Medium – increases HR and contractility of heart; High – increases afterload (vasoconstriction)

Medium – Beta₁ agonist (also has low dose actions)

High – Alpha₁ agonist (also has low and medium dose actions)

For treatment of bradycardias

Blocks muscarinic receptors; Ach normally slows the SA node, so blocking it will speed up the SA node

For treatment of bradycardias

Beta₁-adrenergic agonist; stimulates Beta₁ receptors and increases HR

Suppress conduction in the region where the tachycardia is generated

Preferentially bind to and block sodium channels in cardiac tissue that is damaged (ischemic, depolarized) and firing rapidly

Slow HR, decrease conduction velocity through AV node and increase refractory period of AV node

Inhibit the sympathetic activation of the heart

Prolong the action potential duration and therefore prolong the refractory period

Block the K⁺ channels responsible for repolarizing the heart, it does this in normal tissue beside the dead tissue so that it stops the re-entry circuit

Decrease AV node conduction velocity and increase AV node refractory period

Block calcium channels in cardiac tissue and prolong conduction through the AV node

Anti-platelet = prolonged bleeding time

Inhibits the synthesis of thromboxane A₂  (causes platelets to change shape, release granules and aggregate) by irreversible acetylation of the enzyme cyclooxygenase (COX)

Fibrinolytic = lyses thrombi; must be given within 4-6 hour after infarct

Catalyzes the formation of plasmin from its precursor plasminogen; preferentially activates the plasminogen that is bound to fibrin

Inactive prodrug, hydrolyzed in the GI to active form;HMG CoA Reductase inhibitor = decreases the synthesis of cholesterol

It is a structural analog to HMG CoA, so it partially inhibits the HMG CoA reductase enzyme so that it will not go on to catalyze the formation of cholesterol

Requires hepatic activation; Anti-platelet = prolong bleeding time, but also reduces clotting on implanted stents

Irreversibly inhibits ADP-induced platelet aggregation by preventing binding of ADP to its platelet receptor so ADP mediated activation of glycoprotein GPIIb/IIIa complex is impaired = inhibiting platelet aggregation

Opioid analgesic

Opioid receptor agonist, selective to the mu receptor = analgesic

Weak bases that react with gastric hydrochloric acid to form a salt and water

Reduces intragastric acidity, them may also promote mucosal defense mechanisms through stimulation of prostaglandin production

Competitive inhibitor of the parietal cell H₂ receptors and suppresses basal and meal-stimulated acid secretion

Histamine released from enterocromaffin like cell (ECL) by gastrin or vagal stimulation is blocked from binding to the parietal cell H₂ receptor; direct stimulation of parietal cell by gastrin or Ach results in diminished acid secretion when H₂ is blocked

Catatonia, amnesia and analgesia without loss of conciousness, also increased HR, BP and CO (due to SNS excitation and inhibition of NA reuptake)

Blockade of membrane effects of the excitatory neurotransmitter glutamic acid at the NMDA (N-methyl-D-aspartate) receptor subtype

Decreases BP and systemic vascular resistance without significant alteration in HR or CO

Selective beta₂ agonist and nonselective Beta antagonist

Blocks the vagal slowing and relative tachycardia

Causes reversible (surmountable) blockade of cholinomimetic actions at muscarinic receptors (can be overcome by a large amount of Ach) preventing release of IP₃ and the inhibition of adenyl cyclase

Sympathomimetic – increases BP

Acts directly on alpha receptors as an agonist = vasoconstriction; but may also cause decreased HR due to baroreceptor reflex

Vasoconstrictor and cardiac stimulant

Always acts on Beta₁ receptors to increase HR and contractility; at low doses also get Beta₂ = vasodilation; at intermediate doses get beta₂ and alpha in balance = no effect; at high dose alpha₁ = vasoconstriction

Depolarizing neuromuscular blocking agent  = paralysis

It reacts with nicotinic receptor to open the ion channel and cause depolarization of the motor end plate and spreads to cause contraction in muscle motor units, but it does not allow repolarization so subsequent impulses do not cause contraction

Nondepolarizing neuromuscular blocking agent = paralysis

At nicotinic receptor site it competes with Ach for a spot on the receptor; no Ach in receptor = no contraction; Also blocks muscarinic receptors (blocks vagal response = increase HR)

