Pharmacology Flashcards
Pharmacodynamics?
What a drug does to the body (drug and dynamics begin with d, drug first)
Pharmacokinetics?
What the body does to a drug
What are receptors?
Protein macromolecules
What is an agonist? What do they possess?
Drug that binds to a receptor to produce a cellular response
-Affinity & efficacy
What is affinity?
Strength of association between ligand and receptor
What is efficacy?
Ability of an agonist to evoke a cellular response
What is an antagonist?
Drug that blocks the actions of an agonist
Agonists posses affinity but lack efficacy. True or false?
TRUE
What do agonists possess?
Affinity NOT efficacy
What is competitive antagonism?
Binding of an agonist and antagonist occur at same time (orthosteric) site and is thus competitive
What does competitive antagonism cause?
Parallel rightward shift of agonist concentration response curve with no depression in maximal response
(Less potent but the same efficacy)
What is non-competitive antagonism?
Agonist binds to normal site and antagonist binds to separate (allosteric) site and is thus not competitive
When can activation occur in non-competitive antagonism?
CANNOT occur when antagonist is bound
however both may occupy site simultaneously without activating
What does non-competitive antagonism cause on a graph?
Depress the slope and maximum response curve BUT no rightwards shift
-LOWERs the efficacy, but potency stays the same
Graph of competitive and non competitive antagonism?
Absorption?
Process by which a drug enters the body from its site of administration
Distribution?
Process by which drug leaves circulation and enters tissues perfused by blood
Metabolism?
Process by which tissue enzymes catalyse chemical conversion of a drug to a more polar form that is more readily excreted from the body
Excretion?
Process that removes the drug from the body
Factors controlling drug absorption?
- Solubility - must dissolve
- Chemical stability -some drugs are destroyed by acid
- Lipid to water partition of coefficient - Rate of diffusion increases with lipid solubility
- Degree of ionisation - Only un-ionised forms readily diffuse across lipid bilayer
What does the degree of ionisation in drug absorption depend on?
pKa of the drug and the local pH
What is pKa?
pH at which 50% of the drug is ionized and 50% unionized
Henderson Hasselbalch equation?
pH-pKa= log (A-/AH) = acid
What type of substance is it if Ka is large?
Strong acid
What does henderson hasellbalch equation help you determine?
Determine how active a drug may be in the body
What is oral avilability?
Fraction of drug that reaches the systemic circulation after oral ingestion
What is systemic availability?
Fraction of drug that reaches the systemic circulation after absorption
Routes of administration of drugs?
Enteral= oral, sublingual, rectal Parenteral= IV, Intramuscular and subcutaneous, topical
Volume of distribution? (Vd)
Volume into which a drug appears to be distributed with a concentrationWhat equal to that of plasma
Equation for setting up an IV?
Vd= dose/plasma concentration
What is MEC?
Minimum effective concentration
What is MTC?
Maximum tolerated concentration
What is the equation for therapeutic transfer?
MTC/MEC
What does it mean if the TR of a drug is very high?
The higher the TA the safer the drug
What is first order kinetics?
- The rate of elimination of a drug is directly proportional to drug concentration
- Half life of a drug in inversely proportional to elimination rate constant
How do you find the half life in first order kinetics?
T1/2 = 0.69/kel
What is clearance?
The volume of plasma cleared of drug in unit time
Equation for rate of elimination?
Rate of elimination = Clearance x plasma concentration
Equation for dosing to steady state?
Cpss = Maintenance dose rate/ clearance
When is Css reached?
Approx 5 half lives
What is a loading dose?
Initially higher dose of drug before stepping down to lower maintenance dose
Why is a loading dose used?
Employed to decrease time to steady state for drugs with a long half-life
What is a half-life?
Time for the conc of a drug in plasma to half
What is half-life dependant on?
Vd and Cl
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is ADME?
Factors which influence drug disposition
What does drug metabolism do?
Convert drugs to more polar metabolites not readily absorbed in renal tubules, facilitating excretion
How many phases of drug metabolism?
2
Phase 1 of drug metabolism?
- Oxidation, reduction and hydrolysis
- Makes a drug more polar, adds a chemically reactive group permitting conjugation
Where does phase 1 of drug metabolism occur?
RHS of liver
Phase 2 of drug metabolism occurs on the RHS of the liver. True or False?
FALSE
LHS
Phase 2 of drug metabolism?
Conjugation
-Adds an endogenous compound increasing polarity
3 basic processes involved in renal excretion of drugs and drugs metabolites involved?
- Glomerular filtration
- Active tubular secretion
- Passive reabsorption
What is glomerular filtration?
- Occurs freely for most drugs
- Drugs bound to large plasma proteins exist in blood in equilibrium between unbound and protein bound forms. ONLY unbound can enter filtrate via glomerular filtration
What is active tubular secretion?
Epithelial cells of proximal tube contain 2 transporter systems which actively secrete drugs to lumen of nephron
What does an organic anion transporter handle?
Acidic drugs like penicillins, uric acid, frusemide, thiazides
What does an organic cation transporter handle?
Handles basic drugs
-Morphine
What is the potentially most effective mechanism of drug elimination?
Active tubular secretion
What is passive reabsorption across tubular epithlium?
Concentration of urine favours passive reabsorption of drugs across distal tubule by diffusion
Which factors influence reabsorption in the third step of renal excretion of drugs?
Lipid solubility
Polarity
Urinary flow rate
Urinary pH= alkaline (increases excretion of acids) acidic (increases excretion of bases)
What is depolarisation?
The membrane potential becomes less negative (or even positive)
What is hyperpolarisation?
