P1 YEAR Flashcards
What is the Primary Structure in Proteins?
Definition
Oligopeptide sequnce, planar due to bond character in resonance structure
What is the Secondary Structure in Proteins?
Definition
Polypeptides arrange into secondary structures and are sequence dependent, form spontaneously, and are formed and stablized by hydrogen bonding
What are the components in a Secondary Structure?
- Alpha Helix
- Beta Sheet
- Beta Turns
What is an Alpha Helix?
Definition
Forms by hydrogen bonding between carbonyl oxygen and n+4 amino hydrogen
What is a Beta Sheet?
Definition
Stabilized through hydrogen bonding between adjacent strands (may be parallel or antiparallel)
What is a Beta Turn?
Definition
Cause a 180 degree turn in the polypeptide backbone stabilized by hydrogen bonding between 1st and 4th residue of the turn often include PROLINE and GLYCINE
What is a Type 1 Beta Turn?
Definition
PROLINE lots of steric hindrance
What is a Type 2 Beta Turn?
Definition
GLYCINE rotational freedom
What is the Tertiary Structure of a Protein?
Definition
Form by assembly of secondary structures, it may form a recognizable pattern
Motif
What is the Quaternary Structure of a Protein?
Definition
Composed of two or more polypeptide chains, peptides making up multimer may be either identical or nonidentical will often have an axis symmetry
ex. collagen
What is the Active Site of an Enzyme?
Definition
A specific region on an enzyme where the substance are bound
List the Properties of the Active Site on an Enzyme
- Small part of total volume of enzyme
- Bound to substrates via multiple weak, reverible attractions such as hydrophobic interactions, ionic interactions, hydrogen bond
List the Macronutrients
- Proteins
- Carbohydrates
- Lipids
Define Protein
Definition
Provide essential nitrogen, carbons, electrons as well as essential amino acids that body cannot synthesize
Define Carbohydrates
Definition
Carbons and Electrons, no essential carbs
Define Lipids
Definition
Carbons, electrons, and essential lipids that the body cannot synthesize
What pathway is this: Carbohydrates to Glucose?
Central Pathway: Glycolysis leading to produce Acetyl CoA
What pathway is this: Proteins to Amino Acids?
Amino Acids can also lead to Acetyl CoA
Precursor to producing glucose
What pathway is this: Fats to Glyceral/Fatty Acids?
Beta Oxidation also leads to Acetyl CoA
Glycerol: precursor to producing glucose
Why is Acetyl CoA is so important?
Acetyl CoA goes through Krebs Cycle/ETC to produce CO2, H2O, and ATP
List Membrane Properties
Definition
- Dynamic and Flexible
- Can exist in various phases/transitions
- NOT permeable to large polar solutes or ions
- Permeable to SMALL polar solutes and nonpolar compounds
Depending on their compositions/temperature, the lipid bilayer can exist in what TWO phases?
- Gel Phase
- Fluid Phase
What is the Gel Phase?
Definition
Liquid ORDERED State: individual molecules do NOT move around
What is the Fluid Phase?
Definition
Liquid DISORDERED State: individual molecules CAN move around
Membrane Fluidity: is determined mainly by fatty acid compositon and melting point, more fluid membranes require what?
SHORTER and MORE UNsaturated fatty acids
Melting Temperature DECREASES as what?
Double Bonds are ADDED
At lower temps, cells need more unsaturaed FA
Melting Temperatues INCREASES with what?
LENGTH of SATURATED fatty acids
At higher temps, cells need more long, saturated FA
What is Lateral Diffusion?
Definition
- Indiviudal lipids undergo fast uncatalyzed later diffusion within the layer
- Lipids can move around laterally
What is Transverse Diffusion?
Definition
- Spontaneous flips from one layer to another are rare because the charged head group must transverse the hydrophobic tail region of the membrane
- Flipases
What are Flipases?