Cholinesterase inhibitor

Inhibits cholinesterase, the enzyme that breaks down Ach in the neuromuscular junction, this increases the concentration of Ach = increased activation of sympathetic and parasympathetic ganglia; also relieves vagal block = decreases HR

Decreases TPR and BP

Reversible nonselective alpha₁ and alpha₂ receptor antagonist = blocks vasoconstriction and presynaptic release of NA

Increases HR and contractility = increased Co

Potent beta receptor agonaist

Vasodilation

Reversible alpha₁ selective antagonist; alpha₁ receptors are n the smooth muscle of the vasculature, bladder neck and prostate

Vasodilation

Competitve uroselective alpha₁ antagonist; has more activity against alpha_1A and alpha_1D than the others so it may be important for prostate smooth muscle (BPH)

Cell wall synthesis inhibitor

Active vs. aerobic gram-negative

Inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBP) in cell wall and interference ultimately leads to cell lysis by autolysins

Cell wall synthesis inhibitor

Active vs. beta-lactamase producing staph or penicillin susceptible step and pneumococci

Inhibits bacterial growth by covalently bonding to PBP so the synthesis of peptidoglycan is blocked and the cell dies

Cell wall synthesis inhibitor

Active vs. aerobic gram-positive cocci

Inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBP located in the cell wall, blocking cell wall synthesis and leading to cell lysis

Cell wall synthesis inhibitor

Active vs. gram-positive and orally vs. C. difficile; also vs. MRSA

Inhibits cell wall synthesis early by binding to the D-Ala-D-Ala terminus of the peptidoglycan pentapeptide inhibiting the transglycosylas, preventing further elongation of the peptidoglycan and cross-linking; it becomes weakend and cell is susceptible to lysis

Protein synthesis inhibitor

Binds to 50S ribosomal subunit and inhibits peptide bond formation

Protein synthesis inhibitor

Binds to 50S ribosomal subunit and prevents translocation

Protein synthesis inhibitor

Changes shape of 30S ribosomal subunit and causes code on mRNA to be read incorrectly

Protein synthesis inhibitor

Interferes with attachment of tRNA to mRNA-ribosome complex

Protein synthesis inhibitor

Active vs. gram-negative, esp. Chlamydia and some gram-positives

Binds to the 50S ribosomal subunit and is similar to erythromycin

Protein synthesis inhibitor

Active vs. wide range of gram-positives and gram-negatives, not for use vs. gram-negative aerobes

Binds to the 50S ribosomal subunit of bacteria

Inhibitor of bacterial DNA synthesis

Inhibits Dihydropteroate synthetase enzyme involved in converting PABA to Folate – Folate is needed to form Tetrahydrofolate (THF) which is needed for 1-carbon metabolism, important for purine and pyrimidine synthesis

Inhibitor of bacterial DNA synthesis

Inhibits Dihydrofolate reductase (DHFR) enzyme needed to convert Folate to THF

DNA gyrase inhibitor

Activity vs. gram-positive and gram-negative; also against atypical pneumonia agents, intracellular bugs and anaerobes

Block DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV (blocking of which interferes with separation of replicated chromosomal DNA)

Antibacterial and Antiprotozoal

Active vs. protozoa (Trichomonas, giardia, amebiasis) and anaerobic bacteria (also H. pylori)

Readily taken up by anaerobic organisms and reduced intracellularly; reduced form disrupts DNA’s helical structure thereby inhibiting bacterial nucleic acid synthesis and results in cell death

Agents that disrupt the membrane

Has detergent like properties, binds to phosphatidylethanolamine in cell membrane and causes disruption of the bacterial cell membrane

Antiviral agent activated by viral thymidine kinase, it must by phosphorylated 3 times to be active

Active against herpes viruses

Competitively inhibits viral DNA polymerase; it can incorporate into viral DNA = chain termination; Formation of a complex at the end of DNA may lead to irreversible inactivation of viral DNA polymerase

L-valyl ester of acyclovir; rapidly converted to acyclovir

Same mechanism of action as acyclovir but 3-5 times greater serum levels (=lower dosing) are achieved with oral doses (similar levels to IV acyclovir)

