Term Test 1 Flashcards
Alendronate and Zoledronate
antiresorptive
bisphosphonates
rapid uptake in bone mineral
long term depot
adverse effect: atypical fractures
Denosumab
Antiresorptive
monoclonal antibody
rapid onset and reversible
anti rank L
Teriparatide (anabolic PTH)
low dose PTH increase osteoblast differentiation
and decrease osteoblast apoptosis
high does increase bone resorption
half life 5 min
excretion renal
USE RESTRICTED to 2 years
Romosozumab
block sclerostin to stimulate Wnts (osteoblast formation)
side effect: hypocalcemia, bone pain, increase heart attack and stroke risk
Pramlintide (amylin analogue)
TREAT TYPE 2 DIABETES
- suppress appetite
- slow gastric emptying
- inhibit glucagon release
Colesevelam
inhibit gluconeogenesis
incretins
Liraglutide
GLP-1 receptor agonist increase insulin (glucose dependent) will not lead to hypoglycemia improve beta cells slow gastric emptying weight loss inhibit glucagon release
Dapagliflozin and Canagliflozin
SGLT2 inhibitors decrease plasma glucose kidney decrease heart failure lower blood pressure diuretic
will lead to mycotic infection
Function of Aldosterone
Retain Na, H2O and Cl
excrete K
Increase blood pressure
11B-HSD2
convert cortisol to cortisone (inactive)
present in aldosterone sensitive tissue
glycyrrhetinic acid inhibit 11B-H2D2 which can lead to high cortisol
Addison’s Autoimmune disease
aldosterone insufficiency (decrease BP)
symptoms: hyperpigmentation salt craving fatigue dizziness nausea and vomiting weight loss
Dexamethasone
long-acting glucocorticoids
injection, oral, topical
treat acute inflammation
treats rheumatoid arthritis
Fludrocortisone
Oral
Mineralocorticoids
Treats addisons disease
Cushing’s disease
excess glucocorticoids
purple striae
muscle atrophy
Pasireotide
somatostatin receptor 5 agonist
inhibit corticotropin (CRH)
inhibit ACTH secretion
less cortisol
treats Cushing’s disease
L-thyroxine
T4
treat hypothyroidism
Liothyronine
T3
more potent than L-thyroxine
treat hypothyroidism
Graves’ Disease
cause hyperthyroidism autoimmune stimulation of TSH receptors bulging eyes heat intolerance increase HR BP GOITER (enlarger thyroid) higher chance in women than men
treat with Methimazole
Methimazole
treat graves disease
treat hyperthyroidism
inhibit thyroid peroxidase
Plan B (Levonorgestrel)
inhibit ovulation, fertilization
use within 72 hours
RU486 (Mifepristone)
only available in US
terminate pregnancy
progesterone antagonist
Use with misoprostol
Ulipristal
progesterone antagonist/partial agonist
delays ovulation
antagonist at endometrium
emergency within 5 days
Premarin
long lasting estrogen
use lower dose
Hormone replacement therapy
decrease menopausal symptoms by 90%
Drosperinone
used in oral contraceptives
anti-mineralocorticoids activity
increase risk of thromboembolic disease
increase risk of hypertension
Stilbenes
estrogen antagonist
Tamoxifen
mixed agonist/antagonist antagonist in breast cancer protective in uterus, bone ENDOXIFEN more potent CYP2D6 metabolized (poor metabolizers)
Aromatase inhibitors
depletes estrogen
adjuvant therapy
5 year use limit
side effect: bone lipids hot flashes
Oral contraceptive formulations
Use a combination of estrogen and progesterone
monophasic: all 21 pills containing the same amount of estrogen and progesterone
biphasic: two different amount of estrogen and progesterone
triphasic three different amount
Which 2 enzyme deactivates PGs?
