Revision deck -7-12 Flashcards
wks 7-12 from revsion slides
What are the three factors to consider in the creation of membrane potentials?
Ionic concentrations- Na higher on outside
Electrical forces- opposites attract
ion channels allow ions to move - passive, gated
What are the 4 types of membrane ion channels and how do they open?
Passive- always open
chemically-gated: via binding of neurotransmitter
voltage-gated: response to changes in MP
mechanically gated: physical deformation of rceptors
what does ion flow create?
electrical current and voltage change across the membrane.
What is the RMP due to?
Difference in ICF and ECF ionic concentration
Differential permeability of the membrane to Na and K.
What are ionotropic Receptors, what is their time line and what are some examples?
ligand-gated ion channels
Excitatory receptors = for small cations (Na) for depolarization.
Inhibitory receptors for Cl influx evoking hyperpolarisation
Milliseconds
Nicotinic and ACh receptor
What are Metabotropic GPCRs
GPCRs
Ligand binds to GPCR –> GDP echnage for GTP –> active sub unit –> a-GTP dissociates and activates second messenger –> G inhibits or stmulates cAMP/PLA pathway
seconds long ( indirect, prolonged and complex)
examples are muscarinic and ACh receptors
Describe the ionic bases of resting state of AP
Na and K+ channels closed
Small build-up of negative charges along inside surface equal to build up positive outside.
What is the mechamims of AP propagation?
Local AP currents depolarize adjacent membrane in the forward direction. Can’t travel backwards due to inactivationvoltage-gated ion channels during the refractory period.
What are the five steps of synaptic neurotransmission?
depolarisation by AP (nerve impulse) opens VG Ca2 channels at the presynaptic terminal
Ca influx triggers fusion of synaptic vesicles with the membrane → exocytosis
NTs diffuse across the synaptic cleft
NTs activate postsynaptic LGIC → excitatory/ inhibitory event (graded potential - PSPs)
NT effects terminated by reuptake, degradation, or diffusion
What are the two types of Synaptic potentials
excitatory (EPSP) = depolarising (net positive influx) = closer to threshold potential
inhibitory (IPSP) = hyperpolarising (net negative influx)= further from 0mV
What are the 4 types of neurotransmitters?
Ach
Catecholamines
Idolamines
Amino Acids
What are the actions of ACh?
neuromuscular junction (excitatory) and some ANS/CNS synapses (cardiac= inhibitory)
What are some catecholamines and what do they act on?
Epinephrine, norepinephrine, dopamine
Act on adrenergic receptors
Name 2 inodlamine and 2 amino acid neurotransmitters
Indolamines
Serotonin and histamine
Amino Acids
Glutamate and GABA
Is GABA an excitatory or inhibitory neurotransmitter?
Inhibitor of the CNS
reduce neuronal excitability via inhibiting nerve transmission
Compare and contrast ionotropic and metbotropic.
Similarities
- both use ACh
-moth mechanism of cell communication via receptors
Differnces
- I = Breif and immediate, M= complex and prolonged
-I = excitatory and inhibitory receptors on ion channels M= GPCR and second messenger
describe the effects of hypokalemia
hypokalemia (low ECF ) = extracellular K^ → greater electrochemical gradient driving K^ efflux → hyperpolarisation (MP becomes more negative)
What is the fastest fibre type?
Aa- somatic motorneurons (Skletal)
Describe, in general terms, the neural reflex arc
Sensory receptor – site of stimulus
Sensory neuron – afferent impulses
Integrating center – monosynaptic or polysynaptic within CNS
Motor neuron – efferent impulses towards effector
Effector – muscle fiber/ gland that contracts or secretes in response
What are the two sensory/motor reactions in the patellar reflex?
Sensory neuron synapse:
Excitatory motor inputs = quadricep stimulation
inhibitory motor neuron = hamsiting inhibiton
Describe the patellar reflex
Stimulus: Patellar tendon of quadricep muscle stretches in response to being tapped (mechanically gated)
Sensory receptor: Strech is detected by the muscle spindle fibers in the quadriceps AP sent to sensory neuron
Sensory neuron synapses with excitatory motor inputs stimulate quadriceps – monosynaptic integration
Sensory neuron synapses with inhibitory motor neuron inhibit hamstring inhibition of antagonistic muscle allows extension of agonist (quadricep) to be unopposed.
Outline B Fibre classifications
Small diameter, myelinated = slower than A
preganglionic ANS axons (from CNS autonomic ganglia)
Outline C fibre classifications
Smallest diameter and unmylelinated = slowest
ANS postganglionic axons (from ganglia to target)
Describe the major functions of the cerebrum
Site of conscious thought, sensation, intellect and memory
processes sensory and motor information
Describe the Dinecephalon
Thalamus and hypothalamus
Overall Centres for drives and emotional & behavioral patterns
Hypothalamus: Autonomic regulation of homeostasis
Thalamus: relay station for sensory impulses passing to cortex
Describe the functions of the Brainstem
Midbrain, pons and medulla oblongata
Midbrain = visual/ auditory reflexed
Pons = conveys ascending/descending information
Medulla = autonomic CV and respiratory rhythm control
Describe the structure and function of the Cerebellum.