The membrane potential becomes more negative
Which direction does Na flow in sodium channels?
Inwardly
What is the driving force in sodium channels?
Vm-Ena (negative driving force causes the inward movement of sodium)
Which way does K flow in potassium channels?
Outwardly (when positive)
The driving force is Vm-Ek
Ion channels responsible for action potentials in neurones?
Voltage activated Na channels = depolarizing
Voltage activated K channels = Hyperpolarizing
What are voltage activated Na/K channels activated by?
Membrane depolarization
-Na channels rapid, K channels slight delay
What is positive feedback (upstroke of graph)?
Activation of Na channels is self-reinforcing, the opening of a few channels causes further depolarization
How is the activation of K channels self-limiting?
The outward movement of K causes repolarisation which turns off the stimulus (negative feedback) downstroke of graph ad undershoot due to delayed closure of K channels
What does an absolute refractory period mean?
No stimulus, however strong, can elicit a second AP
Oligodendrocytes?
Produce myelinated cells in CNS (Shwann cells do it in PNS)
What do astrocytes do/look like?
Support homeostasis and maintain BBB
Star shaped
What are the macrophages of the CNS?
Microglia
What do microglia do?
Immune surveillance
Functions of the ANS?
- Carries output from the CNS to the whole of the body other than skeletal muscle
- Regulates visceral functions that are largely involuntary
- Subdivided into sympathetic and parasympathetic
What is main role of sympathetic nervous system?
Coordinates the body’s response to stress, associated with the fight, flight or fright reactions
What is the pre-ganglionic neurone always in sympathetic system?
ACh
What is noradrenaline in the sympathetic nervous system?
Post-ganglionic
Where is the outflow of sympathetic?
Thoraco-lumbra (T1-L2)
What does sympathetic do to
- HR
- Force of contraction ?
Increases them both
What does the sympathetic system decrease?
-Mucous production
What relaxes in a sympathetic response?
- Bronchi relax
- Skeletal muscle relaxation
GI motility is increased in sympathetic response. True or false?
False
Decreased and sphincters are constricted
What type of response does ejaculation occur in?
Sympathetic
What hormone is released in sympathetic response?
Adrenaline from adrenal gland
Vasoconstriction occurs in sympathetic response. True or False?
True
Role of parasympathetic response?
Coordinates the body’s basic homeostatic functions
What is the neuro-transmitter use in parasympathetic response?
ACh for both pre/post ganglionic neurones
Which cranial nerves are parasympathetic?
Cranial nerves 3, 7, 9, 10
What does parasymp do to HR?
Decrease it
Exaplain what happens to bronchi, mucous production, GI motility and blood vessels in parasympathetic?
- Bronchoconstriction
- Stimulates mucous production
- Increased GI motility
- Relaxed sphincters
- NO effect on blood vessels/adrenal glands
Which response does an erection occur in?
Parasympathetic
Process of neurochemical transmission?
- precursor taken up
- Transmitter synthesized and stored
- AP depolarizes
- Calcium influx through voltage-activated channels
- Calcium induced release of transmitter
- Receptor activation
- Enzyme mediated inactivation of transmitter or re-uptake of transmitter
How sympathetic chemical transmission works?
AP is from the CNS
- Travels to pre-synaptic terminal of preganglionic neurone triggering Ca2+ entry and release ACh
- ACh opens ligand-gated ion channel in the postganglionic neurone (this causes depolarization, and generation of AP that travel to pre-synaptic terminal of the neurone, triggering Ca2+ entry and release, usually of noradrenaline
What activates G protein coupled receptors? (adrenorecptors)
Noradrenaline
Differences between sympathetic and parasympathetic chemical transmission?
Parasympathetic
- ACh always the transmitter used by postganglionic neurones
- ACh activates the G protein coupled muscarnic acetylcholine receptors in target cell membrane
What do ligand gated ion channels consist of?
Separate glycoprotein subunits forming a central, ion conducting channel
What do Ligand-gated ion channels allow?
Rapid change in the permeability of membrane to certain ions
They can rapidly alter membrane potential
Types of G protein coupled muscarinic ACh receptor subtypes at parasympathetic neuroeffector junctions?
M1-Gq= stimulates phospholipase C= increased stomach acid secretion
M2-Gi = Inhibition of adenylyl cyclase, opening of K+ channels- decreased HR
M3- Gq = stimulates phospholipase C= Increased saliva secretion and bronchoconstriction
Types of G protein coupled muscarinic ACh receptor subtypes at sympathetic neuroeffector junctions?
B1- Gs = Stimulation of adenylyl cyclase = increased HR and force
B2- Gs = Stimulation of adenylyl cyclase- relaxation of bronchial and vascular smooth muscle
A1- Gq = Stimulation of phospholipase C = Contraction of vascular smooth muscle
A2-Gi = Inhibition of adenylyl cyclase = Inhibition of NA release
What do amphetamines do?
U1 substrate Inibits MAO (monoamine oxidase) Displaces NA into cytoplasm NA accumulates into synaptic cleft causing increased adrenoreceptor stimulation
What is prazozin?
Vasodilator used as anti-hypertensive
Selective, competitive antagonist of a1
What is atenolol?
Selective, competitive antagonist of B1
Used as an anti-anginal and anti-hypertensive agent
What is salbutamol?
Selective against B2
Used as a bronchodilator in asthma
What does atropine do?
- Blocks parasympathetic division of ANS
- Used to reverse bradycardia post MI and in AChE poisoning
What is atropine?
Competitive antagonist of muscarinic ACh receptors , does not block nicotinic ACh recpetors