Cross-link between bases in DNA

Bind covalently to the N7 position of guanine bases

Not an alkylating agent, but acts similarly

Cross-links DNA

Prodrug, has to first be activated in the liver (P450 enzyme); cell cycle phase NON-SPECIFIC

Cross-links DNA

Intercalating agent; wide spectrum of use; cell cycle phase NON-SPECIFIC

Slots into the DNA helix; blockade of DNA synthesis/mRNA production, DNA strand breakage, inhibition of topoisomerase II, release of free radicals

Topoisomerase I inhibitor; prodrug first converted in the liver to an active metabolite SN-38

Interferes with the process that allows strand breaks in single DNA strands

Topoisomerase II inhibitor; Acts in the late S-G₂ phase

Interferes with the process that allows strand breaks in both DNA strands

Purine antagonist; prodrug, has to first be metabolized by the enzyme HGPRT to a nucleotide 6-TIA)

6-TiA inhibits several enzymes in purine synthesis so DNA synthesis is inhibited; it is primarily used to treat childhood leukemias

Pyrimidine antagonist; prodrug first converted to a nucleotide derivative

The nucleotide derivative (5-FdUMP) inhibits the enzyme thymidylate synthetase = inhibition of DNA synthesis

Cofactor antagonist; cell cycle phase SPECIFIC (S phase)

It is taken into the cell by the folate uptake carrier; it then inhibits DHFR, reducing the amount of available THF = reduces DNA synthesis

Vinca alkaloid; affects the microtubule system; used to treat childhood leukemias; cell cycle phase SPECIFIC (M phase)

This drug destabilizes the microtubules which compromises their function and disrupts (poisons) the mitotic spindle

Taxane; affects the microtubule system

This drug causes excessive stability of microtubules causing disruption of the mitotic spindle

Drug vs. Breast cancer

A synthetic peptide analogue of GnRH

Initially stimulates FSH and LH release, then produces a long term inhibition (receptor desensitization and prolonged down regulation)

Drug vs. Breast cancer

Inhibits the aromatase enzyme (involved in production of steroid hormones) and therefore prevents the production of estrogen

Drug vs. Breast cancer

Mainly acts as an estrogen antagonist; a complex drug that is a partial agonist and is also active in other pathways

Glucocorticoids catabolize – lymphoid tissue, skin and connective tissue (to AA), adipose (to FA and glycerol), and muscle (to AA) to ensure enough glucose for the brain; GC can have both GC and MC activity; Has a diurnal action, so more should be given in the morning and less at night

It circulates in plasma bound to corticosteroid binding globulin (CBG) then it enters the cell by facilitated transport and drops the CBG. It binds to GRalpha in the cytoplasm and then forms a dimer and goes into the nucleus. It then binds to its response element (GRE) on DNA and can increase or decrease transcription

Acts at the epithelium of the renal distal and collecting tubules to retain Na, HCO₃^- and water, while promoting K excretion from the distal tubule

Binds to MR in cytoplasm and binding causes dissociation from CBG (for DOC). Then a dimer is formed. It goes into the nucleus and alters gene expression of signaling proteins, which signal to the sodium channels to modulate ion channel activity

Given as a MC replacement therapy; Possesses significant GC activity, but no GC effects seen at typical therapeutic doses

Intermediate to long acting MC

Used to suppress excess GC production in patients with Ectopic ACTH Syndrome

Blocks 11beta-hydroxylation, which is essential for GC activity; it also blocks 18-dehydrogenation

For Cushing’s syndrome (ACTH hypersecretion)

Potent non-selective inhibitor of P450 enzymes.

For Cushing’s syndrome – used in combination with Ketoconozol

Reversible inhibitor of CYP11A1; blocks the conversion of cholesterol to pregnenolone (first step in all steroid biosynthesis blocked – no GC, but also no MC!)