Definition
- Special enzymes that catalyze the transverse diffusion
- Unique unidirectional and bidirectional enzymes to catalyze lipid movement
- Some flipases use energy of ATP to move lipids against the concentration gradient
DEA Numbers
Definition
2 Letters followed by 7 Numbers
How to CHECK a DEA Number?
- Add numbers #1, 3, 5 together
- Add numbers #2, 4, 6 together and multiply by 2
- Add the first and second calculated number together and make sure that matches the last digit
Superscription
Definition
Take Thou
Inscription
Definition
Drug Name and Strength
Subscription
Definition
Directions to the Pharmacist
Sigma
Definition
Directions to the Patient
NDC Numbers
NON-INSURANCE
10 Digit
1st Seg = Labeler Code
2nd Seg = Product Code
3rd Seg = Package Code
NDC Numbers
INSURANCE
11-Digit
5-4-2 format
DAW Codes 0-2
0: no product selection
1: substitution not allowed by provider
2: substitution allowed, patient requested product dispensed
1 Dram = what?
Teaspoon = 5 mL
1 oz = what?
30 g = 30 mL
16 oz = what?
1 pint = 1 pound = 480 grams
Tablespoon = what?
15 mL
1 grain = what?
60 mg
What is Down-Regulation?
Definition
Response of a system to DECREASE the response of the cell due to excessive stimulation by an agonist.
The response can be due to decreased number of recepetors or uncoupling of the receptor from the sign transduction mechanism or both.
Involved in mechanisms of TOLERANCE
What is Up-Regulation?
Definition
The response of a system to increase the response of the cell to a LACK of stimulation by an AGONIST.
The response can be due to either anincrease in receptor number of enhanced coupling of the receptor to the signal transuciton or both.
Involved in mechanisms of SUPERSENSTIVITY
What is Cranial Nerve I?
Olfactory Nerve
ONLY sensory/afferent, goes to olfactory bulb/cortical area
What is Cranial Nerve II?
Optic Nerve
ONLY sensory
How does the Optic Nerve II work to transmit?
- Photoreceptors in the retina transmit visual info to the bipolar cells in the retina.
- Bipolar cells synpase on ganglion cells which have their cells bodines in the retina
- Axons of ganglion cells leave the eyeball and form optic nerves
- Eyeball to Optic Chiasm
- Optic Chaism to Brain
Bipolar Cells
Definition
Primary Sensory Neurons
Do not fire impulses, send info via GRADED signal changes
Ganglion Cells
Definition
Secondary sensory neurons
Eyeball to Optic Chiasm
Definition
Optic Nerve
X Shaped Structure
Optic Chiasm to Brain
Definition
Optic Tract
Posterior diencephalon synapse on lateral GENICULATE nucleus of thalamus
What is Optic Nerve III?
Oculomotor Nerve
Innervates eye muscles, motor AND sensory
Where is the nucleus of the Oculomoter Nerve III?
Exits from the midbrain, nucleus is in the ROSTRAL MIDBRAIN
What type of innervations are possible with Cranial Nerve III?
- Medial Rectus: adduction toward the nose
- Inferor Rectus + Superior Oblique: moves eye down
- Superior Rectus + Inferior Oblique: moves eye up
What is Cranial Nerve IV?
Trochlear Nerve
Motor and Sensory
Where is the nucleus of Trochlear Nerve IV?
Nucleus is in the CAUDAL part of MIDBRAIN
Innervates SUPERIOR OBLIQUE
What Cranial Nerve is the ONLY one to exit DORSALLY?
Trochlear Nerve IV
What is Cranial Nerve V?
Trigeminal Nerve
Sensory FACE and Motor CHEWING
The Trigeminal Nerve V arises from the pons and then the trigeminal ganglion, what are the 3 Divisions of the nerve that leave the ganglion?