Two hemispheres and divided into lobes
Autonomic processing center
Coordinates balance and posture and programs ongoing movements
Define and describe pharmacodynamics.
The action of the drug: what it does to the body
Qualitative = HOW to produce effects
Quantitative = Magnitude of response. = potency, therapeutic efficacy and tolerance.
Describe and define pharmacokinetics
Describes the fate of the drug
Absorption, distribution, metabolism and distribution
What body does to the drug
Describe and define pharmacotherapeutics
Use of drug treatment to cure disease, delay progression and alleviate signs/symptoms of disease
Define and describe side effect and adverse drug effects
Side effect
Drug effects not the primary purpose for giving the drug
Adverse drug effect
Unintended and undesirable response to a drug
What are the main groups of molecular targets for drugs?
Proteins
Nucleic acids
Miscellaneous targets
What are the four types of protein molecular targets
Receptors
ion channles
enzymes
carreir molecules
What are the 4 receptors of protein targets?
Ligand gated Ionotropic
Metabotropic (GPCR)
Kinase-linked
Nuclear receptors
What do protein receptors do?
enhance, mimic, inhibit ot modulate signals.
Drug actions = agonists, antagonist and allosteric modulators.
describe ion channel molecular targets, how they act on drugs and an example.
Transmembrane pores that regulate the flow of ins
Drug actions: Block and modulate
local anaesthetics and tetradoxin
Describe enzyme molecular targets, how they act on drugs and examples
Endogenous protein that catalyzes biochemical reactions
Inhibits or act as a false substrate = inhibits synthesis of normal product and converted into metabolite
paracetamol (COX 1, COX –2 inhibitors, prevents synthesis of PG (FA mediator of inflammation))
Describe carrier molecules (transporters) molecular targets, how they act on drugs and example.
Because many endogenous components are too polar to cross
Drug action = inhibits and can act as false substrate = inhibition of substrate transport
SSRIs- blocks serotonin reuptake channels of postsynpatic neurons
Amphetamines: binsd to catecholamine transporters, taken into neuron and inhibits VMAT-2= increased number of NT released into synaptic cleft
Give examples of ligand-gated, GPCRs, Kinase-linked and Nuclear receptors
Liand gated Ionotropic- nicotinic ACh (post ganglionic), GABA A, Glutamate ionotropic receptors.
Metabotropic (GPCR) - Muscarinic ACh = parasympathetic effectors, Adrenoceptors (sympathetic), peptide receptors,
Kinase-linked – JAK-STAT, Cytokines, IGF/Insulin
Nuclear receptors- Estrogen receptors , steroid/thyrpid receptors
Outline an example of an Ion Channel protein target
e.g. GABA A Cl- channel: GABA antagonsist binds to blocks GABA binding: Vallium = modulator that turns control up –> GABA allows more Cl into cells.
Outline the three actions of drugs acting at receptors
Agonists
- stimulate receptors and mimic messengers
- affinity and efficacy
Antagonist
-block receptors and prevent signal being sent
Allosteric modulators
-act at modulatory site on receptor
-volume control of response to endogenous chemical
What does a lower Ka indicate interms of affinity?
higher affinty
produce effects at low concentartions
Do agonists of equal affinity produce the same size response?
not always
What is an example of a drug that uses antagonising endogenous neurotransmitters and hormones?
B-blockers
A drug that is more potent will….
deliver a response at a lower dose
What are the main routes of administartion?
oral
Parenteral
Inhalation
Epithelial
Sublingual
Rectal
what are the four types of parenteral modes of administration?
Intravenous: directly into blood
Intramuscular: injected into muscle
Subcutaneous: injected under the skin
Intrathecal: injected into the subarachnoid space of the spine
what are the benefits and disadvanatges of intravenous?
intravenous injections are:
common
provide almost immediate effect
deliver large amounts of drug over time
used for drugs that can’t be taken orally and avoids first-pass metabolism
Disadvtatges
- difficult to adminsiter
Describe ionisation and pH
Drug will be ionized when exposed to pH of oppose pKa
Acidic drugs more ionized with higher pH
Must be unionised from to cross membrane
Define Volume of Distribution
Volume of fluid in which amount of drug in the body need to be uniformly distributed to produce observed concertation.
What is the calculation of VD?
Vd = total amount of drug in body/plasma drug concentration
What are the functionalisation reactions of Phase I metabolised catalysed by?
Catalysed by a group of hepatic microsomal enzymes = Cytochrome P450 mono-oxygenase system
Describe phase I reactions of drug metabolism.
