Final Exam - Section V and VI Flashcards
What are the mediators released in late stage of asthma? What are their effects?
- Leukotryines – Slow reacting substance, produced by the lung during inflammation during the early phase. Works via GPCR to cause bronchospasms, mucous secretion, microvascular permeability, and airway edema.
- Cytokines – proinflammatory chemical released from T lymphocytes that activate eosinophils and neutrophils.
- Proteases – Released by neutrophils/eosinophils and they break down proteins that hold cells together and can infiltrate into the smooth muscles can cause contraction. This causes “leaky” vessels leading to swelling and airway edema.
What are the effects of histamine in the nervous system? What receptors are involved?
Stimulates pain and itching via H1 and H3 receptors
What are the effects of histamine in the cardiovascular system?
Decreases BP via vasodilation which causes reflexive tachycardia
What are the effects of histamine in the stomach, lungs and GI system?
Stomach - secretion of HCl
Lungs - bronchoconstriction
GI smooth muscle - contraction
Describe the effects seen in the Triple Response? What mediator causes this?
Also called “Wheal and Flare”
* Causes a wheal to form that increases in size with allergens the patient is sensitive to
* Also causes a flare, redness around the wheal, caused by capillary enodthelium inflammation-vasodilation.
* Sensory nerve endings are also activated leading to itchiness
How do H1 antagonists work? What is their indication? Most common drug?
- Antagonize H1 receptors in the smooth muscle, endothelium, and brain - resemble antimuscarincs
- Prevention and treatment of allergic response and motion sickness/nausea
- Supresses extrapyramidal symptoms
- Benadryl
What are the uses for H2 antagonists?
Compare them to PPIs?
What are 2 drugs in this class?
- Treatment for indigestion by inhibition of HCl secretion
- PPI’s are more effective like nexium and omeprazole
- Rantidine (Zantac) and famotidine (Pepcid)
Describe leukotrienes and their effect in asthma
Slow reacting substance, produced by the lung during inflammation during the early phase. Works via GPCR to cause bronchospasms, mucous secretion, microvascular permeability, and airway edema.
What are the major classes of drugs used in the treatment of COPD and asthma?
Green is short acting and blue is long acting
Describe the MOA of beta agonists used in COPD and asthma?
What are some of these drugs?
B2 selective agonists cause relaxation of airway smooth muscle by increasing activity of adenylyl cyclase which incresaes cAMP leading to bronchodilation.
Beta 2 selective: SABA - Albuterol, terbutaline( inh or IV). LABA - salmoterol, formoterol.
Non-selective beta: Epinephrine, isoproterenol (can cause tachycardias and arrythmias, increases mortality)
Describe the MOA of methylxanthines used in COPD and asthma?
What are some of these drugs?
Proposed to inhibit PDE, preventing the breakdown of cAMP and increasing bronchodilation. Causes urination by inhibiting adenosine receptors.
Theophylline - found in tea, very narrow therapeutic index
Caffeine and theobromine
Describe the MOA of antimuscarinics used in COPD and asthma?
What are some of these drugs?
Causes bronchodilation by acetylcholine inhibition.
Atropine - very low dose
Ipratropium bromide (Atrovent) - more selective than atropine, can be comined with B2 agonists for synergistic effect.
Titotropium - primarily used in COPD, lasts the longest ~24 hours
Describe the MOA of Omalizumab (Xolair) used in COPD and asthma?
Blocks binding of IgE to mast cells
Describe the MOA of the 2 types of leukotriene antagonists used in asthma?
What are some of these drugs?
Interrupt leukotriene synthesis pathway
* Zileuton - Inhibits 5-lipoxygenase
* Montelukast (Singulair) - Inhibits leukotriene binding to receptor
What are serotonin’s effects in the nervous system?
- Precursor to melatonin
- Vomiting reflex mediated in the area postrema
- Pain and itch
- Chemoreceptor reflex = bradycardia and hypotension
- Large effect on mood and mood disorders
- Migraines
What is serotonin’s effects in the respiratory system?
- Facilitates ACh release leading to bronchoconstriction
What is serotonin’s effects in the cardiovascular system?
- Contraction of vascular smooth muscle (not heart or skeletal)
- Leads to platelet aggregation
Released initially during bleeding to constrict blood vessels while clotting cascade is starting.
What are the 3 main 5-HT agonist targets and the drugs that affect them?
5-HT1A – Buspirone
5-HT1D/1B - Sumatriptan
What are the 2 main 5-HT antagonsist targets and the drugs in this class?
