Pharmacology week 2

Start Studying!

Terms

undefined, object

copy deck

Kd - what is it? - low Kd means what?: Affinity
Kd = k2 / k1
- low Kd means high affinity
where is there a good example of "spare receptors"?: myocardial cells contain a large proportion of spare Beta-adrenoceptors
give three examples of ion channels: nicotinic, GABA, NMDA
what does MLD stand for?: Minimum Lethal Dose
fatty acid precursor from which the 2-series of prostaglandins (PG2): arachidonic acid (eicosatetraenoic acid) --> PG2 (2 double bonds)
name three agents that have been found to help block the lipoxygenase pathway: note: these are effective at reducing the occurrence of asthmatic symptoms and the need for Beta-agonists to produce bronchiolar dilation

zileuton, zafirlukast, and montelukast (singulair)
what are the major cyclooxygenase products and their biological activities?: PGE2, PGF2-alpha, PGD2 -- vasodilation, inc vasc. permeability, sensitize to pain, inc body temp, uterine contraction, dec gastric acid, inc gastric mucous, Ca2+ mobilization, inc Na + H20 excretion

PGI2 -- inhibits platelet aggregation, vasodilation

Thromboxane A2 -- induces platelet aggregation, smooth muscle contraction
LTC4 and LTD4: potent contractors of airway smooth muscle

important in generation of inc airway resistance in asthma and immediate hypersensitivity rxns
5 ways AA metabolites contribute to inflammation:: (1) inc capillary permeability

(2) induce local vasodilation and thus redness

(3) production of oxygen gree radicals

(4) promoting infiltration of inflammatory cells

(5) producing inflammation-associated hyperalgesia
Misoprostol (PGE1): inhibits gastric acid and stimulates gastric mucous secretion

used for the treatment of GI ulceration
Mifepristone: RU-486

blocks progesterone receptors causing the uterus to reject the implanted egg
Misoprostol: given two days after RU-486, causes the cervix to soften and dilate and the uterus to contract and expel the embryo
Zafirlukast: aka Accolate

competitive leukotriene receptor blocker
Montelukast: aka Singulair

competitive leukotriene receptor blocker
Zileuton: aka Zyflo

5-LO enzyme inhibitor
Celexocib: aka Celebrex

COX-2 selective inhibitor
diflunisal: difluorophenyl derivative of salicylic acid; competitive inhibitor of cyclooxygenase; more potent anti-inflammatory agent thatn aspirin but has no anti-pyretic effects
why should NSAIDs be used with caution in individuals with reduced renal or liver function?: can dec GFR in those with renal failure, congestive heart disease or cirrhosis of the liver
Ibuprofen: less AIA than indomethacin

analgesic, antipyretic

uses: dysmenorrhea, RA

side effects: well tolerated
Indomethacin: potent AIA, antipyretic

t1/2 = 4-12 hours

use: for RA when ASA ineffective
Naproxen: slightly less AIA than indomethacin, analgesic, antipyretic

absorbption inc by NaHCO3, dec by Al(OH)3 and antacids

t1/2 = 10-17 hours

use: RA
Diclofenac: potent AIA

uses: RA, osteoarthritis

GI effects common
Ketorolac: strong analgesic properties which are likely not due to CO inhibition

oral and injectable for acute pain, post-op analgesia, adjunct use in surgery

NOT good for chronic inflammation
Celecoxib: selective COX-2 inhibitor

uses: osteoarthritis and RA

less GI ulcers and little/no effect on bleeding time
acetaminophen - general: not an AIA or anti-thrombotic agent (does not inhibit cyclooxygenase)

equal to aspirin in analgesic and antipyretic properties
phenacetin: chemically related to acetaminophen and once prevalent in many OTC agents

no longer advised since it is believed to cause analgesic nephropathy
acetaminophen excretion: 80% excreted in urine after liver conjugation primarily with glucoronic acid
N-acetylcysteine: Mucomyst

antidote for acetaminophen poisoning

oxygen free radical scavenger and promotes formation of glutathione
Mecamyline: ganglionic blocker, effective orally, CNS effects
Fick's Law of Passive Diffusion: Diffusion Rate = -DAK[Cout-Cin} / thickness
volume of distribution eqn: Vd = Q/C
Q = amount of drug in body (g)
C = unbound plasma drug conc (g/liter)
Black Cohosh: uses: alleviates menopausal symptoms, ease menstrual discomfort, rheumatism, cough, high cholesterol levels, hardening of the arteries
Chamomile: uses: reduce flatulence and/or diarrhea, treat travel sickness, produce mild sedation, reduce restlessness and irritability, treat the common cold, treat fevers, reduce cough, liver, and gall bladder complaints, inc appetite
Echinacea: stimulate the immune system, treatment for common colds, topically: wounds and burns

- studies indicate no difference from placebo in treating the common cold
Feverfew: uses: prevention of migraine headaches, prevention and treatment of asthma, RA, painful menstrual periods, inflammatory skin conditions such as psoriasis

insufficient evidence for preventing migraine
Garlic: antioxidant, reduce cholesterol and triglycerides, prevent hardening of the arteries and blood clotting, reduce BP, inc effects of the immune system, reduce blood sugar levels, reduce menstrual pain, antibiotic
Ginger: treatment and prevention of motion sickness, inc appetite, red stomach acidity, reduce severe nausea in pregnancy
Ginkgo Biloba: Antioxidant properties. Enhances memory in Alzheimer's. Treatment of cerebrovascular dysfunctions and peripheral vascular disorders
Ginseng: cancer preventive, alleviation of menopausal symptoms, AIA, improve the body's resistance, inc vitality, inc immune function, treatment of cardiovascular diseases, improved physical / sexual performance
Green Tea: Cancer preventive, dental caries, hypercholesterolemia, atherosclerosis, diuretic, stimulant

in vitro and lab animal studies consistent with chemopreventative and atherosclerosis effects
St. John's Wort: uses: depression

has been found to inhibit MAO and 5-HT uptake
Saw Palmetto: BPH, inc sperm production, breast size, inc sexual vigor, mild diuretic
Valerian: sedative, antispasmodic
what are the three conditions that release histamine?: (1) tissue injury