To treat adrenocorical carcinoma

Causes necrosis of zona fasciculate and reticularis – this wipes out the GC producing part but spares the MC producing part (Glomerulosa)

Glucose storage; for Type I diabetics

Rapid acting – onset = 15 min, duration = 3-5 h; Regular (Short) – onset = 30 min, duration  = 5-8h; Intermediate – onset = 1-3h, duration = 18-24h; Long – onset = 4h, duration = 24-36h

Insulin Secretagogues (need pancreas to be functional and producing insulin)

Close K channels on pancreatic beta cell – cause depolarization leading to insulin secretion

Insulin Secretagogues (need pancreas to be functional and producing insulin)

Close K channels on pancreatic beta cell – cause depolarization leading to insulin secretion

Bind to same site as sulfonylureas and an additional site

Reduce fasting plasma glucose levels and improves whole body insulin stimulated glucose metabolism (insulin sensitivity); Does not depend on a functioning beta cell

Decreases hepatic and renal gluconeogunesis; reduces intestinal absorption of glucose; increases peripheral glucose uptake and utilization (increase in glucose transporters in skeletal muscle/adipose – GLUT 1-4); reduces plasma glucogon levels

Insulin sensitizer (need functioning beta cell) ; work primarily on fat and muscle to enhance glucose uptake and utilization

Peroxisome proliferators receptor gamma (PPARgamma) agonists; PPARgamma regulates insulin responsive genes; increases insulin sensitivity

Delays absorption of starch and disaccharides because it does let larger pieces to be chopped up

Competitive, reversible inhibitors of alpha-glucosidase; delays postprandial absorption of starch and disaccharides; thus decreasing postprandial hyperglycemia

Sedative-hypnotic - Used to treat anxiety and insomnia; differ based on onset of action, half lives and whether or not the have active metabolites; if they have active metabolites they are likely to be longer acting

Bind to GABA_A receptor on Cl^- channels on the gamma subunit; it does not act directly with the GABA_A receptor, but it increase the affinity for GABA to bind; This increases the FREQUENCY of channel opening; so more Cl goes into the cell and hyperpolarizes the cell

Sedative-hypnotic; other effects: Anticonvulsant, muscle relaxation, respiratory and cardiovascular depression, can be used a anesthesia by IV

Binds to a separate binding site on GABA_A receptor; they facilitate the actions of GABA by increasing the DURATION of the Cl channel opening; at high concentration it may also be a GABA-mimetic

Relieves anxiety WITHOUT causing marked SEDATION or euphoric effects; no hypnotic, anticonvulsant or muscle relaxant properties

Partial agonist (agonist and antagonist properties) at brain 5-HT_1A receptors, but also has affinity for D₂ receptors in the brain; takes more than a week to take effect

Tricyclic Antidepressant

Block the amine (norepinephrine and/or serotonin) reuptake pumps, which terminate amine neurotransmission; This permits the neurotransmitter to persist in the synaptic cleft for longer

2^nd generation heterocyclic antidepressant

Inhibit the reuptake of amines into the nerve terminal; different drugs have different selectivities for Serotonin, NA and Dopamine

3^rd generation heterocyclic antidepressant

Potent antihistaminic with greater sedating effects than the other second and third generation antidepressants; combines 5-HT₂ receptor and alpha-adrenoceptor antagonism; blocking alpha₂ receptors blocks NA negative feedback = more NA

Selective Serotonin Reuptake Inhibitor (SSRI)

Potentiates serotonin in the CNS by inhibiting reuptake

Monoamine Oxidase Inhibitors (MAOI)

Binds irreversibly to monoamine oxidase; MAO-A is primarily responsible for NA, Serotonin and tyramine metabolism; MAO-B is more selective for dopamine metabolism; blocking them will increase these amines; MAO is actually inside the nerve terminal, so it increases the amount of stored amine

Used for Partial seizures and Generalized Tonic-Clonic Seizures

Alters Na channel, prolongs opening time; essentially blocks Na channels

Used for Partial seizures and Generalized Tonic-Clonic Seizures

Like phenytoin: Blocks Na channels and inhibits high frequency repetitive firing in neurons and acts presynaptically to decrease synaptic transmission

Used for Generalized Tonic-Clonic Seizures (or as an adjunct for Partial seizures)

Blocks Na channels

Adjunct for treatment of partial seizures

Blocks glycine activation of NMDA receptors (glutamate) and inhibit initiation of seizures

Adjunct for treatment of partial seizures

May alter GABA metabolism or alter reuptake by presynaptic GABA transporters

Adjunct for treatment of all types of seizures

Blocks voltage-sensitive NA channels and has another MOA (inhibits release of excitatory AA such as glutamate?)