5-HT2A – Phenoxybenzamine, Cyproheptadine
5-HT3 (only ion channel serotonin receptor)- Ondansetron
What are the 3 hyperthermia disorders?
What causes them?
What are the treatments?
Serotonin syndrome:
1. Caused by excess serotonin from a long list of drugs that increase amount of serotonin at the synapse
2. Treatment is sedation with benzos, paralysis, and intubation/ventilation
Neuroleptic malignant syndrome:
1. Caused by dopamine blocking antipsychotics
2. Treatment is IV benadryl
Malignant hyperthermia
1. Caused the RyR being open for a long time causing muscle rigidity (volatile anesthetics, succinylcholine)
2. Treatment is Dantrolene
List the 4 categories of antidepressant medications in order of treatment severity (low to high)?
- SSRI
- SNRI
- TCA
- MAOI
What is the MOA of TCA? Name a drug in this class?
Inhibits SERT, NET, and some anticholinergic effects
Ex: Amitriptyline (Elavil)
What is the MOA of SSRIs?
What are some drugs in this class?
- Inhibits SERT
- Prozac, Zoloft
What is the MOA of SNRI’s?
List the drugs in this category.
- Inhibits SERT and NET
- Useful for depression and pain disorders
- Pristique and Cymbalta
Describe the MOA and uses of lacosamide (Vimpat)?
- Blocks Na+ channels
- Used for focal seizures
List the drugs of choice for focal seizures, generalized tonic-clonic seizures, absence, myoclonic seizures, infantile spasms, and status epilepticus
- Abscence – ethosuximide
- Focal – carbamazepine (tegretol)
- Generalized tonic-clonic – Phenytoin (dilantin)
- Myoclonic – Valproic acid or clonazepam (klonopin)
- Status epilepticus – IV benzodiazepam
- Infantile spasms - Vigabatrin
Describe the pharmacokinetics and adverse effects of valproic acid?
- Toxicity: GI upset
- Inhibits metabolism of many drugs
- Displaces phenytoin from plasma proteins
Describe albumin binding site competition and relation to phenytoin levels?
- Drugs that are protein bound compete for the same inert binding sites on albumin
- If multiple drugs are competing for the same site, one drug will be displaced and have an increased plasma concetration
- This occurs when valproic acid and phenytoin are given together. Valproic acid will displace the phenytoin bound to albumin, increasing the plasma concentration to potentially fatal levels.
Describe the difference in free and therapeutic doses for phenytoin?
What causes this?
Therapeutic: 10-20 mcg/mL
Free: 1-2.5 mcg/mL
phenytoin is mostly bound to albumin, only about 10% is in the free form
Describe the process of thromobogenesis?
Normal and warfarin INR ranges?
Normal: 0.8-1.2
Warfarin: 2-3
What are the phases of platelet formation?
- Adhesion
- Aggregation
- Secretion
- Cross-linking of adjacent platelets
What does thrombin activate?
Activates: factors V, VIII, XI, XIII, and protein C
Draw the coagulation cascade.
Draw the fibrinolysis pathway, including mediators involved.
- t-PA, urokinase, and streptokinase activates plasminogen to plasmin
- Plasmin will induce breakdown of fibrinogen and fibrin
- Aminocapuric acid - prevents clot breakdown by inhibiting activation of plasminogen
What are the indirect thrombin inhibitors and their MOA?
- Unfractionated heparin: Enhances the activity of antithrombin by 1000X which irreversibly binds thrombin AND factor Xa - most effective
- LMWH: Enhances antithrombin specifically to factor X, not effecting thrombin - less effective
- Fondaparinux: Specific for only enhancing antithrombin- least effective.
What is the MOA of Warfarin?
- MOA: blocks gamma-carboxylation of glutamate residues via inhibition of vitamin K reductase, inhibiting production of factors II, VII, IX, X.
- Blocks REDOX cycle of vitamin K
List the antiplatelet drugs and their MOA?
- Aspirin: COX-1 inhibitor preventing formation of TXA2 preventing platelet aggregation
- Clopidogrel: Irreversably inhibits ADP receptors on platelets
- Abcixamab: inhibits receptors IIb/IIIa preventing cross linking by fibrin
What are the endocrine functions of the pancreas?
- Contain the Islets of Langerhans; the controls centers for blood glucose
- Insulin from beta cella
- Glucagon from alpha cells
Describe the structure of insulin?