- Hydroxy prostaglandin dehydrogenase (HPGD1) at C15
2. Carbonyl reductase 1 (CBR1) at C9
4 types of PGE2 receptors
EP receptor: 1,3 = Gq
2,4 = Gs
Rheumatoid Arthritis
autoimmune disease causing destruction and inflammation of join-associated tissue
pain swelling, redness
1st line of treatment, NSAIDS
2nd line glucocorticoids
Mechanistic of action of corticosteroids (dexamethasone)
Prevent PLA2 actions
cant produce prostaglandins from arachidonic acid
binds to glucocorticoids receptors
inactivates NF-KB
enable anti inflammatory transcription
inhibit inflammatory cytokines transcription
Aspirin (ASA)
irreversibly inhibit COX
covalent modification of SER529
blocks AA from entry
COX 2 selectivity
larger pocket in COX2 allow for selectivity
Inhibition of COX
inhibit PGE2 and PGI2 formation
alter arteriosclerotic plaque formation
lead to heart attack or stroke
COX2 inhibition can increase BP and hypertension stroke, heart attack and heart failure
Infliximab, Adalimumab, Golimumab
monoclonal antibody
anti TNF-a
binds to TNF-a instead of receptor
block NF-kB for inflammatory cytokines gene transcription
treats rheumatoid arthritis
Paracetamol (Tylenol)
2 distinct pathways Cox inhibitor 1. acts as reducing agent in peroxidase site of COX 2. conjugates with AA block PG from synthesizing
Alprostadil
PGE1
second line treatment for erectile dysfunction
vasodilator and inhibits platelet aggregation
treat infants with congenital heart disease
Misoprostol
synthetic PGE1
treat peptic ulceration
prevent production of gastric acid
longer half life than Alprostadil (PGE1)
Epoprostenol
PGI2 vasodilator treat pulmonary hypertension prevents platelet aggregation extremely short half-life 3-5 min Iloprost (30min) Treprostinil (4hrs)
Dinoprostone, Dinoprost, Carboprost
PGE2, PGF2a, analogue of PGF2a
carboprost have longest half life
treat postpartum hemorrhage terminate pregnancy (promote uterine contractions)
What cause degranulation?
The ligation of MULTIVALENT antigen by IgE bound to FCeRI cause clustering which promotes degranulation
Actions of mast cell degranulation (histamine)
Swelling and mucus production
Increase blood flow and permeability
Increase peristalsis
vasoconstriction
2 types of histamine receptors
Have a total of 4 subtypes
H1 receptor: Gq/G11 PLC, expression in immune cells (neutrophils, macrophages, dendritic cells)
H2 receptor: Gs, in gastrointestinal cells, antihistamine used in peptic ulcer, GERD
H1 Antihistamine (inverse agonist)
1st generation: contain alkyl amine
2nd generation: contain piperidine (cyclic amine)
1st generation antihistamine can ligate muscarinic, adrenergic, dopaminergic serotonergic
side effects: drowsiness, tachycardia, dilation of pupils, reduction in mucus production
2nd generation: less able to cross BBB and more selective for H1 receptors.
constitutively active (inverse agonist) antihistamine stabilize inactive state
H2 receptor
histamine release by mast cell but can also release by enterochromaffin-like cells (ECL) in the stomach
H+ production in stomach
Parietal, cells export H+ via H+/K+ ATPase
Histamine increase export of H+ through increase cAMP
H+ are produced by CARBONIC ANHYDRASE
Weak base therapy
treat hyperacidity
acts by neutralizing stomach acid via donation of basic anions such as OH and CO3
calcium carbonate
magnesium hydroxide
H2 receptor antagonist (Cimetidine)
decrease gastric secretion
some drugs are inverse agonist
longer acting compared to antacids
less cAMP production less H+ export
Proton pump inhibitors (Omeprazole)
PRODRUGS (require acid to activate)
block H+/K+ ATPase pump at parietal cells
prevents acid secretion
better than H2 histamine blockers because other factors can produce histamine
conserved benzimidazole sulfoxide
Mechanistic of action of PPIs
forms covalent adduct to inhibit ability of pump to export protons
prodrug only activates in acidic environment
proton pump mostly restricted to parietal cells so less side effect
Adverse effect of using PPIs
Reduction in stomach acid
Hypochlorhydria (too high pH)
Polyps can be cancerous
can worsen H. Pylori infection due to increase survival cuz of higher stomach pH
How does H. Pylori survives in stomach acid?
bacterial UREASE enzyme produce AMMONIA with H2O to quench HCL
can lead to destruction of stomach epithelium and ulceration
Detection methods of H. Pylori
13C Assay (breath test) check to see if there is 13CO2 in breath
PCR test (stool sample)
Inflammatory Bowel Disease (IBD)
inflammation of digestive tract
Crohn’s disease
Chronic diarrhea, abdominal pain, fever, weight loss
Ulcerative colitis (restricted to large intestine)
Leukocytes produce inflammatory cytokines by TLR stimulation leads to inflammation
Mesalazine
first line treatment of IBD
second line treatment: glucocorticoids
Fecal microbiota transplantation
Transplantation of a healthy donor’s stool to a IBD patient
altering composition of gut microbiota repertoire
How to measure lung function?
