors? what are the time frames of these effects?
desensitisation - reduced response - few minutes
tolerance - reduced response - prolonged use
resistance - loss of effectiveness - chemotherapeutic drug