A peptide containing the active form:
-alpha and beta chain held together by sulfide bonds
Proform:
-C peptide chain that is cleaved and has no known function. Not found in synthetic insulin
Describe the role of insulin secretagogues to cause insulin release?
- Glucose - transported into beta cells via GLUT2, metabolized to create ATP. ATP closes K+ channels depolarizing the membrane. This causes Ca channels to open allowing Ca to destabilize insulin vesicles, causes exocytosis and insulin release.
- This also caused by amino acids, hormones, fatty acids, incretins, and drugs (B agonists)
This happens constantly (constituitive activity) but increases with glucose levels
Describe the insulin receptor pathway?
- Insulin lasts ~6 mins in the bloodstream
- Binds to insulin RTK, causing dimerization
- The beta subunits are phosphoylated causing activation of insulin response substrates (IRS)
- Main effect is to move the GLUT transporter to the cell surface
Describe the MOA and examples of alpha-glucosidase inhibitors?
MOA: blocks digestion of complex carbohydrates
Drugs: Acarbose
Describe the MOA and of bile acid binding resins?
MOA: bind to bile acids to prevent reabsorption of glucose and cholesterol
Describe the MOA and examples of incretin-based therapies?
GLP-1 agonists MOA: increase action of GLP-1 stimulating insulin release and inhibiting glucagon release.
DPP-4 antagonists MOA: DPP-4 normally inactivates GLP-1, antagonists prevent GLP-1 breakdown.
Drugs: GLP-1: semaglutide. DPP-4: sitagliptin
Describe the MOA and examples of gliflozins?
MOA: Inhibts SGLT2 preventing glucose reabsorption in the PCT
Drugs: -flozins
Describe the process of atherogenesis?
- LDL sequestered in intima of vessels when in excess
- LDL is oxidized inside the cell triggering an immune response
- WBC differentiate into macrophages that swallow the cholesterol
- Cholesterol is not broken down in the body and crystalizes in the foam cell causing it to rupture and become necrotic, triggering more WBC
- This becomes large enough that it becomes plaque and is bulging into the vessel, narrowing it.
This is an immune process that creates endothelial inflammation
How can you determine CAD risk from LDL/HDL ratio?
Average risk is ~ 3.5 for males and females. The higher the ratio the greater the risk.
What is the MOA of statins?
Side effects?
MOA: Decrease cellular cholesterol synthesis by competitively inhibiting HMG-CoA reductase
Side effects: Avoid in pregnancy, Increased liver enzymes, CK elevation causing muscle pain
Describe the MOA of Niacin (Vitamin B3)?
Side effects?
MOA: Reduces VLDL secretion from the liver, increases HDL
Side effects: Flushing, ithcing, dry skin, increased liver enzymes cutaneous vasodilation
Describe the MOA of ezetimibe and side effects?
MOA: Inhibits intesinal absorption of cholesterol by inhibition of NPC1L1
What is the MOA of PCSK9 inhibitors?
Drugs?
Inhibits PCSK9 preventing binding to LDLR causing them to be recycled and the LDL-C to remain in the lysosome. Given with statins bc statins increase PCSK9.
Evolocumab
Describe disruption of the cell membrane and the drugs that work by this mechanism?
- Used primarily in gram (-)
- Creates pores in cell membranes leading to cell death.
- Polymyxin, daptomycin
Describe inhibition of nucleic acid synthesis and the drugs that work by this mechanism?
Inhibit RNA polymerase (Rifamycin)
Quinolones - Inhibit DNA gryrase
Describe inhibition of folic acid synthesis and the drugs that work by this mechanism?
Competively block PABA and preventing folic acid synthesis which prevents DNA/RNA synthesis
Drugs: sulfonamides, trimethoprim
What are the components of a virus and their function?
- Nucleic acids - contains DNA or RNA that will reprogram the host cell
- Capsid – Shell surrounds the nucleic acid.
- Envelope – Usually a modified piece of the host cell membrane.
- Spikes – Found on both naked and enveloped viruses. Project from either the nucleocapsid or envelope and target specific cell protiens within in the host.
What is the MOA of acyclovir?
- Normally the virus will replicate by growing the DNA chain by attaching phosphate groups to the ribose sugar of the DNA substrate.
- Acyclovir looks exactly like the host DNA except that the ribose sugar is missing.
- The virus cannot tell the difference between Acyclovir and endogenous DNA. So, the virus will attempt to use acyclovir to grow the DNA chain but because there is nowhere to attach the next group, the DNA replication cycle is terminated.
Called a “chain terminator”