- Opthalmic V1: SENSORY
- Maxillary V2: SENSORY
- Mandibular: SENSORY AND MOTOR
What is the ONLY structure in the CNS that uses electrical synapses and not chemical?
Trigeminal Mesencephalic Nucleus
What is Cranial Nerve VI?
Abducens Nerve
Motor and Sensory
CAUDAL Pons
What is Cranial Nerve VII?
Facial Nerve
Motor, Sensory, and PNS
What elements does Facial Nerve VI control?
- Motor: facial expression
- PNS: salivary and lacrimal glands
- Sensory: skin of ear, taste buds
What is Cranial Nerve VIII?
Vestibulocochlear Nerve
ONLY sensory
Pontomedullary Junction
What is Cranial Nerve IX?
Glossopharyngeal Nerve
Motor, Sensory, and PNS
What elements does Glosspharyngeal Nerve IX control?
- Motor: pharynx
- PNS: parotid gland
- Sensory: baroreceptors, BP, O2, taste
What is Cranial Nerve X?
Vagus Nerve
Motor, Sensory, and PNS
What are elements of Vagus Nerve X?
- Exits Medulla
- Majority of PNS: heart/organs
What is Cranial Nerve XI?
Spinal Accessory Nerve
ONLY SOMATIC MOTOR - neck muscles
What is Cranial Nerve XII?
Hypoglossal Nerve
ONLY SOMATIC MOTOR - tongue
Depolarization of Hair Cells
HEARING
- K+ enters the cell = DEPOLARIZATION
- Sterocilia (in hair cells) K+ channels and tip links connect stereocilia
- Stereocilia bend towards the TALLEST stereocilia aka the tension of the tip length INCREASES = OPEN K+ channels
- Depolarization causes Ca2+ to enter which releases glutamate
Repolarization of Hair Cells
HEARING
- If stereocilia bends towards the SHORTER stereocilia, there is LESS tension and the K+ channels CLOSE
- K+ remains inside = REPOLARIZATION
Perilymph in HAIR cells has what concentration gradient?
HIGH Na+ and LOW K+
Endolymph in HAIR Cells has what concentration gradient?
Stereocilia area
LOW Na+ and HIGH K+
What are the 3 Phases of the Uterine Cycle?
- Proliferative Phase
- Secretory Phase
- Menstrual Phase
Proliferative Phase has what hormone actions?
Time from the end of menses to ovulation
- Increase ESTROGEN levels = stimulate growth and development of endometrium
- INDUCE PROGESTERONE receptors needed for secretory phase
Secretory Phase has what hormone actions?
Between ovulation and menstruation onset
- INCREASED PROGESTERON = maturation of endometrial, stimulate glandular secretion, inhibit myometrial contractions
suitable environment for implantation and embryo
Menstrual Phase has what hormone actions?
- FALL in ESTROGEN and PROGESTERONE
- Causes PROSTAGLANDIN production = smooth muscle contraction (cramps, endometrium sloughing)
When does Glucose appear in the Urine?
MECHANISM
- When the concentration of glucose in the filtrate increases, the cotransporters are saturated and cannot absorb = DECREASED reabsorption and INCREASED filtered glucose
- Glucose stays in the PROXIMAL tubule due to saturation = excretion
- Reabsorption STOPS = Increased Excretion
What are the THREE forms of Carbon Dioxide CO2 Transport in the blood?
- Dissolved CO2 in Plasma
- Bound CO2 = hemoglobin RBC
- Chemically Modified CO2 = MOST IMPORTANT aka conversion of CO2 to BICARBONAYE VIA CARBONIC ANHYDRASE
What is the MAJOR and MOST important factor of CO2 transport in the blood?
Plasma Bicarbonate
Ideal Gas Law
PV = nRT
PV = (W/MW) x RT
Combined Gas Law
P1V1/T1 = P2V2/T2
PV/T = k
Gibbs Free Energy
G = nRT (ln(a2/a1))
What 5 Excipients are used as Tonicity Agents?
