Pharm Final Flashcards
(635 cards)
1
Q
Define pharmacology/medical pharmacology
A
Study of the effects of drugs in the body
2
Q
Define toxicology
A
Undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems
3
Q
What are the different types of drug groups?
A
Agonists, partial agonist, antagonist, inverse agonists, agonist mimics
4
Q
Define pharmacodynamics
A
The effects of the drug on the body
5
Q
Define pharmacogenomics
A
Looking at genetic profile to determine how you will respond to drug
The primary reason patients respond differently to the same drug
6
Q
Define pharmacokinetics
A
Effects of the body on the drug (half-life, can it cross barriers, ADME, etc)
7
Q
Drugs can either be an ______ or an ______
A
agonist; antagonist
8
Q
Define agonist
A
Binding to specific site elicits a conformational change in the protein that is bound which activates the receptor, producing the same, or similar, effect to that of a native ligand
9
Q
Define antagonist
A
Competitive in nature to agonists and they bind to a specific receptor before an agonist can, inhibiting the response to the amount of normal constituent activity
10
Q
Define receptor
A
A large protein, usually on the cell surface, that can bind to drugs or endogenous ligands
11
Q
Define endogenous
A
Produced inside the organism or cell
12
Q
Define Exogenous
A
Growing or originating from outside the organism
13
Q
Define poisons
A
Non-biological substances (arsenic or lead)
14
Q
Define toxins
A
Biological substances from living organisms (mushrooms)
15
Q
Define partial agonist
A
Like agonists in binding sites but can act like antagonists if in the presence of an agonist because it only produces a partial response and prevents the agonist from binding.
16
Q
Define inverse agonist
A
Favor the inactive receptors which effectively makes them stronger forms of an antagonist because they lower the constitutive form of the receptor
17
Q
Define stereoisomerism
A
Same chemical formula, but doesn’t behave the same in the body
Optical isomers (D:L; R:S) - applies to more than half the body
18
Q
Define physiologic antagonist
A
two different drugs bind to different receptors and have opposite effects
Ex: epi binding to beta receptors and increasing HR, while acetylcholine binds to muscarinic receptors and decreases HR
19
Q
Differentiate between competitive inhibitor and allosteric inhibitor
A
Competitive inhibitor: a drug that binds to the same active site as the agonist, competing for that binding site
Allosteric inhibitor: binds to a different site on the receptor, preventing the agonist from binding and eliciting a response, even at high agonist concentrations (can’t be surmounted)
20
Q
What 4 things make up pharmacokinetics?
A
Absorption, distribution, metabolism, elimination
21
Q
How does the Henderson-Hasselbach equation apply in pharm?
A
In practice, pKa is pH at which ionized and un-
ionized concentrations are equal
If pH < pKa; favors protonated form
If pH > pKa; favors unprotonated form
22
Q
How do you solve for the therapeutic ratio?
A
TD50 / ED50
23
Q
What is a dose-response curve?
A
A graph illustrating different pharmacologic potencies and different maximal efficacies
24
Q
What is the goal of rational dosing?
A
To achieve desired beneficial effect
with minimal adverse effects
25
Bond strength is indirectly proportional to ____
Specificity
26
Flux is directly proportional to _______
Concentration
27
Kd is indirectly proportional to ________
Drug binding affinity
28
Drug safety is directly proportional to the _______
Therapeutic index (TI)
29
Volume of distribution (Vd) is directly proportional to the _____
Concentration of a drug outside of the systemic circulation
30
Define volume of distribution
The space available in the body to contain the drug
31
Define clearance
The ability of the body to eliminate the drug
32
Define rate of elimination
The rate at which the drug is eliminate from the body
33
Define half-life
The time it takes for the drug concentration to decrease by 50%
34
Define steady-state dosing, maintenance, and loading dose
Steady state: administering just enough to replace how much the body is eliminating per hr
Maintenance: maintain steady state of a drug by giving enough to replace eliminated drug
Loading dose: used when needing to reach steady state quickly
35
What are the parameters affecting passive diffusion?
Molecular Weight
pKa
Lipid solubility
Plasma protein binding
36
What are the 4 basic mechanisms of transmembrane signaling?
1. Direct crossing to intercellular receptor (lipid
soluble)
2. Enzymatic action mediated by ligand binding (Tyrosine kinase activated receptors)
3. Ligand gated ion channel
4. G protein receptor
37
Explain ligand-gated ion channels
Ligand gates ion channels open in response to the binding of a specific ligand
38
Explain GPCR structure
Receptor:
Seven transmembrane spanning domains, with an extracellular ligand-binding site (amino terminal) and an intracellular G protein-binding site (carboxy terminal). Several downstream effects possible
G-Proteins
- Trimeric: alpha, beta, gamma
- GDP (inactive) → GTP (active)
39
How many families/genes do drug efflux transporters have?
Seven families (A-G), over 50 genes
40
Define allosteric
The drug binds to a different site on the receptor (away from the active site)
41
Define orthosteric
The drug binds directly the the active site
42
Differentiate how a full agonist, partial agonist, antagonist, and inverse agonist would look on a graph
- Full agonist has the max response
- Partial agonist is slightly above constitutive activity, but below full agonist
- Antagonist is equal to constitutive activity
- Inverse agonist is below constitutive activity
*See page 6 of review for reference*
43
What is permeation? What are the 4 different types?
Ways to get the drug from outside the body to the inside of the body where it will eventually work
- Aqeuous
- Lipid
- Endo/exocytosis
- Special carriers
44
What is aqueous diffusion?
Water soluble drugs can cross membranes
45
What is lipid diffusion?
Lipid soluble drugs can cross membranes (steroid nuclei drugs)
46
What are special carriers?
Something that will bind to a large molecule, bring it into the cell and oftentimes may stay in the cell or then pushed outside of the cell
47
What is endocytosis?
Membrane engulfs drug, brings it in and spits it out the other side; usually due to clathrin coated pits in receptors that bind that drug and bring it in
This is an important mechanism for very large drugs to get across impermeable membranes
48
What is exocytosis?
Merging of the vesicle with the membrane
49
What are examples of aqueous components in aqueous diffusion?
Blood, ECF, ICF
50
What are things that can't cross the membrane through aqueous diffusion?
Highly charge molecules: Will interact with the cell surface and won't be able to cross the cell membrane
Bound to large proteins (carriers): can't cross the barrier while bound to large proteins
51
Potency is measured by ____
EC50 (effective concentration fr 50% of the maximum effect)
52
A drug with a lower EC50 is considered more _____
Potent
53
List the components of the blood-brain barrier
Vascular endothelium with tight junctions, astrocytes, pericytes
These constrict the entry of most drugs in the brain
54
Describe drug biotransformation
Chemical modifications that a drug undergoes in the body, typically to make it more water-soluble and easier to excrete
55
Some metabolites become ____ after biotransformation
Active
56
Major phase 1 metabolic reactions include (4) _____ and are primarily catalyzed by _____
Oxidation, reduction, dehydrogenation, hydrolysis
Cytochrome P450
57
If a drug induces a metabolic enzyme it will ______ the metabolism and clearance of other drugs that are substrates of that enzyme
Increase
This potentially reduces efficacy
58
If a drug inhibits a metabolic enzyme, it will ______ the metabolism and clearance of other drugs that are substrates of that enzyme
Decrease
This potentially increases toxicity
59
What can induction of a metabolic enzyme do?
Enhance synthesis, inhibit degradation
60
What can inhibition of a metabolic enzyme do?
- Decrease or irreversible inhibit P450
- Competitive inhibition by co-administering drugs metabolized by the same P450
61
What are potential results of induction of p450?
- Decreased drug effect: if metabolism deactivates the drug
- Increased drug effect: if metabolism activates the drug
62
Define agonist mimic
Doesn't bind to the active site, but can still elicit a response as if they did (cocaine, meth)
63
Differentiate between competitive and non-competitive antagonist
Competitive: bind and inhibit agonist response; can be countered by increasing amounts of agonist (surmountable)
Non-competitive: irreversible and insurmountable
64
What is an example of an organic compound?
Carbohydrate, lipid, protein, nucleic acids
65
What is an example of an inorganic compound?
Lithium, iron, hydrogen, oxygen
66
What are the receptor interactions?
Appropriate size, electrical charge, shape, composition
67
What is Bmax?
The maximum number of receptors available for the drug to bind to
68
What is EMax?
The maximum response or effect that can be achieved by the drug
69
What is Kd?
Drug concentration at which 50% of the receptors are occupied
70
What is TD50?
The point where we see 50% of toxic side effects
71
What is important about a dose-response curve in regards to therapeutic index?
The distance in between the ED50 line and LD50 line is the therapeutic index
72
An agonist + a noncompetitive antagonist will _______ the agonist effect
Decrease
73
On a dose-response curve, the higher the response, the _____ efficacious a drug is
More
74
Define target concentration
The desired concentration of the drug in the body to achieve the desired effect
75
Define bioavailability
The fraction of the administered dose that reaches the systemic circulation
76
A high volume of distribution (Vd) means the drug is distributed to the tissues ___________
Outside of the blood
77
A high clearance means the drug is eliminated from the body _________
More rapidly
78
Differentiate between first order and zero order elimination
First order: clearance is constant, rate of elimination varies with concentration
Zero order: rate of elimination is constant, clearance varies with concentration
79
First-order elimination
Occurs with most drugs
80
Zero-order elimination
Occurs when the body's ability to eliminate a drug has reached it's maximum capability
As the dose and drug concentration increase, the amount eliminated per hr does not
81
What is a racemic mixture?
Refers to a combination of optical isomers
Remember R-ketamine and S-ketamine, where S-ketamine is four times more potent than R-ketamine but has increased risk of dissociative effects and hallucinations.
82
What are the 4 main causes of drug variation?
Genetic factors
Physiologic factors (age, sex)
Environmental factors (diet, smoking)
Pharmacokinetic factors (ADME)
83
Describe the cell signaling process
1. signaling molecules (drug, endogenous ligand) binds to the receptor
2. the receptor undergoes a confirmational change
3. activation of signal transduction proteins (G proteins, kinases)
4. Generation of second messengers
5. Activation effector proteins that elicit the cellular response
84
Phosphorylation cascade
Inactive Protein is activated by a drug or endogenous ligand → Kinase 1 (active) → Kinase 2 (active) possibly 2 or more kinases→ Kinase 3 (active) possibly more than the previous number of activated kinases→ Eventually reaches effector protein (active response)
85
Describe RTK structure
Extracellular ligand-binding domain, a single transmembrane domain, and an intracellular tyrosine kinase domain.
86
What is an example of a ligand gated ion channel?