Spirometry
Forced Vital Capacity (FVC)
Forced Expiratory Volume (FEV)
FEV1 = 80%FVC in 1s (normal) reduced FEV (30% to 60% decrease)
4 features of asthma
Remodeling
Edema
Immune cells
Bronchospasm (contraction of airways)
Atropine
non-selective muscarinic M2 M3 antagonist
Tiotropium (Spiriva)
muscarinic receptor antagonist
binds to M2 briefly but long lasting effect on M3
bronchodilation
Ipratropium Bromide
Quaternary ammonium derivative: does not cross BBB or circulatory system
USED AS RESCUE MEDICATION
less effective than B2 Adrenergic Agonist
Theophylline, Theobromine, caffeine
Methylxanthines
low costs
targets CNS kidney, cardiac ,skeletal and smooth muscle
4th line treatment because narrow therapeutic index (TI)
Roflumilast
PDE-4 Inhibitor
lead to accumulation of cAMP
can increase signalling of B2 Adr Receptors
bronchial relaxation
Albuterol, Terbutaline, Salmeterol, Formoterol
B2 Adrenergic Agonists
relax smooth muscle in bronchioles
inhibit release of bronco-constricting mediators and vascular leakage
reduce cardiac stimulation
RESCUE MEDICATION
B2 agonist MOA
Gs leads to increase cAMP
decrease intracellular calcium
inhibit MLCK
vasodilation and muscle relaxation
Beclomethasone and Ciclesonide (prodrug)
Corticosteroids, anti inflammatory
Most effective in treating chronic and severe asthma
inhibit production of inflammatory cytokines
inhibit eicosanoid synthesis
high does can initiate systemic effects
Montelukast
Leukotriene Pathway inhibitors
second line maintenance treatment with B2 Adr agonist
block lipoxygenase to synthesize leukotrienes from arachidonic acid
Cromolyn and Nedocromil
stable yet soluble salts
decrease bronchial reactivity
use prior to exercise or allergen exposure
alter function of delayed Cl- channel inhibit cell activation
Mast cell stabilizers
block degranulation
inhibit release of histamine and leukotrienes
widely prescribed in children
Anti-IgE monoclonal antibodies
Omalizumab
binds to IgE and block degranulation
reduce bronchial inflammation
expensive
adverse effect: local irritation, rare anaphylaxis
reserved for chronic severe asthma sufferers inadequately controlled by inhaled corticosteroids or long lasting B2 Adr Ag
GOLD STANDARD ASTHMA THERAPY
inhaled glucocorticoids and Long Acting B2 Agonist
glucocorticoids: reduce production of leukotrienes
beta agonist: cause bronchodilation
Symbicort: Budesonide + Formoterol
Advair: Fluticasone + Salmeterol
Biased agonist
a drug that selectively activates one pathway while sparing another pathway
B2 agonist only activates classical signalling (relaxation) but does not activate alternative signalling (B-arrestin) desensitization
Chronic Obstructive Pulmonary Disease (COPD)
Chronic bronchitis
- inflammation and swelling of the lining of the airways
- increase production of mucus
- daily cough with production of sputum for 3 months, two years in a row
Emphysema
- permanent enlargement of alveoli due to destruction of walls between alveoli
- decrease elasticity of the lung
- increase dead air volume
- destruction of alveolar walls
- necessary to breath more often
CHRONIC IRREVERSIBLE AND PROGRESSIVE
SYMPTOMS: chronic cough. shortness of breath (dyspnea), frequent respiratory, cyanosis, pulmonary hypertension
5 Treatment strategies for COPD
- quit smoking
- bronchodilators and decrease airway inflammation
- vaccination: influenza & pneumonia
- regular oxygen supplementation
- pulmonary rehabilitation
Treatment for Acute Bronchitis
- Acute mucokinetic agents
- decrease respiratory tract fluid production via atropine - Mukokinetic agents (expectorants)
- prevent drying out of secretions
- increase productive cough (clear mucus from tract)
- Guaifenesin (mucinex) - Mucolytic agents
-liquefy mucus
-Acetyl cysteine
-reduce viscosity of mucus
-antioxidant
usually given as aerosols
adverse effect: nausea vomiting stomatitis
Antitussive Drugs (drugs that suppress coughing)
prevent chronic cough leads to fatigue
Opioid Agents: CODEINE, HYDROCODONE
cough suppression
elevates cough threshold
Non-opioid agents: Dextromethorphan
no analgesic/additive properties
half as potent as codeine
fewer adverse effect