- Dextrose
- Glycerin
- Mannitol
- Potassium Chloride
- Sodium Chloride
Wetting Agents
Defintion: Excipients
Added to disperse solids in continuous liquid phase
Flocculating Agents
Defintion: Excipients
Added to floc the drug particles
Thickeners/Viscosity Modifiers
Defintion: Excipients
Added to increase the viscosity of suspension
Buffers pH
Defintion: Excipients
Added to stabilize the suspension to a desired pH range
Colorants, Flavors, Sweeteners
Defintion: Excipients
Added to impart desired color and taste to suspension, improve elegance
glucose, sucrose, sorbital, peppermint oil, saccharin
Preservative
Defintion: Excipients
Added to prevent microbial growth
What are the most commonly used excipients in capsules/tablets?
- Lactose
- Sucrose
- Calcium Sulfate
- Di-Calcium Phosphate
- Starch
- Magnesium Stearate
What is pKa?
Refers to the pH at which the charged and uncharged forms of a molecule are present in an equal proportion
Henderson-Hasselbach Weak Acids
pH = pKa + log [salt]/[acid]
Acid = UNionized
Salt = IONized
Henderson-Hasselbach Weak Base
pH = pKa + log [base]/[salt]
Titration of Weak Acid w/ Strong Base
Equivalence Point = acid is completely neutralized with base
Half Equivalence Point = [acid] = [salt] aka pH = pKa
When does Maximum Buffer Capacity occur?
pH = pKa
aka choose a buffer with a pKa value close to the desired pH
List the 5 basic components of the Medication Use Process
- Prescribing
- Transcribing and Documenting
- Dispensing
- Administering
- Monitoring
Liophilicity
Definition
The ability of drug molecule to interact with and cross lipid bilayer
PASSIVE diffusion
Nonpolar + Polar Regions
What are the factors controlling Drug Absorption?
- Solubility of Drug
- Dissolution Rate
- Concentration
- Circulation at the Site of Absorption
- Surface Area of Absorbing Site
Pros/Cons: Oral Route
Administration
- Most common, preferred, safest
- Small Intestine = major site of absorption due to large surface area
- First-Pass Efect
Pros/Cons: Buccal/Sublingual Route
Administration
- Quick absorption –> transcellular diffusion
- Avoids first pass metabolism
- Unsuitable for bitter tasting drugs
Pros/Cons: Rectal Route
Administration
- Limited Absorption: low surface area
- Great for peds
- Avoids first-pass
- Slow, incomplete, irregular absorption
- Irritation of rectal mucosa
Pros/Cons: Parenteral Routes
Administration
SQ: slow absorption, prolonged action
IM: most common, rapid absorption
IV: most rapid, danger
Pros/Cons: Transdermal Route
Administration
- Facilitated by carriers and devices
- Constant delivery of drug
- Slow process, long term therapy
Pros/Cons: Nasal Route
Administration
- Rapid absorption
- Limited surface area
- Limited dose
- Damage to nasal lining with long term use
Pros/Cons: Pulmonary Route
Administration
- Absorption is passive diffusion
- Particles less than 5um preferred
- Must reach terminal bronchioles and alveoli
- Retention and Clearance problematic
List the Phase I Reactions
Chemical Reaction, Non-Synthetic
- Oxidations
- Reductions
- Hydrolses
Oxidation Reactions
Associated Elements
Phase I
Catalyzing Enzymes:
1. P450
2. Flavin Monnoxygenase
3. Amine Oxidase
4. Dehydrogenations
Reduction Reactions
Associated Elements
Phase I
- Relative uncommon pathway for drug mettabolism
- Yield active or toxic metabolites
- Introduce hydroxyl and amine groups
- SOA: microsomal and cytosolic enzymes
Hydrolyses Reactions
Associated Elements
Phase I
- Epoxide Hydrolase: gets ride of epoxide produced from oxidation
- Esterases: converting ester prodrugs (SOA: all over the body)
- Peptide Hydrolase
- Lactone
Phase I Reactions introduces or exposes one the reactive groups onto the xenobiotic, list the possible reactive growups
- Hydroxyl -OH
- Amino -NH2
- Carboxyl -COOH
- Sulfhydryl -SH
causes increased reactivity and hydrophilicity
List the Phase II Reactions
Conjugations, Group Transfer
- Glucuronidation
- Sulfation
- Glutathione
- Amino Acid Conjugation
- Acetylation
- Methylation
Glucuronidation Reactions
Associated Elements
Phase II
- MAJOR reaction and strongly INCREASES water solubility
- Enzyme: Glucuronosyltransferase UGT
- Co-Factor: UDP-Glucuronic Acid GA
- Precursor: Glucose – abundant making it the MOST common reaction
What is the most important endogenous substrate for UGT?