Nicotinic ACh receptor; the receptor opens when ACh binds to it
87
Process of a ligand gated ion channel
1. The signal molecule binds to the receptor
2. Surrounding ions go through the channel and elicit a response
88
Explain the mechanism of GPCR signaling
1. Ligand binds to the GPCR, causing a conformational change.
2. The conformational change activates the associated G protein.
3. The activated G protein dissociates into its α and βγ subunits.
4. The Gα subunit releases its bond to GDP and binds with GTP which then activates an effector protein (e.g., adenylyl cyclase).
5. The effector protein generates second messengers (e.g., cAMP, IP3).
6. The second messengers initiate downstream signaling cascades.
89
What do second messengers do?
Amplify and propagate the signal initiated by the first messenger (drug, ligand)
90
What is desensitization?
The process where the cell reduces its responsiveness to a stimulus overtime
91
What is a voltage gated ion channel?
Ion channels that open and close in response to changes in the membrane potential
92
Define the generic pathway of CYP450 metabolism
The generic pathway of CYP450 metabolism involves the drug binding to the enzyme, followed by a series of oxidation and reduction reactions followed by dehydrogenation, and then release of the metabolite via hydrolysis.
93
Define the role of drug efflux transporters
They actively pump drugs out of cells, reducing intracellular drug concentrations. This can contribute to drug resistance.
Ex: ATP-binding cassette (ABC)
94
What are the major drug efflux transporters?
ABCB1: broadest substrate specificity; wide distribution and are critical to maintenance of the blood brain barrier
ABCC: antineoplastics
ABCG2: breast cancer resistance protein; also an efflux transporter of folate
95
What is the difference in inotropic and metabotropic ion channels?
- Ionotropic ion channels directly allow the passage of ions across the membrane.
- Metabotropic ion channels indirectly regulate ion movement through second messenger signaling. (E.g. GPCR activates cAMP which opens an ion channel)
96
What are common examples of second messengers
cAMP
IP3 (Inositol triphosphate)
Diacylglycerol
Calcium
cGMP
97
Describe the structure of a neuron
A cell with a nucleus with dendrites (fingers on the outside), connected to an axon. At the end of the axon, there is a telodendria (looks like little fingers at the end). Telondendria are also known as synaptic boutons
*Refer page 24 in the review*
98
Neurons send action potentials/signals from the __________ to the _________
Neuron cell body
Telondendria
99
Where are neurotransmitters stored?
Telodendria
100
Where does the information coming into the neuron come in?
Dendrites
101
Describe the neuron process:
- Once information is in dendrites it can send a “go” or “stop” signal to nucleus of neuron to either activate or suppress activation of neuron
- Decision in cell body can activate the axon hillock and this will generate action potential
- Action potential can go faster if myelin sheath is present; this is known as saltatory conduction.
- Action potential will reach the telodendria (capped with synaptic boutons)
- Synaptic boutons release neurotransmitter into the synapse and the neurotransmitter binds to receptors on the postsynaptic cell
- Neurotransmitters are stored in synaptic terminal/boutons but they are actually made in the neuron itself
102
What is a synapse?
Gap between the neuron and the cell
103
What are the types of synapses?
Chemical: release neurotransmitters into the synapse (ACh, GABA)
Electrical: pass electrical current from one cell to the other through gap junctions (commonly in the heart)
104
What are the 6 main classes of neurotransmitters?
- Esters (ACh): cholinergic
- Monoamines (norepinephrine, serotonin, dopamine, many catecholamines): adrenergic
- Amino acids (glutamate, GABA)
- Purines (adenosine, ATP)
- Peptides (substance P, endorphins)
- Inorganic gases (Nitric oxide)
105
Why are inorganic gasses considered a neurotransmitter?
It is released by effector cell and has effect on postsynaptic cell
106
Afferent is going ____ the CNS; Efferent is going _____ from CNS
Towards
Away
107
What are the efferent divisions?
Somatic nervous system: controls skeletal muscle; conscious control
Autonomic nervous system: includes parasympathetic and sympathetic; no conscious control over
108
The autonomic nervous system is seperated into:
Parasympathetic, sympathetic, and enteric
109
Neuron cell body clusters in the CNS are called _____
Nuclei
110
Neuron cell body clusters in the PNS are called ________
ganglia
111
Describe the sympathetic nervous system
Known for fight or flight (increasing HR, bronchiole dilation, shunt blood to skeletal muscles and away from GI)
Affects a lot of our CV system. Widespread impact, reaches organs and tissues
112
Describe the parasympathetic nervous system
Rest and digest system
This brings you back down to normal. It conserves energy and shunts blood to GI and endocrine system. Innervates only specific visceral structures, effects are shorter lived
113
The gut has its own nervous system called
Enteric nervous system: associated with causing "gut feelings"
114
Where do the fibers origin in the sympathetic nervous system?
Thoracolumbar region of the spinal cord
115
Where do the fibers origin in the parasympathetic nervous system?
Brain and sacral spinal card
116
What is the length of fibers in the sympathetic nervous system?
short preganglionic and long postganglionic
117
What is the length of fibers in the parasympathetic nervous system?
Long preganglionic and short postganglionic
118
Where is the location of the ganglia in the sympathetic nervous system?
Close to the spinal cord
119
Where is the location of the ganglia in the parasympathetic nervous system?
In the visceral effector organs
120
What is the difference in receptors in the SNS and PNS?
SNS: beta and alpha receptors - GPCR
PNS: muscarinic (GPCR) and nicotinic receptors (ion channel)
121
How does the alpha and beta receptor work in the SNS?
SA node is primary node that sets the pace for the heart – if we release norepinephrine or epinephrine, it binds to beta 1 and 2 receptors and increases heart rate and heart contractility
122
Where does the PNS primarily work through?
Vagus nerve: PNS stimulation is not constant, it returns to homeostasis and shuts off
123
Define sympathomimetics
drugs that mimic the sympathetic nervous system (mimic fight or flight)
124
Define cholinomimetic (aka parasympathomimetics)
drugs that mimic acetylcholine
125
Define parasympatholytics (aka antimuscarinics/parasympathoplegic)
Drugs that block parasympathetic nervous system
126
Define sympatholytics/Sympathoplegic (alpha or beta blockers/sympathoplegic)
drugs that block sympathetic nervous system response
127
List the ANS receptors
Cholinergic (receptors that bind to and are activated by ACh)
Adrenergic (respond to norepinephrine and epi)
128
What are the adrenergic receptors divided into?
Alpha 1/Alpha2
Beta 1-3
Dopamine (1-5)
129
What does alpha 1 do?
activates Gq → GDP to GTP → activates phospholipase C → activates IP3 and DAG (second messengers)
130
What does alpha 2 do?
activates Gi → inhibits adenylyl cyclase → inhibits cAMP
131
What does beta 1-3 do?
activates Gs → stimulates adenylyl cyclase → produce cAMP
132
What does IP3 do after it's activated?
Goes to sarcoplasmic reticulum where calcium is produced in the cell (binds to calcium channels) → Calcium is mobilized into the cell → activates protein kinase → MLCK activated → interacts with actin to contract the muscle cell
133
What does DAG do after it's activated?
activates protein kinase C: this is something that inhibits myosin light-chain phosphatase → MLCK doesn't get stripped up the phosphate
134
When you think of beta 1, think of the _____
heart
135
What is the pathway for beta 1 (and beta 2)?
GDP to GTP → stimulates adenyl cyclase → ATP to cAMP → activates protein kinase A → (2 effects) 1. More calcium gets in from the outside 2. Protein kinase A is going to stimulate calcium release from sarcoplasmic reticulum
136
In the heart, beta 2 = ______. In the periphery, beta 2 = _________
Contraction
Relaxation
137
How does beta 2 work in the periphery?
Increases in cAMP → inhibit myosin light-chain kinase (MLCK is going to phosphorylate myosin and make it so that it can interact with actin in a form of contraction.) → relaxation
138
What are the cholinergic receptors divided into?
Nicotinic and muscarinic (1-5)
139
Which muscarinic receptors are stimulatory?
1, 3, 5
140
What will the muscarinic Gq activate?
Gq activates phospholipase activation. → increase IP3 and DAG
141
Which muscarinic receptors are inhibitory?
2 and 4
142
What does muscarinic Gi inhibit?
Adenylyl cyclase
143
Where can our cholinergic nicotine receptors be?
Ganglionic, skeletal muscle, neuronal CNS
144
What is different about nicotinic receptors vs muscarinic receptors?
Muscarinic receptors are GPCRs, nicotinic are ion channels
145
Where are the muscarinic receptor subtypes found?
Pacing centers of the heart
Smooth muscle
Nerves
Glands
Endothelium
146
Where are our dopamine receptors?
Most are in the brain, but there are some in the CV system and smooth muscle in the kidney
147
Effects of alpha 1 (sympathetic)
Smooth blood vessels: contract
GI Sphincter smooth muscle: contract
Kidney/urinary sphincter: contract
Liver: glycogenolysis
*reference page 29*
148
Effects of alpha 2 (sympathetic)
GI tract wall smooth muscle: relax
*reference pg 29*
149
Effects of beta 1 (sympathetic)
SA node: accelerates
Contractility: increases
Kidney: renin release
*reference pg 29*
150
Effects of beta 2 (sympathetic)
SA node: accelerates
Contractility: increases
Skeletal blood vessels: relax
Bronchiolar smooth muscle: relax
GI tract wall smooth muscle: relax
Bladder: relax
Liver: glycogenolysis
*reference pg 29*
151
Effects of M2 (parasympathetic)
SA node: decelerates
Contractility: decreases
152
Effects of M3 (parasympathetic)
Smooth blood vessels: relax
Bronchiolar smooth muscle: contract
GI wall smooth muscle: contract
GI spinchter smooth muscle: relax
GI secretions: increase
Bladder: contract
Urinary spinchter: relax
153
What is the autonomic feedback loop?
1. Baroreceptors sense increased pressure and send it to the vasomotor center
2. If MAP is high, it will send to PNS and decrease CO and HR
3. If MAP is too low, it will send to SNS → sends norepi which binds to beta 1 to increase CO; norepi will also bind to alpha to increase BP
4. If MAP is low, SNS will also increase HR, contractility, and venous tone; so works on chronotropic and inotropic
154
What is the hormonal feedback loop?
1. MAP low → kidney sees this (juxtaglomerular apparatus) → release renin → changes angiotensinogen to angiotensin (1,2) → aldosterone → constrict blood vessels, take up more water, produce less urine
155
What are the direct acting adrenergic agonists?
Albuterol
Clonidine
Dobutamine
Dopamine
Epi
Isoproterenol
Norepi
156
What are the indirect acting adrenergic agonists?
Amphetamines
157
What is a direct and indirect acting adrenergic agonist?
Ephedrine
158
What organ system to beta receptors determine direct effects?
Heart
159
What does stimulation of beta receptors in the heart do?