Functionalization reactions: functional group added/ exposed
Results in loss of pharmacological activity = more reactive products
Important for prodrugs
Describe phase II drug metabolism
Covalent linkage made between functional group of drug or metabolite from Phase I
Produce highly polar molecules which are rapildy excreted in urine
Usually = decreased activity and more active metabolites
What may the conjugatefof Phase II reactions in Drug metabolism be og?
glucuronic acid, sulphate, glutathione, amino acids, methyl groups or acetyl groups.
What is an exmaple of Phase I and phase II drug metabolism?
Phase I: Aspirin – oxidation, hydroxylation, dealkylation, deamination, hydrolysis —> Salicylic acid (derivative) – Conjugation–> Glucuronide
What is first pass metabolism AKA
presystemic metabolism
How does first-pass metabolism limit oral administartion?
higher dose is needed
large individual variation
some drugs can’t be given orally at all
Compare innate and adaptive immune response.
Innate is nonspecific whilst adaptive in specific
innate uses first and second but adaptive uses a third line of defense
innate is the immediate response that is limited and has a lower potency, adaptive is longer and stronger
Adaptive involves the activation of
What are the granular and agrnaular leukocytes?
granular = neutrophils, eosinophils and basophils
agranular = lymphocytes and monocytes
What are the three types of Antigen-presenting cells?
Dendritic cells, macrophages and B cells
Describe Dentric cells
Mobile sentinels of boundry tissue
Phagocytoise pathogens, then enter lymphatics to present T cells to lymph nodes
Link between innate and adaptive
How do macrophages act as antigen presenting cells?
Widely distributed
Present antigens to activate other T cells
Activated macrophage = voracious phagocytic killer
Triggers powerful inflammatory responses
Who do B cells present antigens to?
Helper T cells
What cells produce Antiboides (which ones create and which ones secterte)
Lymphocytes produce them:
B cells= create
Plasma cells= secrete
Differentiate between the 1st and 2nd line of defences
Both are innate
1st = surface barriers (skin, mucous)
2nd = internal defences (phagocytes, NK cells, Inflammation, Antimicrobial proteins and fever)
What cells are used in humoural immunity vs cell-mediated immunity?
humoral = B
Cell mediated = T
What is adaptive immunity?
Ability to defend against a specific invading agent
Highly evolved responses that are stimulated by exposure to infectious agent and increase in magnitude
What are the two ways in which lymphocytes of Cellular immunity act?
Indirectly releasing chemicals that enhance inflammatory response
OR
activating other lymphocytes or macrophages
Describe what happens to the antigen after it recognised and bound in cell-mediated immunity.
small number of T cells proliferate and differentiated it clone of effector cell
antigen is eliminated
Describe the action of humoral immunity on antigens
Lymphocytes produce antiboides which circulate freely in the blood
Antigen recognised and bound
Marked for destruction by phagocytes
Helper T cells constimulte the B cell —> B cell proliferates and differentiates –> clone of effector produces antibodies –. antigen eliminated
Describe the mechanism of action of Naturally Acquired immuity
contact with pathogen –> Antigen recogition by B cells and T cells –> formation of antibody secreting plasma cells, cytotoxic T cells, B and T memory cells.
What are two modes of natrual passive immunity
IgG transferred from mother to foetus across placenta . IgA from mother to baby via breast milk.
Describe Artificially acquired active immunity with an example.
Vaccine (dead or attenuated) –> stimulates cell mediated and humoral immune response –> production of memory cells (immunogenic)
What are two examples of Artificially acquired passive immunity?
intravenous injections of IgG antibodiesand anti-venom for snake bite
What does patholody involve?
causes (aetiology) and underlying mechanisms (pathogenesis)
When is cell injury reversible?
in the early stages or mild forms or in functional and morphological changes if the stimulus is removed
When does cell injury become irreverisble and what does it lead to?
when there is continued damage and leads to cell death as the cells can’t recover.
Outline the stages in the cellular response to stress and noxious stimuli
Stress –> Adaption – (inability to adapt) –> cell injury)
Cell injury reversible –> normal cell
Cell injury irreveirble –> necrosis/ apoptosis
What are the hallmarks of reversible cell injury?
Reduced oxidative phosphorylation = depletion of ATP
Cellular swelling from changes in ion concentrations and water influx
Intracellular organelles show alterations
Outline the steps in the development of disease.
Etiology –> pathogenesis (mechanism) –> abnormalities in cells and tissue (molecular, functional and morphologic) –> clinical manifestations
Compare necrosis to apopotosis
necrosis = pathological, Apoptosis = physiological
necrosis= enlarged cell size Apoptosis = reduced cell size
necrosis: plasma membrane disrupted, Apoptsois = plasma membrane altered strcutre but in tact
what are the five stages of phagocytosis?
Chemotaxis, adherence, ingestion, digestion, and killing