Adjucnct for treatment of all types of seizures

Blocks voltage-sensitive NA channels, augments GABA activation of GABA_A receptor, blocks kainite and AMPA glutamate receptors

Used for Generalized Absence, Myoclonic or Atonic seizures

Blocks T-type Ca channels in thalamic neurons

It increases dopamine in the brain for Parkinson’s because it crosses the BBB and then is converted to dopamine by LAAD

L-dopa is taken up by dopaminergic neurons in the substantia nigra and converted to dopamine by L-Amino Acid Decarboxylase (LAAD)

Given with L-dopa so it doesn’t get converted to dopamine in the tissues, but it does NOT cross the BBB

Inhibits the conversion of L-dopa to dopamine by LAAD in peripheral dissues

Direct acting dopamine receptor agonist

Increases the release of dopamine from the nigrostriatal neurons or inhibits the reuptake of dopamine by these neurons

Increases oral bioavailability and half-life of L-dopa

Inhibits COMT (normally degrades dopamine)

Antipsychotic

(All antipsychoitcs block D₂ receptor – variation in degree of blockade in relation to actions on other receptors)

Block alpha₁ adrenoceptors more potently than D₂ receptors; also strongly block 5-HT₂ receptors; low affinity for D₁ receptors

Antipsychotic – most widely used

Act mainly on D₂ receptors, some effect on 5-HT₂ and alpha₁

Antipsychotic

Rispiridone – equally potent in blocking D₂ and 5-HT₂; Clozapine – better at blocking D₄, 5-HT₂, alpha₁ and histamine H₁ (blockage of H₁ gives the sedative effects) than D₁ or D₂

Adverse effects for all antipsychotics:

1. Behavioural effects (pseudodepression)

2. Neurological effects (Dopamine blockade = Parkinson’s, akeathisia, acute dystonic reactions, tardive dyskinesia)

3. ANS (muscarinic blockade = constipation, urinary retention; alpha blockade = orthostatic hypotension or impaired ejaculation)

4. Metabolic and endocrine (weight gain, loss of libido, impotence;dopamine blockade = hyperprolactinemia,)

5. Toxic or allergic effects (agranulocytosis (esp. clozapine), choleostatic jaundice)

6. Ocular complications (Thioridazine only)

7. Cardiac toxicity (Thioridazine)

8. Neuroleptic Malignant Syndrome (life threatening – due to sensitivity to extrapyramidal effects of the drugs)

NSAID: Analgesic, Antipyretic, Anti-inflammatory, Anti-platelet

Irreversibly acetylates COX1 and COX2 to inhibit them and cause a decrease in prostaglandin synthesis however it has much more COX1 inhibition than COX2 (166 x more)

NSAID: Analgesic, Antipyretic, Anti-inflammatory

Competitive (reversible) inhibitor of COX1 and COX2 (binds to a different binding site); however it has more COX1 inhibition than COX2 (15 x more)

NSAID: Analgesic, Antipyretic, Anti-inflammatory

Competitive (reversible) inhibitor of COX1 and COX2 (binds to a different binding site); it has almost equal inhibition of COX1 and COX2 = less GI side effects

Atypical NSAID: Analgesic and Antipyretic

Inhibits COX3 centrally (in CNS); also activates spinal 5-HT3 receptors (spinal gating – suppresses pain in ascending spinal cord); spinal/supraspinal synergy occurs

Mu agonist opioid

Binding to a receptor coupled to a G protein can: close voltage-gated Ca channels on presynaptic nerve terminals and thereby reduce transmitter release and hyperpolarize and thus inhibit postsynaptic neurons by opening K channels

Kappa  agonist/Mu antagonist opioid

Binding to a receptor coupled to a G protein can: close voltage-gated Ca channels on presynaptic nerve terminals and thereby reduce transmitter release and hyperpolarize and thus inhibit postsynaptic neurons by opening K channels

Mu antagonists opioid

Binding to a receptor coupled to a G protein can: close voltage-gated Ca channels on presynaptic nerve terminals and thereby reduce transmitter release and hyperpolarize and thus inhibit postsynaptic neurons by opening K channels

Blockade of voltage-gated sodium channels – this blocks Na channels from opening during an action potential and allowing Na into the cell to cause depolarization – so it blocking depolarization