Increased CO
Decreased peripheral resistance
160
How do you solve for CO?
SV (70ml/beat) X HR (75 beat/min) = CO (ml/min)
This would equal 5250 ml/min
161
What are examples of catecholamines?
Epi
Norepi
Isoproterenol
Dopamine
Dobutamine
162
What receptors does epi work on?
Alpha 1 & 2, Beta 1 & 2
163
What is the structure of a catecholamine?
Catechol group and amine group
164
What receptors does norepinephrine work on?
Alpha 1 & 2, Beta 1
165
What receptors does isoproterenol work on?
Beta 1 & 2
166
What receptors does dopamine work on?
D 1-5; higher doses alpha 1 and beta 1
167
What receptor does dobutamine work on?
Beta 1
168
When would you use an adrenoceptor antagonist as treatment?
HTN related to phenochromocytoma
169
What are examples of reversible adrenoceptor antagonist drugs?
Phentolamine, tolazoline, prazosin, labetalol, propanolol, metoprolol, atenolol, terazoin, doxazosin
170
What is an example of an irreversible adrenoceptor antagonist? Why is it irreversible?
Phenoxybenzamine
It forms a covalent bond; requires new receptors
171
What do beta antagonists do in the heart?
Negative inotropic
Negative chronotropic
172
What do beta antagonists do in the blood vessels?
Opposes B2 mediated vasodilation
Acute: increased peripheral resistance
Chronic: decreased peripheral resistance (mechanism unclear)
173
What are examples of beta antagonist drugs?
Propanolol
Metoprolol
Atenolol
Esmolol
174
Where does propranolol work?
Beta 1 and 2
175
Where does metoprolol and atenolol work?
Mainly B1 selectivity
176
What 2 diseases is it safer to use metoprolol or atenolol when picking a beta blocker?
COPD, diabetes
177
Esmolol is _________ acting
ultra short
178
What are cholinomimetics (direct acting) mode of action?
- Bind to and active M or N receptors
- Esters of choline, alkaloids
179
What are cholinomimetics (indirect acting) mode of action?
Inhibit hydrolysis of ACh
- inhibit action of acetylcholinesterase
- prolongs effects of ACh released at junction
180
What are cholinomimetic effects on the eye?
- muscarinic agonists: miosis
- increase intracocular drainage
181
What are cholinomimetic effects on the CV system?
- reduction in peripheral vascular resistance
- vasodilation (reduction in BP; reflex tachycardia)
In large doses, can cause bradycardia
182
What are examples of indirect acting cholinomimetics?
Simple alcohols
- quaternary ammonium group (ex: edrophonium)
Carbonic acid esters of alcohols
- quaternary or tertiary ammonium group (ex: carbamates and neostigmine)
Organic derivatives of phosphoric acid
- Ex: organophosphate
183
What are the major therapeutic uses of indirect cholinomimetics?
Disease of the eye
GI and urinary tracts
Neuromuscular junction (myasthenia gravis)
- autoimmune against ACh receptor
Atropine OD
184
S/S of organophosphate exposure? What is the treatment?
SLUDGE-M
Tx: atropine, pralidoxime
185
What is edrophonium used for?
Diagnostic test for MG
186
What does SLUDGE-M stand for?
Salivation
Lacrimation
Urination
Defecation
GI motility
Emesis
Miosis (constriction of the pupil)
187
S/S of muscarinic excess? What can cause this, and what is the treatment?
SLUDGE-M
Caused by poisonous mushrooms
Tx: atropine
188
S/S of atropine OD? What can cause this, and what is the treatment?
BRAND
Caused by belladona
Tx: physostigmine
189
What does BRAND stand for?
Blind, red, absent bowel sounds, nuts, dry
190
What type of receptors are all adrenergic receptors?
GPCR
191
In angina classification, what is the difference in stable, unstable, and variant?
Stable: angina of effort (classic)
Unstable: acute coronary syndrome
Variant: Prinzmetal, angina inversa
192
What are the causes of stable, unstable, and variant angina?
Stable: plaque
Unstable: plaque
Variant: hyperreactive vessels
193
What are the precipitating factors of stable, unstable, and variant angina?
Stable: exercise, stress
Unstable: resting
Variant: resting/vasospasm
194
Stable angina is ______ and may be relieved by ______
Brief
Rest
195
Unstable angina is an __________
Emergency
196
Variant angina is considered ______ with only _______ of anginas being this type
Rare
2%
197
What are NO, nitrates, nitrites actions on vascular smooth muscle?
Activate GC, increase cGMP: relaxation
Good: increase venous capacitance, decrease ventricular preload, decrease heart size, decrease CO
Bad: orthostatic hypotension, syncope, HA, reflex tachycardia
198
What are beta-2 agonists actions on vascular smooth muscle?
GPCR, cAMP, relaxation (mainly respiratory)
199
What are beta blockers actions on vascular smooth muscle?
Decrease demand (HR)
200
What are calcium channel blockers actions on vascular smooth muscle?
Less total calcium: relaxation
201
What is sildenafil actions on vascular smooth muscle?
Block PDE5, increase cGMP: relaxation
202
Describe the pathway of blood vessel contraction in periphery
*Involves an influx of calcium*
1. Calcium is released from SR and binds to calmodulin
2. Calcium calmodulin activates MLCK (MLCK is responsible for adding phosphate group to myosin light chain)
3. Phosphorylated myosin can interact with actin, causing contraction
203
Pathway of relaxation in the periphery
1. Beta 2 agonists increase cAMP production
2. cAMP deactivates MLCK
3. Increase in cGMP will dephosphorylate MLCK (cGMP can be increased by NO)
4. This will cause relaxation
204
What is the other way that relaxation in the periphery can occur (in terms of guanylyl cyclase)?
1. NO activates guanylyl cyclase
2. GC turns GTP into cCMP
3. gCMP desphosphorylates MLCK, causing relaxation
205
What type of drug is sildenafil, and what is its MOA?
PDE inhibitor
Inhibits breakdown of cAMP and cGMP by blocking phosphodiesterase
Postive inotropic effects
206
What type of channels do calcium channel blockers work on?
L-type in the vascular smooth muscle and heart
Relaxation:
- some effects on GI, GU, uterine
Long lasting smooth muscle relaxation, reduce BP
207
What do CCB do in the heart?
Decrease contractility
Decrease SA node pacemaker rate
Decrease AV node conduction velocity
208
When it comes to selectivity, what are the two main types of CCB and what is their focus? *sorry I know this is worded weird*
Dihydropyridines: more peripheral vasculature
Verapamil and Diltiazem: more cardiac
209
What is the toxicity associated with CCB?
Serious cardiac suppression (rare)
Bradycardia
AV block
CHF
210
Small facts about beta blockers
- not vasodilators
- used in angina of effort and silent (ambulatory) ischemia
211
Beneficial effects of beta blockers
Decrease oxygen demand
- decrease HR
- decrease BP
- decrease contractility
212
What are the 4 anatomical control sites that antihypertensives work on?
- diuretics: deplete sodium
- sympathoplegics: decrease PVR and CO
- direct vasodilators: relax vascular smooth muscle
- anti-angiotensins: block activity or production
Antihypertensives can act on 1 or more of these
213
What is the hydraulic equation?
BP = CO X PVR
214
Cardiac output is a function of:
stroke volume
heart rate
venous capacitance (preload)
215
What drugs are CNS sympathoplegics?
methyldopa
clonidine
216
What do CNS sympathoplegics do? (clonidine and methyldopa)
Primary antihypertensive activity due to alpha agonist activity in the brainstem; decreases sympathetic stimulation
Bind more tightly to alpha 2 than alpha 1
217
Propanolol MOA and what does it do?
Antagonizes beta 1 and 2 receptors
Lowers BP, decreases CO, inhibits renin
218
What is propanolol toxicity associated with?
Beta blockade
219
What are the alpha 1 adrenoceptor antagonist? How do they work?
Prazosin, terazosin, doxazosin
Block alpha 1 at arterioles and venues
Dilates both resistance and capacitance vessels
BP is more reduced in upright position
220
Vasodilators example
Minoxidil
Hydralazine
Sodium nitroprusside
Fenoldopam
221
What is minoxidil MOA?
Opens K+ channels in smooth muscle
- stabilized potential, less likely to contract
Dilates arteries and arterioles
222
What is hydralazine MOA?
Dilates arterioles (NO production)
223
What is the toxicity associated with hydralazine?
HA, nausea, sweating, flushing
224
What is sodium nitroprusside used for?
HT emergencies, cardiac failure
Dilates arterial and venous vessels
225
MOA of sodium nitroprusside
Relaxes vascular smooth muscle
- breaks won in blood to release NO
- increases intracellular cGMP
226
What is fenolopam used for?
HTN emergencies, post op HTN
Peripheral arteriolar dilator
227
MOA of fenoldopam
Agonist of D1 receptors
228
What does D1 and D5 work on?
Brain, effector tissues, smooth muscle of the renal vascular bed
229
What does D2 work on?
Brain, effector tissues, smooth muscle, presynaptic nerve terminals
230
What does D3 work on?
Brain
231
What does D4 work on?
Brain, CV system
232
What do ACE inhibitors do?
Block ACE, which is what converts angiotensin 1 to angiotensin 2
This causes decreased BP
233
What do ARBS do?
Block angiotensin II so it can't convert to aldosterone
234
What does aldosterone do?
Increased sodium and water retention
235
Definition of heart failure
When the heart fails to meet the metabolic demands of the tissues or not pumping properly (inadequate CO)
236
Causes of HF
Most common: CAD
Chronic BP
Uncontrolled hyperthyroidism
Graves disease
237
How does CAD cause HF?
Coronary artery disease → angina→ MI (death of cardiac myocytes→ cannot proliferate→ scar tissue replaces them making heart pump ineffectively) → scarring/remodeling→ heart failure
238
What are the two types of HF?
Systolic: reduced cardiac function
Diastolic: reduced cardiac filling (peripheral), cardiac hypertrophy
239
Describe systolic HF
Heart is not pumping due to thin heart muscle walls
Decreased CO and EF
240
Describe diastolic HF
Heart muscle is too thick, so it's pumping effectively but unable to pump as much blood because there isn't room
Decreased CO with normal EF
241
What is congestive heart failure?
Increased left ventricle pressure at end diastole
Results in increased pulmonary pressure (pulmonary edema)
242
Pathway of normal cardiac contractility
1. Trigger calcium enters cell
2. binds to channel in SR, release stored calcium
3. Frees actin to interact with myosin
243
What are the 4 factors in cardiac performance?
Preload
Afterload
Contractility
HR
244
Define preload
Measure of stretch, not volume
If there is increased blood volume or venous tone, this will increase preload
245
Define after load
Force that the heart has to pump against
Essentially is our BP: the higher the BP, the higher the after load
246
Define contractility
Contraction of myocytes (inotropy)
247
MOA of digoxin
Inhibits Na/K ATPase pump to maintain normal resting potential
Positive inotrope
248
What is the EC50 and TC50 of digoxin?