Phase II
Bilirubin
Sulfation Reaction
Associated Elements
Phase II
- Enzyme: Sulfotransferases SULs
- Co-Factor: PAPS
- Cojugating Agent: Sulfate Group
- Target Groups: Phenols, Alcohols, and Amines
What is PAPS and why is it important in APAP metabolism?
3’-Phosphoadenosine-5’-Phosphosulfate
PAPS is depleted in APAP overdose and causes hepatotoxicity
Glutathione Conjugation Reaction
Associated Elements
Phase II
- Enzyme: Glutathione S-Transferases GSTs
- Co-Factor: Glutathione
- Conjugatinge Agent: Glutathione GSH
- Target Groups: Electrophic Functions Grooups
- Depleted GSH in APAP overdose leads to hepatotoxicity
Acetylation Reaction
Associated Elements
Phase II
- Enzyme: N-Acetyltransferases NATs, Cytosolic Enzymes
- Co-Factor: Acetyl Coenzyme A
- Target Groups: Aromatic AMines and Alcohols
Acetylation of what may lead to hepatotoxicity?
Isoniazid INH
Alpha 1 Receptor
Important Elements
Antagonist: Prazosin
G Protein: Galphaq
Effects: Increase IP3 and DAG
EXCITATORY
Alpha 2 Receptor
Important Elements
Antagonist: Yohimbine
G Protein: Galphai
Effects: Decrease cAMP
Inhibit Sympathetic
What is the antagonist for Alpha 2b/c type receptors?
Prazosin
B Receptors
Important Elements
Antagonist: Propranolol
G Protein: Galphas
Effects: increase cAMP common to all
Beta 1 Receptor
Important Elements
Antagonist: Betaxolol
Location: Heart, Juxtaglomerular Apparatus JGA of the Kidney
Stimulated by: NE potentially innervated
Beta 2 Receptor
Important Elements
Antagonist: Butoxamine
Vasodilation, reduction of BP, relaxation of smooth muscle
Non-Innervated Receptors: NE from bloodstream
Beta 3 Receptor
Important Elements
Location: Adipose Tissue
Function: not clear
Med: Mirabegron (Myrbetriq)
Histamine
Components
- Communicated between cells through interacting with receptors on the outside
- Blasts a signalling response to severe cells
- Rapidly metabolized
What are the multiple effects of histamine and how is this possible?
- Inflammation
- Anaphylaxis
- Gastric Acid Secretion
- Neurotransmission
- Possible through four different histamine receptors located in different tissues
What are drugs Inducing Immunity?
Vaccines and Passive Antibodies
What are drugs Inhibiting Immunity?
Immunosuppressive agents
What are drugs that Modify Immunity or Related Responses?
Cytokines, Anti-Inflammatories
What are drugs Helping the Immune System?
Anti-Infectives or Antineoplastics
What are drugs to Evaluate Immunity or Antigens?