(2) allergic rxns

(3) drugs / foreign compds
H1 receptors: mediate effects on smooth muscle leading to vasodilation, inc vascular permeability, and contraction of nonvascular smooth muscle

effects blocked by classic antihistamine
H2 receptors: mediate histamine stimulation of gastric acid secretion and may be involved in cardiac stimulation
H3 receptors: feedback inhibitors in CNS GI tract, lung, heart
what are the three main cardiovascular responses to histamine (H1 responses)?: (1) dilation of resistance vessels

(2) inc capillary permeability

(3) triple effect
what effect can histamine have on smooth vessels of bronchioles?: especially in asthmatics, histamine causes contraction of nonvascular smooth muscle
what effects does histamine have on the exocrine glands?: - potent stimulator of gastric secretion (H2)

- enhances salivary and lacrimal gland secretion (H1)

- stimulates chromaffin cells in adrenal medulla to secrete catecholamines
what main effect does histamine have on the NS?: H1 stimulates pain and itching
what are the pharmacological actions of H1 blockers?: - inhibits contaction of GI and bronchial smooth muscle

- inhibits triple response

- inhibits salivary and lacrimal

- inhibits release of EPI from adrenal medulla (stim by histamine)

- depression of CNS

- inhibition of nausea and vomiting
what are the pharmacological effects of the H2-receptor antagonists: - competitive antagonists at the H2 receptors

- inhibits secretory fxn of gastric mucosa

- reduces volume of gastric acid and concent. of pepsin
xenobiotic: a chemical that interacts with an organism that is not found in the normal metabolic pathway of that organism
toxicity exposure - acute - sub acute - sub chronic - chronic: acute: single dose w/in 24 h

sub acute: repeated exposure for < 4 wks

sub chronic: 1-3 months

chronic: > 3 months
cholinergic overdose effects: SLUGBAM

Salivation
Lacrimation
Urination
GI Distress
Bronchorrhea
Abodminal Cramps
Miosis
nicotinic overdose effects: MTWTHF

Mydriasis
Tachycardia
Weakness
Hyperthermia
Fasciculations
give an example of a non-depolarizing neuromuscular blocking agent: tubocurarine
give an example of a depolarizing blocking agent: succinylcholine
describe what happens when succinylcholine interacts with a NMJ: Phase 1: more stable agonist than ACh, causes persistent depolarizaation of the muscle end plate, yielding fasciculations

Phase II: succinylcholine will desensitize the muscle nicotinic receptors, resulting in repolarization of the M, but the end plate remains blocked
what type of paralysis do you get with nondepolarizing neuromuscular blocking agents?: relaxed, flaccid paralysis
can NMJ blocked (nondepolarizing drugs) be reversed?: yes, by inc [ACh]
is codeine a weak base or acid?: weak base
give two examples of drugs used effectively topically: nitroglycerine (angina)
scopolamine (motion sickness)
discuss how capillary permeability varies with the following tissues: liver / kidney / brain: liver in permeable to most drugs (no endothilial cells)

kidney is permeable to most non-protein-bound drugs (fenestrated endothelium)

Brain has limited permeability to most drugs (endothelium with tight jxns)
compare the elimination half-life of diazapam in the infant and in the elderly: diazepam is a highly lipid-soluble drug

infant has very little fat, elderly has the most

therefore will be cleared quickly in the infant but slowly in the elderly
connection b/t grapefruit juice and drug metabolism: grapefruit juice can inhibit P450 enzymes and dec metabolism of certain drugs
oxidative polymorphism affecting phenytoin: P450 2C19 polymorphism, inc toxicity, deficient para-hydroxylation in the liver
2 eqns for t1/2: t1/2 = 0.693 / ke

t1/2 = 0.693 Vd / CL
eqn for ke: ke = CL/Vd
eqn for Vd: Vd = Q/C
eqn for Css: Css = (F x D) / (CL x T)
eqn for LD: LD = (Css x Vd) / F
eqn for MD: MD = (Css x CL x T) / F
what is an example of a mixed acting sympathomimetic agent?: ephedrine
name 4 selective beta-2 agonists: albuterol, ritodrine, terbutaline, metaproterenol
name 2 selective beta1-antagonists: dobutamine, prenalternol
name 2 selective alpha1-agonists: methoxamine, phenylephrine
name 2 selective alpha2-agonists: clonidine, guanfacine
name two MAO Inhibitors: Pargyline, Tranylcypromine
Ephedrine: (mixed action)
· direct action (alpha- and beta-receptors)
· indirect action to release norepinephrine
meperidine: opioid

toxicity=tremors, excitation, cardiac effects

has an active metabolite which is a proconvulsant and hallucinogenic --> contraindicated in patients with renal failure (metabolite not effectively cleared)
which opioid is very toxic when combined with alcohol?: propoxyphene
does fentanyl have a long or short duration of action?: short

Start Studying!

Deck Info

Number of cards 84