EC50: 1 ng/ml
TC50: 2 ng/ml
249
What are the effects of digoxin on other organs?
Affects all excitable tissues d/t inhibition of Na/K pump
- Smooth muscle
- CNS
250
What is an example of PDE inhibitor?
Milrinone
251
What is the crescent shaped node in the right atrium?
SA node / pacemaker
252
What is the rate of contraction at the SA node?
75 beats/min
253
What is the node at the junction of the aria and ventricles?
AV node
254
What is the bundle at the interventricular septum? Another name for this?
Atrioventricular bundle
Bundle of His
255
What are the fibers within the muscle of the ventricular walls?
Purkinje
256
What are the phases of a cardiac action potential?
Phase 4 (straight horizontal line)
Phase 0 (straight vertical line)
Phase 1 (peak at the top)
Phase 2 (horizontal line at the top of the graph)
Phase 3 (downward slanted line)
Phase 4 (straight horizontal line)
*reference pg 73*
257
Explain phase 4 in cardiac action potential
-96 mv
K+ channels close, membrane potential is at resting
258
Explain phase 0 in a cardiac action potential
Fast Na+ channels open, Na+ goes into cell
259
Explain phase 1 of cardiac action potential
K+ and Cl- go out of cell
*Per Schmidt, K+ inward rectifying channels close*
260
Explain phase 2 of cardiac action potential
Ca+ comes into the cell
K+ goes out of the cell
261
Explain phase 3 of cardiac action potential
K+ continues to leave, returning cell to resting membrane potential into phase 4
262
What is an example of a disturbance of impulse conduction?
Heart block/reentry
263
In order for reentry to occur: (3)
- There must be an obstacle (scar tissue)
- Block must be unidirectional
- Conduction time must be long enough to reenter same areas after refractory period
264
What are the 4 classes of antiarrhythmic agents?
Class I: sodium channel blockade
Class II: sympatholytic (alpha and beta adrenergic inhibition)
Class III: prolong action potential duration (other mechanisms besides sodium channels; K+)
Class IV: block cardiac calcium channel currents (CCB)
265
What are the divisions of class I antiarrhythmics?
A
B
C
266
Describe class 1A of antiarrhythmics
Drug: Quinidine
APD/ERP: lengthens
Dissociation: Intermediate
State Affinity: Activated
267
Describe class 1B of antiarrhythmics
Drug: Lidocaine
APD/ERP: shortens
Dissociation: Fast
State Affinity: inactivated, some activated
268
Describe class 1C of antiarrhythmics
Drug: flecainide
APD/ERP: no effect
Dissociation: slow
State Affinity: inactivated
269
What is the only anti arrhythmic with all 4 class effects?
Amiodarone
270
What is the drug of choice for VT?
Amiodarone
271
What are the initial, symptomatic, and chronic treatments of bradycardia?
Initial: Underlying cause, d/c drugs
Symptomatic: 1st: atropine; 2nd: epi, dopamine
Chronic: pacemaker
272
What are the initial, symptomatic, and chronic treatments of a heart block?
Initial: 1st degree - not usually treated (asymptomatic)
Symptomatic: atropine; transcutaneous pacing
Chronic: pacemaker
273
What are the initial, symptomatic, and chronic treatments of SVT?
Initial: assess cause, r/o atrial flutter
Symptomatic: adenosine
Chronic: CCB, beta blockers
274
What are the initial, symptomatic, and chronic treatments of sinus tach?
Initial: assess cause, r/o wide complex
Symptomatic: adenosine, CCB, cardioversion
Chronic: catheter abrasion; ICD
275
What are the symptomatic and chronic treatments of VT (wide complex)?
Symptomatic: amiodarone, lidocaine, magnesium (torsades)
Chronic: amiodarone, satolol
276
What are the symptomatic and chronic treatments of afib?
Symptomatic: diltiazem, verapamil
Chronic: beta blockers, amiodarone
277
What are the symptomatic and chronic treatments of vfib?
Symptomatic: CPR, defib, epi, vasopressin
Chronic: amio, lido, mag
278
What are the 5 classes of diuretics?
Carbonic anhydrase inhibitors
Loop diuretics
Thiazides
Potassium sparing diuretics
Agents that alter water excretion
279
Where do carbonic anhydrase inhibitors work?
Proximal tubule
280
Explain what goes on the proximal tubule (brief)
NHE3 starts cycle
- countercurrent exchange
- H+ binds to barcyrbonate to form carbonic acid
Carbonic anhydrase
- conversion of carbonic acid into water and CO2
*See pg 80 for picture*
281
Where do loop diuretics work?
Loop of henle
282
Explain what goes on the loop of henle (descending/ascending) *brief
Descending
- water reabsorption (hypertonic medullary interstitium)
Ascending
- impermeable to water
- active transport of NaCl via NKCC2
- K+ excess, diffusion, causes charge in lumen
- charge difference drives out cations
*see pg 81*
283
Where do you have passive diffusion of water?
Descending loop of henle
284
Where do you have active transport of NaCl?
Ascending loop of henle
285
Where in the tubule is impermeable to water?
Ascending loop of henle
286
What can the urinary concentration get up to?
1200
287
T/F: Loop diuretic have no development of acidosis
True
288
Loop diuretics are the most ______ diuretics
Efficacious
289
What are examples of loop diuretics?
Furosemide
Ethacrynic acid
290
MOA of loop diuretics
Inhibit NKCC2 pump
- selectively inhibit NaCL reabsorption in the thick ascending loop
291
Where do thiazides work?
Distal convoluted tubule
292
DCT has a _____ amount of sodium reabsorption
low
293
In the DCT, there is active ______ reabsorption done by ______
Calcium
PTH
294
MOA of thiazides
Block NCC
- inhibit NaCl transporter
- some inhibition of CA activity
295
What is the thiazide prototype?
hydrochlorothiazide
296
What types of cells are present in the collecting tubule?
Principal cells
297
Explain principal cells
Sites for water, Na+, and K+ transport
No cotransporter atypically, only cation channels
Builds a (-) charge in lumen
298
Why do the principal cells build a negative charge in the lumen
- More Na+ in than K+ out
- Drives Cl- out through the paracellular route
*see pg86*
299
Diuretics upstream result in excess ______ in the CT
Sodium
300
Some diuretics block NaCl, which causes _____ to leave via _______ route
Chloride
Paracellular
301
Some diuretics block NaHCo3, which means _____ can't leave through ______ route, and drives _______ depletion
HCO3
Paracellular
Potassium
*see pg 87 for picture*
302
What hormones are working at the CT?
Aldosterone
ADH
303
What does aldosterone do at the CT?
Increase Na+ and water reuptake (ENaC)
Increase blood volume
304
What diuretics are responsible for blocking aldosterone receptors? Example?
Potassium sparing diuretics
Spironolactone
305
What does ADH do at the CT?
- Increases water reabsorption
- Adds preformed AQP2 to apical membrane
- Increases blood volume
- Makes more concentrated urine
306
What is an antagonist to ADH?
Conivaptan
307
What is an example of osmotic diuretics and what is it used for primarily?
Mannitol
Reduce ICP (promote removal of renal toxins)
308
What is mannitol associated toxicity?
- Extracellular volume expansion
- Rapidly distributed to extracellular compartments
Dehydration
- excessive use without water replacement
309
See pg 93 for picture related to allergy
I had no idea how to put a flashcard over this lmao
310
What are the 4 histamine receptors in humans? What type of receptor are they?
H1, H2, H3, H4
GPCR
311
What is H1 responsible for?
bronchoconstriction
vasodilation
312
Antihistamines are what type of drug?
Example?
H1 selective inverse agonist
Diphenhydramine (most useful for type I hypersensitivity)
313
What are common histamine effects?
Nervous system
- Stimulates pain/itching
CV
- lower BP (vasodilation)
- increase HR (reflex tachy)
Sectretory
- stomach: secretes hydrochloric acid (H2)
Lungs
- bronchoconstriction
GI Smooth muscle
- contraction (peristalsis)
314
What is the "wheal and flare"?
Microcirculation smooth muscle
Capillary endothelium
Sensory nerve endings
"triple response"
315
What can h1 receptor antagonists be used for?
Sedation
- resembles antimuscarinic
- sleep aids
- children may have reverse effects
Antinausea/antiemetic
- motion sickness
Antiparkinsonism
- suppress extrapyramidal symptoms
Local anesthesia
- block Na+ channels in excitable membranes
Other
- inhibition of mast cell release
316
H2 receptor agonists are not as _______ as PPIs
effective
317
There is heavy OTC use in ______
H2 receptor antagonists
318
What is another mediator that is liberated from the lung during inflammation? What type of receptor?
Leukotrienes
GPCR
319
Leukotrienes are a ____ reacting substance of anaphylaxis
Slow
320
What do leukotrienes produce?
- bronchospasm
- mucous secretion
- microvascular permeability
- airway edema
321
What are the 3 types of drugs used in asthma?
Bronchodilators
Anti-inflammatory
Leukotriene antagonists
322
What 3 classes are in bronchodilators?
Beta agonist
Antimuscarinics
Methylxanthines
323
What 3 classes are in anti-inflammatory agents?
Steroids
Slow anti-inflammatory drugs
Antibodies
324
What 2 classes are in leukotriene antagonists?
Lipoxygenase inhibitors
Receptor inhibitors
325
What is a toxic effect of sympathomimetics?
Skeletal muscle tremor
326
What drugs are included in sympathomimetics?
Epi (arrythmogenic)
Isoproterenol (arrythmogenic, increased mortality)
Terbutaline
Formoterol
Salmeterol
327
What are the safer options out of the list of sympathomimetics?
Terbutaline
Formoterol
Salmeterol
Beta2 selective, long acting (lipid soluble)
328
List the administration routes for sympathomimetics
Epi: SQ, Inh (320 mcg) - 60-90 min effect
Isoproterenol: Inh (80-120 mcg) - 60-90 min effect
Terbutaline: Inh, IV
Formoterol: Inh
Salmeterol: Inh
329
What are examples of methylxanthines?
Theophylline, theobromine, caffeine
330
Methylxanthines MOA
Several proposed, none established
- inhibits PDE
- inhibits adenosine receptors
- anti-inflammatory action
331
Pharmacodynamics of Methylxanthines
Bronchodilation
CNS stimulation
332
What is the clinical use of muscarinic antagonist?
- effective bronchodilators: block contraction of airway smooth muscle, mucus secretion
- parasympathetic blockage
333
What are examples of muscarinic antagonists?