Immunodiagnostics
TH1 Cytokine
Elements
Secrete: IL2, IFNy, IL12, and TNFB
Stimulate: cell mediated responses, bacterial killing, Ig class switch
Block: function of TH2 cells
IFNy Cytokine
Elements
Enahnces: macrophages, PMH, cytotoxic activity
Proinflammatory
TH2 Cytokine
Elements
Mediate Anti-Parastitic Immunity
Promote IgE class switch
Block TH1 and Th17
Th17 - IL17 Cytokine
Elements
Mycobaterial/Fungal surveillance, allergy, and autoimmune disease
TReg Cytokine
Elements
TGFB and IL10
Promote mucosal immunity
What interleukin is secreted by various antigen presenting cells and most cell types?
Similar to TNFa, proinflammatory
Interleukin I
Which Interleukin is produced by Th1 and other T cells that promotes T cell proliferation?
Supports T cell growth, enhances NK cytotoxic activity
Interleukin 2
Which Interleukin is produced primarily by TH2, TReg, and M2 and is Anti-Inflammatory?
Performs TH2 stuff
Interleukin 10
Which Interleukin is the Prototypical TH2 cytokine and induced Ig class switch to IgG?
Stimulates mast cell growth of TH2
Interleukin 4
What are the 4 main types of Infectious Disease?
- Toxigenic
- Extracellular
- Facultative
- Intracellular
Toxigenic Infection
Exotoxin solube protein secreted by bacteria outside the bacterial cell
- Diptheria, Tetanus
- Leads to Septic Shock
What cytokines are involved in Septic Shock?
- IL-1beta
- TNF-alpha
What are protective mechanisms in Toxigenic Infection?
- IgM Bacteriolysins
- IgG Anti-Capsular Antibody
- IgM Antibody for Lipid A
Extracellular Infection
Most susceptible to curent anti-infectives
- Antiphagocytic Capsule: importat virulence factor for bacteria
- Acute Inflammatory Response: IL-8 Chemokine attrachs NK cells
Faculative Intraceullar Infection
Mycobacteria
- Resistant to NK killing
- Monocyte involvement
- Efferent Phase: cell mediated immunity
Obligate Intracellular Inffection
Viruses
- Interfern type 1 is major nonspecific defense
- CD8+ cytoxic T cells most important for recovery
- IgA and/or IgG prevent reinfection
What are the Classifications of Immunodeficiency?
- Primary: congenital developmental defects
- Secondary: acquired disorders (viral, neoplasm, lifestyle)
Primary or Inherited Immunodeficiency
TYPES
- Aspienia
- C3 Deficiency: complement
- Chronic Granulomatous Disease: phagocyte function
- MBL Deficiency: opsonization, phagocytosis
- SCID: T and B cell
Secondary or Acquired Immunodeficiency
TYPES
- Viral: HIV, measles
- Neoplasm: leukemia, lymphoma
- Lifestyle: alcohol abuse
- Trauma: burns
- Latrogenic: drugs, allograft
List the 4 Types of Ointment Bases
- Oleaginous Base
- Absorption Base
- Water Removable Base (Oil in Water)
- Water Soluble Base
List and Classify Oleginous Bases
- Emollient
- White Petrolatum
- White Ointment
- Yellow Ointment
List and Classify Absorption Bases
- Incorporate small volume of aqueous solutions in hydrocarbon base
- Hydrophilic Petrolatum aka Aquaphor
List and Classify Water Removable Bases
- Easily washed from skin
- Creams
- Sodium Lauryl Sulfate + White Petrolatium + Methylparaben
List and Classify Water Soluble Bases
- Do NOT contain oleaginous component
- Greaseless
- PEG Ointment
What should be avoided in Suppository formulation since it enhances degradation of oleaginous bases?
Water
What is a suspending agent that can be added to suppositories to decrease the drug settling out?
Silica Gel
What can be added to delay the release of drugs suppositories by forming a gel that delays dissolution?
- Methylcellulose
- Alginic Acid