Atropine: parenteral
Ipratropium bromide: COPD
Tiotropium (24 hr): COPD
334
MOA of leukotriene pathway inhibitors & examples
Inhibit synthesis pathway
- inhibit 5 lipoxygenase (ex: zileuton)
- inhibit binding to the receptor (ex: zafirlukast, montelukast)
335
What type of drug is omalizumab (Xolair)?
Anti-IgE monoclonal antibody
336
MOA of Xolair
Targets portion of IgE that binds to mast cells
- does not activate IgE already on mast cells
- does not provoke degranulation
337
Xolair lessens ________ severity, and decreases ______ requirement and _________
asthma
corticosteroid
hospitalizations
338
List serotonin effects on the body
Nervous system
- melatonin precursor
- vomiting reflex
- pain and itch (similar to histamine)
- chemoreceptor reflex (bradycardia, hypotension)
Respiratory
- facilitate ACh release: constriction
- hyperventilation
Gi
- overproduction (diarrhea)
CV:
- contraction of vascular SM (exception: smooth muscle/heart)
- platelet aggregation
339
What are the serotonin receptors for this class? (1st gen)
5-HT 1A
5-HT 1D/1B
5-HT 2
5-HT 3
340
Explain 5-HT1A receptor, give an example, and uses
Agonist
Example: buspirone
Uses: anxiolytic (GAD, OCD)
341
Explain 5-HT 1D/1B receptor, give an example, and uses
Agonist
Ex: triptans
Uses: Migraine HA
342
What is toxicity associated with triptans?
Recurrence of migraine
Serotonin syndrome (triptans + SSRI, MAOI)
343
Explain 5-HT 2 receptor, give an example, and uses
Antagonist
Ex: phenoxybenzamine
Uses: carcinoid tumors, cyproheptadine (cold induced urticaria)
344
Explain 5-HT 3 receptor, give an example, and uses
Antagonist
Ex: ondansetron
Uses: anti-emetic
345
List the 3 main types of hyperthermic syndromes
Serotonin syndrome
Neuroleptic syndrome
Malignant hyperthermia
346
List common precipitating drugs, clinical presentation, and treatment for serotonin syndrome
Drugs:
SSRI, MAOI, St Johns wort, triptans, tramadol
Presentation:
HTN, tremor, hyperthermia, hyperactive bowel, coma
Tx:
Sedation (benzes), intubation, 5-H2 blocker
347
List common precipitating drugs, clinical presentation, and treatment for neuroleptic malignant syndrome
Drugs:
D-2 blocking antipsychotics
Presentation:
HTN, hyperthermia, acute severe Parkinsonism
Tx:
Diphenhydramine, cooling, benzos if needed
348
List common precipitating drugs, clinical presentation, and treatment for malignant hyperthermia
Drugs:
volatile anesthetics, succs
Presentation:
hyperthermia, HTN, tachycardia, muscle rigidity
Tx:
Dantrolene, cooling
349
What are the 3 main classes of antidepressants?
SSRI (SNRI)
TCA
MAOI
350
All antidepressants carry a black box warning for increased ___________
Suicidal tendencies
351
What is the MOA of SSRI/SNRI & examples
Inhibit SERT
- Prozac, zoloft
Inhibit SERT and NET
- pristique, Cymbalta
352
MOA of TCAs and example
Inhibit SERT, NET, and anticholinergic
- Elavil
353
What are the two main classes of seizures and divisions underneath those?
Focal
- simple partial
- complex partial
- partial seizures secondarily generalized
Generalized
- tonic-clonic (grand mal)
- absence (petit mal)
- tonic
- atonic
- clonic and myoclonic
- infantile spasms
354
What is the emergency treatment for all seizure types?
Benzos
355
What is the drug of choice for focal seizures?
Lamotrigine
356
What drugs can be used for all focal seizures + generalized tonic clonic?
Phenytoin, phenobarbital, carbamazine
357
What is the drug of choice for absence seizures?
Ethosuxamide
358
What drugs can be used for all generalized seizures, except tonic clonic and infantile?
Valproic acid
359
What is the drug of choice for infantile spasms?
Vigabatrin
360
What is the toxicity associated with carbamazepine (tegretol)
diplopia, ataxia, GI, drowsiness
361
What is the toxicity associated with phenobarbital?
Sedation, hepatic enzyme inducer
362
What is the toxicity associated with ethosuximide?
GI, lethargy, hiccup, euphoria
363
Ethosuximide is only available as _______
syrup
364
What is the toxicity associated with valproic acid?
Hepato, GI, sedation, fine tremor, drug displacement
365
What are the plasma levels for phenytoin?
Therapeutic:
10-20 mcg/ml
Free phenytoin:
1-2.5 mcg/ml
Toxic:
30-50 mcg/ml
Lethal:
>100 mcg/ml
366
What is the toxicity associated with phenytoin?
drug displacement
367
Why would you prefer to use a 2nd gen H1 receptor antagonist than a 1st gen?
More systemic effects, less CNS (does not cross BBB)
368
What does thrombogensis do in the blood vessels?
- vasconstriction
- formation of platelet plugs
- regulation of coagulation and fibrinolysis
369
What are the 4 phases of platelets?
1. Adhesion
2. Aggregation
3. Secretion
4. Cross-linking of adjacent platelets
370
Platelet aggregation pathway
1. Damage exposes collagen and von willebrand factor
2. Collagen binds to platelets specifically at the glycoprotein 1-A receptor.
- Von willebrand factor binds to platelets at the glycoprotein 1-B receptor.
3. adenosine(ADP), thromboxane A-2, and serotonin(5 HT) is released
4. Serotonin causes vasoconstriction of smooth muscle on vessels and it binds to serotonin receptors on other platelets which activates those platelets.
4. ADP and thromboxane A2 also bind to additional receptors on other platelets that are going to activate more platelets
5. Once the second platelet is activated it degranulates and releases additional ADP, thromboxane A2 and 5 HT.
It’s a positive feedback mechanism where multiple platelets are going to join together to be cross linked into this network
371
Common pathway steps
1. Factor 10 is activated.
2. Factor 10 activates the inactive form of thrombin (aka prothrombin) to its active form called thrombin.
3. Thrombin increases the release of more thrombin, it activates platelets, and it converts the inactive form of fibrinogen into the active form of fibrin.
4. Fibrin helps platelets aggregate together and it forms a mesh network to trap platelets.
372
Steps in the intrinsic pathway
- Damage to the surface activates factor XII(12)
- XII activates factor XI(11)
- XI activates factor IX(9)
- IX + VIII(8) activates factor X(10)
this starts the common pathway
373
What is the result of DIC?
Generalized blood coagulation
Consumption of factors and platelets
Spontaneous bleeding
374
Cause of DIC
Massive tissue injury
Malignancy
Bacterial sepsis
Abruptio Placentae
375
Treatment of DIC
Plasma transfusions
Underlying cause
10%-50% mortality
376
Pathway for fibrinolysis
Plasminogen → plasmin (active form) → breaks down fibrin into FSP and fibrinogen into degradation products
○ tPA activates plasminogen into plasmin (active form)
○ Urokinase and streptokinase also do this ^^
377
What can we use to keep a clot from breaking down (fibrinolytic inhibitor)? how does it work?
Aminocaproic acid
transischemic acid (TXA)
inhibits the breakdown of plasminogen to plasmin
378
What are examples of fibrinolytics?
Tissue plasminogen activator (t-PA)
Urokinase
Streptokinase
379
What protects clots of lysis?
Aminocaproic acid
380
What does indirect thrombin inhibitors do? What are examples of each?
Enhances antithrombin activity
- unfractionated heparin (HMW)
- LMW heparin
- fondaparinux
381
What does HMW do?
Decreased thrombin and factor Xa
382
What adverse effects can come from HMW? How do you treat?
HIT, bleeding
Protamine sulfate
383
What does LMW do?
Decrease factor Xa
384
What does fondaparinux do?
Decrease factor Xa
385
What does direct thrombin inhibitors do? Give examples of each
Either
Bind to active and sublate recognition sites of thrombin
- Hirudin (from leeches; lepirudin is recombinant)
- Bivalirudin (Angiomax)
Bind only to thrombin active sites
- argatroban
- melagatran
386
What does hirudin target?
Thrombin in clot
387
MOA of warfarin
Inhibits vit. K cycling
388
What is the onset of action of warfarin?
8-12 hour delay
389
The therapeutic range of warfarin is defined by _____. The goal is to reduced _______ activity by _____ of normal
INR
Prothrombin
25%
390
Normal INR
INR target for warfarin
0.8-1.2
2-3
391
How does t-PA work?
Preferentially activates plasminogen that is bound to fibrin
392
What is streptokinase synthesized by?
Streptococci
393
What is urokinase synthesized by? How does it work?
Kidneys
Lyses the thrombus from within
394
What are the different types of platelet inhibition? Examples?
Inhibition TXA2 synthesis : ASA
Blocking ADP : Plavix and ticlid
- reduce platelet aggregation
Blocking GP2&3 : Abiciximab
395
What are different platelet changes that can be seen?
Shape
Granule release
Aggregation
396
Vitamin K is ____ soluble
Fat
397
Where do you get vitamin K from?
Leafy green vegetables
Gut bacteria
398
Vitamin K confers activity on:
Prothrombin
Factors VII, IX, X
399
Vitamin K has a _______ effect
delayed
400
Vitamin K is necessary for ____________
efficient blood coagulation
401
MOA of aminocaproic acid
Completely inhibits plasminogen activation
402
Uses for aminocaproic acid
- adjunctive hemophilia therapy
- bleeding from fibrinolytic therapy
- intracranial aneurysms
- post surgical bleeding
403
What are the two major types of secretory issues in the pancreas?
Exocrine
Endocrine
404
What does the exocrine gland do?
Releases digestive enzymes into the duodenum to help with protein and carb digestion
405
Where is the endocrine gland? What does it consist of?
Smallest portion of the pancreas, in locations called pancreatic islets
Islet of langerhans
406
What does the islet of langerhans consist of? What do these cells release?
Alpha cells: release glucagon and proglucagon
beta cells: release of insulin, proinsulin, C peptide, and amylin
delta cell: releases somatostatin
407
What is the approximate percent of islet mass of alpha and beta cell?
Alpha: 20%
Beta: 75%
408
What is diabetes mellitus? What are the 4 types?
Elevated blood glucose
Type I: insulin dependent
Type II: non-insulin dependent
Type III: other causes (pancreatitis, drug therapy, etc)
Type IV: gestational
409
Function of beta cells
Proform
Activated in granules
410
C peptide has ________ function
no known
411
Insulin secretion pathway
When BG is high, we will get a large influx of glucose through Glut 2 transporters into the beta cell.
That glucose is metabolized via glycolysis to produce ATP
High levels of ATP bind to the potassium channels on the cell surface (inward rectifying K+ channel that maintains the normal membrane polarization).
ATP closes the potassium channels, depolarizing the membrane making us more positive.
This causes VG- CA++ channels to open
Ca++ rushes into cell and increased Ca++ levels bind to the vesicle complex that contains the stored insulin
The vesicle then fuses with the cell membrane and releases insulin into the blood
412
What type of receptor is insulin?
Tyrosine kinase
413
What are the effects of an insulin receptor?
- Membrane translocation of GLUT
- Increased glycogen formation
- Activation of multiple transcription factors
414
What are the 4 types of insulin preparations?
Rapid acting
Short acting
Intermediate acting
Long acting
415
Rapid acting insulin examples
lispro
aspart
glulisine
416
Short acting insulin examples
novolin
humulin
417
Intermediate acting insulin examples
NPH, isophane
418
Long acting insulin examples
glargine
detemir
419
8 classes of oral anti diabetic agents
Biguanides
Insulin secretagogues
Thiazolidinediones
Alpha-glucosidase inhibitor
Incretin-based therapies
Amylin analogs
Bile acid sequestrant
SGLT2 inhibitors
420
MOA of biguanides and example
Block glucose formation in the liver
Metformin
421
MOA of insulin secretagogues and example
K+ channel
Sulfonylureas
422
MOA of thiazolidinediones
PPAR mediated increase in insulin signal
423
Other classes in incretin-based therapies
GLP1 agonist
DPP4 antagonist
424
MOA of amylin analogs
suppress glucagon release
425
MOA of SGLT2 inhibitors and example
Prevent glucose absorption in PCT
Gliflozins
426
Plaque formation is _________
inflammatory
427
What is the cholesterol 3 part synthesis in cells?
- mevalonate from acetyl-coa
- conversion of mevalonate to squalene
- cyclization of squalene to cholesterol
428
Atherogenesis pathway
- excess LDL gets sequestered underneath the intima of the artery
- WBC come in
- differentiate into macrophages (proinflammatory)
- Swallow up LDL
- proinflammatory-> releases things to oxidase LDL
-now oxidized LDL enters blood stream and antibodies are formed against it.
- Macrophage itself can’t break down cholesterol so macrophages build up. Called foam cells
- crystallization of the cholesterol inside of the foam cell makes them rupture
INFLAMMATION= positive feed back
when they all die it forms a calcified plaque
429
4 types of lipoproteins
Chlomicrons
VLDL
LDL
HDL
430
Where are chylomicrons formed? What do they do? Where are they degraded?
Formed in the intestine (dietary)
Carry triglycerides and cholesterol
Degraded by liver
431
Where is VLDL secreted? What is is converted to?
Secreted by liver, travel to peripheral tissues
Converted to LDL
432
What does LDL do? What happens in excess?
Transporter
Excess gets stuck in arteries
433
What does HDL do? Decreased levels are associated with what?
Scavenger of cholesterol from cells
Atherosclerosis
434
Normal total cholesterol
<200
435
Normal LDL
<130
436
Normal HDL (men and women)
>40
>50
437
Normal triglycerides
<120
438
Drug classes for lowering cholesterol
Statins (HMG-CoA reductase inhibitors)
Niacin
Fibrates
Binding resins
Absorption inhibitors
PCSK9 inhibitors
439
MOA of statins
Structural analogs of HMG-CoA reductase
Decrease cellular cholesterol synthesis
Increase LDLR
- scavenge LDL from blood
- major effect on liver
Modest decrease in triglycerides
Small increase in HDL
440
Dosing and uses in statins
Dose range from 10-80 mg
Absorption enhanced by food - at night
Restricted use in children, pregnant, lactating
441
Statin toxicity
Elevated liver enzymes
- increased with liver damage, pts of Asian descent
CK elevations
- muscle pain or weakness
442
What does niacin do? Dosing?
Decreases VLDL, LDL
- reduces VLDL secretion from liver
Increases HDL
Incorporated into NAD
Cutaneous vasodilation
Dosing 2-6 g daily
443
What do fibrates do?
Decrease VLDL, modest decrease in LDL
Increase lipolysis in liver
444
Toxicity in fibrates
*Rare*
GI upset
Arrhythmias
Elevated liver enzymes
Potentiation of coumarin
Myopathy
445
What do bile acid binding resins do? Dosing?
Isolated increases in LDL
Large cation exchange resins (not absorbed)
Bind bile acids - prevent reabsorption
Primary hypercholesterolemia
May increase VLDL
Granular preparations
Dosing: 5 g/day; up to 30 g/day
446
Absorption inhibitor MOA
block NPC1L1 transporter from transporting cholesterol from the bile acid into the body
447
Example of absorption inhibitor
Ezetimibe
448
PCSK9 pathway and example
PCSK9 binds to LDL-r. Goes into clatherin coated pit. Receptor is now marked for destruction by the lysosome.
This leads to a decrease in LDL-r
less cholesterol being taken in d/t limited receptors=more in bloodstream
statin increase PCSK9
Example: Evolocumab
449
MAB- PCSK 9 inhibitors are never given
alone, always with a statin
Lowers LDL by 65% if given with statin
450
side effects of MAB- PCSK 9 inhibitor
Risk of hypocholesterolemia
451
General properties of antimicrobial agents
Selective toxicity
Spectrum of activity
Modes of action
Side effects
Resistance of microorganisms
452
5 modes of action of antibiotics
Inhibition of cell wall synthesis
Disruption of cell membrane function
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
Action as antimetabolites
453
Examples of cell wall inhibition antibiotic drugs
Penicillin, bacitracin, cephalosporin, vancomycin
454
Examples of disruption of cell membrane antibiotics
Polymyxin
455
Examples of protein synthesis inhibitor antibiotics
Tetracycline
Erythromycin
Streptomycin
Chlormphenicol
456
Examples if nucleic acid inhibitors antibiotics
Rifamycin (transcription, mRNA synthesis)
Quinolones (DNA replication, inhibit DNA gyrase)
Metronidazole
457
Examples of antimetabolite antibiotics
Sulfonilamide
Trimethoprim
458
What is the structure of penicillin and cephalosporin? What type of bacteria?
Beta lactam ring
Gram (+) cocci; anaerobes
459
Adverse reactions of penicillins
Hypersensitivity
- most common drug allergy
- can cross react with similar abx
Allergic reactions
- anaphylactic shock (0.05%)
- skin rash (<1%)
- oral lesions
- hemolytic anemia
- interstitial nephritis
460
Cephalosporins are _______ to b-lactamase
More resistant
461
Cephalsporins are a ________ spectrum
broader
462
Uses for cephalosporins
UTI, Staph
Alternative to PCN (less allergy)
463
Vancomycin is resistant to _________
b-lactamase
464
Vancomycin is known as the drug of _______
last resort
465
Vancomycin is an alternative to _________ and can be used for _______
PCN resistant bacteria
MRSA
466
Vancomycin toxicity
10% adverse reactions
Irritating to tissues
Chills/fever
Ototoxicity
Nephrotoxicity
"red neck syndrome"
467
Polymyxins act as _________ and bind to ________
detergents
phospholipids
468
Polymyxins are especially effective against _________ which have an ______ membrane
Gram (-) bacteria
outer
469
Tetracyclines are __________
bacteriostatic
470
Pharmacokinetics of tetracyclines
readily absorbed
widely distributed
471
Tetracyclines have the _____ spectrum of activity of any abx
widest
472
Tetracyclines destroy the normal _________ and often produce severe _______
Intestinal microbiota
GI disorders/bone deposition disorders
473
What is the prototype drug of macrolides? Where does it come from?
Erythromycin
Streptomycin Erythreus
474
What are semi-synthetic derivatives of macrolides?
Clarithromycin (biaxin)
Azithromycin (Zithromax)
475
What spectrum do macrolides work on?
(+), (-), atypicals
476
Quinolones have excellent ______ activity and good _______ activity
gram (-)
gram (+)
477
Types of quinolones and uses
Cipro
levoquin
floxin
Uses: UTI, RTI, bone/join infections, ADR
478
Antimetabolites are structurally similar to ______ and work on _______
PABA
synthesis of folic acid
479
Antimetabolite toxicity
Allergenic
May precipitate in urine
Hematopoetic disturbances
480
Uses of antimetabolites and examples
Pneumocystis, toxoplasmosis
- in conjunction with trimethoprim
- bactrim, septra
481
Unique properties of viruses
Infectious particles
- rather than organisms
Active or inactive
- rather than alive or dead
Obligate intracellular parasites
- cannot multiply unless they invade a specific host cell
- must instruct the genetic and metabolic machinery of the host cell to make and release new viruses
482
Components of viruses (some may or may not have all)
Capsid: protein coating of outer shell
Envelope
Naked virsus
Spikes
483
Uses for antivirals
HSV
Cytomegalovirus
Varicella zoster
Hepatitis B/C
Influenza
HIV
RSV
Covid
484
Acyclovir MOA
missing OH group
herpes can’t tell difference and mistakes it for DGTP and results in chain termination. This blocks nucleic acid synthesis
485
Antiretroviral nucleoside/nucleotide analogs
Zidovudine (Azidothymidine, AZT)
- combined with other virals in highly active antiretroviral therapy (HAART)
- inhibitor of reverse transcriptase
Lamivudine
486
Lamivudine MOA
Inhibits HBV DNA polymerase and HIV reverse transcriptase
487
Antivirals used to treat influenza
Tamiflu
Relenza: powder (used for prevention if exposed)
Xofluza
488
Types of flu are separated by:
Type A and Type B
Hemaglutinin
Neuroaminidase
489
Define tremor
Rhythmic movement around joint
490
Define chorea
Muscle jerks in various areas
491
Define ballismus
WILD, violent abnormal movements
*subtype of chorea
492
Define athetosis
Slow, writhing and twisting movement
493
Define dystonia
Non-movement related abnormal posture
494
Define tics
Single, repetitive movements, especially with the face
495
Define choreathetosis
Chorea + athetosis
Intermittent, regular jerking movements and regularized flowing/twisting movements
496
Dopamine pathway (indirect)
Not enough dopamine → use indirect pathway → stimulates basal ganglia using glutamate → stimulates thalamus → stimulates motor cortex → causes Parkinson's tremors → lose direct pathway → lose fine motor control
497
Dopamine pathway (direct)
Dopamine comes from the pars compacts in the sustantia nigra → striatum → GABA and substance P inhibit the basal ganglia → inhibits the thalamus → inhibits motor cortex
498
Parkinsons presentation:
TRAP (tremor, rigidity, akinesia, postural instability)
Cognitive decline
499
Patho of Parkinsons
Most common genetic predisposition: alpha synuclein gene (SNCA)
- SNCA produces the alpha synuclein protein which controls neurotransmitter release in dopaminergic neurons and the neurons that turn on or off the dopaminergic neurons.
Alpha synuclein
- Found in CNS neurons - specifically in substantia nigra
- Found in Lewy bodies - concentrations of alpha synuclein that conglomerates together
500
Treatments of Parkinsons
Exercise (physical therapy)
Restore dopamine levels
Avoid:
- dopamine receptor antagonists (antipsychotics)
- MPTP: destroys dopaminergic neurons
501
What are drugs can we give to restore dopamine levels?
Levodopa
Dopamine receptor agonist: pramipexole, ropinirole, rotigotine
MAOI: selegiline, rasagiline
COMTi: tolcapone, entacapone
CNS antimuscarinics: control dopaminergic release
Apomorphine: for "off periods", akinesia (ex: amantadine)
502
What are the considerations of levodopa? Side effects?
Only 1%-3% can cross BBB, use with crabidopa
S/S: n/v, depression, hallucination (use primavanserin), dyskinesia, on/off periods
503
What causes Huntington's?
GABA is reduced at the basal ganglia
Reduction in choline acetyltransferase (ChAT)
Excess dopamine
504
Treatments of Huntingtons
Tetrabenzine
- depletes dopamine
Dopamine receptor blockers
- haloperidol
- Genetic counseling, ST/PT/OT
505
What is the cell damage pathway to arachidonic acid?
cell damage
releases eicosanoids (signaling molecule) to release membrane phospholipids
phospholipase uses those to create arachidonic acid.
AA can do the cox or Lox pathway
506
See pg 166 for arachidonic acid pathway
LOX/COX
507
cox1 vs cox2
cox1-constitutive, widespread, converts aa into pg and txa2
“housekeeping” does homeostatic functions so generally don’t want to inhibit
Cox2- stimulus (cytokines) dependent. Facilitates inflammatory response so inhibiting is beneficial.
508
pros and cons to cox 2 specific drugs
pros:
* no impact on plt aggregation
* no GI effects
* no impact on COX 1
- good for arthritis
cons:
* debilitating side effects
* sulfonamide so allergy risk
* black box warning for adverse CV events
509
Does aspirin favor cox 1 or 2? What is the clinical use?
Cox 1
Clinical use:
- widely used, not for severe pain (1200-1500 mg TID)
- rheumatoid arthrities, fever
- clot prevention (81-325 mg/day)
510
Aspirin platelet effect
aspirin binds to serine molecule and prevents aa from getting into the cell
which blocks COX which blocks TXa2 which prevents plt. aggregation and it forms and irreversible block.
plts that are circulating for 8-10 days will be impacted as well as all the plts being produced
This is why you have to stop asa several days before surgery.
511
List other NSAIDS for this class and if they favor cox 1 or 2
Celecoxib: Cox2
Ibuprofen: Cox1 = Cox2
Indomethacin: Cox and Lox
Acetaminophen (not an NSAID, but it was on the table, possible cox2)
512
List use, adverse effects, and other considerations for celecoxib
Use: arthritis
Adverse: CV BB warning
Other: it is a sulfonamide, so high allergy alert
513
List use, adverse effects, and other considerations for ibuprofen
Use: pain, inflammation
Adverse: NSAIDS, agranulocytosis, aplastic anemia
Less GI upset than ASA
514
List use, adverse effects, and other considerations for indomethacin
Use: arthritis, gout, PDA
Adverse: GI (1/3 pts)
515
List use for acetaminophen
Use: pain, fever
516
Acute effect of glucocorticoids
Suppress inflammation
Mobilize energy stores
Improve cognitive function
Salt and water retention
517
Chronic effect of glucocorticoid
Immunosuppression
Diabetes, obesity, muscle wasting
Depression
HTN
518
List examples of drug classes that use glucocortiocid transcription
Annexin-1 (lipocortin-1)
- suppresses phospolipase A2
- inhibit leukocyte response
Secretary leukoprotease inhibitor
IL-10: immunosuppressive enzyme
InH-NFkB
519
List drug examples of glucocorticoid and route of admin
Hydrocortisone, prednisone, dexamethasone
Route: topical, oral, parenteral, injected, inhaled
520
What are DMARDS? What are they used for?
Disease modifying anti-rheumatic drugs
- reduced inflammation
- decreased damage to bones and joints
521
DMARDS are often given in conjunction with ______
NSAIDS
522
Non-biologic DMARDS
methotrexate, cyclophosphamide, cyclosporine
523
Biologic DMARDS
Abatacept (Orencia), rituximab (Rituxan), adaimumab (humira)
524
What are A beta fibers for?
nNon-noxious mechanical stimuli
525
What are A delta fibers for?
Noxious heat, mechanical stimuli (sharp pain, produces initial reflex response)
526
What are C fibers for?
Noxious chemical, heat, and mechanical stimuli (slow, burning pain)
527
Pathway for sensation (brief)
Primary afferent neurons (A beta, delta, C fibers) → dorsal root ganglion → spinal cord (3 different paths) → thalamus
528
What are the 3 main pain pathways?
Spinothalamic: primary pain
Spinoreticular: emotional sense of pain
Spinomesencephalic: gate theory of pain, ends in periqueductal gray matter
529
What does tissue damage release? What receptors?
Bradykinin
B1 (inflammatory)
B2 (constitutive)
530
What does the AA pathway produce?
COX/LOX pathway
Prostaglandins
531
Noxious chemicals work on ______ channel action potentials
sodium
532
Affective sensation
pain in processes in CNS and we want to do something about it
Brain picks 1 of the 3 pain pathways
533
Almost every opioid is going to target the ____ receptor
Mu
534
Gate theory of pain
A fibers can sometimes shut down C fibers since they are technically faster
Why we “rub” an area we just hurt to help control pain
“Gates” in spinal cord allow pain signal through but they can be adjusted to increase or decrease pain sensation
Pain pathway
Small fibers (C) – readily transmit pain through gate
Large fibers (A) – can suppress pain signaling (close gates)
535
Different opioid classifications
Agonists
Partial agonists
Antagonists
536
Receptor specificity in opioids
Mu
- full agonist: morphine/fentanyl
- partial agonist: codeine, oxycodone
antagonist: narcan
Delta
Kappa
537
Pharmacokinetics of opioids
A: well absorbed (IM, SQ, Oral)
D: Highly perfused tissues - accumulation
M:
*morphine: phase II to active forms (M3G, M6G)
*esters (heroin): tissues esterases to morphine
* other: phase I (CYP3A4, CYP2D6)
E: mainly in urine
538
Pharmacodynamics of opioids
MOA:
* bind to receptors in brain and spinal cord
* modulation of pain
*receptor effects
- reduced neurotransmitter release
- hyper polarize postsynaptic neurons
539
What neurotransmitters are reduced by opioids?
glutamate, ACh, NE, serotonin, substance P
540
CNS effects of opioids
Analgesia: sensory/emotional aspects
Euphoria: dysphoria
Sedation
Resp. depression: brainstem
Cough suppression
Miosis (always, used as a marker)
Increased muscle tone: trunk
N/V
Hyperthermia (mu) or hypothermia (kappa)
541
Analgesia is used in ___ and ____ pain; it is not as effect in _____ and ______
severe/constant
sharp/intermittent
542
In terminal illness, analgesia is used in a ____ interval and with ______ release
FIxed
Sustained
543
When analgesia is used in obstetrics, it's important to use __________
Fetal monitoring
544
Other uses for analgesia:
Pulmonary edema
Cough
Diarrhea
Shivering
Anesthesia
*preop (anxiety) or post (pain)
*periop: anesthetic (fentanyl)
*epidural
545
Minimal or no degree of tolerance that develops with opioids
Miosis
Constipation
Convulsions
Antagonist actions
546
Moderate degree of tolerance to opioids
Bradycardia
547
High degree of tolerance with opioids
Analgesia
Euphoria/dysphoria
Mental clouding
Sedation
Respiratory Depression
Antidiuresis
N/V
Cough suppression
548
Cautions with opioids
Drug OD
- use narcan
Head injuries
- opioids may enhance resp. depression (lethal)
Impaired pulm. function
Pregnancy
- fetal dependence
549
What are the classes within strong agonist opioids?
Phenanthrenes
Phenylheptylamines
Phenylpiperidine
550
Phenanthrenes (strong agonist) drugs
Morphine
Dilaudid
Heroin
551
Phenylheptylamines drug and uses
Methadone
Uses: chronic pain (morphine intolerance)
opioid abuse
552
Phenylpiperidine (strong agonist) drugs
Fentanyl: different analogs and routes
Meperidine (demerol)
553
Demerol uses and side effects
Post op shivering (K-opioid receptor)
side effects:
Antimuscarinic effects (tachycardia)
(-) inotrope
Seizures
554
List the classes within moderate agonists of opioids
Phenantheres
Phenylpiperidines
555
Phenanthrenes (moderate agonist) drugs
Codeine
Oxycodone
*these are more effective in combinations*
556
Percocet is a combination of
Oxycodone + acetaminophen
557
Percodan is a combination of
Oxycodone + aspirin
558
Phenylpiperidine (moderate agonist) drugs and uses
Loperamide (imodium) : diarrhea
*low incidence of abuse*
559
Opioid antagonist are a derivative of _______. Examples are___
morphine
Naloxone
Naltrexone
Naloxegol
560
Opioid antagonists complete and dramatically reverse opioid effects in _______. ______ has a short duration and some opioid effects may return
1-3 minutes
Naloxone
561
Opioid antagonist have _____ effect in the absence of an ______
Little
Agonist
562
5 classifications of sedative-hypnotics and examples
Benzos
- diazepam, midazolam
Barbiturates
- phenobarbital
Ethanol and chloral hydrate
Sleep aids
- zolpidem, ramelteon (addition potential)
Anxiolytics
- Buspirone
563
Clinical uses for sedative-hypnotics
Relief of anxiety
Insomnia
Sedation and amnesia before/during medical procedures
Treatment of epilepsy/seziures
Component of balanced anesthesia
Control of ethanol or other sedative-hypnotic withdrawal states
Muscle relaxation in neuromuscular disorders
Diagnostic aids for treatment in psychiatry
564
Describe the Alcohol dehydrogenase pathway (AD)
Ethanol is broken down by alcohol dehydrogenase (ADH) into acetaldehyde.
If we are drinking at moderate levels, acetaldehyde is broken down by aldehyde dehydrogenase → then produced into acetate → acetate can be broken down into lipids/glucose or it can be breathed out
Alcohol dehydrogenase and Acetaldehyde both utilizes NAD (nicotinamide adenine dinucleotide) → NAD is converted into NADH → NADH goes through electron transport chain to make ATP/energy
565
what drug can inhibit alcohol dehydrogenase?
What is the result of this?
Fomepizole
increases our ethanol levels
566
Acetaldehyde is a toxic compound that produces what symptoms?
headaches, N/V
Associate acetaldehyde with hangover symptoms
567
Disulfiram (antabuse) MOA
Who is a target for this drug and why?
inhibits aldehyde dehydrogenase that converts acetaldehyde into acetate (so you’ll have more acetaldehyde in the body)
This can be given to chronic alcoholics. Within minutes of drinking alcohol, they have these hangover symptoms
The goal is to make them feel bad so they stop drinking
568
Describe the Microsomal ethanol-oxidizing system (MEOS) pathway
This pathway produces NADPH as a byproduct, instead of NAD/NADH
These individuals get less calories from alcohol. They tend to be thinner as well (this is because they aren’t having the conversion of NAD → ATP → calories)
This pathway still produces acetaldehyde
569
Which pathway is going to increase in activity with people who have chronic alcohol use?
MEOS
570
What are the treatment options for alcohol withdrawal syndrome and alcohol-use disorders?
Detoxification: Taper sedative to benzodiazepines
Alcohol counseling
Meds:
Naltrexone
Acamprosate
Disulfiram
571
How does Naltrexone work?
Long acting opioid antagonist
Patients must be opioid free before initiating because it could cause acute withdrawal syndrome from opioids
572
How does Acamprosate work?
Deals with the desire for alcohol
GABA channels in CNS decrease over time → patient has withdrawals and does not have normal brain function → acamprosate increases GABA activity
Adjunct therapy, not effective alone
573
Anesthesia can be separated into ____ and _______
Barbituates
Benzos
574
Barbituates examples & pharmacokinetics
Thiopental and methohexital
Very lipid soluble; penetrating brain tissue rapidly
Short duration of action
575
Benzo examples and reversal agent
Diazepam
Lorazepam
Midazolam
Flumazenil
576
Benzos may contribute to a persistent _________
Postanethetic respiratory depression
577
Describe the process from discovering a drug till it gets on the market.
A. In vitro studies-done on the cell to find a lead compound
B. apply for a patent
C. animal testing
D. investigational new drug has to be approved
E. clinical testing in 3 phases
1. is it safe pharmacokinetics 20-100 broke college students healthy
2. does it work on patients? double blind sick people100-200
3. does it work on pts. with the disease? 1000-6000
F. Marketing
4. post marketing surveillance
578
List herbal supplements
Echinacea
Garlic
Ginkgo biloba
St Johns Wort
Ginseng
Milk thistle
Saw Palmetto
Co Q10
Glucosamine
Melatonin
579
Echinacea claims and possible issues
Immune function, inflammation
Issue: GI upset
580
Garlic claims and possible issues
Lower cholesterol, coagulation, cancer, anti-bacterial
Issue: odor (breath, body), coagulation
581
Ginkgo claims
Increased blood flow, memory, dementia
582
St Johns wort claims and possible issues
Depression
Issue: Induce CYP
583
Ginseng claims
Memory, immunity, analgesia
584
Milk thistle claims
Hepatotoxicity
585
Saw Palmetto Claims
BPH
586
Co Q10 claims
Blood pressure, MI
587
Glucosamine claims
Joint health
588
Melatonin claims
Depression, jet lag
589
Traditional treatments of neoplasia
Surgery, radiation, chemo
590
Define Primary, Adjuvant, and Neoadjuvant Chemotherapy
Primary: chemo is primary treament; no surgery or radiation
Neoadjuvant: chemo is used to reduce tumor size prior to and after surgery
Adjuvant: chemo after surgery; reduces resurgence of tumor
591
Toxicity of chemo
*attacks rapidly dividing cells*
- N/V
- bone marrow depression
- alopecia
-abortion
- fetal death
- teratogenicity
- carcinogenicity
- immunosuppression
592
Differentiate the different cell types of cancers
Carcinoma
* epithelial origin; highly replicative; skin, GI tract
Sarcoma
* connective tissue or muscle; slow growing
Leukemia
* "liquid"; cancer of the immune cells in the blood
Lymphoma
* "solid" cancer of the immune cells in lymph nodes
593
Alkylating agents are the ____ and ______ diverse class
largest
most
594
Groups of alkylating agents
Nitrogen Mustards (cyclophosamide, chlorambucil)
Nitrosoureas (can cross BBB)
Alkyl Sulfonate
Platinum Analogs (cisplatin, carboplatin)
595
MOA of cisplatin
enters cell
forms highly reactive platinum complexes
cross links
dna damage
inhibits cell proliferation
596
Cisplatin is ____ bound to plasma proteins and concentrates in the ____
Highly
kidney, intestine, testes
597
Cisplatin _____ penetrates the BBB and is slowly excreted in the _____
Poorly
Urine
598
Uses of cisplatin
Testicular cancer (85%-95% curative)
Ovarian cancer
Other solid tumors (lung, esophagus, gastric)
599
MOA of methotrexate?
dihydrofolate reductase- interferes with DNA and RNA synthesis
600
What are the different actions of methotrexate?
Cytotoxic actions
Immunosuppressive actions
Anti-inflammatory actions
601
How does methotrexate have cytotoxic actions?
- predominant in bone marrow
- ulceration of intestinal mucosa
- crosses placenta, interferes with embryogenesis (fetal death)
602
How does methotrexate have immunosuppressive actions?
Prevents clonal expansion of B and T lymphocytes
603
How does methotrexate have anti-inflammatory actions
Interferes with release of inflammatory cytokines
604
Other antineoplastic drugs
*Just know name and class*
Antimetabolites: 6-MP, 5-FU
Plant based: Vincristine, paclitaxel
Antibiotics: dactinomycin, doxorubicin, bleomycin
Hormonal agents: corticosteroids, tamoxifen, fluvestrant
Miscellaneous: imatinib, trastuzumab, rituximab
605
Explain defense mechanisms of the host
1. Host defenses split into innate and acquired
2. Innate is split into the first and second of defense
3. The first line of defense includes physical barriers, chemical barriers, genetic components to keep microbes from penetrating sterile body compartments
4. The second line of defense includes phagocytosis, inflammation, fever, antimicrobial proteins that comes into play when agents make it past the surface defenses
5. The acquired defense includes the 3rd line of defense
6. The 3rd line of defense includes active (infection) and passive (maternal antibodies), which combines into B and T cells
*see pg 197 for reference*
606
Immune system cytokines
- Interleukins (signal among leukocytes)
- Interferons (antiviral proteins that may act as cytokines)
- Growth factors (proteins that simulate stem cells to divide)
- Tumor necrosis factor (secreted by macrophages and T cells to kill tumor cells and regulate immune responses)
-Chemokines (chemotactic cytokines that signal leukocytes to move
607
Immune response picture *see pg 199*
1. Hyposensitives are split into primary immunodeficiency and secondary immunodeficiency
2. Primary immunodeficiency is split in type I and type II
3. Type 1 is immediate (hay fever, anaphylaxis)
4. Type II is antibody mediated (blood type incompatibilities)
5. Secondary immunodeficiency is split into type III and type IV
6. Type III is immune complex (rheumatoid arthritis, serum sickness)
7. Type IV is cell mediated, cytotoxic (contact dermatitis, graft rejection)
608
Immunodeficiency is split into ____ and ____ , which means _____ and ______
Primary (born with)
Secondary (acquired)
609
Primary immunodeficiency includes:
DiGeorge Syndrome: No thymus (no T cells)
Agammaglobinemia: No B cells (no antibodies)
Severe combined immunodeficiency disorder (SCID): no B or T cells
610
Secondary immunodeficiency inclues
Acquired immune deficiency syndrome
611
Hypersensitive is the _______ of the immune system to innocuous stimuli (AKA as _____)
overreaction
allergy
612
4 types of hypersensitivity
A: anaphylaxis, allergy
C: cytotoxic
I: Immune complex
D: delayed
613
Define autoimmunity
Immune response against normal, healthy tissue
614
Who is more affected by autoimmunity, male or females?
Females
615
What is SLE?
Autoantibodies against DNA
616
What is MS?
Autoantibodies and T cells against neurons and myelin
617
What is MG?
Destruction of ACh receptors
618
Autoimmune disease of thyroid
Hashimoto's
Grave's
619
Autoimmune disease of adrenals
Addison's disease (hypocortisolism)
620
Autoimmune disease of the pancreas
Insulin-dependent diabetes
Cytotoxic T cells attack beta cells (insulin)
621
What are the 5 immunosuppressive agents?
Glucocorticoids
*Suppress immune response, mimic naturally occurring adrenal corticosteroids
Calcineurin inhibitors
* T cell activation pathway
Cytotoxic agents
*Kill rapidly proliferating cells
Immunosuporresive antibodies
* antibodies created in the lab, directing against cell surface antigens
Additional Agents
622
Glucocorticoids interfere with cell cycle of _______
Activated B & T cells
623
Glucocorticoids decrease ______ cells in spleen and lymph nodes
lymphoid
624
Glucocorticoids are used for:
Adrenal insufficiency
Suppression of allergy and inflammatory reactions
Asthma
Transplantation
625
Side effects of glucocorticoids
Immunodeficiency, exogenous Cushing's syndrome
626
Examples of calcineurin inhibitors
Cyclosporine
Tacrolimus
627
What are cyclosporine (calcineurin inhibitor) used for and what are the toxicities?
Uses:
transplantation, GVHD, other autoimmune disorders
Toxicities:
Kidney, BO, hyperglycemia, liver, seziures
628
Tacrolimus can be used topical for
Atopic dermatitis and psoriasis
*Similar uses and toxicities to cyclosporin
629
What are examples of cytoxic agents? MOA?
Azathioprine
MOA:
-Antimetabolite targeting proliferating cells (immunosuppressive, anti-cancer)
-Metabolized by xanthine oxidase to mercaptopurine
- Interferes with purine metabolism
Cyclophosphamide
MOA: acylating agent
- destroys proliferating lympoid/cancer cells
- potent in autoimmune disorders in smaller doses
630
What is azathioprine used for and side effects?
Uses: graft rejection, lupus, Crohn's, MS
Side effect: leukcytopenia caused by bone marrow suppression
631
Immunosuppressive antibody examples
Muromonab, RhoGAM, Adalimumab
632
Additional examples of immunosuppressive agents
Sirolimus
Mycophenylate
Mofetil
Thalidomide derivatives
633
Most commonly used alkylating agent
Cyclophosphamide
634
Monoclonal antibody used as treatment for RH- mothers who give birth to RH+ babies
RhoGAM
635
Describe desensitization
Beta arrestin binds to the OH groups attached to the end of the carboxyl terminal on the 7TM protein and blocks further activity from occurring.
The protein gets "eaten" by the cell via a clathrin pit.
opt 1. drug breaks off of receptor: G-protein gets moved back to the cell surface to be reused.
opt.2 Lysosome merges with the ligand and the lysosome degrades the entire drug&receptor
